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Neuropsychological AssessmentNEUROPSYCHOLOGICALASSESSMENTFifth EditionMuriel Deutsch LezakDiane B. HowiesonErin D. BiglerDaniel TranelOxford University Press, Inc., publishes works that furtherOxford University’s objective of excellencein research, scholarship, and education.Oxford New YorkAuckland Cape Town Dar es Salaam Hong Kong KarachiKuala Lumpur Madrid Melbourne Mexico City NairobiNew Delhi Shanghai Taipei TorontoWith offices inArgentina Austria Brazil Chile Czech Republic France GreeceGuatemala Hungary Italy Japan Poland Portugal SingaporeSouth Korea Switzerland Thailand Turkey Ukraine VietnamCopyright © 1976, 1983, 1995, 2004, 2012 by Oxford University Press, Inc.Published by Oxford University Press, Inc.198 Madison Avenue, New York, New York 10016www.oup.comOxford is a registered trademark of Oxford University PressAll rights reserved. No part of this publication may be reproduced,stored in a retrieval system, or transmitted, in any form or by any means,electronic, mechanical, photocopying, recording, or otherwise,without the prior permission of Oxford University Press.Library of Congress Cataloging-in-Publication DataNeuropsychological assessment / Muriel D. Lezak … [et al.]. — 5th ed.p. cm.Includes bibliographical references and index.ISBN 978–0–19–539552–51. Neuropsychological tests. I. Lezak, Muriel Deutsch.RC386.6.N48L49 2012616.8’0475—dc232011022190http://www.oup.com/Dedicated in gratitude for the loving support from our spouses, JohnHowieson, Jan Bigler, and Natalie Denburg; and in memory of SidneyLezak whose love and encouragement made this work possible.PrefaceDirect observation of the fully integrated functioning of living human brains will probablyalways be impossible.M.D. Lezak, 1983, p. 15What did we know of possibilities, just a little more than a quarter of acentury ago? The “black box” ofclassical psychology is no longer impenetrable as creativeneuroscientists with ever more revealing neuroimaging techniques aredevising new and powerful ways of finding windows into the black box. Inneuroimaging we can now trace neural pathways, relate cortical areas toaspects of thinking and feeling—even “see” free association in the “default”state—and are discovering how all this is activated and integrated incomplex, reactive, and interactive neural systems. We may yet uncover thenature of (self- and other-) consciousness and how synapticinterconnections, the juices that flow from them, and the myriad otherongoing interactive neural processes get translated into the experience ofexperiencing. We can never again say “never” in neuroscience.Yet, as entrancing and even astonishing as are the findings the newtechnologies bring to neuroscience, it is important to be mindful of theirroots in human observations. As these technologically enhancedobservations of the brain at work open the way for new insights about brainfunction and its behavioral correlates they also confirm, over and overagain, the foundational hypotheses of neuropsychology—hypothesesgenerated from direct observations by neuropsychologists and neurologistswho studied and compared the behavior of both normal and brain impairedpersons. These foundational hypotheses guide practitioners in the clinicalneurosciences today, whether observations come from a clinician’s eyes andears or a machine. In the clinic, observations of brain function bytechnological devices enhance understanding of behavioral data andsometimes aid in prediction, but cannot substitute for clinical observations.When the earliest neuroimaging techniques became available, somethought that neuropsychologists would no longer be needed as it hadbecome unnecessary to improve the odds of guessing a lesion site, a onceimportant task for neuropsychologists. Today’s advanced neuroimagingtechniques make it possible to predict with a reasonable degree of accuracyremarkably subtle manifestations, such as the differences between sociallyisolated brain injured patients who will have difficulty in social interactionsalthough actively seeking them, versus those who may be socially skilledbut lack incentive to socialize. Yet this new level of prediction, rather thansubstituting for human observation and human intervention, only raisesmore questions for experienced clinical neuroscientists: e.g., whatcircumstances exacerbate or alleviate the problem? what compensatoryabilities are available to the patient? is the patient aware of the problem and,if so, can this awareness be used constructively? is this a problem thataffects employability and, if so, how? and so on. Data generated by newneurotechnologies may help identify potential problem areas:neuropsychologists can find out how these problems may play out in reallife, in human terms, and what can be done about them.Thus, in the fifth incarnation of Neuropsychological Assessment, wehave tried to provide a wide-ranging report on neuropsychology as scienceand as a clinical specialty that is as relevant today as it was when it firstappeared 35 years ago. Certainly what is relevant in 2012 is somewhatdifferent from 1976 as the scope of activities and responsibilities ofneuropsychologists has enlarged and the knowledge base necessary forclinical practice as well as for research has expanded exponentially.Three major additions distinguish the first and the fifth editions ofNeuropsychological Assessment. Most obvious to the experiencedneuropsychologist is the proliferation of tests and the wealth of readilyavailable substantiating data. Second, a book such as this must providepractically useful information for neuropsychologists about the generations—yes, generations—of neuroimaging techniques that have evolved in thepast 30 years. Further, especially exciting and satisfying is confirmation ofwhat once was suspected about the neural organization underlying brainfunctions thanks to the marriage of sensitive, focused, clinical observationswith sensitive, focused, neuroimaging data. In this edition we convey whatis known about the enormity of interwoven, interactive, and interdependentcomplexities of neuronal processing as the brain goes about its business andhow this relates to our human strengths and frailties.What remains the same in 2012 as it was in 1976 is the responsibility ofclinicians to treat their patients as individuals, to value their individuality,and to respect them. Ultimately, our understandings about human behaviorand its neural underpinnings come from thoughtful and respectfulobservations of our patients, knowledge of their histories, and informationabout how they are living their lives.Muriel Deutsch LezakDiane B. HowiesonErin D. BiglerDaniel TranelAcknowledgmentsOnce again we want to honor our neuropsychologist friends, colleagues,and mentors who have died in the past few years. Most of what is written inthis text and much of contemporary neuropsychology as science or clinicalprofession, relies on their contributions to neuropsychology, whetherdirectly, or indirectly through their students and colleagues. We are deeplygrateful for the insightful, innovative, integrative, and helpfully practicalwork of William W. Beatty, Edith F. Kaplan, John C. Marshall, Paul Satz,Esther Strauss, and Tom Tombaugh. The authors gratefully acknowledgeTracy Abildskov in creating the various neuroimaging illustrations, Jo AnnPetrie’s editing, and Aubrey Scott’s artwork.Many of David W Loring’s important contributions to the fourth editionof Neuropsychological Assessment enrich this edition as well. We miss hishand in this edition but are grateful to have what he gave us. And thanks,too, to Julia Hannay for some invaluable chapter sections retained from thefourth edition. Special thanks go to Kenneth Manzell for his aid inpreparing the manuscript and illustrations. We are fortunate to have manycolleagues and friends in neuropsychology who—at work or in meetings—for her injuries. This examination demonstrated a small but definiteimpairment of auditory span, concentration, and mental tracking. The patient reported apervasive sense of unsureness which she expressed in hesitancy and doubt about almosteverything she did. These feelings of doubt had undermined her trust in many previouslyautomatic responses, destroying a lively spontaneity that was once a very appealing feature ofher personality. Further, like many postconcussion patients, she had compounded the problemby interpreting her inner uneasiness as symptomatic of “mental illness,” and psychiatricopinion confirmed her fears. Thus, while her cognitive impairment was not an obstacle torehabilitation, her bewildered experience of it led to disastrous changes in her personal life. Aclear explanation of her actual limitations and their implications brought immediate relief ofanxiety and set the stage for sound counseling.The concerned family, too, needs to know about their patient’s conditionin order to respond appropriately (D.N. Brooks, 1991; Camplair, Butler, andLezak, 2003; Lezak, 1988a, 1996; Proulx, 1999). Family members need tounderstand the patient’s new, often puzzling, mental changes and what maybe their psychosocial repercussions. Even quite subtle defects in motivation,in abilities to plan, organize, and carry out activities, and in self-monitoringcan compromise patients’ capacities to earn a living and thus render themsocially dependent. Moreover, many brain impaired patients no longer fiteasily into family life as irritability, self-centeredness, impulsivity, or apathycreate awesome emotional burdens on family members, generate conflictsbetween family members and with the patient, and strain family ties, oftenbeyond endurance (Lezak, 1978a, 1986a; L.M. Smith and Godfrey, 1995).3. Treatment-1: Treatment planning and remediation. Today, much more ofthe work of neuropsychologists is involved in treatment or research ontreatment (Vanderploeg, Collins, et al., 2006). Rehabilitation programs forcognitive impairments and behavioral disorders arising fromneuropathological conditions now have access to effective behavioraltreatments based on neuropsychological knowledge and tested byneuropsychological techniques (for examples from different countries see:A.-L. Christensen and Uzzell, 2000; Cohadon et al., 2002; Mattioli et al.,2010; and B.[A]. Wilson, Rous, and Sopena, 2008). Of particularneuropsychological importance is the ongoing development of treatmentprograms for soldiers sustaining brain injuries in the Gulf, Iraq, andAfghanistan wars as well as for those injured from terrorist acts (Helmick,2010).In the rehabilitation setting, the application of neuropsychologicalknowledge and neuropsychologically based treatment techniques toindividual patients creates additional assessment demands: Sensitive,broadgauged, and accurate neuropsychological assessment is necessary fordetermining the most appropriate treatment for each rehabilitation candidatewith brain dysfunction (B. Levine, Schweizer, et al., 2011; Raskin andMateer, 2000; Sloan and Ponsford, 1995; B.[A]. Wilson, 2008). Inaddressing the behavioral and cognitive aspects of patient behavior, theseassessments will include both delineation of problem areas and evaluationof the patient’s strengths and potential for rehabilitation. In programs of anybut the shortest duration, repeated assessments will be required to adaptprograms and goals to the patient’s changing needs and competencies. Sincerehabilitation treatment and care is often shared by professionals from manydisciplines and their subspecialties, such as psychiatrists, speechpathologists, rehabilitation counselors, and occupational and physicaltherapists, a current and centralized appraisal of patients’neuropsychological status enables these treatment specialists to maintaincommon goals and understanding of the patient. In addition, it may clarifythe problems underlying patients’ failures so that therapists know howpatients might improve their performances (e.g., Greenwald and Rothi,1998; B.[A]. Wilson, 1986).A 30-year-old lawyer, recently graduated in the top 10% of his law school class, sustained aruptured right anterior communicating artery aneurysm. Surgical intervention stopped thebleeding but left him with memory impairments that included difficulty in retrieving storedinformation when searching for it and very poor prospective memory (i.e., remembering toremember some activity originally planned or agreed upon for the future, or remembering tokeep track of and use needed tools such as memory aids). Other deficits associable to frontallobe damage included diminished emotional capacity, empathic ability, self-awareness,spontaneity, drive, and initiative-taking; impaired social judgment and planning ability; andpoor self-monitoring. Yet he retained verbal and academic skills and knowledge, goodvisuospatial and abstract reasoning abilities, appropriate social behaviors, and motor function.Following repeated failed efforts to enter the practice of law, his wife placed him in arecently organized rehabilitation program directed by a therapist whose experience had beenalmost exclusively with aphasic patients. The program emphasized training to enhanceattentional functions and to compensate for memory deficits. This trainee learned how to keepa memory diary and notebook, which could support him through most of his usual activitiesand responsibilities; and he was appropriately drilled in the necessary memory and notetakinghabits. What was overlooked was the overriding problem that it did not occur to him toremember what he needed to remember when he needed to remember it. (When his car keyswere put aside where he could see them with instructions to get them when the examinationwas completed, at the end of the session he simply left the examining room and did not thinkof his keys until he was outside the building and I [mdl] asked if he had forgotten something.He then demonstrated a good recall of what he had left behind and where.)One week after the conclusion of this costly eight-week program, while learning the routeon a new job delivering to various mail agency offices, he laid his memory book downsomewhere and never found it again—nor did he ever prepare another one for himself despitean evident need for it. An inquiry into the rehabilitation program disclosed a lack ofappreciation of the nature of frontal lobe damage and the needs and limitations of personswith brain injuries of this kind.The same rehabilitation service provided a virtually identical training program to a 42-year-old civil engineer who had incurred severe attentional and memory deficits as a result ofa rear-end collision in which the impact to his car threw his head forcibly back onto the headrest. This man was keenly and painfully aware of his deficits, and he retained strongemotional and motivational capacities, good social and practical judgment, and abilities forplanning, initiation, and self-monitoring. He too had excellent verbal and visuospatialknowledge and skills, good reasoning ability, and no motor deficits. For him this program wasvery beneficial as it gave him the attentional training he needed and enhanced hisspontaneously initiated efforts to compensate for his memory deficits. With this training hewas able to continue doing work that was similar to what he had done before the accident,only on a relatively simplified level and a slower performance schedule.4. Treatment-2: Treatment evaluation. With the everincreasing use ofrehabilitation and retraining services must come questions regarding theirworth (Kashner et al., 2003; Prigatano and Pliskin, 2003; B.[A]. Wilson,Gracey, et al., 2009). These services tend to be costly, both monetarily andin expenditure of professional time. Consumers and referring cliniciansneed to ask whether a given service promises more than can be delivered, orwhetherwhat is produced in terms of the patient’s behavioral changes haspsychological or social value and is maintained long enough to warrant thecosts. Here again, neuropsychological assessment can help answer thesequestions (Sohlberg and Mateer, 2001; Trexler, 2000; Vanderploeg, 1998;see also Ricker, 1998; and B.[A]. Wilson, Evans, and Keohane, 2002, for adiscussion of the cost-effectiveness of neuropsychological evaluations ofrehabilitation patients).Neuropsychological evaluation can often best demonstrate theneurobehavioral response—both positive and negative—to surgicalinterventions (e.g., B.D. Bell and Davies, 1998, temporal lobectomy forseizure control; Yoshii et al., 2008, pre- and postsurgical and radiationtreatment for brain cancer; Selnes and Gottesman, 2010, coronary arterybypass surgery; McCusker et al., 2007; Vingerhoets, Van Nooten, andJannes, 1996, open-heart surgery) or to brain stimulation (e.g., Rinehardt etal., 2010; A.E. Williams et al., 2011, to treat Parkinson’s disease; Vallar,Rusconi, and Bernardini, 1996, to improve left visuospatial awareness).Testing for drug efficacy and side effects also requiresneuropsychological data (Meador, Loring, Hulihan, et al., 2003; Wilken etal., 2007). Examples of these kinds of testing programs can be found formedications for many different conditions such as cancer (C.A. Meyers,Scheibel, and Forman, 1991), HIV (human immunodeficiency virus)(Llorente, van Gorp, et al., 2001; Schifitto et al., 2007), seizure control (Wuet al., 2009), attentional deficit disorders (Kurscheidt et al., 2008; Riordanet al., 1999), multiple sclerosis (Fischer, Priore, et al., 2000; S.A. Morrow etal., 2009; Oken, Flegel, et al., 2006), hypertension (Jonas et al., 2001;Saxby et al., 2008), and psychiatric disorders (Kantrowitz et al., 2010), tolist a few.5. Research. Neuropsychological assessment has been used to study theorganization of brain activity and its translation into behavior, and toinvestigate specific brain disorders and behavioral disabilities (this book,passim; see especially Chapters 2, 3, 7, and 8). Research withneuropsychological assessment techniques also involves their development,standardization, and evaluation. Their precision, sensitivity, and reliabilitymake them valuable tools for studying both the large and small—andsometimes quite subtle—behavioral alterations that are then observablemanifestations of underlying brain pathology.The practical foundations of clinical neuropsychology are also based to alarge measure on neuropsychological research (see Hannay, Bieliauskas, etal., 1998: Houston Conference on Specialty Education and Training inClinical Neuropsychology, 1998). Many of the tests used inneuropsychological evaluations—such as those for arithmetic or for visualmemory and learning—were originally developed for the examination ofnormal cognitive functioning and recalibrated for neuropsychological use inthe course of research on brain dysfunction. Other assessment techniques—such as certain tests of tactile identification or concept formation—weredesigned specifically for research on normal brain function. Theirsubsequent incorporation into clinical use attests to the very lively exchangebetween research and practice. This exchange works especially well inneuropsychology because clinician and researcher are so often one and thesame.Neuropsychological research has also been crucial for understandingnormal behavior and brain functions and the association of cognition withthe underlying functional architecture of the brain (Mahon and Caramazza,2009). The following areas of inquiry afford only a partial glimpse intothese rapidly expanding knowledge domains. Neuropsychologicalassessment techniques provide the data for interpreting brain mappingstudies (e.g., Friston, 2009). Cognitive status in normal aging and diseasestates has been tracked by neuropsychological assessments repeated overthe course of years and even decades (e.g., Borghesani et al., 2010; M.E.Murray et al., 2010; Tranel, Benton, and Olson, 1997) as well as staging ofdementia progression (O’Bryant et al., 2008). The contributions ofdemographic characteristics to the expression of mental abilities are oftenbest delineated by neuropsychological findings (e.g., Ardila, Ostrosky-Solis, et al., 2000; Kempler et al., 1998; Vanderploeg, Axelrod, et al.,1997). Increasingly precise analyses of specific cognitive functions havebeen made possible by neuropsychological assessment techniques (e.g.,Dollinger, 1995; Schretlen, Pearlson, et al., 2000; Troyer, Moscovitch, andWinocur, 1997).6. Forensic neuropsychology. Neuropsychological assessment undertakenfor legal proceedings has become quite commonplace in personal injuryactions in which monetary compensation is sought for claims of bodilyinjury and loss of function (Heilbronner and Pliskin, 2003; Sweet, Meyer, etal., 2011). Although the forensic arena may be regarded as requiring somedifferences in assessment approaches, most questions referred to aneuropsychologist will either ask for a diagnostic opinion (e.g., “Has thisperson sustained brain damage as a result of … ?”) or a description of thesubject’s neuropsychological status (e.g., “Will the behavioral impairmentdue to the subject’s neuropathological condition keep him from gainfulemployment? Will treatment help to return her to the workplace?”). Usuallythe referral for a neuropsychological evaluation will include (or at leastimply) both questions (e.g., “Are the subject’s memory complaints due to… , and if so, how debilitating are they?”). In such cases, theneuropsychologist attempts to determine whether the claimant has sustainedbrain impairment which is associable to the injury in question. When theclaimant is brain impaired, an evaluation of the type and amount ofbehavioral impairment sustained is intrinsically bound up with thediagnostic process. In such cases the examiner typically estimates theclaimant’s rehabilitation potential along with the extent of any need forfuture care. Not infrequently the request for compensation may hinge on theneuropsychologist’s report.In criminal cases, a neuropsychologist may assess a defendant whenthere is reason to suspect that brain dysfunction contributed to themisbehavior or when there is a question about mental capacity to stand trial.The case of the murderer of President Kennedy’s alleged assailant remainsas probably the most famous instance in which a psychologist determinedthat the defendant’s capacity for judgment and self-control was impaired bybrain dysfunction (J. Kaplan and Waltz, 1965). Interestingly, the possibilitythat the defendant, Jack Ruby, had psychomotor epilepsy was first raised byDr. Roy Schafer’s interpretation of the psychological test findings andsubsequently confirmed by electroencephalographic (EEG) studies. At thesentencing stage of a criminal proceeding, the neuropsychologist may alsobe asked to give an opinion about treatment or potential for rehabilitation ofa convicted defendant.Use of neuropsychologists’ examination findings, opinions, andtestimony in the legal arena has engendered what, from some perspectives,seems to be a whole new industry dedicated to unearthing malingerers andexaggerators whose poor performances on neuropsychological tests makethem appear to be cognitively impaired—or more impaired, in cases inwhich impairment may be mild. To this end, a multitude of examinationtechniques and new tests have been devised (Chapter 20). Whether theproblem of malingering and symptom exaggeration in neuropsychologicalexaminations is as great as the proliferation of techniques for identifyingfaked responding would suggest remains unanswered. Certainly, whendealing with forensic issues the examining neuropsychologist must be alertto the possibility that claimants in tort actions or defendants in criminalcases may—deliberately or unwittingly—perform below their optimal level;but the examinermust also remain mindful that for most examinees theirdignity is a most prized attribute that is not readily sold. Moreover, baserates of malingering or symptom exaggeration probably vary with thepopulation under study: TBI patients in a general clinical population wouldprobably have a lower rate than those referred by defense lawyers who havean opportunity to screen claimants—and settle with those who areunequivocally injured—before referring the questionable cases for furtherstudy (e.g., Fox et al., 1995; see Stanczak et al., 2000, for a discussion ofsubject-selection biases in neuropsychological research; Ruffalo, 2003, for adiscussion of examiner bias).The Multipurpose ExaminationUsually a neuropsychological examination serves more than one purpose.Even though the examination may be initially undertaken to answer a singlequestion such as a diagnostic issue, the neuropsychologist may uncovervocational or family problems, or patient care needs that have beenoverlooked, or the patient may prove to be a suitable candidate for research.Integral to all neuropsychological assessment procedures is an evaluation ofthe patient’s needs and circumstances from a psychological perspective thatconsiders quality of life, emotional status, and potential for socialintegration. When new information that has emerged in the course of anexamination raises additional questions, the neuropsychologist will enlargethe scope of inquiry to include newly identified issues, as well as thosestated in the referral.Should a single examination be required to serve several purposes—diagnosis, patient care, and research—a great deal of data may be collectedabout the patient and then applied selectively. For example, the examinationof patients complaining of short-term memory problems can be conductedto answer various questions. A diagnostic determination of whethershortterm memory is impaired may only require finding out if they recallsignificantly fewer words of a list and numbers of a series than the slowestintact adult performance. To understand how they are affected by suchmemory dysfunction, it is important to know the number of words they canrecall freely and under what conditions, the nature of their errors, theirawareness of and reactions to their deficit, and its effect on their day-to-dayactivities. Research might involve studying immediate memory inconjunction with a host of metabolic, neuroimaging, andelectrophysiological measures that can now be performed in conjunctionwith neuropsychological assessment.THE VALIDITY OF NEUROPSYCHOLOGICAL ASSESSMENTA question that has been repeatedly raised about the usefulness ofneuropsychological assessments concerns its “ecological” validity.Ecological validity typically refers to how well the neuropsychologicalassessment data reflect everyday functioning, or predict future behavior orbehavioral outcomes. These questions have been partially answered—almost always affirmatively—in research that has examined relationshipsbetween neuropsychological findings and ultimate diagnoses, e.g., thedetection of dementia (Salmon and Bondi, 2009), betweenneuropsychological findings and imaging data (Bigler, 2001b), and betweenneuropsychological findings and employability (Sbordone and Long, 1996;B.[A]. Wilson, 1993).Most recently very specific studies on the predictive accuracy ofneuropsychological data have appeared for a variety of behavioralconditions, many focused on everyday functioning (see Marcotte and I.Grant, 2009). For example, prediction of treatment outcome for substanceabuse patients rested significantly on Digit Span Backward and BeckDepression Inventory scores (Teichner et al., 2001). Hanks and colleagues(1999) found that measures of aspects of executive function (Letter-NumberSequencing, Controlled Oral Word Association Test, Trail Making Test-B,Wisconsin Card Sorting Test) along with story recall (Logical Memory)“were strongly related to measures of functional outcome six months afterrehabilitation” (p. 1030) of patients with spinal cord injury, orthopedicdisorders, or TBI. HIV+ patients’ employability varied with theirperformances on tests of memory, cognitive flexibility, and psychomotorspeed (van Gorp, Baerwald, et al., 1999) as well as neuropsychologicalmeasures of multitasking (J.C. Scott et al., 2011). Test scores that correlatedsignificantly with the functional deficits of multiple sclerosis came from theCalifornia Verbal Learning Test-long delay free recall, the Paced AuditorySerial Addition Test, the Symbol Digit Modalities Test, and two recall itemsfrom the Rivermead Behavioural Memory Test (Higginson et al., 2000).Several components of the very practical prediction of ability to performactivities of daily living (ADL) have been explored with neuropsychologicalassessments (A. Baird, Podell, et al., 2001; Cahn-Weiner, Boyle, andMalloy, 2002; van der Zwaluw et al., 2010) as has their accuracy forpredicting real-world functional disability in neuropsychiatric disorders andpredicting who is ready to drive after neurological injury or illness or atadvanced ages (K.A. Ryan et al., 2009; Sommer et al., 2010; Whelihan,DiCarlo, and Paul, 2005). On reviewing several hundred examinationprotocols of persons referred for neuropsychological assessment, J.E.Meyers, Volbrecht, and Kaster-Bundgaard (1999) reported that discriminantfunction analysis of these data was 94.4% accurate in identifyingcompetence and noncompetence in driving.Scores on an arithmetic test battery were strongly related to those on anADL questionnaire (Deloche, Dellatolas, et al., 1996). For geriatric patients,scores from the Hooper Visual Organization Test above all, but also theBoston Naming Test and immediate recall of Logical Memory and VisualReproduction were predictive of their safety and independence in severalactivity domains (E.D. Richardson, Nadler, and Malloy, 1995). Acomparison of rehabilitation inpatients who fail and those who do notshowed that the former made more perseverative errors on the WisconsinCard Sorting Test and performed more poorly on the Stroop and VisualForm Discrimination tests (Rapport, Hanks, et al., 1998).A variety of neuropsychological assessment techniques have been usedfor TBI outcome predictions (Sherer et al., 2002). S.R. Ross and hiscolleagues (1997) report that two tests, the Rey Auditory Verbal LearningTest and the Trail Making Test together and “in conjunction with agesignificantly predicted psychosocial outcome after TBI as measured bypatient report” (p. 168). A review of studies examining work status afterTBI found that a number of tests used for neuropsychological assessmentwere predictive, especially “measures of executive functions andflexibility” (p. 23); specifically named tests were the Wisconsin CardSorting Test, a dual—attention and memory—task, the Trail Making Test-B, and the Tinker Toy Test; findings on the predictive success (for workstatus) of memory tests varied considerably (Crepeau and Scherzer, 1993).Another study of TBI patients’ return to work found that“Neuropsychological test performance is related to important behavior inoutpatient brain-injury survivors” (p. 382), and it further noted that “nomeasures of trauma severity contributed in a useful way to this prediction(of employment/unemployment)”(p. 391) (M.L. Bowman, 1996). T.W.Teasdale and colleagues (1997) also documented the validity of tests—ofvisuomotor speed and accuracy and complex visual learning given beforeentry into rehabilitation—as predictors of return to work after rehabilitation.Intact performance on verbal reasoning, speed of processing, and visuo-perceptual measures predicted functional outcome one year after the TBIevent (Sigurdardottir et al., 2009).WHAT CAN WE EXPECT OF NEUROPSYCHOLOGICALASSESSMENT IN THE 21ST CENTURY?Neuropsychological Assessment (1976) was the first textbook to include“Neuropsychological” and “Assessment” in its title. Thefirst citablepublication with “clinical neuropsychology” in its title was Halgrim KWe’s1963 article, followed by the first citable journal article with“neuropsychological assessment” in its title in 1970 by M.L. Schwartz andDennerll. By early 2011, the National Library of Medicine has listed almost56,000 articles related to neuropsychological assessment! This numberalone represents a powerful acknowledgment of neuropsychologicalassessment’s importance for understanding brain function, cognition, andbehavior.In the first chapter of the last two editions of NeuropsychologicalAssessment predictions were made about the future of neuropsychology.Historically, neuropsychologists focused on adapting existing psychologicalassessment tests and techniques for use with neurological andneuropsychiatric patients while developing new measures to assess thespecific cognitive functions and behavioral dysfunctions identified inneuropsychological research. In 2004 it was predicted that with theirincreased efficiency and capacity, assessments by computers—already abusy enterprise—would continue to proliferate. Computerized assessmentshave not become the major avenue for neuropsychological evaluations, butwe believe we can safely predict that the proportion of assessments usingcomputerized programs—for administration, scoring, and data storage,compilation, and analysis—will continue its rapid growth. However,whether computerization will take over most of the work done by clinicalneuropsychologists today is both doubtful and—for a humanistic professionsuch as ours—undesirable.What is new is the variety of computer-based assessment programs nowavailable (e.g., Wild, Howieson, et al., 2008). One type of especial interestis computerized virtual reality assessment programs with “real-world”characteristics; e.g., learning a path through a realistic-looking park(Weniger et al., 2011). Furthermore, some animal-based cognitive tasks likethe water maze can be adapted with computer and virtual reality technologysuch that the wealth of data and hypotheses from animal research can beextrapolated to human studies (Goodrich-Hunsaker et al., 2010). Paper-and-pencil measures cannot make this anthropomorphic jump but thecomputer can. Computer-based assessment methods also permitneuropsychology to extend into rural settings via telemedicine in which aneuropsychologist can evaluate the patient from a distance (Cullum,Weiner, et al., 2006). All of these developments portend that future editionsof Neuropsychological Assessment will include more information aboutcomputer-based assessment methods.All that said, the big revolution to come in neuropsychologicalassessment will likely be multifaceted, dependent in part on the emergenceof what has been termed neuroinformatics (Jagaroo, 2010) and also on theconfluence of three factors: (1) cognitive ontologies, (2) collaborativeneuropsychological knowl edge bases, and (3) universally available andstandardized assessment methods, largely based on computerizedassessments (Bilder, 2011). Bilder emphasizes the importance of traditionalbroad-based clinical and neuroscience training in neuropsychology.Additionally, he believes that the advantage of using computer-basedassessment methods linked with i nformatics technology will be such thattechnology-based assessment techniques will not only be able to establishtheir own psychometric soundness but make “… more subtle taskmanipulations and trial-by-trial analyses, which can be more sensitive andspecific to individual differences in neural system function”(p. 12). Heenvisions computer technology assisting in establishing Web-based datarepositories with much larger sample sizes than what exist for conventionalneuropsychological methods. With larger and more diverse sample sizes,more customized approaches to neuropsychological assessment may bepossible.Neuropsychological assessment techniques need to be adaptive andintegrated with other neurodiagnostic and assessment methods, so thatneuropsychology maintains its unique role while continuing to contribute tothe larger clinical neuroscience, psychological, and medical knowledgebase. Neuroimaging methods of analysis have become automated. Whatused to take days to weeks of painstaking tracing of images can now, withthe proper computer technology, be done in a matter of minutes to hours(Bigler, Abildskov, et al., 2010). Algorithms are now being developedintegrating neuropsychological data with structural and functionalneuroimaging so that the relevance of a particular lesion or abnormalitywith a neuropsychological finding may be more readily elucidated(Voineskos et al., 2011; Wilde, Newsome, et al., 2011). Moreover, tests usedfor neuropsychological assessments are being adapted for administrationduring functional neuroimaging (M.D. Allen and Fong, 2008a,b) such that,on completion of a combined neuroimaging and neuropsychologicalassessment session not only will neuropsychologists have psychometricdata on cognitive performance but they will be able to visualize brainactivation patterns related to specific tests and also have a detailedcomparison of the brain morphometry of this patient with a large normativesample.One measure of the degree to which neuropsychology has become anaccepted and valued partner in both clinical and research enterprises is itsdispersion to cultures other than Western European, and its applications tolanguage groups other than those for which tests were originally developed.With all the very new digital and social network communicationpossibilities of the 21st century, neuropsychology is facing importantchallenges for both greater cross-cultural sensitivity (Gasquoine, 2009;Pedraza and Mungas, 2008; Shepard and Leathem, 1999) and morelanguage- appropriate tests (see Chapter 6, pp. 144–145). Increaseddemands for neuropsychological assessment of persons with limited or noEnglish language background has been the impetus for developing tests inother languages that have been standardized on persons in the other cultureand language groups; use of interpreters is only a second-best partialsolution (Artioli i Fortuny and Mullaney, 1998; LaCalle, 1987; see p. 143–144). In the United States and Mexico, test developers and translators havebegun to respond to the need for Spanish language tests with appropriatestandardization (e.g., Ardila, 2000b; Cherner et al., 2008; Ponton and Leon-Carrion, 2001). Studies providing norms and analyses of tests in Chinesereflect the increasing application of neuropsychological assessment in theFar East (A.S. Chan and Poon, 1999; Hua, Chang, and Chen, 1997; L. Luand Bigler, 2000).HIV, a problem for all countries and language groups, offers an exampleof the worldwide need for neuropsychological assessment and generallyaccepted and adequately normed tests (Maruta et al., 2011). A common,universally agreed upon cognitive assessment strategy is important forunderstanding HIV-related cognitive and neurobehavioral impairments,outlining treatments and assessing their effectiveness, as well as fortracking disease progression (K. Robertson, Liner, and Heaton, 2009). Thedevelopment of internationally accepted neuropsychological measures forHIV patients is underway (Joska et al., 2011). Ideally such research-basedtests will be developed with interdisciplinary input to tailor the assessmenttask to the needs of particular groups of individuals and/or conditions (H.A.Bender et al., 2010).While real progress has been made over the last few decades inunderstanding cognitive and other neuropsychological processes and how toassess them, further knowledge is needed for tests and testing procedures tobe sufficiently organized and standardized that assessments may be reliablyreproducible, practically valid, and readily comprehensible. Yet, the rangeof disorders and disease processes, the variations and overlaps in theirpresentations across individuals, theirpharmacologic and other treatmenteffects, make it unlikely that any “one size fits all” battery can be developedor should even be contemplated. Today’s depth and breadth ofneuropathological and psychological knowledge coupled with increasinglysensitive statistical techniques for test evaluation, and the advent ofcomputer-based assessments should—together—lead to improvements intasks, procedures, possibilities, and effectiveness of neuropsychologicalassessment.One means of achieving such a goal while retaining the flexibilityappropriate for the great variety of persons and problems dealt with inneuropsychological assessment could be a series of relatively short fixedbatteries designed for use with particular disorders and diseases and specificdeficit clusters (e.g., visuomotor dysfunction, short-term memorydisorders). Neuropsychologists in the future would then have at theirdisposal a set of test modules and perhaps structured interviews (eachcontaining several tests) that can be upgraded as knowledge increases andthat can be applied in various combinations to answer particular questionsand meet specific patients’ needs.2 Basic ConceptsIf our brains were so simple that we could understand them, we would be so simple that wecould not.AnonymousEXAMINING THE BRAINHistorically, the clinical approach to the study of brain functions involvedthe neurological examination, which includes study of the brain’s chiefproduct—behavior. The neurologist examines the strength, efficiency,reactivity, and appropriateness of the patient’s responses to commands,questions, discrete stimulation of particular neural subsystems, andchallenges to specific muscle groups and motor patterns. The neurologistalso examines body structures, looking for evidence of brain dysfunctionsuch as swelling of the retina or atrophied muscles. In the neurologicalexamination of behavior, the clinician reviews behavior patterns generatedby neuroanatomical subsystems, measuring patients’ responses in relativelycoarse gradations, and taking note of important responses that might bemissing. The mental status portion of the neurological exam is specificallyfocused on “higher” behavioral functions such as language, memory,attention, and praxis.Neuropsychological assessment is another method of examining the brainby studying its behavioral product, but in far more detail than what iscovered in the mental status portion of a neurological exam. Being focusedon behavior, neuropsychological assessment shares a kinship withpsychological assessment: it relies on many of the same techniques,assumptions, and theories, along with many of the same tests. Similar topsychological assessment, neuropsychological assessment involves theintensive study of behavior by means of interviews and standardized testsand questionnaires that provide precise and sensitive indices ofneuropsychological functioning. Neuropsychological assessment is, in short,a means of measuring in a quantitative, standardized fashion the mostcomplex aspects of human behavior—attention, perception, memory, speechand language, building and drawing, reasoning, problem solving, judgment,planning, and emotional processing.The distinctive character of neuropsychological assessment lies in aconceptual frame of reference that takes brain function as its point ofdeparture. In a broad sense, a behavioral study can be considered“neuropsychological” so long as the questions that prompted it, the centralissues, the findings, or the inferences drawn from the findings, ultimatelyrelate to brain function. And as in neurology, neuropsychological findingsare interpreted within the clinical context of the patient’s presentation and inthe context of pertinent historical, psychosocial, and diagnostic information(see Chapter 5).Laboratory Techniques for Assessing Brain FunctionSome of the earliest instruments for studying brain function that remain inuse are electrophysiological (e.g., see Daube, 2002, passim). These includeelectroencephalography (EEG), evoked and event-related potentials (EP,ERP), and electrodermal activity. EEG frequency and patterns not only areaffected by many brain diseases but also have been used to study aspects ofnormal cognition; e.g., frequency rates have been associated with attentionalactivity for decades (Boutros et al., 2008; Oken and Chiappa, 1985). EEG isespecially useful in diagnosing seizure disorders and sleep disturbances, andfor monitoring depth of anesthesia. Both EP and ERPs can identifyhemispheric specialization (R.J. Davidson, 1998, 2004; Papanicolaou,Moore, Deutsch, et al., 1988) and assess processing speed and efficiency(J.J. Allen, 2002; Picton et al., 2000; Zappoli, 1988).Magnetoencephalography (MEG), the magnetic cousin of EEG thatrecords magnetic rather than electrical fields, has also been used to examinebrain functions in patients and healthy volunteers alike (Reite, Teale, andRojas, 1999). As MEG can have a higher resolution than EEG, it can moreprecisely identify the source of epileptic discharges in patients with a seizuredisorder. Because MEG is expensive the cost may often be prohibitive,especially for clinical applications; to date, the technique has not entered intoregular clinical usage. EEG and MEG are both distinguished by theircapacity to provide very high, fidelity measurements of the temporal aspectsof neural activity, but neither technique has very good spatial resolution.MEG and EEG produce prodigious data sets from which investigators, usingsophisticated quantitative methods, have developed applications such as“brain mapping” (F.H. Duffy, Iyer, and Surwillo, 1989; Nuwer, 1989).Whether this is a valid clinical approach to be used in the routine assessmentof neurological patients, however, has remained controversial, especiallygiven that both techniques are fraught with thorny problems regardingsource localization—i.e., it is very difficult to know the exact neural sourceof the signals produced by these techniques, especially if the signalsoriginate in deeper brain structures.Electrodermal activity (measured as skin conductance response [SCR])reflects autonomic nervous system functioning and provides a sensitive andvery robust measure of emotional responses and feelings (Bauer, 1998; H.D.Critchley, 2002; Zahn and Mirsky, 1999). Electrodermal activity and otherautonomic measures such as heart rate, respiration, and pupil dilation havealso been used to demonstrate various nonconscious forms of brainprocessing (J.S. Feinstein and Tranel, 2009; Tranel, 2000). For example,when patients with prosopagnosia (who cannot recognize familiar faces at aconscious level, see p. 444) were shown pictures of family members andother familiar individuals, they said they did not recognize the faces;however, these patients showed a robust SCR—a nonconscious recognitionresponse (Tranel and Damasio, 1988). In another example, a patient withsevere inability to acquire new information (anterograde amnesia, see p. 29)had large SCRs to a neutral stimulus that had previously been paired with aloud aversive tone during a fear conditioning paradigm, despite having norecollection of the learning situation (Bechara, Tranel, et al., 1995). In yetanother experiment, a patient with one of the most severe amnesias everrecorded produced large, discriminatory SCRs to persons who had beensystematically paired with either positive or negative affective valence,despite having no conscious, declarative knowledge of the persons (Traneland Damasio, 1993).Other methods that enable visualization of ongoing brain activity arecollectively known as “functional brain imaging” (for a detailed review ofcontemporary neuroimaging technology see Neuroimaging Primer,Appendix A, pp. 863–871). These techniques have proven useful forexploring both normal brain functioning and the nature of specific braindisorders (Huettel et al., 2004; Pincus and Tucker, 2003, passim; P.Zimmerman and Leclercq, 2002). One of the older functional brain imagingtechniques, regional cerebral blood flow (rCBF), reflects the brain’smetabolic activity indirectly as it changes the magnitude of blood flow indifferent brain regions. rCBF provides a relatively inexpensive means forvisualizing and recording brain function (D.J. Brooks, 2001; Deutsch,Bourbon, et al., 1988).Beginning in the mid-1970s, neuroimaging has become a critical part ofthe diagnostic workup for most patients with known or suspectedneurological disease. Computerized tomography (CT) and magneticresonance imaging (MRI) techniques reconstruct different densities andconstituents of internal brain structures into clinically useful three-dimensional pictures of the intracranial anatomy (Beauchamp and Bryan,1997; R.O. Hopkins, Abildskov, et al., 1997; Hurley, Fisher, and Taber,2008). Higher magnet strengths for MRI, e.g., 3 Tesla (the current standard;Scheid et al., 2007) or 7 Tesla (not yet approved for routine clinical use withhuman participants; Biessels et al., 2010), have allowed even more fine-grained visualization of neural structure. A number of advanced techniqueshave evolved from MRI (e.g., diffusion weighted imaging; perfusionimaging), giving the clinician an unprecedented degree of detailedinformation regarding neural constituents. The timing of these procedures isa major factor in their usefulness, not only as to what kinds of informationwill be visualized but also in the choice of specific diagnostic tools. A CTmight be best suited for acute head injury when skull fracture and/orbleeding are suspected, whereas MRI (with diffusion tensor imaging [DTI])might be the study of choice in the chronic stages of head injury, when theclinician is especially concerned about white matter integrity.Positron emission tomography (PET) visualizes brain metabolismdirectly as glucose radioisotopes emit decay signals, their quantity indicatingthe level of brain activity in a given area (Hurley, Fisher, and Taber, 2008).PET not only contributes valuable information about the functioning ofdiseased brains but has also become an important tool for understandingnormal brain activity (Aguirre, 2003; M.S. George et al., 2000; Rugg, 2002).Single photon emission computed tomography (SPECT) is similar to PETbut less expensive and involves a contrast agent that is readily available.Comparison of interictal and ictal SPECT scans (i.e., between and duringseizures) in epilepsy surgery candidates has been valuable for identifying thesite of seizure onset (So, 2000). In experimental applications, proceduressuch as PET and SPECT typically compare data obtained during anactivation task of interest (e.g., stimulus identification) to data from a restingor other “baseline” state, to isolate the blood flow correlates of thebehavioral function of interest.These procedures have limitations. For example, PET applications arelimited by their dependence on radioisotopes that have a short half-life andmust be generated in a nearby cyclotron (Hurley, Fisher, and Taber, 2008).Cost and accessibility are other factors—these procedures have beenexpensive and available mainly at large medical centers. This has changed inrecent years, and now PET and especially SPECT are fairly widelyavailable, and not prohibitively expensive—and increasingly, covered byinsurance plans. One important clinical application for PET is in thediagnosis of neurodegenerative diseases. For example, manyneurodegenerative diseases, including Alzheimer’s disease andfrontotemporal dementia, produce brain alterations that are detectable withPET even when structural neuroimaging (CT or MRI) fails to show specificabnormalities (D.H.S. Silverman, 2004). The diagnostic accuracy of PET toassess dementia has shown convincingly that PET and, in particular, that the18F-FDG PET procedure (which involves a resting study) can demonstrateclear patterns of abnormality that aid in the diagnosis of dementia and in thedifferential diagnosis of various neurodegenerative diseases (D.H.S.Silverman, 2004). 18F-FDG PET may be especially informative in the early,milder phases of the disease when diagnostic certainty based on the usualprocedures (including neuropsychological assessment) tends to be moreequivocal.Functional magnetic resonance imaging (fMRI) is a technique thatcapitalizes on the neural phenomenon that increasing neuronal activityrequires more oxygen; the amount of oxygen delivered by blood flow (or theblood volume; see Sirotin et al., 2009) actually tends to exceed demand,creating a ratio of oxygenated to deoxygenated blood that is known as theBOLD signal which can be precisely and accurately measured andquantified. This signal is highly localizable (normally by mapping theBOLD response onto a structural MRI) at an individual subject level, givingfMRI a remarkably high degree of spatial resolution which permitsvisualization of brain areas that are “activated” during various cognitivetasks. The popularity of fMRI as a means of studying brain-behaviorrelationships exploded during the late 1990s and throughout the 2000s, notonly because of its superior spatial resolution but also due in large measureto the facts that fMRI is widely available, noninvasive, and does not requirea “medical” context for its application.Thus fMRI is a popular method for investigating all manner ofpsychological processes such as time perception (S.M. Rao, Mayer, andHarrington, 2001), semantic processing (Bookheimer, 2002), emotionalprocessing (M.S. George et al., 2000; R.C. Gur, Schroder, et al., 2002) ,response inhibition (Durston et al., 2002), face recognition (Joseph andGathers, 2002), somatosensory processing (Meador, Allison, Loring et al.,2002), sexual arousal (Arnow et al., 2002), and many, many others. Perhapsmore so than the other techniques discussed, fMRI has and will continue tobe involved with neuropsychology as well as cognitive neuroscience ingeneral, in part due to its widespread use.fMRI is not without controversy, though: the technique has suffered frombeing used and abused by investigators whose knowledge of the brain and ofhistorical brain-behavior relationship studies is woefully inadequate (forcritical discussions and examples, see Coltheart, 2006; Fellows et al., 2005;Logothetis, 2008). Even the nature of the basic signal that is measured withfMRI continues to be debated (Logothetis and Wandell, 2004; Sirotin et al.,2009). As neuropsychology evolves through the 2010s, it will be interestingto see whether and how fMRI settles into a reliable constituent slot in thearmamentarium of techniques for studying and measuring brain functionsand brain–behavior relationships.The need to identify cerebral language and memory dominance inneurosurgery candidates led to the development of techniques such as theWada test (intracarotid injection of amobarbital for temporarypharmacological inactivation of one side of the brain) and electrical corticalstimulation mapping (Loring, Meador, Lee, and King, 1992; Ojemann,Cawthon, and Lettich, 1990; Penfield and Rasmussen, 1950). Not only havethese procedures significantly reduced cognitive morbidity followingepilepsy surgery, but they have also greatly enhanced our knowledge ofbrain-behavior relationships. Atypical language representation, for example,alters the expected pattern of neuropsychological findings, even in theabsence of major cerebral pathology (S.L. Griffin and Tranel, 2007; Loring,Strauss, et al., 1999) . These procedures have limitations in that they areinvasive and afford only a limited range of assessable behavior due to therestrictions on patient response in an operating theater and the short durationof medication effects (Thierry, 2008). Generalizability of data obtained bythese techniques is further restricted by the fact that patients undergoingsuch techniques typically have diseased or damaged brains (e.g., a seizuredisorder)which could have prompted reorganization of function (S.L.Griffin and Tranel, 2007).Many of the same questions addressed by the Wada test and corticalstimulation mapping in patients may be answered in studies of healthyvolunteers using such techniques as transcranial magnetic stimulation (L.C.Robertson and Rafal, 2000), functional transcranial Doppler (Knecht et al.,2000), magnetoencephalography/magnetic source imaging (Papanicolaou etal., 2001; Simos, Castillo, et al., 2001), and fMRI (J.R. Binder, Swanson, etal., 1996; J.E. Desmond, Sum, et al., 1995; Jokeit et al., 2001). Thesetechniques, which are less invasive than the Wada test and corticalstimulation mapping, have had increasing use in recent years, although theyhave yet to supplant the time-tested Wada as a reliable means of localizinglanguage function presurgically.NEUROPSYCHOLOGY’S CONCEPTUAL EVOLUTIONNeuropsychology’s historical roots go deep into the past; Darby and Walsh(2005) begin their condensed history of neuropsychology with a 1700 BCEpapyrus describing eight cases of traumatic head injury. Other writers havetraced this history in greater detail (e.g., Finger, 1994; N.J. Wade andBrozek, 2001). Some dwelt on more recent (mostly 19th and early 20thcentury) and specific foundation-laying events (e.g., Benton, 2000; Benton[collected papers in L. Costa and Spreen, 1985]; Finger, 2000). As befittinga text on neuropsychological assessment, this brief historical review beginsin the 20th century, when neuropsychology began providing tools andexpertise for clinical assessments in psychology, psychiatry, and theneurosciences.Throughout the 1930s and 40s and well into the 50s, the determination ofwhether a patient had “brain damage” was often the reason for consultationwith a psychologist (at that time the term “neuropsychologist” did not exist).During these years, most clinicians treated “brain damage” or braindysfunction as if it were a unitary phenomenon—often summed up under theterm “organicity.” It was well recognized that behavioral disorders resultedfrom many different brain conditions, and that damage to different brainsites caused different effects (Babcock, 1930; Klebanoff, 1945). It was alsowell established that certain specific brain-behavior correlates, such as therole of the left hemisphere in language functions, appeared with predictableregularity. Yet much of the work with “brain damaged” patients continued tobe based on the assumption that “organicity” was characterized by onecentral and therefore universal behavioral defect (K. Goldstein, 1939; Yates,1954). Even so thoughtful an observer as Teuber could say in 1948 that“Multiple-factor hypotheses are not necessarily preferable to an equallytentative, heuristic formulation of a general factor—the assumption of afundamental disturbance … which appears with different specifications ineach cerebral region”(pp. 45–46).The early formulations of brain damage as a unitary condition that iseither present or absent were reflected in the proliferation of single functiontests of “organicity” that were evaluated, in turn, solely in terms of how wellthey distinguished “organic” from psychiatric patients or normal, healthypersons (e.g., Klebanoff, 1945; Spreen and Benton, 1965; Yates, 1954). The“fundamental disturbance” of brain damage, however, turned out to beexasperatingly elusive. Despite many ingenious efforts to devise a test orexamination technique that would be sensitive to organicity per se—aneuropsychological litmus paper, so to speak—no one behavioralphenomenon could be found that was shared by all brain injured persons butby no one else.In neuropsychology’s next evolutionary stage, “brain damage” was nolonger treated as a unitary phenomenon, but identification of its presence (ornot) continued to be a primary goal of assessment. With increasingappreciation of the behavioral correlates of discrete lesions, the search forbrain damage began to focus on finding sets of tests of different functionsthat, when their scores were combined, would make the desireddiscriminations between psychiatric, “organic,” and normal subjects. TheHunt-Minnesota Test for Organic Brain Damage (H.F. Hunt, 1943), forexample, included the 1937 Stanford-Binet Vocabulary Test and six tests oflearning and retention in auditory and visual modalities, considered to be“sensitive to brain deterioration.” It had the advantage that identification ofbrain damaged persons could be accomplished in 15 minutes! Halstead’s(1947) “Impairment Index,” based on a combined score derived from abattery generating ten scores from seven tests of more or less discretefunctions requiring a much lengthier examination, also reflects the search for“brain damage” (see also p. 118).Another landmark pioneer who led neuropsychology’s evolution in themid-part of the 20th century was Alexander Luria (e.g., 1964; A.-L.Christens, Goldberg, Bougakov, 2009; Tranel, 2007). For Luria, use ofsymptoms made evident by neuropsychological assessment to infer “local”brain dysfunction was the essence of neuropsychology. Luria’s focus was onqualitative analysis: he stressed the value of careful qualitativeneuropsychological analysis of cognitive and behavioral symptoms, but healso included some psychometric instruments in his examinations. Luriaemphasized the importance of breaking down complex mental andbehavioral functions into component parts. Historical impetus for this camefrom an attempt to reconcile the long-running feud between“localizationists”—aware of specialized brain areas—and the one-diagnosis-fits-all “antilocalizationists.” Luria noted that apparent contradictionsbetween these two camps grew out of the oversimplified nature of theanalyses. He pointed out that higher mental functions represent complexfunctional systems based on jointly working zones of the brain cortex, andhe emphasized the importance of dissecting the structure of functions andthe physiological mechanisms behind those functions. Luria’s point seemspatently obvious to us now—but that it took so long to enter the mainstreamof neuropsychology is a lesson that cannot be ignored in neuropsychologyand cognitive neuroscience.Like the concept “sick,” the concept “brain damage” (or “organicity” or“organic impairment”—the terms varied from author to author but themeaning was essentially the same) has no etiological or pathologicalimplications, nor can predictions or prescriptions be based on such adiagnostic conclusion. Still, “brain damage” as a measurable conditionremains a vigorous concept, reflected in the many test and battery indices,ratios, and quotients that purport to represent some quantity or relativedegree of neurobehavioral impairment.Advances in diagnostic medicine, with the exception of certain cases withmild or questionable cognitive impairment, have changed the educatedreferral question to the neuropsychologist from simply whether (or not) thepatient has a brain disorder, to inquiry into the patient’s cognitive strengthsand deficits, emotionality, and capacity to function in the real world. In mostcases, the presence of “brain damage” has been clinically established andoften verified radiologically before the patient even gets to theneuropsychologist. However, the site and extent of a lesion or the diagnosisof a neurobehavioral disease are not in themselves necessarily predictive ofthe cognitive and behavioral repercussions of the known condition, as theyvary with the nature, extent, location, and duration of the lesion; with theage, sex, physical condition, and psychosocial background and status of thepatient; and with individual neuroanatomical and physiological differences(see Chapters 3, 7, and 8). Not only does the pattern of neuropsychologicaldeficits differ with different lesion characteristics and locations, but twopersons with similar pathology and lesion sites may have distinctly differentneuropsychological presentations(De Bleser, 1988; Howard, 1997; Luria,1970), and patients with damage at different sites may present similardeficits (Naeser, Palumbo, et al., 1989).These seemingly anomalous observations make sense when consideringthat, in different brains, different cognitive functions may rely on the sameor similar circuits and, in turn, the same functions may be organized indifferent circuits. Needless to say, human behavior—especially whensuffering specific kinds of impairments—is enormously complex: that is aninescapable truth of clinical neuropsychology. Thus, although “braindamage” may be useful as a general concept that includes a broad range ofbehavioral disorders, when dealing with individual patients the concept ofbrain damage only becomes meaningful in terms of specific behavioraldysfunctions and their implications regarding underlying brain pathologyand real-world functioning. The neuropsychological assessment helps todetermine what are the (practical, social, treatment, rehabilitation,predictable, legal and, for some conditions, diagnostic) ramifications of theknown brain injury or evident brain disorder.CONCERNING TERMINOLOGYThe experience of wading through the older neuropsychological literatureshares some characteristics with exploring an archaeological dig into a long-inhabited site. Much as the archaeologist finds artifacts that are both similarand different, evolving and discarded; so a reader can find, scattered throughthe decades, descriptions of various neuropsychological disorders in terms(usually names of syndromes or behavioral anomalies) no longer in use andforgotten by most, terms that have evolved from one meaning to another, andterms that have retained their identity and currency pretty much as when firstcoined. Thus, many earlier terms for specific neuropsychological phenomenahave not been supplanted or fallen into disuse so that even now one can findtwo or more expressions for the same or similar observations. This richterminological heritage can be very confusing (see, for example, Lishman’s[1997] discussion of the terminological confusion surrounding “confusion,”and other common terms that are variously used to refer to mental states, towell-defined diagnostic entities, or to specific instances of abnormalbehavior).In this book we have made an effort to use only terms that are currentlywidely accepted. Some still popular but poorly defined terms have beenreplaced by simpler and more apt substitutes for these older items inclassical terminology. For example, we distinguish those constructionaldisorders that have been called “constructional apraxia” from theneuropsychologically meaningful concept of praxis (and its disorder,apraxia), which “in the strict sense, refers to the motor integration used toexecute complex learned movements” (Strub and Black, 2000). Thus, wereserve the term “apraxia” for dysfunctions due to a breakdown in thedirection or execution of complex motor acts; “constructional defects” or“constructional impairment” refers to disorders which, typically, involveproblems of spatial comprehension or expression but not motor control.Moreover, the term “apraxia” has problems of its own, as differentinvestigators define and use such terms as “ideational apraxia” and“ideokinetic apraxia” in confusingly different ways (compare, for example,Hecaen and Albert, 1978; Heilman and Rothi, 2011; M. Williams, 1979).Rather than attempt to reconcile the many disparities in the use of theseterms and their definitions, we call these disturbances simply “apraxias” (seealso Hanna-Pladdy and Rothi, 2001). We use current and well-acceptedterms but will also present, when relevant, a term’s history.DIMENSIONS OF BEHAVIORBehavior may be conceptualized in terms of three functional systems: (1)cognition, which is the information-handling aspect of behavior; (2)emotionality, which concerns feelings and motivation; and (3) executivefunctions, which have to do with how behavior is expressed. Components ofeach of these three sets of functions are as integral to every bit of behavior asare length and breadth and height to the shape of any object. Moreover, likethe dimensions of space, each of these components can be conceptualizedand treated separately even though they are intimately interconnected incomplex behavior. The early Greek philosophers were the first to conceiveof a tripartite division of behavior, postulating that different principles of the“soul” governed the rational, appetitive, and animating aspects of behavior.Present-day research in the behavioral sciences tends to support thephilosophers’ intuitive insights into how the totality of behavior isorganized. These classical and scientifically meaningful functional systemslend themselves well to the practical observation, measurement, anddescription of behavior and constitute a valid and transparent heuristic fororganizing behavioral data generally.In neuropsychology, the “cognitive” functions have received moreattention than the emotional and control (executive) systems. This probablystems from observations that the cognitive defects of brain injured patientstend to be prominent symptoms. Cognitive functions are also more readilyconceptualized, measured, and correlated with neuroanatomicallyidentifiable systems. A less appreciated fact is that the structured nature ofmost medical and neuropsychological examinations does not provide muchopportunity for subtle emotional and control deficits to become evident. Forneuropsychological examinations, this is a significant limitation that can leadto erroneous conclusions and interpretations of data. The examination ofpersons with known or suspected brain disorders should, as much aspossible, incorporate opportunities for patients to exhibit emotional andexecutive behaviors and/or their deficiencies. This recommendation must beheeded as brain damage rarely affects just one of the three behavioralsystems: the disruptive effects of most brain lesions, regardless of their sizeor location, usually involve all three systems (Lezak, 1994; Prigatano, 2009).For example, Korsakoff’s psychosis, a condition most commonly associated with severechronic alcoholism, has typically been described with an emphasis on cognitive dysfunction,and in particular, the profound learning and memory impairment that is a hallmark of thiscondition. Yet chronic Korsakoff patients also exhibit radical changes in affect and inexecutive functions that may be more crippling and more representative of the psychologicaldevastations of this disease than the memory impairments. These patients tend to beemotionally flat, to lack the impulse to initiate activity and, if given a goal requiring morethan an immediate one- or two- step response, they are unable to organize, set into motion,and carry through a plan of action to reach it. Everyday frustrations, sad events, orworrisome problems, when brought to their attention, will arouse a somewhat appropriateaffective response, as will a pleasant happening or a treat; but the arousal is transitory,subsiding with a change in topic or distraction such as someone entering the room. Whennot stimulated from outside or by physiological urges, these responsive, comprehending,often well-spoken and well-mannered patients sit quite comfortably doing nothing, not evenattending to a TV or nearby conversation. When they have the urge to move, they walkabout aimlessly.The behavioral defects characteristic of many patients with right hemisphere damage alsoreflect the involvement of all three behavioral systems. It is well known that these patientsare especially likely to show impairments in such cognitive activities as spatial organization,integration of visual and spatial stimuli, and comprehension and manipulation of perceptsthat do not readily lend themselves to verbal analysis. Right hemisphere damaged patientsmay also experience characteristic emotional dysfunctions suchas an indifference reaction(ignoring, playing down, or being unaware of mental and physical disabilities and situationalproblems), uncalled-for optimism or even euphoria, inappropriate emotional responses andinsensitivity to the feelings of others, and loss of the self-perspective needed for accurateself-criticism, appreciation of limitations, or making constructive changes in behavior orattitudes. Furthermore, despite strong, well-expressed motivations and demonstratedknowledgeability and capability, impairments in the capacity to plan and organize complexactivities and thinking immobilize many right hemisphere damaged patients.Behavior problems may also become more acute and the symptompicture more complex as secondary reactions to the specific problemscreated by the brain injury further involve each system. Additionalrepercussions and reactions may then occur as the patient attempts to copewith succeeding sets of reactions and the problems they bring (Gainotti,2010). The following case of a man who sustained a relatively minor braininjury demonstrates some typical interactions between impairments indifferent behavioral systems.A middle-aged clerk, the father of teenage children, incurred a left-sided head injury in a caraccident and was unconscious for several days. When examined three months after theaccident, his principal complaint was fatigue. His scores on cognitive tests were consistentlyhigh average (between the 75th and 90th percentiles). The only cognitive difficultydemonstrated in the neuropsychological examination was a slight impairment of verbalfluency exhibited by a few word-use errors on a sentence-building task. This verbal fluencyproblem did not seem grave, but it had serious implications for the patient’s adjustment.Because he could no longer produce fluent speech automatically, the patient had toexercise constant vigilance and conscious effort to talk as well as he did. This effort was acontinuous drain on his energy so that he fatigued easily. Verbal fluency tended todeteriorate when he grew tired, giving rise to a vicious cycle in which he put out more effortwhen he was tired, further sapping his energy at the times he needed it the most. He feltworn out and became discouraged, irritable, and depressed. Emotional control too was nolonger as automatic or effective as before the accident, and it was poorest when he was tired.He “blew up” frequently with little provocation. His children did not hide their annoyancewith their grouchy, sullen father, and his wife became protective and overly solicitous. Thepatient perceived his family’s behavior as further proof of his inadequacy and hopelessness.His depression deepened, he became more self-conscious about his speech, and the fluencyproblem frequently worsened.COGNITIVE FUNCTIONSCognitive abilities (and disabilities) are functional properties of the individual that are notdirectly observed but instead are inferred from … behavior… . All behavior (includingneuropsychological test performances) is multiply determined: a patient’s failure on a testof abstract reasoning may not be due to a specific impairment in conceptual thinking butto attention disorder, verbal disability, or inability to discriminate the stimuli of the testinstead.Abigail B. Sivan and Arthur L. Benton, 1999The four major classes of cognitive functions have their analogues in thecomputer operations of input, storage, processing (e.g., sorting, combining,relating data in various ways), and output. Thus, (1) receptive functionsinvolve the abilities to select, acquire, classify, and integrate information; (2)memory and learning refer to information storage and retrieval; (3) thinkingconcerns the mental organization and reorganization of information; and (4)expressive functions are the means through which information iscommunicated or acted upon. Each functional class comprises many discreteactivities—such as color recognition or immediate memory for spokenwords. Although each function constitutes a distinct class of behaviors,normally they work in close, interdependent concert. Despite the seemingease with which the classes of cognitive functions can be distinguishedconceptually, more than merely interdependent, they are inextricably boundtogether—different facets of the brain’s activity. For example, A.R.Damasio, H. Damasio, and Tranel (1990) described the memory(information storage and retrieval) components of visual recognition. Theyalso noted the role that thinking (concept formation) plays in the seeminglysimple act of identifying a visual stimulus by name. Both practicalapplications and theory-making benefit from our ability to differentiate thesevarious components of behavior.Generally speaking, within each class of cognitive functions a divisionmay be made between verbal and nonverbal functions, where “verbal” refersto functions that mediate verbal/symbolic information and “nonverbal”refers to functions that deal with data that cannot be communicated in wordsor symbols, such as complex visual or sound patterns. This distinction reallyrefers to the types of material being processed (verbal versusnonverbalizable), rather than the functions per se. However, this distinctionis a time-tested heuristic tied to observations that these subclasses offunctions differ from one another in their neuroanatomical organization andin their behavioral expression while sharing other basic neuroanatomical andpsychometric relationships within the functional system.The identification of discrete functions within each class of cognitivefunctions varies—at least to some extent—with the perspective andtechniques of the investigator. Examiners using simple tests that elicitdiscrete responses can study highly specific functions. Multidimensionaltests that call for complex responses measure broader and more complexfunctions. Although different investigators may identify or define some ofthe narrower subclasses of functions differently, they tend to agree on themajor functional systems and the large subdivisions. It is important toacknowledge that functional divisions and subdivisions are, to some extent,conceptual constructions that help the clinician understand what goes intothe typically very complex behaviors and test responses of their brainimpaired patients. Discrete functions described here and in Chapter 3 rarelyoccur in isolation; normally, they contribute to larger functional patternselaborated in the highly organized cerebrum.It is important for the examiner to be mindful that some functions maynot be assessed; e.g., when, due to practical considerations of time or testenvironment, relevant tests are not administered, or when the examination islimited to a commercially available battery of tests. In such instances, theexaminer may not gain information about how an impaired function iscontributing to a patient’s deficits, or the examiner may not even be aware ofthe integrity (or lack thereof) of these untested functions (Teuber, 1969).Attentional functions differ from the functional groups listed above inthat they underlie and, in a sense, maintain the activity of the cognitivefunctions. To carry the computer analogy a step further, attentional functionsserve somewhat as command operations, calling into play one or morecognitive functions. For this reason, they are classified as mental activityvariables (see pp. 36–37).Neuropsychology and the Concept of Intelligence: BrainFunction Is Too Complex To Be Communicated in a SingleScoreClinical research on intelligence has difficulties as a blackberry-bush has thorns.D.O. Hebb, 1949Historically, cognitive activity was often attributed to a single function,usually under the rubric of “intelligence.” Early investigators treated theconcept of intelligence as if it were a unitary variable which, somewhat akinto physical strength, increased at a regular rate in the course of normalchildhood development (Binetet Simon, 1908; Terman, 1916) and decreasedwith the amount of brain tissue lost through accident or disease (L.F.Chapman and Wolff, 1959; Lashley, 1938). It is not hard to understand whysuch a view was appealing. For some clinicians its attractiveness issupported by the consistent finding that intraindividual correlations betweenvarious kinds of mental abilities tend to be significant. From aneuropsychological perspective, Piercy (1964) thought of intelligence as “atendency for cerebral regions subserving different intellectual functions to beproportionately developed in any one individual. According to this notion,people with good verbal ability will tend also to have good nonverbal ability,in much the same way as people with big hands tend to have big feet”(p.341). The performance of most adults on cognitive ability tests reflects boththis tendency for test scores generally to converge around the same level andfor some test scores to vary in differing degrees from the central tendency(Carroll, 1993; Coalson and Raiford, 2008; J.D. Matarazzo and Prifitera,1989).Also, some neuropsychologists have attempted to identify the neuralcorrelates of “general intelligence,” the construct commonly referred to asSpearman’s g (Spearman, 1927). In psychometric theory, g is considered ageneral factor of intelligence that contributes to all cognitive activities,reflecting an individual’s overall tendency to perform more or less well oncognitive tasks. Some studies suggest a relationship between specific neuralsectors (e.g., the dorsolateral prefrontal cortex [dlPFC]) and this concept ofintelligence. For example, dlPFC activation has been reported in ostensibly“high g” tasks such as the Raven Progressive Matrices and similar measures(J. Duncan et al., 2000; J.R. Gray et al., 2003; Njemanze, 2005). M.J. Kaneand Engle (2002) proposed a prominent role for the dlPFC in novelreasoning and psychometric g.Other studies have lent support to a relationship between g and thedlPFC. Patients with disproportionate damage to dlPFC were selectivelyimpaired on tasks requiring multiple relational premises, including matrix-reasoning-like tasks, suggesting again an association between the dlPFC andg (Waltz et al., 1999). In a large-scale lesion-deficit mapping study,Glascher, Rudrauf, and colleagues (2010) investigated the neural substratesof g in 241 patients with focal brain damage using voxel-based lesion-symptom mapping. Statistically significant associations were found betweeng and a circumscribed network in frontal and parietal cortex, including whitematter association tracts and frontopolar cortex. Moreover, the neuralcorrelates of g were highly coextensive with those associated with full scaleIQ scores. These authors suggest that general intelligence draws onconnections between regions that integrate verbal, visuospatial, workingmemory, and executive processes. Koziol and Budding (2009) provided asimilar appraisal, noting that cognitive competency depends on “flexibilityof interaction”between cortical/cognitive centers and adaptive features ofsubcortical systems.The work on g notwithstanding, the mental abilities measured by“intelligence”tests include many different cognitive functions, as well asother kinds of functions such as attention and processing speed (Ardila,1999a; Frackowiak, Friston, and Frith, 1997; Glascher, Tranel, et al., 2009).Neuropsychological research has contributed significantly to refinements inthe definition of “intelligence”(Glascher, Tranel, et al., 2009; Mesulam,2000b). One of neuropsychology’s earliest findings was that the summationscores (i.e., “intelligence quotient”[“IQ”] scores) on standard intelligencetests do not bear a predictably direct relationship to the size of brain lesions(Hebb, 1942; Maher, 1963). When a discrete brain lesion produces deficitsinvolving a broad range of cognitive functions, these functions may beaffected in different ways. Abilities most directly served by the damagedtissue may be destroyed; associated or dependent abilities may be depressedor distorted; other abilities may be spared or even heightened or enhanced(see pp. 346–347). In degenerative neurological conditions, such asAlzheimer’s disease, major differences in the vulnerability of specific mentalabilities to the effects of the brain’s deterioration appear as some functionsare disrupted in the early stages of the disease while others may remainrelatively intact for years (see Chapter 7, passim). Moreover, affectedfunctions tend to decline at different rates.In normal aging, different mental functions also undergo change atdifferent rates (e.g., Denburg, Cole, et al., 2007; Denburg, Tranel, andBechara, 2005; Salthouse, 2009, 2010; pp. 356–360). In cognitively intactadults, too, singular experiences plus specialization of interests and activitiescontribute to intraindividual differences (e.g., Halpern, 1997). Socializationand cultural differences, personal expectations, educational limitations,emotional disturbance, physical illness or handicaps, and brain dysfunctionare but some of the many factors that tend to magnify intraindividual testdifferences to significant proportions (e.g., see A.S. Kaufman, McLean, andReynolds, 1988; Sternberg, 2004; Suzuki and Valencia, 1997). Subtlemeasurements of brain substance and function have shown that somepersons’ brains may undergo highly differentiated development typicallyinvolving an area or related areas in response to repeated experience and,especially, to intense practice of a skill or activity (Restak, 2001).Another major problem with a construct such as Spearman’s g is that itcannot account for theories of multiple intelligences (Gardner, 1983) and, inparticular, fails to incorporate emotional abilities and social intelligence(e.g., Salovey and Mayer, 1990). These important aspects of behavioralcompetency become evident in their absence—with paradigmatic examplesin the oftcited observations of patients with damage to prefrontal cortices,especially in the ventromedial prefrontal cortex (vmPFC), who typicallymanifest major disruptions of complex decision-making, planning, socialconduct, and emotional regulation, but have remarkably well-preservedconventional intelligence as measured by standard mental ability tests. Apatient (EVR) reported by Eslinger and Damasio (1985) is a case in point:his WAIS-R IQ scores were well into the superior range (Verbal IQ score =129; Performance IQ score = 135; Full Scale IQ score = 135), but he wasprototypical of someone with severely disrupted decision-making, planning,and social conduct following vmPFC damage. Similar patients have beendescribed by other investigators (e.g., Blair and Cipolotti, 2000; P.W.Burgess and Shallice, 1996; Shallice and Burgess, 1991). Mostneuropsychologists who have seen many patients with injuries from motorvehicle accidents have similar stories.Such findings have led to the conclusion that, when considering the roleof the frontal lobes in human intellect, it is important to distinguish betweenintelligence as a global capacity to engage in adaptive, goal-directedbehavior, and intelligence as defined by performance on standardpsychometric instruments (e.g., Bechara, H. Damasio, Damasio, andAnderson, 1994; P.W. Burgess, Alderman, Forbes, et al., 2006; A.R.Damasio, Anderson, and Tranel, 2011). Although the frontal corticesconstitute a necessary anatomical substrate for human intelligence as aglobal adaptive capacity, extensive frontal lobe damage may have little or noimpact on abilities measured by intelligence tests. Real life intelligentbehavior requires more than basic problem solving skills: in real lifeproblems, unlike most artificial problems posed by tests, the relevant issues,rules of engagement, and endpoints are often not clearly identified. Inaddition, real life behaviors often introduce heavy time processing andworking memory demands, including a requirement for prioritizationhave stimulated our thinking and made available their work, theirknowledge, and their expertise. The ongoing 2nd Wedns. NeuropsychologyCase Conference in Portland continues to be an open-door free-for-all andyou are invited.It has been a pleasure to work with our new editor, Joan Bossert, whohas not only been encouraging and supportive, but has helped us throughsome technical hoops and taught us about e-publishing. Tracy O’Hara,Development Editor, has done the heroic task of organizing the productionidiosyncrasies of four writers into a cohesive manuscript while helping withsome much needed data acquisition. Book production has been carefullytimed and managed by Sr. Production Editor Susan Lee who makes housecalls. Thanks, OUP team, for making this book possible. Last to getinvolved but far from least, our gratitude goes out to Eugenia Cooper Potter,best known as Genia, whose thorough scouring and polishing of text andreferences greatly helped bring this book to life.ContentsList of FiguresList of TablesI THEORY AND PRACTICE OFNEUROPSYCHOLOGICAL ASSESSMENT1. The Practice of Neuropsychological AssessmentExamination purposesThe multipurpose examinationThe Validity of Neuropsychological AssessmentWhat Can We Expect of Neuropsychological Assessment in the21st Century?2. Basic ConceptsExamining the BrainLaboratory Techniques for Assessing Brain FunctionNeuropsychology’s Conceptual EvolutionConcerning TerminologyDimensions of BehaviorCognitive FunctionsNeuropsychology and the Concept of Intelligence: Brain Function IsToo Complex To Be Communicated in a Single ScoreClasses of Cognitive FunctionsReceptive FunctionsMemoryExpressive FunctionsThinkingMental Activity VariablesExecutive FunctionsPersonality/Emotionality Variables3. The Behavioral Geography of the BrainBrain Pathology and Psychological FunctionThe Cellular SubstrateThe Structure of the BrainThe HindbrainThe MidbrainThe Forebrain: Diencephalic StructuresThe Forebrain: The CerebrumThe Limbic SystemThe Cerebral Cortex and BehaviorLateral OrganizationLongitudinal OrganizationFunctional Organization of the Posterior CortexThe Occipital Lobes and Their DisordersThe Posterior Association Cortices and Their DisordersThe Temporal Lobes and Their DisordersFunctional Organization of the Anterior CortexPrecentral DivisionPremotor DivisionPrefrontal DivisionClinical Limitations of Functional Localization4. The Rationale of Deficit MeasurementComparison Standards for Deficit MeasurementNormative Comparison StandardsIndividual Comparison StandardsThe Measurement of DeficitDirect Measurement of DeficitIndirect Measurement of DeficitThe Best Performance MethodThe Deficit Measurement Paradigm5. The Neuropsychological Examination: ProceduresConceptual Framework of the ExaminationPurposes of the ExaminationExamination QuestionsConduct of the ExaminationExamination FoundationsExamination ProceduresProcedural Considerations in Neuropsychological AssessmentTesting IssuesExamining Special PopulationsCommon Assessment Problems with Brain DisordersMaximizing the Patient’s Performance LevelOptimal versus Standard ConditionsWhen Optimal Conditions Are Not BestTalking to PatientsConstructive Assessment6. The Neuropsychological Examination: InterpretationThe Nature of Neuropsychological Examination DataDifferent Kinds of Examination DataQuantitative and Qualitative DataCommon Interpretation ErrorsEvaluation of Neuropsychological Examination DataQualitative Aspects of Examination BehaviorTest ScoresEvaluation IssuesScreening TechniquesPattern AnalysisIntegrated Interpretation7. Neuropathology for NeuropsychologistsTraumatic Brain InjurySeverity Classifications and Outcome PredictionNeuropathology of TBIPenetrating Head InjuriesClosed Head InjuriesClosed Head Injury: Nature, Course, and OutcomeNeuropsychological Assessment of Traumatically Brain InjuredPatientsModerator Variables Affecting Severity of Traumatic Brain InjuryLess Common Sources of Traumatic Brain InjuryCerebrovascular DisordersStroke and Related DisordersVascular DisordersHypertensionVascular Dementia (VaD)MigraineEpilepsyDementing DisordersMild Cognitive ImpairmentDegenerative DisordersCortical DementiasAlzheimer’s Disease (AD)Frontotemporal Lobar Degeneration (FTLD)Dementia with Lewy Bodies (DLB)Subcortical DementiasMovement DisordersParkinson’s Disease/Parkinsonism (PD)Huntington’s Disease (HD)Progressive Supranuclear Palsy (PSP)Comparisons of the Progressive DementiasOther Progressive Disorders of the Central Nervous SystemWhich May Have Important Neuropsychological EffectsMultiple Sclerosis (MS)Normal Pressure Hydrocephalus (NPH)Toxic ConditionsAlcohol-Related DisordersStreet DrugsSocial DrugsEnvironmental and Industrial NeurotoxinsInfectious ProcessesHIV Infection and AIDSHerpes Simplex Encephalitis (HSE)Lyme DiseaseChronic Fatigue Syndrome (CFS)Brain TumorsPrimary Brain TumorsSecondary (Metastatic) Brain TumorsCNS Symptoms Arising from Brain TumorsCNS Symptoms Arising from Cancer TreatmentOxygen DeprivationAcute Oxygen DeprivationChronic Oxygen DeprivationCarbon Monoxide PoisoningMetabolic and Endocrine DisordersDiabetes Mellitus (DM)Hypothyroidism (Myxedema)Liver DiseaseUremiaNutritional Deficiencies8. Neurobehavioral Variables and Diagnostic IssuesLesion CharacteristicsDiffuse and Focal EffectsSite and Size of Focal LesionsDepth of LesionDistance EffectsNature of the LesionTimeNonprogressive Brain DisordersProgressive Brain DiseasesSubject VariablesAgeSex DifferencesLateral AsymmetryPatient Characteristics: Race, Culture, and EthnicityThe Uses of Race/Ethnicity/Culture DesignationsThe Language of AssessmentPatient Characteristics: Psychosocial VariablesPremorbid Mental AbilityEducationPremorbid Personality and Social AdjustmentProblems of Differential DiagnosisEmotional Disturbances and Personality DisordersPsychotic DisturbancesDepressionMalingeringII A COMPENDIUM OF TESTS ANDASSESSMENT TECHNIQUES9. Orientation and AttentionOrientationAwarenessTimePlaceBody OrientationFinger AgnosiaDirectional (Right–Left) OrientationSpaceAttention, Processing Speed, and Working MemoryAttentional CapacityWorking Memory/Mental TrackingConcentration/Focused AttentionProcessing SpeedComplex Attention TestsDivided AttentionEveryday Attention10. PerceptionVisual PerceptionVisual InattentionVisual ScanningColor PerceptionVisual RecognitionVisual OrganizationVisual InterferenceAuditory PerceptionAuditory AcuityAuditory DiscriminationAuditory InattentionAuditory–Verbal PerceptionNonverbal Auditory ReceptionTactile PerceptionTactile SensationTactile InattentionTactile Recognition and Discrimination TestsOlfaction11. Memory I: TestsExamining MemoryVerbal MemoryVerbal AutomatismsSupraspanWordsStory RecallVisual MemoryVisual Recognition MemoryVisual Recall: Verbal ResponseVisual Recall: Design ReproductionVisual LearningHidden ObjectsTactile MemoryIncidental LearningProspective MemoryRemote MemoryRecall of Public Events and Famous PersonsAutobiographic MemoryForgetting12. Memory II: Batteries, Paired Memory Tests, and QuestionnairesMemory BatteriesPaired Memory TestsMemory Questionnaires13. Verbal Functions and Language SkillsAphasiaAphasia Tests and BatteriesAphasia ScreeningTesting for Auditory ComprehensionVerbal ExpressionNamingVocabularyDiscourseVerbal ComprehensionVerbal Academic SkillsReadingWritingSpellingKnowledge Acquisition and Retention14. Construction and Motor PerformanceDrawingCopyingMiscellaneous Copying TasksFree DrawingAssembling and BuildingTwo-Dimensional ConstructionThree-Dimensional ConstructionMotor SkillsExamining for ApraxiaNeuropsychological Assessment of Motor Skills and Functions15. Concept Formation and ReasoningConcept Formationandweighing of multiple options and possible outcomes. Altogether, suchfactors seem to conspire against patients with frontal lobe damage, who,despite good “IQ”scores, cannot effectively deploy their intelligence in realworld, online situations.Thus, knowledge of the complexities of brain organization and braindysfunction makes the unitary concept of intelligence essentially irrelevantand potentially hazardous for neuropsychological assessment. “Cognitiveabilities”or “mental abilities”are the terms we will use when referring tothose psychological functions dedicated to information reception,processing, and expression, and to executive functions—the abilitiesnecessary for metacognitive control and direction of mental experience.“IQ”and other summation or composite scoresThe term IQ is bound to the myths that intelligence is unitary, fixed, and predetermined…. As long as the term IQ is used, these myths will complicate efforts to communicate themeaning of test results and classification decisions.D. J. Reschly, 1981“IQ”refers to a derived score used in many test batteries designed to measurea hypothesized general ability, viz., “intelligence.” IQ scores obtained fromsuch tests represent a composite of performances on different kinds of items,on different items in the same tests administered at different levels ofdifficulty, on different items in different editions of test batteries bearing thesame name, or on different batteries contributing different kinds of items(M.H. Daniel, 1997; Loring and Bauer, 2010; Urbina, 2004). Composite IQscores are often good predictors of academic performance, which is notsurprising given their heavy loading of school-type and culturally familiaritems; many studies have shown that performance on “intelligence”tests ishighly correlated with school achievement (e.g., Ormrod, 2008; see alsoSternberg, Grigorenko, and Kidd, 2005). For neuropsychologists, however,composite IQ scores represent so many different kinds of conflated andconfounded functions as to be conceptually meaningless (Lezak, 1988b).In neuropsychological assessment, IQ scores—whether they be high orlow—are notoriously unreliable indices of neuropathic deterioration.Specific defects restricted to certain test modalities, for example, may give acompletely erroneous impression of significant intellectual impairment whenactually many cognitive functions may be relatively intact but the total scoreis depressed by low scores in tests involving the impaired function(s).A year after sustaining three concussions in soccer play within one month, a 16-year-oldhigh school student and her mother were informed that she never was a good student andnever could be as her full scale IQ score was 60. At the time of the examination she wastroubled with headaches and dizziness, and a depressed state—being unable to function in anoisy, bright classroom, she was tutored at home, had become socially isolated, and wasunable to engage in sports. Not surprisingly, her Wechsler battery scaled scores on the twotimed visuographic tests were 1, and she scored 3s on each of the three attention tests (DigitSpan, Letter/number Sequencing, Arithmetic). Most other scores were in the 9th to 16thpercentile range except for a Scaled Score of 10 on Matrix Reasoning; the IQ score had beencomputed on a Comprehension score of 7, but when rescored it was 8.Shortly thereafter a visual misalignment was found, she began vision training and alsoentered a rehabilitation program focused on dizziness and balance problems. On ImPACTtesting (see p. 760), given weeks after taking this examination, all scores werewhich would be submerged or entirely obfuscated by an IndexScore.One must never misconstrue a normal intelligence test result as an indication of normalintellectual status after head trauma, or worse, as indicative of a normal brain; to do sowould be to commit the cardinal sin of confusing absence of evidence with evidence ofabsence [italics, mdl]. (Teuber, 1969)In sum, “IQ”as a score is often meaningless and not infrequentlymisleading as well. In fact, in most respects “IQ"—whether concept, score,or catchword—has outlived whatever usefulness it may once have had. Inneuropsychological practice in particular, it is difficult to justify anycontinued use of the notion of “IQ.”CLASSES OF COGNITIVE FUNCTIONSWith our growing knowledge about how the brain processes information, itbecomes increasingly more challenging to make theoretically acceptabledistinctions between the different functions involved in human informationprocessing. In the laboratory, precise distinctions between sensation andperception, for example, may depend upon whether incoming information isprocessed by analysis of superficial physical and sensory characteristics orthrough pattern recognition and meaningful (e.g., semantic) associations.The fluidity of theoretical models of perception and memory in particularbecomes apparent in the admission that “We have no way of distinguishingwhat might be conceived of as the higher echelons of perception from thelower echelons of recognition… . [T]here is no definable point ofdemarcation between perception and recognition”(A.R. Damasio, Tranel,and Damasio, 1989, p. 317).A.R. Damasio and colleagues were stressing their appreciation that no“line”clearly divides perceptual processes from recognition processes. Thisbecomes evident when considering studies of nonconscious “recognition”inprosopagnosia see p. 444). These patients cannot provide any overtindication that they recognize familiar faces yet respond withpsychophysiological responses to those faces, indicating that both perceptionand some aspects of memory are still operating successfully but withoutconscious awareness (e.g., Bauer and Verfaellie, 1988; Tranel and Damasio,1985; Tranel and Damasio, 1988). The same can be said for many othercognitive functions. It is typically unclear, and in most cases virtuallyimpossible, to demarcate a distinctive boundary where one function stopsand the other begins.Rather than entering theoretical battlegrounds on ticklish issues that arenot especially germane to most practical applications in neuropsychology,we shall discuss cognitive functions within a conceptual framework that hasproven useful in psychological assessment generally and inneuropsychological assessment particularly. In so doing, however, weacknowledge that there are sophisticated and valid conceptualizations ofcognitive functions in the experimental literature that may differ from theorganizational structure we proffer. As neuropsychology evolves, we hopethat reliable and valid lessons from that literature will continue to inform thepractice of clinical neuropsychology and, especially, inform the developmentof specific tests for measuring specific functions.Receptive FunctionsEntry of information into the central processing system proceeds fromsensory stimulation, i.e., sensation, through perception, which involves theintegration of sensory impressions into psychologically meaningful data, andthence into memory. Thus, for example, light on the retina creates a visualsensation; perception involves encoding the impulses transmitted by thearoused retina into a pattern of hues, shades, and intensities eventuallyrecognized as a daffodil in bloom.The components of sensation can be fractionated into very small andremarkably discrete receptive units. The Nobel Prize-winning research ofHubel and Weisel (1968) demonstrated that neurons in the visual cortex arearranged in columns that respond preferentially to stimuli at specificlocations and at specific orientations. This early work was later replicatedand extended by Margaret Livingstone and David Hubel (1988) who showedthat discrete neural units are dedicated to the processing of elementarysensory properties such as form versus color versus movement. Moreover,the fractionation at this basic sensory level is paralleled by like dissociationsat the cognitive/behavioral level, where, for example, patients can selectivelylose the capability to see form, or to see color, or to see depth or movement(e.g., A.R. Damasio, Tranel, and Rizzo, 2000).Sensory receptionSensory reception involves an arousal process that triggers centralregistration leading to analysis, encoding, and integrative activities. Theorganism receives sensation passively, shutting it out only, for instance, byholding the nose to avoid a stench or closing the eyes to avoid bright light.Even in soundest slumber, a stomach ache or a loud noise will rouse thesleeper. However, the perception of sensations also depends heavily onattentional factors (Meador, Allison, et al., 2002; Meador, Ray et al., 2001).Neuropsychological assessment and research focus primarily on the fivetraditional senses: sight, hearing, touch, taste, and smell— although—commensurate with their importance in navigating the world—sight andhearing have received most attention.Perception and the agnosiasPerception involves active processing of the continuous torrent of sensationsas well as their inhibition or filtering from consciousness. This processingcomprises many successive and interactive stages. The simplest physical orsensory characteristics, such as color, shape, or tone, come first in theprocessing sequence and serve as foundations for the more complex“higher”levels of processing that integrate sensory stimuli with one anotherand with past experience (Fuster, 2003; A. Martin, Ungerleider, and Haxby,2000; Rapp, 2001, passim).Normal perception in the healthy organism is a complex processengaging many different aspects of brain functioning (Coslett and Saffran,1992; Goodale, 2000; Lowel and Singer, 2002). Like other cognitivefunctions, the extensive cortical distribution and complexity of perceptualactivities make them highly vulnerable to brain injury. Perceptual defectsresulting from brain injury can occur through loss of a primary sensory inputsuch as vision or smell and also through impairment of specific integrativeprocesses. Although it may be difficult to separate the sensory from theperceptual components of a behavioral defect in some severely brain injuredpatients, sensation and perception each has its own functional integrity. Thiscan be seen when perceptual organization is maintained despite very severesensory defects or when perceptual functions are markedly disrupted inpatients with little or no sensory deficit. The nearly deaf person can readilyunderstand speech patterns when the sound is sufficiently amplified, whereassome brain damaged persons with keen auditory acuity cannot make sense ofwhat they hear.The perceptual functions include such activities as awareness,recognition, discrimination, patterning, and orientation. Impairments inperceptual integration appear as disorders of recognition, classically knownas the “agnosias” (literally, no knowledge). Teuber (1968) clarified thedistinction between sensory and perceptual defects by defining agnosia as “anormal percept stripped of its meanings.” In general, the term agnosiasignifies lack of knowledge and denotes an impairment of recognition.Since a disturbance in perceptual activity may affect any of the sensorymodalities as well as different aspects of each one, a catalogue of discreteperceptual disturbances can be quite lengthy. For example, Benson (1989)listed six different kinds of visual agnosias. Bauer (2011) identified threedistinctive auditory agnosias, and M. Williams (1979) described anotherthree involving various aspects of body awareness. These listscan beexpanded, for within most of these categories of perceptual defect there arefunctionally discrete subcategories. For instance, loss of the ability torecognize faces (prosopagnosia or face agnosia), one of the visual agnosias,can occur with or without intact abilities to recognize associatedcharacteristics such as a person’s facial expression, age, and sex (Tranel,A.R. Damasio, and H. Damasio, 1988). Other highly discrete dissociationsalso occur within the visual modality, e.g., inability to recognize a person’sface with intact recognition for the same person’s gait, or inability torecognize certain categories of concrete entities with intact recognition ofother categories (e.g., man-made tools vs. natural objects, animals versusfruits and vegetables) (H. Damasio, Tranel, Grabowski, et al., 2004; Tranel,Feinstein, and Manzel, 2008; Warrington and James, 1986). Suchdissociations reflect the processing characteristics of the neural systems thatform the substrates of knowledge storage and retrieval.One basic dichotomy that has proven useful, at least at the heuristic level,is the distinction between “associative”and “apperceptive”agnosia. Thisdistinction is an old one (Lissauer, 1890); it refers to a basic difference in themechanism underlying the recognition disorder. Associative agnosia isfailure of recognition that results from defective retrieval of knowledgepertinent to a given stimulus. Here, the problem is centered on memory: thepatient is unable to recognize a stimulus (i.e., to know its meaning) despitebeing able to perceive the stimulus normally (e.g., to see shape, color,texture; to hear frequency, pitch, timbre; and so forth). Apperceptiveagnosia, by contrast, is disturbance of the integration of otherwise normallyperceived components of a stimulus. Here, the problem is centered more onperception: the patient fails to recognize a stimulus because the patientcannot integrate the perceptual elements of the stimulus even though thoseindividual elements are perceived normally. It should be clear that the centralfeature in designating a condition as “agnosia”is a recognition defect thatcannot be attributed simply or entirely to faulty perception. Even though thetwo conditions may show some overlap, in clinical practice it is usuallypossible to make a distinction between these two basic forms of agnosia(e.g., Tranel and Grabowski, 2009).MemoryIf any one faculty of our nature may be called more wonderful than the rest, I do think itis memory. There seems something more speakingly incomprehensible in the powers, thefailures, the inequalities of memory, than in any other of our intelligences. The memory issometimes so retentive, so serviceable, so obedient—at others, so bewildered and so weak—and at others again, so tyrannic, so beyond control!—We are to be sure a miracle everyway—but our powers of recollecting and forgetting, do seem peculiarly past finding out.Jane Austen, Mansfield Park, 1814 [1961]Central to all cognitive functions and probably to all that is characteristicallyhuman in a person’s behavior is the capacity for memory, learning, andintentional access to knowledge stores, as well as the capacity to“remember”in the future (e.g., to use memory to “time travel”into the future,to imagine what will be happening to us at some future time, to plan forfuture activities, and so on). Memory frees the individual from dependencyon physiological urges or situational happenstance for pleasure seeking;dread and despair do not occur in a memory vacuum. Severely impairedmemory isolates patients from practically meaningful contact with the worldabout them and deprives them of a sense of personal continuity, renderingthem helplessly dependent. Even mildly to moderately impaired memory canhave a very disorienting effect.Different memory systemsSurgery for epilepsy, in which the medial temporal lobes were resectedbilaterally, unexpectedly left the now famous patient, HM, with a severeinability to learn new information or recall ongoing events, i.e., he had aprofound amnesia (literally, no memory), which, in his case, wasanterograde (involving new experiences; see p. 28). Careful studies of HMby Brenda Milner (1962, 1965) and later by Corkin (1968) and N.J. Cohenand Squire (1980) showed that, despite his profound amnesia, HM wascapable of learning new motor skills and other procedural-based abilities thatdid not rely on explicit, conscious remembering. This remarkabledissociation was replicated and extended in other severely amnesic patients,including the patient known as Boswell studied by the Damasio group atIowa (Tranel, A.R. Damasio, H. Damasio, and Brandt, 1994). Such work hasprovided the foundation for conceptualizing memory functions in terms oftwo long-term storage and retrieval systems: a declarative system, or explicitmemory, which deals with facts and events and is available to consciousness;and a nondeclarative or implicit system, which is “nonconscious”(B. Milner,Squire, and Kandel, 1998; Squire and Knowlton, 2000).Depending on one’s perspective, the count of memory systems or kindsof memory varies. From a clinical perspective, Mayes (2000a) divideddeclarative memory into semantic (fact memory) and episodic(autobiographic memory), and nondeclarative memory into item-specificimplicit memory and procedural memory (see also Baddeley, 2002).Numerous other divisions and subclassifications of memory systems havebeen proposed (e.g., B. Milner et al., 1998; Salmon and Squire, 2009). Onreviewing the memory literature, Endel Tulving (2002b) found no fewer than“134 different named types of memory.” For clinical purposes, however, thedual system conceptualization— into declarative (explicit) andnondeclarative (implicit) memory with its major subsystems—provides auseful framework for observing and understanding patterns of memorycompetence and deficits presented by patients.Declarative (explicit) memoryMost memory research and theory has focused on abilities to learn about andremember information, objects, and events. For all intents and purposes, thisis the kind of memory that patients may be referring to when complaining ofmemory problems, that teachers address for most educational activities, andthat is the “memory”of common parlance. It has been described as “themental capacity of retaining and reviving impressions, or of recalling orrecognizing previous experiences … act or fact of retaining mentalimpressions”(J. Stein, 1966) and, as such, always requires awareness(Moscovitch, 2000) . Referring to it as “explicit memory,” Demitrack and hiscolleagues (1992) pointed out that declarative memory involves “a consciousand intentional recollection”process. Thus, declarative memory refers toinformation that can be brought to mind and inspected in the “mind’s eye,”and, in that sense, “declared”(Tranel and Damasio, 2002).Stages of memory processingDespite the plethora of theories about stages (R.C. Atkinson and Shiffrin,1968; G.H. Bower, 2000; R.F. Thompson, 1988) or processing levels (S.C.Brown and Craik, 2000; Craik, 1979), for clinical purposes a three- stage orelaborated two-stage model of declarative memory provides a suitableframework for conceptualizing and understanding dysfunctional memory(McGaugh, 1966; Parkin, 2001; Strub and Black, 2000).1. Registration, or sensory, memory holds large amounts of incominginformation briefly (on the order of seconds) in sensory store (Balota et al.,2000; Vallar and Papagno, 2002). It is neither strictly a memory function nora perceptual function but rather a selecting and recording process by whichperceptions enter the memory system. The first traces of a stimulus may beexperienced as a fleeting visual image (iconic memory, lasting up to —200msec) or auditory “replay”(echoic memory, lasting up to —2,000 msec),indicating early stage processing that is modality specific (Fuster, 1995;Koch and Crick, 2000). The affective, s et(perceptual and responsepredisposition), and attention-focusing components of perception play anintegral role in the registration process (S.C. Brown and Craik, 2000;Markowitsch, 2000). Information being registered is further processed asshort-term memory, or it quickly decays.2a. I mmediate memory, the first stage of s hort-term memory (STM) storage,temporarily holds information retained from the registration process. Whiletheoretically distinguishable from attention, in practice, short-term memorymay be equated with simple immediate span of attention (Baddeley, 2000;Howieson and Lezak, 2002b; see p. 402). Immediate memory serves “as alimited capacity store from which information is transferred to a morepermanent store”and also “as a limited capacity retrieval system”(Fuster,1995; see also Squire, 1986). Having shown that immediate memorynormally handles about seven “plus or minus two”bits of information at atime, G.A. Miller (1956) observed that this restricted holding capacity of“immediate memory impose[s] severe limitations on the amount ofinformation that we are able to perceive, process, and remember.” Immediatememory is of sufficient duration to enable a person to respond to ongoingevents when more enduring forms of memory have been lost. It typicallylasts from about 30 seconds up to several minutes.Although immediate memory is usually conceptualized as a unitaryprocess, Baddeley (1986, 2002) showed how it may operate as a set ofsubsystems “controlled by a limited capacity executive system,” whichtogether is working memory, the temporary storage and processing systemused for problem solving and other cognitive operations that take place overa limited time frame. Baddeley proposed that working memory consists oftwo subsystems, one for processing language—the “phonological loop"—and one for visuospatial data—”the visuospatial sketch pad.” The functionsof working memory are “to hold information in mind, to internalizeinformation, and to use that information to guide behavior without the aid ofor in the absence of reliable external cues”(Goldman-Rakic, 1993, p. 15).Numerous studies have supported Hebb’s (1949) insightful hunch thatinformation in immediate memory is temporarily maintained inreverberating neural circuits (self-contained neural networks that sustainneural activity by channeling it repeatedly through the same network)(Fuster, 1995; McGaugh et al., 1990, passim; Shepherd, 1998). If notconverted into a more stable biochemical organization for longer lastingstorage, the electrochemical activity that constitutes the immediate memorytrace spontaneously dissipates and the memory is not retained. For example,only the rare reader with a “photographic”memory will be able to recallverbatim the first sentence on the preceding page although almost everyonewho has read this far will have just seen it.2b. Rehearsal is any repetitive mental process that serves to lengthen theduration of a memory trace (S.C. Brown and Craik, 2000). With rehearsal, amemory trace may be maintained for hours (in principle, indefinitely).Rehearsal increases the likelihood that a given bit of information will bepermanently stored but does not ensure it (Baddeley, 1986).2c. Another kind of short-term memory may be distinguished fromimmediate memory in that it lasts from an hour or so to one or two days—longer than a reverberating circuit could be maintained by even the mostconscientious rehearsal efforts, but not yet permanently fixed as learnedmaterial in long-term storage (Fuster, 1995; Tranel and Damasio, 2002).This may be evidence of an intermediate step “in a continuous spectrum ofinterlocked molecular mechanisms of … the multistep, multichannel natureof memory”(Dudai, 1989).3. Long-term memory (LTM) or secondary memory— i.e., learning, theacquisition of new information— refers to the organism’s ability to storeinformation. Long-term memory is most readily distinguishable from short-term memory in amnestic patients, i.e., persons unable to retain newinformation for more than a few minutes without continuing rehearsal.Although amnesic conditions may have very different etiologies (seeChapter 7, passim), they all have in common a relatively intact short-termmemory capacity with significant long-term memory impairments (Baddeleyand Warrington, 1970; O’Connor and Verfaellie, 2002; Tranel, H. Damasio,and Damasio, 2000).The process of storing information as long-term memory—i.e.,consolidation—may occur quickly or continue for considerable lengths oftime, even without active, deliberate, or conscious effort (Lynch, 2000;Mayes, 1988; Squire, 1987). Learning implies consolidation: what is learnedis consolidated. Larry Squire has written that “Consolidation best refers to ahypothesized process of reorganization within representations of storedinformation, which continues as long as information is beingforgotten”(Squire, 1986, p. 241). Many theories of memory consolidationpropose a gradual transfer of memory that requires processing fromhippocampal and medial temporal lobe structures to the neocortex for longerterm storage (Kapur and Brooks, 1999; B. Milner et al., 1998).“Learning”often requires effortful or attentive activity on the part of thelearner. Yet when the declarative memory system is intact, much informationis also acquired without directed effort, by means of incidental learning(Dudai, 1989; Kimball and Holyoak, 2000). Incidental learning tends to besusceptible to impairment with some kinds of brain damage (S. Cooper,1982; C. Ryan, Butters, Montgomery, et al., 1980).Long-term memory storage presumably involves a number of processesoccurring at the cellular level, although much of this is poorly understood inhumans. These processes include neurochemical alterations in the neuron(nerve cell), neurochemical alterations of the synapse (the point ofinteraction between nerve cell endings) that may account for differences inthe amount of neurotransmitter released or taken up at the synaptic juncture,elaboration of the dendritic (branching out) structures of the neuron toincrease the number of contacts made with other cells (Fuster, 1995; Levitanand Kaczmarek, 2002; Lynch, 2000), and perhaps pruning or apoptosis(programmed cell death) of some connections with disuse (Edelman, 1989;Huttenlocher, 2002) and in brain development (Low and Cheng, 2006;Walmey and Cheng, 2006).Memories are not stored in a single local site; rather, memories involvecontributions from many cortical and subcortical centers (Fuster, 1995;Markowitsch, 2000; Mendoza and Foundas, 2008), with “different brainsystems playing different roles in the memory system”(R.F. Thompson,1976). Encoding, storage, and retrieval of information in the memory systemappear to take place according to both principles of association (Levitan andKaczmarek, 2002; McClelland, 2000) and “characteristics that are unique toa particular stimulus”(S.C. Brown and Craik, 2000, p. 98). Thus, much ofthe information in the long-term storage system appears to be organized onthe basis of meaning and associations, in contrast to the short-term storagesystem where it is organized in terms of contiguity or of sensory propertiessuch as similar sounds, shapes, or colors (G.H. Bower, 2000; Craik andLockhart, 1972). Breakdown in storage or retrieval capacities results indistinctive memory disorders.Recent and remote memory are clinical terms that refer, respectively, toautobiographical memories stored within the last few hours, days, weeks, oreven months and to older memories dating from early childhood (e.g., Struband Black, 2000; see also Neisser and Libby, 2000). In intact persons it isvirtually impossible to determine where recent memory ends and remotememory begins, for there are no major discontinuities in memory from thepresent to early wisps of infantile recollection. However, a characteristicautobiographical “memory bump”begins around age ten and lasts untiltheearly 30s, such that persons typically can recollect more numerous and morevivid memories from this time period of their life (Berntsen and Rubin,2002; D. Rubin and Schulkind, 1997; see Buchanan et al., 2005, 2006, forneuropsychological studies related to this phenomenon).AmnesiaImpaired memory—amnesia—results from a disturbance of the processes ofregistration, storage, or retrieval. The severity of the amnesia can range fromsubtle to profound: on the more severe end of the spectrum, patients can losevirtually all of their episodic memory and capacity to learn new information(e.g., Damasio, Eslinger, et al., 1985; J.S. Feinstein, Rudrauf, et al., 2010;Scoville and Milner, 1957). Lesion location is a major factor determining thespecific nature of the memory impairment (e.g., Tranel and Damasio, 2002).Time-limited memory deficits can occur in conditions such as head injury,electroconvulsive therapy (ECT), and transient global amnesia. In suchcases, the amnesia is limited to a fairly discrete period (e.g., minutes orhours) while memories before and after that period remain intact.The most common form of amnesia, anterograde amnesia, is an inabilityto acquire new information normally. It is the most typical memoryimpairment that follows the onset of a neurological injury or condition and istantamount to impaired learning. Anterograde amnesia is a hallmarksymptom of Alzheimer’s disease. Moreover, it occurs with nearly allconditions that have an adverse impact on the functioning of the mesialtemporal lobe and especially the hippocampus (see pp. 83–86). The kind andseverity of the memory defect vary somewhat with the nature of the disorder(O’Connor and Verfaellie, 2002; Y. Stern and Sackeim, 2008) and extent ofhippocampal destruction (J.S. Allen et al., 2006).Loss of memory for events preceding the onset of brain injury, often dueto trauma, is called retrograde amnesia. The time period for the memory losstends to be relatively short (30 minutes or less) with TBI but can beextensive (E. Goldberg and Bilder, 1986). When retrograde amnesia occurswith brain disease, loss of one’s own history and events may go back yearsand even decades (N. Butters and Cermak, 1986; Corkin, Hurt, et al., 1987;J.S. Feinstein, Rudrauf, et al., 2010). There can be a rough temporal gradientto retrograde amnesia in that newer memories tend to be more vulnerable toloss than older ones on a sort of “first in, last out”principle (M.S. Albert,Butters, and Levin, 1979; Squire, Clark, and Knowlton, 2001).Many patients show a striking dissociation between anterograde andretrograde memory; typically, anterograde memory is impaired andretrograde is spared. This pattern indicates that the anatomical structuresinvolved in new learning versus those required for retrieval of old memoriesare different (Markowitsch, 2000; Tranel and Damasio, 2002). Theacquisition of new declarative information requires a time-sensitive,temporary processing system that is important for the formation and short-term maintenance of memories (the hippocampal complex, pp. 83–86).Long-term and permanent memories are maintained and stored elsewhere,especially in anterolateral areas of the temporal lobe and higher ordersensory association cortices (R.D. Jones, Grabowski, and Tranel, et al.,1998).Long-enduring retrograde amnesia that extends back for years or decadesis usually accompanied by an equally prominent anterograde amnesia; thesepatients neither recall much of their history nor learn much that is new.Dense retrograde amnesia in the absence of any problems with anterogradememory is highly uncommon as a bona fide neurological condition;complaints of such a problem raise the question of other, often psychiatric,factors at play (Kritchevsky et al., 2004; Stracciari et al., 2008).A 52-year-old machine maintenance man complained of “amnesia”a few days after his headwas bumped in a minor traffic accident. He knew his name but denied memory for anypersonal history preceding the accident while registering and retaining postaccident events,names, and places normally. This burly, well-muscled fellow moved like a child, spoke in asoft—almost lisping—manner, and was only passively responsive in interview. He waswatched over by his woman companion who described a complete personality change sincethe accident. She reported that he had been raised in a rural community in a southeasternstate and had not completed high school. With these observations and this history, ratherthan begin a battery of tests, he was hypnotized.Under hypnosis, a manly, pleasantly assertive, rather concrete-minded personalityemerged. In the course of six hypnotherapy sessions the patient revealed that, as a prizefighter when young, he had learned to consider his fists to be “lethal weapons.” Some yearsbefore the accident he had become very angry with a brother-in-law who picked a fight andwas knocked down by the patient. Six days later this man died, apparently from a previouslydiagnosed heart condition; yet the patient became convinced that he had killed him and thathis anger was potentially murderous. Just days before the traffic accident, the patient’s soninformed him that he had fathered a baby while in service overseas but was not going to takeresponsibility for baby or mother. This enraged the patient who reined in his anger only withgreat effort. He was riding with his son when the accident occurred. A very momentary lossof consciousness when he bumped his head provided a rationale—amnesia—for a new,safely ineffectual personality to evolve, fully dissociated from the personality he fearedcould murder his son. Counseling under hypnosis and later in his normal state helped him tolearn about and cope with his anger appropriately.Aspects and elements of declarative memoryRecall vs. recognition. The effectiveness of the memory system also dependson how readily and completely information can be retrieved. Informationretrieval is remembering, which, when it occurs through recall, involves anactive, complex search process (S.C. Brown and Craik, 2000; Mayes, 1988).The question, “What is the capital of Oregon?” tests the recall function.When a like stimulus triggers awareness, remembering takes place throughrecognition. The question, “Which of the following is the capital of Oregon:Albany, Portland, or Salem?” tests the recognition function. Retrieval byrecognition is much easier than free recall for both intact and brain impairedpersons (N. Butters, Wolfe, Granholm, and Martone, 1986; M.K. Johnson,1990). On superficial examination, retrieval problems can be mistaken forlearning or retention problems, but appropriate testing techniques canilluminate and clarify the nature of the memory defect.Elements of declarative memory. That there are many different kinds ofmemory functions becomes abundantly clear with knowledge of pathologicalbrain conditions, as dissociations between the different mnestic disordersemerge in various neurological disorders (Shimamura, 1989; Stuss andLevine, 2002; Verfaellie and O’Connor, 2000). For example, in addition tothe basic distinction between short-term and long-term memory, memorysubsystems are specialized for the nature of the information to be learned,e.g., verbal or nonverbal. Thus, there is a fairly consistent relationshipbetween the side of the lesion and the type of learning impairment, such thatdamage to the left hippocampal system produces an amnesic syndrome thataffects verbal material (e.g., spoken words, written material) but sparesnonverbal material; conversely, damage to the right hippocampal systemaffects nonverbal material (e.g., complex visual and auditory patterns) butspares verbal material (e.g., Milner, 1974; O’Connor and Verfaellie, 2002).After damage to the left hippocampus, for example, a patient may lose theability to learn new names but remain capable of learning new faces andspatial arrangements (e.g., Tranel, 1991). Conversely,damage to the righthippocampal system frequently impairs the ability to learn new geographicalroutes (e.g., Barrash et al., 2000: see also p. 400). Another distinction can bemade for modality specific memory, which depends on the specific sensorymodality of testing and is most often identified when examining workingmemory (Conant et al., 1999; Fastenau, Conant, and Lauer, 1998).Brain disease can affect different kinds of memories in long-term storagedifferentially: the dissociations that can manifest in brain damaged patientsoften seem remarkable. For example, a motor speech habit, such asorganizing certain sounds into a word, may be wholly retained while rulesfor organizing words into meaningful speech are lost (H. Damasio andDamasio, 1989; Geschwind, 1970). Recognition of printed words ornumbers may be severely impaired while speech comprehension and picturerecognition remain relatively intact. Moreover, neural structures in differentparts of the left temporal lobe are important for retrieving names of objectsfrom different conceptual categories; thus, focal damage to the anteriorand/or lateral parts of the left temporal lobe may result in category-relatednaming defects such that a patient can retrieve common nouns but not propernouns, or can retrieve names for tools/utensils but not names for animals(e.g., H. Damasio, Tranel, Grabowski, et al., 2004; Tranel, 2009). Similarpatterns of dissociations have been reported for retrieving conceptualknowledge for concrete entities, i.e., recognizing the meaning of things suchas animals, tools, or persons (e.g., Tranel, H. Damasio, and A.R. Damasio,1997; Warrington and McCarthy, 1987; Warrington and Shallice, 1984).An important distinction is between episodic and semantic memory(Tulving, 2002a). Episodic memory refers to memories that are localizablein time and space, e.g., your first day in school. Semantic memory refers to“timeless and spaceless”knowledge, for instance, the alphabet or themeanings of words. The clinical meaningfulness of this distinction becomesevident in patients who manifest retrograde amnesia for episodic informationthat extends back weeks and even years, although their semantic memory—fund of information, language usage, and practical knowledge—may beentirely intact (Warrington and McCarthy, 1988).Another useful distinction is between effortful and automatic memory,which refers to whether learning involves active, effortful processing orpassive acquisition (Balota et al., 2000; Hasher and Zacks, 1979; M.K.Johnson and Hirst, 1991). Clinically, the difference between automatic andeffortful memory commonly shows up in a relatively normal immediaterecall of digits or letters that is characteristic of many brain disorders (e.g.,TBI, Alzheimer’s disease, multiple sclerosis)—recall that requires littleeffortful processing, in contrast to reduced performance on tasks requiringeffort, such as reciting a string of digits in reverse. Aging can also amplifythe dissociation between effortful versus automatic memory processing.Other subtypes of memory have been identified, based mainly onresearch in memory disordered patients. Source memory (K.J. Mitchell andJohnson, 2000; Schacter, Harbluk, and McLachlan, 1984; Shimamura, 2002)or contextual memory (J.R. Anderson and Schooler, 2000; Parkin, 2001;Schacter, 1987) refers to knowledge of where or when something waslearned, i.e., the contextual information surrounding the learning experience.Prospective memory is the capacity for “remembering to remember,” and itis also an aspect of executive functioning (Baddeley, Harris, et al., 1987;Brandimonte et al., 1996, passim; Shimamura, Janowsky, and Squire, 1991).The importance of prospective memory becomes apparent in those patientswith frontal lobe injuries whose memory abilities in the classical sense maybe relatively intact but whose social dependency is due, at least in part, totheir inability to remember to carry out previously decided upon activities atdesignated times or places (Sohlberg and Mateer, 2001). For example, it maynot occur to them to keep appointments they have made, although whenreminded or cued it becomes obvious that this information was not lost butrather was not recalled when needed.Another form of “future”memory is future episodic memory. Humanshave a remarkable ability to time travel mentally; that is, we are able torevisit our past experiences through our memories, as well as imagine futureexperiences and situations. Research has suggested that the structuresinvolved in creating memories for past experiences may also be necessaryfor imagining and simulating future experiences (Hassabis et al., 2007). Thecreation of future scenarios requires drawing upon past experiences to guideone’s representation of what might happen in the future. The hippocampusmay be involved in flexibly recombining past autobiographical informationfor use in novel future contexts (Konkel et al., 2008). Functionalneuroimaging studies corroborated conjectures that the hippocampus isinvolved in both creating memories for the past and creating and imaginingthe future (see Addis et al., 2006; Schacter and Addis, 2007).Nondeclarative memoryThe contents of nondeclarative memory have been defined as “knowledgethat is expressed in performance without subjects’ phenomenologicalawareness that they possess it”(Schacter, McAndrews, and Moscovitch,1988). Two subsystems are clinically relevant: procedural memory, andpriming or perceptual learning (Baddeley, 2002; Mayes, 2000b; Squire andKnowlton, 2000). Classical conditioning is also considered a form ofnondeclarative memory (Squire and Knowlton, 2000). Different aspects ofnondeclarative memory and learning activities are processed withinneuroanatomically different systems (Fuster, 1995; Squire and Knowlton,2000; Tranel and Damasio, 2002; pp. 49, 95).Procedural, or skill memory, includes motor and cognitive skill learningand perceptual—”how to"— learning. Priming refers to a form of cuedrecall in which, without the subject’s awareness, prior exposure facilitatesthe response. Two elements common to these different aspects of memoryare their preservation in most amnesic patients (O’Connor and Verfaillie,2002; Tranel, Damasio, H. Damasio, and Brandt, 1994) and that they areacquired or used without awareness or deliberate effort (Graf et al., 1984;Koziol and Budding, 2009; Nissen and Bullemer, 1987). That proceduralmemory is a distinctive system has long been apparent from observations ofpatients who remember nothing of ongoing events and little of their pasthistory, yet retain abilities to walk and talk, dress and eat, etc.; i.e., theirwell-ingrained habits that do not depend on conscious awareness remainingintact (Fuster, 1995; Gabrieli, 1998; Mayes, 2000b). Moreover, proceduralmemory has been demonstrated in healthy subjects taught unusual skills,such as reading inverted type (Kolers, 1976) or learning the sequence for aset of changing locations (Willingham et al., 1989).ForgettingSome loss of or diminished access to information—both recently acquiredand stored in the past—occurs continually as normal forgetting. Normalforgetting rates differ with psychological variables such as personalmeaningfulness of the material and conceptual styles, as well as with agedifferences and probably some developmental differences. Normal forgettingdiffers from amnesic conditions in that only amnesia involves theinaccessibility or nonrecording of large chunks of personal memories.The mechanism underlying normal forgetting is still unclear. What isforgotten seems to be lost from memory through disuse or interference bymore recently or vividly learned information or experiences (Mayes, 1988;Squire, 1987). Perhaps most important of these processes is “autonomousdecay … due to physiologic and metabolic processes with progressiveerosion of synaptic connections”(G.H. Bower, 2000). Fuster (1995) pointedout thatinitial “poor fixation of the memory”accounts for some instances offorgetting. This becomes most apparent in clinical conditions in whichattentional processes are so impaired that passing stimuli (in conversation oras events) are barely attended to, weakly stored, and quickly forgotten(Howieson and Lezak, 2002b). Rapid forgetting is characteristic of manydegenerative dementing conditions, e.g., Alzheimer’s disease (Bondi,Salmon, and Kaszniak, 2009; Dannenbaum et al., 1988; Gronholm-Nymanet al., 2010), frontotemporal dementia (Pasquier et al., 2001) , and vasculardementia (Vanderploeg, Yuspeh, and Schinka, 2001).There is also the Freudian notion that nothing is really “lost”frommemory and the problem is with faulty or repressed retrieval processes. Thisview is not scientifically tenable, although psychodynamic suppression orrepression of some unwanted or unneeded memories can take place andaccount for certain types of “forgetting.” This “forgotten”material can beretrieved, sometimes spontaneously, sometimes with such psychologicalassistance as hypnosis (e.g., case report, p. 30).Expressive FunctionsExpressive functions, such as speaking, drawing or writing, manipulating,physical gestures, and facial expressions or movements, make up the sum ofobservable behavior. Mental activity is inferred from them.ApraxiaDisturbances of purposeful expressive functions are known as apraxias(literally, no work) (Liepmann, [1900] 1988). The apraxias typically involveimpairment of learned voluntary acts despite adequate motor innervation ofcapable muscles, adequate sensorimotor coordination for complex actscarried out without conscious intent (e.g., articulating isolated spontaneouswords or phrases clearly when volitional speech is blocked, brushing crumbsor fiddling with objects when intentional hand movements cannot beperformed), and adequate comprehension of the elements and goals of thedesired activity. Given the complexity of purposeful activity, it is notsurprising that apraxia can occur with disruption of pathways at differentstages (initiation, positioning, coordination, and/or sequencing of motorcomponents) in the evolution of an act or sequential action (Grafton, 2003;Heilman and Rothi, 2011).Apraxic disorders may appear when pathways have been disrupted thatconnect the processing of information (e.g., instructions, knowledge of toolsor acts) with centers for motor programming or when there has been abreakdown in motor integration and executive functions integral to theperformance of complex learned acts (Mendoza and Foundas, 2008). Thus,when asked to show how he would use a pencil, an apraxic patient who hasadequate strength and full use of his muscles may be unable to organizefinger and hand movements relative to the pencil sufficiently well tomanipulate it appropriately. He may even be unable to relate the instructionsto hand movements although he understands the nature of the task.Apraxias tend to occur in clusters of disabilities that share a commonanatomical pattern of brain damage (Mendoza and Foundas, 2008, passim).For example, apraxias involving impaired ability to perform skilled tasks oncommand or imitatively and to use objects appropriately and at will arecommonly associated with lesions near or overlapping speech centers. Theytypically appear concomitantly with communication disabilities (Heilmanand Rothi, 2011; Kertesz, 2005; Meador, Loring, Lee, et al., 1999). A morenarrowly defined relationship between deficits in expressive speech (Broca’saphasia) and facial apraxia further exemplifies the anatomical contiguity ofbrain areas specifically involved in verbal expression and facial movement(Kertesz, 2005; Kertesz and Hooper, 1982; Verstichel et Cambier, 2005),even though these disorders have been dissociated in some cases (Heilmanand Rothi, 2011). Apraxia of speech, too, may appear in impaired initiation,positioning, coordination, and/or sequencing of the motor components ofspeech. These problems can be mistaken for or occur concurrently withdefective articulation (dysarthria). Yet language (symbol formulation)deficits and apraxic phenomena often occur independently of one another(Haaland and Flaherty, 1984; Heilman and Rothi, 2011; Mendoza andFoundas, 2008).Constructional disordersConstructional disorders, often classified as apraxias, are actually notapraxias in the strict sense of the concept. Rather, they are disturbances “informulative activities such as assembling, building, drawing, in which thespatial form of the product proves to be unsuccessful without there being anapraxia of single movements”(Benton, 1969a). They often occur with lesionsof the nonspeech hemisphere and are associated with defects of spatialperception (Benton, 1973, 1982), although constructional disorders anddisorders involving spatial perception can manifest as relatively isolatedimpairments. Different constructional disorders also may appear in relativeisolation. Thus, some patients will experience difficulty in performing allconstructional tasks; others who make good block constructions mayconsistently produce poor drawings; still others may copy drawings well butbe unable to do free drawing. Certain constructional tasks, such as clockdrawing, are useful bedside examination procedures as the multiple factorsrequired for success (planning, spatial organization, motor control) makesuch a seemingly simple task sensitive to cognitive impairments resultingfrom a variety of conditions (M. Freedman, Leach, et al., 1994; Tranel,Rudrauf, et al., 2008; see pp. 594–606).AphasiaAphasia (literally, no speech) can be defined as an acquired disturbance ofthe comprehension and formulation of verbal messages (A.R. Damasio andDamasio, 2000). Aphasia can be further specified as a defect in the two-waytranslation mechanism between thought processes and language; that is,between the organized manipulation of mental representations whichconstitutes thought, and the organized processing of verbal symbols andgrammatical rules which constitutes sentences. In aphasia, either theformulation or comprehension of language, or both will be compromised. Anaphasic disorder can affect syntax (the grammatical structure of sentences),the lexicon (the dictionary of words that denote meanings), or wordmorphology (the combination of phonemes that results in word structure).Deficits in various aspects of language occur with different degrees ofseverity and in different patterns, producing a number of distinctivesyndromes (or subtypes) of aphasia. Each syndrome has a defining set ofneuropsychological manifestations, associated with a typical site of neuraldysfunction. The designation of different syndromes of aphasia dates back tothe 19th century observations of Broca, Wernicke, and other neurologists(Grodzinsky and Amunts, 2006, Historical Articles, pp. 287–394). Theessence of those early classifications has stood the test of time very well.With refinements in analysis at both behavioral and neuro- anatomicallevels, it has become possible to identify different aphasia syndromesreliably, as seen in several typical classificatory schemes (e.g., Benson, 1993[ten types]; A.R. Damasio and Damasio, 2000 [eight types]; Kertesz, 2001[ten types]; Mendoza and Foundas, 2008 [six types]; Verstichel et Cambier,2005 [nine types]) (see Table 2.1).Many investigators have taken issue with the usual typologies as havingoutlived both their usefulness and contradictory new data (e.g., A. Basso,2003; D. Caplan, 2011; Caramazza, 1984). While it is true that thetraditional diagnostic categories for aphasia map only loosely ontobehavioral and anatomical templates, they have survived because of theirutility in summarizing and transmitting information about certain generalconsistencies across individuals with aphasia (A.R. Damasio and Damasio,2000; Darby and Walsh, 2005; Festa et al., 2008). However, the presentationof aphasic symptoms alsovaries enough from patient to patient and inindividual patients over time that clear distinctions do not hold up in manycases (M.P. Alexander, 2003; Wallesch, Johannsen-Horbach, and Blanken,2010). Thus, it is not surprising that the identification of aphasia syndromes(sets of symptoms that occur together with sufficient frequency as to“suggest the presence of a specific disease”or site of damage [Geschwindand Strub, 1975]) is complicated both by differences of opinion as to whatconstitutes an aphasia syndrome and differences in the labels given thosesymptom constellations that have been conceptualized as syndromes.TABLE 2.1 Most Commonly Defined Aphasic SyndromesFor syndrome descriptions, see Benson, 1993; A.R. Damasio and Damasio, 2000; Goodglass andKaplan, 1983a; Kertesz, 2001; Tranel and Anderson, 1999; Verstichel et Cambier, 2005.*Denotes syndromes named in all the above references.Several alternative ways of classifying the aphasias have been suggested,most focusing on different patterns of impairment and ability-sparinginvolving such aspects of verbal communication as speech fluency,comprehension, repetition, and naming (e.g., Table 2.1). Like other kinds ofcognitive defects, language disturbances usually appear in clusters of relateddysfunctions. For example, agraphia (literally, no writing) and alexia(literally, no reading) only rarely occur alone; rather, they are often foundtogether and in association with other communication deficits (Coslett, 2011;Kertesz, 2001; Roeltgen, 2011). In contrast to alexia, which denotes readingdefects in persons who could read before the onset of brain damage ordisease, dyslexia typically refers to developmental disorders in otherwisecompetent children who do not make normal progress in reading (Coltheart,1987; Lovett, 2003). Developmental dysgraphia differs from agraphia on thesame etiological basis (Ellis, 1982).ThinkingThinking may be defined as any mental operation that relates two or morebits of information explicitly (as in making an arithmetic computation) orimplicitly (as in judging that this is bad, e.g., relative to that) (Fuster, 2003).A host of complex cognitive functions is subsumed under the rubric ofthinking, such as computation, reasoning and judgment, concept formation,abstracting and generalizing; ordering, organizing, planning, and problemsolving overlap with executive functions.The nature of the information being mentally manipulated (e.g., numbers,design concepts, words) and the operation being performed (e.g., comparing,compounding, abstracting, ordering) define the category of thinking. Thus,“verbal reasoning”comprises several operations done with words; itgenerally includes ordering and comparing, sometimes analyzing andsynthesizing (e.g., Cosmides and Tooby, 2000). “Computation”may involveoperations of ordering and compounding done with numbers (Dehaene,2000; Fasotti, 1992), and distance judgment involves abstracting andcomparing ideas of spatial extension.The concept of “higher”and “lower”mental processes originated with theancient Greek philosophers. This concept figures in the hierarchical theoriesof brain functions and mental ability factors in which “higher”refers to themore complex mental operations and “lower”to the simpler ones. The degreeto which a concept is abstract or concrete also determines its place on thescale. For example, the abstract idea “a living organism”is presumed torepresent a higher level of thinking than the more concrete idea “my catPansy"; the abstract rule “file specific topics under general topics”is likewiseconsidered to be at a higher level of thinking than the instructions “file ‘fir’under ‘conifer,’ file ‘conifer’ under ‘tree’.”The higher cognitive functions of abstraction, reasoning, judgment,analysis, and synthesis tend to be relatively sensitive to diffuse brain injury,even when most specific receptive, expressive, or memory functions remainessentially intact (Knopman, 2011; Mesulam, 2000a). Higher functions mayalso be disrupted by any one of a number of lesions in functionally discreteareas of the brain at lower levels of the hierarchy (Gitelman, 2002) . Thus, ina sense, the higher cognitive functions tend to be more “fragile”than thelower, more discrete functions. Conversely, higher cognitive abilities mayremain relatively unaffected in the presence of specific receptive, expressive,and memory dysfunctions (E. Goldberg, 2009; Pincus and Tucker, 2003).Problem solving can take place at any point along the complexity andabstraction continua. Even the simplest activities of daily living demandsome problem solving, e.g., inserting tooth brushing into the morning routineor determining what to do when the soap dish is empty. Problem solvinginvolves executive functions as well as thinking since a problem first has tobe identified. Patients with executive disorders can look at an empty soapdish without recognizing that it presents a problem to be solved, and yet beable to figure out what to do once the problem has been brought to theirattention.Arithmetic concepts and operations are basic thinking tools that can bedisrupted in specific ways by more or less localized lesions giving rise toone of at least three forms of acalculia (literally, no counting) (Denburg andTranel, 2011; Grafman and Rickard, 1997). The three most commonacalculias involve impairment of (1) appreciation and knowledge of numberconcepts (acalculias associated with verbal defects); (2) ability to organizeand manipulate numbers spatially as in long division or multiplication of twoor more numbers; or (3) ability to perform arithmetic operations(anarithmetria). Neuroimaging studies have further fractionated componentsof number processing showing associations with different cerebral regions(Dehaene, 2000; Gitelman, 2002).Unlike other cognitive functions, thinking cannot be tied to specificneuroanatomical systems, although the disruption of feedback, regulatory,and integrating mechanisms can affect complex cognitive activity moreprofoundly than other cognitive functions (Luria, 1966) . “There is no …anatomy of the higher cerebral functions in the strict sense of the word … .Thinking is regarded as a function of the entire brain that defieslocalization”(Gloning and Hoff, 1969).As with other cognitive functions, the quality of any complex operationwill depend in part on the extent to which its sensory and motor componentsare intact at the central integrative (cortical) level. For example, patientswith certain somatosensory defects tend to do poorly on reasoning tasksinvolving visuospatial concepts (Farah and Epstein, 2011; Teuber, 1959);patients whose perceptual disabilities are associated with lesions in thevisual system are more likely to have difficulty solving problems calling onvisual concepts (B. Milner, 1954; Harel and Tranel, 2008). Verbal defectstend to have more obvious and widespread cognitive consequences thandefects in other functional systems because task instructions are frequentlyverbal, self-regulation and self-critiquing mechanisms are typically verbal,and ideational systems—even for nonverbal material—are usually verbal(Luria, 1973a). The emphasis on verbal mediation, however, should not beconstrued as obligatory, and it is abundantly clear that humans withoutlanguage can still “think”(e.g., see Bermudez, 2003; Weiskrantz, 1988). Oneneed only interact with a patient with global aphasia, or a young preverbalchild, to see nonlanguage thinking demonstrated.Mental Activity VariablesThese are behavior characteristics that have to do with the efficiency ofmental processes. They are intimately involved in cognitive operations butdo not have a unique behavioral end product. They can be classified roughlyinto three categories: level of consciousness, attentional functions, andactivity rate.ConsciousnessThe concept of consciousness has eluded a universally acceptable definition(R. Carter,2002; Dennett, 1991; Prigatano, 2009). Thus, it is not surprisingthat efforts to identify its neural substrate and neurobiology are still at thehypothesis-making stage (e.g., Koch and Crick, 2000; Metzinger, 2000,passim). Consciousness generally concerns the level at which the organismis receptive to stimulation or is awake. The words “conscious”or“consciousness”are also often used to refer to awareness of self andsurroundings and in this sense can be confused with “attention.” To maintaina clear distinction between “conscious”as indicating an awake state and“conscious”as the state of being aware of something, we will refer to thelatter concept as “awareness”(Merikle et al., 2001; Sperry, 1984; Weiskrantz,1997) . In the sense used in this book, specific aspects of awareness can beblotted out by brain damage, such as awareness of one’s left arm or someimplicit skill memory (Farah, 2000; Schacter, McAndrews, and Moscovitch,1988). Awareness can even be divided, with two awarenesses coexisting, asexperienced by “split-brain”patients (Baynes and Gazzaniga, 2000;Kinsbourne, 1988; Loring, Meador, and Lee, 1989). Moreover, beyond theawake state and awareness, Prigatano (2010) includes “conscious awarenessof another’s mental state”as the third component of a theoretical model ofconscious. Yet consciousness is also a general manifestation of brain activitythat may become more or less responsive to stimuli but has no separableparts.Level of consciousness ranges over a continuum from full alertnessthrough drowsiness, somnolence, and stupor, to coma (Plum and Posner,1980; Strub and Black, 2000; Trzepacz and Meagher, 2008). Even slightdepressions of the alert state may significantly diminish a person’s mentalefficiency, leading to tiredness, inattention, or slowness. Levels of alertnesscan vary in response to organismic changes in metabolism, circadianrhythms, fatigue level, or other organic states (e.g., tonic changes) (Stringer,1996; van Zomeren and Brouwer, 1987). Brain electrophysiologicalresponses measured by such techniques as electroencephalography andevoked potentials vary with altered levels of consciousness (Daube, 2002;Frith and Dolan, 1997). Although disturbances of consciousness mayaccompany a functional disorder, they usually reflect pathological conditionsof the brain (Lishman, 1997; Trzepacz et al., 2002).Attentional functionsAttention refers to capacities or processes of how the organism becomesreceptive to stimuli and how it may begin processing incoming or attended-to excitation (whether internal or external) (Parasuraman, 1998). Definitionsof attention vary widely as seen, for example, in Mirsky’s (1989) placementof attention within the broader category of “information processing”andGazzaniga’s (1987) conclusion that “the attention system … functionsindependently of information processing activities and [not as] … anemergent property of an ongoing processing system.” Many investigatorsseem most comfortable with one or more of the characteristics that WilliamJames (1890) and others ascribed to attention (e.g., see Leclercq, 2002;Parasuraman, 1998; Pashler, 1998). These include two aspects, “reflex”(i.e.,automatic processes) and “voluntary”(i.e., controlled processes). Othercharacteristics of attention are its finite resources and the capacities both fordisengagement in order to shift focus and for responsivity to sensory orsemantic stimulus characteristics. Another kind of difference in attentionalactivities is between sustained tonic attention as occurs in vigilance, and theresponsive shifting of phasic attention, which orients the organism tochanging stimuli. “At its core, attention includes both perceptual andinhibitory processes—when one attends to one thing, one is refraining fromattending to other things”(Koziol and Budding, 2009, p. 71; see alsoKinsbourne, 1993).Most investigators conceive of attention as a system in which processingoccurs sequentially in a series of stages within the different brain systemsinvolved in attention (Butter, 1987; Luck and Hillyard, 2000). This systemappears to be organized in a hierarchical manner in which the earliest entriesare modality specific while late-stage processing—e.g., at the level ofawareness—is supramodal (Butter, 1987; Posner, 1990). Disorders ofattention may arise from lesions involving different points in this system(L.C. Robertson and Rafal, 2000; Rousseaux, Fimm, and Cantagallo, 2002).A salient characteristic of the attentional system is its limited capacity(Lavie, 2001; Pashler, 1998; Posner, 1978) . Only so much processingactivity can take place at a time, such that engagement of the system inprocessing one attentional task calling on controlled attention can interferewith a second task having similar processing requirements. Thus, one maybe unable to concentrate on a radio newscast while closely following asporting event on television yet can easily perform an automatic (in thiscase, highly overlearned) attention task such as driving on a familiar routewhile listening to the newscast. (The use of cell phones while driving,however, is an entirely different story as it creates attentional defects that canhave disastrous consequences; see Caird et al., 2008; Charlton, 2009;McCartt et al., 2006.)Another key characteristic involves bottom-up processes which biasattention toward salient “attention-getting”stimuli like a fire alarm, and top-down processes determined by the observer’s current goals (C.E. Connor etal., 2004). For example, one of the many studies of the interplay betweenbottom-up and top-down visual attention processes found that, under certaintask conditions attention is automatically directed toward conspicuousstimuli, despite their irrelevance and possible detrimental effect onperformance. In contrast, top-down attentional biases can be sufficientlystrong to override stimulus-driven responses (Theeuwes, 2010).Attentional capacity varies not only between individuals but also withineach person at different times and under different conditions. Depression orfatigue, for example, can temporarily reduce attentional capacity in healthypersons (Landro, Stiles, and Sletvold, 2001; P. Zimmerman and Leclercq,2002). An aging brain (Parasuraman and Greenwood, 1998; Van der Lindenand Collette, 2002) and brain injury may irreversibly reduce attentionalcapacity (L.C. Robertson and Rafal, 2000; Rousseaux, Fimm, andCantagallo, 2002).Simple immediate span of attention—how much information can begrasped at once—is a relatively effortless process that tends to be resistant tothe effects of aging and many brain disorders. It may be considered a formof working memory but is an integral component of attentional functioning(Howieson and Lezak, 2002b). Four other aspects of attention are morefragile and thus often of greater clinical interest (Leclercq, 2002; Mateer,2000; Posner, 1988; Van der Linden and Collette, 2002). (1) Focused orselective attention is probably the most studied aspect and the one peopleusually have in mind when talking about attention. It is the capacity tohighlight the one or two important stimuli or ideas being dealt with whilesuppressing awareness of competing distractions. It may also be referred toas concentration. Sohlberg and Mateer (1989) additionally distinguishbetween focused and selective attention by attributing the “ability to responddiscretely”to specific stimuli to the focusing aspect of attention and thecapacity to ward off distractions to selective attention. (2) Sustainedattention, or vigilance, refers to the capacity to maintain an attentionalactivity over a period of time. (3) Divided attention involves the ability torespond to more than one task at a time or to multiple elements or operationswithin a task, as in a complex mental task. It is thus very sensitive to anycondition that reduces attentional capacity. (4) Alternating attention allowsfor shifts in focus and tasks.Whilethese different aspects of attention can be demonstrated bydifferent examination techniques, even discrete damage involving a part ofthe attentional system can create alterations that affect more than one aspectof attention. Underlying many patients’ attentional disorders is slowedprocessing, which can have broad-ranging effects on attentional activities(Gunstad et al., 2006).Patients with brain disorders associated with slowed processing—certain traumatic braininjuries and multiple sclerosis, for example—often complain of “memory problems,”although memory assessment may demonstrate minimal if any diminution in theirabilities to learn new or retrieve old information. On questioning, the examiner discoversthat these “memory problems”typically occur when the patient is bombarded by rapidlypassing stimuli. These patients miss parts of conversations (e.g., a time or place formeeting, part of a story). Many of them also report misplacing objects as an example oftheir “memory problem.” What frequently has happened is that on entering the house withkeys or wallet in hand they are distracted by children or a spouse eager to speak to themor by loud sounds or sight of some unfinished chore. With no recollection of what theyhave been told or where they set their keys, they and their families naturally interpretthese lapses as a “memory problem.” Yet the problem is due to slowed processing speedwhich makes difficult the processing of multiple simultaneous stimuli. Given anexplanation of the true nature of these lapses, patients and families can alter ineffectivemethods of exchanging messages and conducting activities with beneficial effects on thepatient’s “memory.” (Howieson and Lezak, 2002b)Impaired attention and concentration are among the most common mentalproblems associated with brain damage (Leclercq, Deloche, and Rousseaux,2002; Lezak, 1978b, 1989), and also with psychiatric disease (R.A. Cohen etal., 2008). When attentional deficits occur, all the cognitive functions may beintact and the person may even be capable of some high-level performances,yet overall cognitive productivity suffers.Activity rateActivity rate refers to the speed at which mental activities are performed andto speed of motor responses. Behavioral slowing is a common characteristicof both aging and brain damage. Slowing of mental activity shows up mostclearly in delayed reaction times and in longer than average totalperformance times in the absence of a specific motor disability. It can beinferred from patterns of mental inefficiency, such as reduced auditory spanplus diminished performance accuracy plus poor concentration, althougheach of these problems can occur on some basis other than generalizedmental slowing. Slowed processing speed appears to contribute significantlyto the benign memory lapses of elderly persons (Luszcz and Bryan, 1999;D.C. Park et al., 1996; Salthouse, 1991a).EXECUTIVE FUNCTIONSThe executive functions consist of those capacities that enable a person toengage successfully in independent, purposive, self-directed, and self-serving behavior. They differ from cognitive functions in a number of ways.Questions about executive functions ask how or whether a person goes aboutdoing something (e.g., Will you do it and, if so, how and when?); questionsabout cognitive functions are generally phrased in terms of what or howmuch (e.g., How much do you know? What can you do?). So long as theexecutive functions are intact, a person can sustain considerable cognitiveloss and still continue to be independent, constructively self-serving, andproductive. When executive functions are impaired, even if only partially,the individual may no longer be capable of satisfactory self-care, ofperforming remunerative or useful work independently, or of maintainingnormal social relationships regardless of how well preserved the cognitivecapacities are—or how high are the person’s scores on tests of skills,knowledge, and abilities. Cognitive deficits usually involve specificfunctions or functional areas; impairments in executive functions tend toshow up globally, affecting all aspects of behavior. Moreover, executivedisorders can affect cognitive functioning directly in compromised strategiesto approaching, planning, or carrying out cognitive tasks, or in defectivemonitoring of the performance (E. Goldberg, 2009; Lezak, 1982a; Tranel,Hathaway-Nepple, and Anderson, 2007).A young woman who survived a severe motor vehicle accident displayed a complete lack ofmotivation with inability to initiate almost all behaviors including eating and drinking,leisure or housework activities, social interactions, sewing (which she had once done well),or reading (which she can still do with comprehension). Although new learning ability isvirtually nonexistent and her constructional abilities are significantly impaired, her cognitivelosses are relatively circumscribed in that verbal skills and much of her backgroundknowledge and capacity to retrieve old information—both semantic and episodic—are fairlyintact. Yet she performs these cognitive tasks—and any other activities—only whenexpressly directed or stimulated by others, and then external supervision must be maintainedfor her to complete what she began.Many of the behavior problems arising from impaired executivefunctions may be apparent to casual or naive observers, but they may notappreciate their importance with respect to the patient’s overall behavioralcompetence. For experienced clinicians, these problems are symptoms orhallmarks of significant brain injury or dysfunction that may be predictive ofmore social and interpersonal problems ahead (Lezak, 1996). Among themare a defective capacity for self-control or self-direction such as emotionallability (see pp. 39, 387) or flattening, a heightened tendency to irritabilityand excitability, impulsivity, erratic carelessness, rigidity, and difficulty inmaking shifts in attention and in ongoing behavior.Other defects in executive functions, however, are not so obvious. Theproblems they occasion may be missed or not recognized as“neuropsychological”by examiners who see patients only in the well-structured inpatient and clinic settings in which psychiatry and neurologypatients are commonly observed (Lezak, 1982a). Perhaps the most serious ofthese problems, from a psychosocial standpoint, are impaired capacity toinitiate activity, decreased or absent motivation (anergia), and defects inplanning and carrying out the activity sequences that make up goal-directedbehaviors (Darby and Walsh, 2005; Lezak, 1989; Luria, 1966). Patientswithout significant impairment of receptive or expressive functions whosuffer primarily from these kinds of executive control defects are oftenmistakenly judged to be malingering, lazy or spoiled, psychiatricallydisturbed, or—if this kind of defect appears following a legally compensablebrain injury—exhibiting a “compensation neurosis”that some interestedpersons may believe will disappear when the patient’s legal claim has beensettled.The crippling defects of executive functions are vividly demonstrated by the case of a handsurgeon who had had a hypoxic (hypoxia: insufficient oxygen) event during a cardiac arrestthat occurred in the course of minor facial surgery. His cognitive abilities, for the most part,were not greatly affected; but initiating, self-correcting, and self-regulating behaviors wereseverely compromised. He also displayed some difficulty with new learning—not so muchthat he lost track of the date or could not follow sporting events from week to week butenough to render his memory, particularly prospective memory, unreliable for most practicalpurposes.One year after the anoxic episode, the patient’s scores on Wechsler Intelligence Scaletests ranged from high average (75th percentile) to very superior (99th percentile), excepton Digit Symbol, performed without error but at a rate of speed that placedConcept Formation Tests in Verbal FormatsConcept Formation Tests in Visual FormatsSymbol PatternsSortingSort and ShiftReasoningVerbal ReasoningReasoning about Visually Presented MaterialMathematical ProceduresArithmetic Reasoning ProblemsCalculations16. Executive FunctionsThe Executive FunctionsVolitionPlanning and Decision MakingPurposive ActionSelf-RegulationEffective PerformanceExecutive Functions: Wide Range Assessment17. Neuropsychological Assessment BatteriesAbility and AchievementIndividual AdministrationPaper-and-Pencil AdministrationBatteries Developed for Neuropsychological AssessmentBatteries for General UseBatteries Composed of Preexisting TestsBatteries for Assessing Specific ConditionsHIV+SchizophreniaNeurotoxicityDementia: Batteries Incorporating Preexisting TestsTraumatic Brain InjuryScreening Batteries for General UseComputerized Neuropsychological Assessment Batteries18. Observational Methods, Rating Scales, and InventoriesThe Mental Status ExaminationRating Scales and InventoriesDementia EvaluationMental Status Scales for Dementia Screening and RatingMental Status and Observer Rating Scale CombinationsScales for Rating ObservationsTraumatic Brain InjuryEvaluating SeverityChoosing Outcome MeasuresOutcome EvaluationEvaluation of the Psychosocial Consequences of Head InjuryEpilepsy Patient EvaluationsQuality of LifePsychiatric Symptoms19. Tests of Personal Adjustment and Emotional FunctioningObjective Tests of Personality and Emotional StatusDepression Scales and InventoriesAnxiety Scales and InventoriesInventories and Scales Developed for Psychiatric ConditionsProjective Personality TestsRorschach TechniqueStorytelling TechniquesDrawing Tasks20. Testing for Effort, Response Bias, and MalingeringResearch ConcernsExamining Response Validity with Established TestsMultiple AssessmentsTest Batteries and Other Multiple Test SetsWechsler ScalesBatteries and Test Sets Developed for NeuropsychologicalAssessmentMemory TestsSingle TestsTests with a Significant Motor ComponentSpecial Techniques to Assess Response ValiditySymptom Validity Testing (SVT)Forced-Choice TestsVariations on the Forced-Choice ThemeOther Special Examination TechniquesSelf-Report Inventories and QuestionnairesPersonality and Emotional Status InventoriesAppendix A: Neuroimaging PrimerAppendix B: Test Publishers and DistributorsReferencesTest IndexSubject IndexList of FiguresThe Behavioral Geography of the BrainFIGURE3.1Schematic of a neuron. Photomicrograph. (See color Figure 3.1)FIGURE3.2(a) Axial MRI, coronal MRI, sagittal MRI of anatomical divisions of the brain. (See colorFigure 3.2a, b, and c)FIGURE3.3Lateral surface anatomy postmortem (left) with MRI of living brain (right)FIGURE3.4Ventricle anatomy. (See color Figure 3.4)FIGURE3.5Scanning electron micrograph showing an overview of corrosion casts from the occipitalcortexFIGURE3.6Major blood vessels schematicFIGURE3.7Thalamo-cortical topography demonstrated by DTI tractography. (See color Figure 3.7)FIGURE3.8Memory and the limbic systemFIGURE3.9Cut-away showing brain anatomy viewed from a left frontal perspective with the leftfrontal and parietal lobes removed. (See color Figure 3.9)FIGURE3.10DTI (diffusion tensor imaging) of major tracts. (See color Figure 3.10)FIGURE3.11DTI of major tracts through the corpus callosum. (See color Figure 3.11)FIGURE3.12Representative commissural DTI ‘streamlines’ showing cortical projections and corticalterminations of corpus callosum projections. (See color Figure 3.12)FIGURE3.13Schematic diagram of visual fields, optic tracts, and the associated brain areas, showing leftand right lateralization in humansFIGURE3.14Diagram of a “motor homunculus” showing approximately relative sizes of specific regionsof the motor cortexFIGURE3.15Example of global/local stimuliFIGURE3.16Example of spatial dyscalculia by a traumatically injured pediatricianFIGURE3.17aAttempts of a 51-year-old right hemisphere stroke patient to copy pictured designs withcolored blocksFIGURE3.17bAttempts of a 31-year-old patient with a surgical lesion of the left visual association area tocopy the 3 × 3 pinwheel designFIGURE3.18Overwriting (hypergraphia) by a 48-year-old college-educated retired police investigatorsuffering right temporal lobe atrophyFIGURE3.19Simplification and distortions of four Bender-Gestalt designs by a 45-year-old assemblyline workerFIGURE3.20The lobe-based divisions of the human brain and their functional anatomyFIGURE3.21Brodmann’s cytoarchitectural map of the human brainFIGURE3.22Lateral view of the left hemisphere, showing the ventral “what” and dorsal “where” visualpathways in the occipital-temporal and occipital-parietal regionsFIGURE3.23(a) This bicycle was drawn by the 51-year-old retired salesman who constructed the blockdesigns of Figure 3.17aFIGURE3.24aFlower drawing, illustrating left-sided inattentionFIGURE3.24bCopy of the Taylor Complex Figure (see p. 575), illustrating inattention to the left side ofthe stimulusFIGURE3.24cWriting to copy, illustrating inattention to the left side of the to-be-copied sentences;written by a 69 year-old manFIGURE3.24dExample of inattention to the left visual fieldFIGURE3.25Ventral view of H.M.’s brain ex situ using 3-D MRI reconstructionFIGURE3.26The major subdivisions of the human frontal lobes identified on surface 3-D MRIreconstructions of the brainThe Rationale of Deficit MeasurementFIGURE4.1Calculations test errors (circled) made by a 55-year-old dermatologist with a contre coupThe Neuropsychological Examination: ProceduresFIGURE5.1An improvised test for lexical agraphiaFIGURE5.2Copies of the Bender-Gestalt designs drawn on one page by a 56-year-old sawmill workerwith phenytoin toxicityThe Neuropsychological Examination: InterpretationFIGURE6.1House-Tree-Person drawings of a 48-year-old advertising managerFIGURE6.2This bicycle was drawn by a 61-year-old who suffered a stroke involving the right parietallobeFIGURE6.3The relationship of some commonly used test scores to the normal curve and to one anotherNeuropathology for NeuropsychologistsFIGURE7.1This schematic is of a neuron and depicts various neuronal membrane and physiologicaleffects incurred during the initial stage of TBI (See color Figure 7.1)FIGURE7.2Proteins are the building blocks of all tissues including all types of neural cells and in thisdiagram the Y-axis depicts the degree of pathological changes in protein integrity with TBIFIGURE7.3There are two pathways that lead to a breakdown in the axon from TBI, referred to asaxotomyFIGURE CT scans depicting the trajectory prior to neurosurgery depicting the trajectory and path of7.4 a bullet injury to frontotemporal areas of the brainFIGURE7.5MRI demonstration of the effects of penetrating brain injuryFIGURE7.6Postmortem section showing the central penetration wound from a bullet which produces apermanent cavity in the brainFIGURE7.7Diagram showing impulsive loading from the rear (left) and front (right) with TBIFIGURE7.8Mid-sagittal schematic showing the impact dynamics of angular decelerations of the brainas the head hits a fixed objectFIGURE7.9Wave propagation and contact phenomena following impact to the headFIGURE7.10The colorized images represent a 3-D CT recreation of the day-of-injury hemorrhagesresulting from a severe TBI (See color Figure 7.10)FIGURE7.11Mid-sagittal MRI with an atrophied corpus callosum and old shear lesion in the isthmus(See color Figure 7.11)FIGURE7.12MRI comparisons at different levels of TBI severity in children with a mean age of 13.6FIGURE7.133-D MRI reconstruction of the brain highlighting the frontal focus of traumatichemorrhages associated with a severe TBI.(Seethis performancelow in the average score range. His Trail Making Test speed was within normal limits andhe demonstrated good verbal fluency and visual discrimination abilities—all in keeping withhis highest educational and professional achievements. On the basis of a clinicalpsychologist’s conclusion that these high test scores indicated “no clear evidence oforganicity”and a psychiatric diagnosis of “traumatic depressive neurosis,” the patient’sinsurance company denied his claim (pressed by his guardian brother) for disabilitypayments. Retesting six years later, again at the request of the brother, produced the samepattern of scores.The patient’s exceptionally good test performances belied his actual behavioral capacity.Seven years after the hypoxic episode, this 45-year-old man who had had a successfulprivate practice was working for his brother as a delivery truck driver. This youthful-looking, nicely groomed man explained, on questioning, that his niece bought all of hisclothing and even selected his wardrobe for important occasions such as this examination.He knew neither where nor with what she bought his clothes, and he did not seem toappreciate that this ignorance was unusual. He was well-mannered and pleasantly responsiveto questions but volunteered nothing spontaneously and made no inquiries in an hour-and-a-half interview. His matter-of-fact, humorless manner of speaking remained unchangedregardless of the topic.When asked, the patient reported that his practice had been sold but he did not know towhom, for how much, or who had the money. This once briefly married man who hadenjoyed years of affluent independence had no questions or complaints about living in hisbrother’s home. He had no idea how much his room and board cost or where the moneycame from for his support, nor did he exhibit any curiosity or interest in this topic. He saidhe liked doing deliveries for his brother because “I get to talk to people.” He had enjoyedsurgery and said he would like to return to it but thought that he was too slow now. Whenasked what plans he had, his reply was, “None.”His sister-in-law reported that it took several years of rigorous rule-setting to get thepatient to bathe and change his underclothes each morning. He still changes his outerclothing only when instructed. He eats when hungry without planning or accommodatinghimself to the family’s plans. If left home alone for a day or so he may not eat at all,although he makes coffee for himself. In seven years he has not brought home or asked forany food, yet he enjoys his meals. He spends most of his leisure time in front of the TV.Though once an active sports enthusiast, he has made no plans to hunt or fish in seven years,but he takes pleasure in these sports when accompanying relatives.Since he runs his own business, the patient’s brother is able to keep the patient employed.The brother explained that he can give the patient only routine assignments that require nojudgment, and these only one at a time. As the patient finishes each assignment, he calls intohis brother’s office for the next one. Although he knows that his brother is his guardian, thepatient has never questioned or complained about his legal status. When the brotherreinstituted suit for the patient’s disability insurance, the company again denied the claim inthe belief that the high test scores showed he was capable of returning to his profession. Itwas only when the insurance adjustor was reminded of the inappropriateness of the patient’slifestyle and the unlikelihood that an experienced, competent surgeon would contentedlyremain a legal dependent in his brother’s household for seven years that the adjustor couldappreciate the psychological devastation the surgeon had suffered.PERSONALITY/EMOTIONALITY VARIABLESChanges in emotion and personality are common with brain disorders andafter brain injury (Gainotti, 2003; Lezak, 1978a; Lishman, 1997; see Chapter7, passim). Some changes tend to occur as fairly characteristic behaviorpatterns that relate to specific anatomical sites (e.g., S.W. Anderson, Barrash,et al., 2006; R.J. Davidson and Irwin, 2002). Among the most commondirect effects of brain injury on personality are emotional dulling,disinhibition, diminution of anxiety with associated emotional blandness ormild euphoria, and reduced social sensitivity (Barrash, Tranel, andAnderson, 2000). Heightened anxiety, depressed mood, and hypersensitivityin interpersonal interactions may also occur (Blumer and Benson, 1975; D.J.Stein and Rauch, 2008; Yudofsky and Hales, 2008, passim).Some of the emotional and personality changes that follow brain injuryseem to be not so much a direct product of the illness but develop asreactions to experiences of loss, chronic frustration, and radical changes inlifestyle. Consequently, depression is probably the most common singleemotional characteristic of brain damaged patients generally, with pervasiveanxiety following closely behind (J.F. Jackson, 1988; Lezak, 1978b). Whenmental inefficiency (i.e., attentional deficits typically associated with slowedprocessing and diffuse damage) is a prominent feature, obsessive-compulsive traits frequently evolve (Lezak, 1989; D.J. Stein and Rauch,2008) . Some other common behavior problems of brain injured people areirritability, restlessness, low frustration tolerance, and apathy (Blonder et al.,2011).It is important to recognize that the personality changes, emotionaldistress, and behavior problems of brain damaged patients are usually theproduct of the complex interactions involving their neurological disabilities,present social demands, previously established behavior patterns andpersonality characteristics, and ongoing reactions to all of these (Gainotti,1993). When brain injury is mild, personality and the capacity for self-awareness usually remain fairly intact so that emotional andcharacterological alterations for the most part will be reactive and adaptive(compensatory) to the patients’ altered experiences of themselves. Asseverity increases, so do organic contributions to personality and emotionalchanges. With severe damage, little may remain of the premorbid personalityor of reactive capabilities and responses.Some brain injured patients display emotional instability characterized byrapid, often exaggerated affective swings, a condition called emotionallability. Three kinds of lability associated with brain damage can bedistinguished.1. The emotional ups and downs of some labile patients result fromweakened executive control and lowered frustration tolerance. This is oftenmost pronounced in the acute stages of their illness and when they arefatigued or stressed. Their emotional expression and their feelings arecongruent, and their sensitivity and capacity for emotional response areintact. However, emotional reactions, particularly under conditions of stressor fatigue, will be stronger and may last longer than was usual for thempremorbidly.2. A second group of labile patients have lost emotional sensitivity and thecapacity for modulating emotionally charged behavior. They tend tooverreact emotionally to whatever external stimulation impinges on them.Their emotional reactivity can generally be brought out in an interview byabruptly changing the subject from a pleasant topic to an unpleasant one andback again, as these patients will beam or cloud up with each topic change.When left alone and physically comfortable, they may appear emotionless.3. A third group of labile patients differs from the others in that their feelingsare generally appropriate, but brief episodes of strong affective expression—usually tearful crying, sometimes laughter—can be triggered by even quitemild stimulation. This has sometimes been termed pseudobulbar state(Blonder et al., 2011; Lieberman and Benson, 1977; R.G. Robinson andStarkstein, 2002) . It results from structural lesions that involve the frontalcortex and connecting pathways to lower brain structures. The feelings ofpatients with this condition are frequently not congruent with theirappearance, and they generally can report the discrepancy. Because they tendto cry with every emotionally arousing event, even happy or exciting ones,family members and visitors see them crying much of the time and oftenmisinterpret the tears as evidence of depression. Sometimes the bewilderedpatient comes to the same mistaken conclusion and then really does becomedepressed. These patients can be identified by the frequency, intensity, andirrelevancy of their tears or guffaws; the rapidity with which the emotionalreaction subsides; and the dissociation between their appearance and theirstated feelings.Although most brain injured persons tend to undergo adverse emotionalchanges, for a few, brain damage seems to make life more pleasant. This canbe most striking in those emotionally constricted, anxious, overlyresponsible people who become more easygoing and relaxed as a result of apathological brain condition. A clinical psychologist wrote about himselfseveral years after sustaining significant brain damage marked by almost aweek in coma and initial rightsided paralysis:People close to me tell me that I am easier to live with and work with, now that I am not thehighly self-controlled person that I used to be. My emotions are more openly displayed andmore accessible, partially due to the brain damage which precludes any storing up ofemotion, and partially due to the maturational aspects of this whole life-threateningexperience… . Furthermore, my blood pressure is amazingly low. My one-track mind seemsto help me to take each day as it comes without excessive worry and to enjoy the simplethings of life in a way that I never did before. (Linge, 1980)However, their families may suffer instead, as illustrated in the followingexample:A young Vietnam War veteran lost the entire right frontal portion of his brain in a land mineexplosion. His mother and wife described him as having been a quietly pleasant,conscientious, and diligent sawmill worker before entering the service. When he returnedhome, all of his speech functions and most other cognitive abilities were intact. He wascompletely free of anxiety and thus without a worry in the world. He had also become veryeasygoing, self-indulgent, and lacking in both drive and sensitivity to others. His wife wasunable to get him to share her concerns when the baby had a fever or the rent was due. Notonly did she have to handle all the finances, carry all the family and home responsibilities,and do all the planning, but she also had to see that her husband went to work on time andthat he did not drink up his paycheck or spend it in a shopping spree before getting home onFriday night. For several years his wife tried to cope with the burdens of a carefree husband.She finally left him after he had ceased working and had begun a pattern of monthlydrinking binges that left little of his considerable compensation checks.One significant and relatively common concomitant of brain injury is analtered sexual drive (Foley and Sanders, 1997a,b; Wiseman and Fowler,2002; Zasler, 1993). A married person who has settled into a comfortablesexual activity pattern of intercourse two or three times a week may begindemanding sex two and three times a day from the bewildered spouse. Moreoften, the patient loses sexual interest or capability (L.M. Binder, Howieson,and Coull, 1987; Forrest, 2008; Lechtenberg, 1999). Moreover, some braindamaged men are unable to achieve or sustain an erection, or they may haveejaculatory problems secondary to nervous tissue damage (D.N. Allen andGoreczny, 1995; Foley and Sanders, 1997b). This can leave the partnerfeeling unsatisfied and unloved, adding to other tensions and worriesassociated with cognitive and personality changes in the patient (Lezak,1978a; Zasler, 1993).Patients who become crude, boorish, or childlike as a result of braindamage no longer are welcome bed partners and may be bewildered andupset when rejected by their once affectionate mates. Younger persons whosustain brain damage before experiencing an adult sexual relationship maynot be able to acquire acceptable behavior and appropriate attitudes (S.W.Anderson, Bechara, et al., 1999). Adults who were normally functioningwhen single often have difficulty finding and keeping partners because ofcognitive limitations or social incompetence resulting from theirneurological impairments. For all these reasons, the sexual functioning ofmany brain damaged persons will be thwarted. Although some sexualproblems diminish in time, for many patients they seriously complicate theproblems of readjusting to new limitations and handicaps by adding anotherstrange set of frustrations, impulses, and reactions.3 The Behavioral Geography of theBrainSo much is now known about the brain—and yet so little, especially howcognitive processes emerge from brain function. Current technology hasvisualized the structure of the brain so well that even minute details of cellstructure can be seen with electron microscopy and other techniques. Forexample, structural changes in the neuron associated with learning can bemicroscopically identified and living cells imaged (Bhatt et al., 2009; Nagerlet al., 2008). Contemporary neuroimaging permits the visualization andanalysis of the major pathways of the brain (Schmahmann and Pandya,2006) ; these are readily imaged in the living individual (Pugliese et al.,2009). Now neuroimaging techniques can identify which brain areas areinvolved in a particular task and how brain regions come “on line”during amental task.This beginning understanding of the complexities of brain activation laysthe foundation for a neuroscience-based revision of the big questions self-conscious humans have asked for centuries: What is the neural (anatomic,physiologic) nature of consciousness (e.g., R. Carter, 2002; Crick and Koch,2005; Dehaene, 2002) ? What are the relative contributions and interactionsof genotype and experience (Huttenlocher, 2002; Pennington, 2002; vanHaren et al., 2008)? What are the neuroanatomic bases of “self”(S.C.Johnson, Ries, et al., 2007; Legrand and Ruby, 2009; Rilling, 2008)?New technology has supported many traditional beliefs about the brainand challenged others. The long-held belief that neurons do not proliferateafter early stages of development is incorrect. It is now known that newneurons are produced in some brain regions of adults in a number ofmammalian species, including human, perhaps playing a role in brain injuryrepair, new learning, and maintenance of healthy neural functioning (Basakand Taylor, 2009). Adult neurogenesis has been identified in thehippocampus and olfactory bulb in mammalian brains—including human—and implicated in other limbic regions, in the neocortex, striatum, andsubstantia nigra (E. Gould, 2007). Neurogenesis in the hippocampus isthought to be especially critical for maintaining normal cognition andemotional well-being (Alleva and Francia, 2009; Elder et al., 2006). Theimportance of these findings for neuropsychology, human aging and diseasesare just beginning to emerge.In addition, the roles of many brain regions are far more complex andfunctionally interconnected than previously thought. The basal ganglia andcerebellum, once believed to be background motor control centers, areincreasingly appreciated for their influences on cognition and psychiatricdisorders (Baillieux et al., 2008; Dow, 1988; Grahn et al., 2009; Manto,2008). Even the motor cortex appears to play an active role in processingabstract learned information (A.F. Carpenter et al., 1999). How singleneurons participate in unified neural function can be seen within all neuralsystems including those once thought to be dedicated to a single function,like motor ability (C. Koch and Segev, 2000). The importance of subtleaberrations coming from a few neurons disrupting larger networks is centralto the model of cerebral dysfunction offered by Izhikevich and Edelman(2008) and reinforces the principle that strategically occurring lesions orabnormalities albeit small may nonetheless influence neuropsychologicalfunction (Geschwind, 1965).This chapter presents a brief and necessarily superficial sketch of some ofthe structural arrangements in the human central nervous system that areintimately connected with behavioral function. This sketch is followed by areview of anatomical and functional interrelationships that appear withenough regularity to have psychologically meaningful predictive value (P.Brodal, 1992). More detailed information on neuroanatomy and itsbehavioral correlates is available in such standard references as Afifi andBergman (1998), Hendelman (2000), and Nolte (1999). A.R. Damasio andTranel (1991), Mesulam (2000c), and Harel and Tranel (2008) provideexcellent reviews of brain-behavior relationships. Reviews of the braincorrelates for a variety of neuropsychological disorders can be found inFeinberg and Farah (2003a), Heilman and Valenstein (2011), Kolb andWhishaw (2009), Mendoza and Foundas (2007), Rizzo and Eslinger (2004),and Yudofsky and Hales (2008). Physiological and biochemical events inbehavioral expression add another important dimension toneuropsychological phenomena. Most work in these areas is beyond thescope of this book. Readers wishing to learn how neural systems,biochemistry, and neurophysiology relate to behavioral phenomena canconsult M.F.F. Bear et al. (2006), Cacioppo and Bernston (2005), and Kandelet al. (2010).BRAIN PATHOLOGY AND PSYCHOLOGICAL FUNCTIONThere is no localizable single store for the meaning of a given entity or eventwithin a cortical region. Rather, meaning is achieved by widespreadmultiregional activation of fragmentary records pertinent to a given stimulusand according to a combinatorial code specific or partially specific to theentity … the meaning of an entity, in this sense, is not stored anywhere in thebrain in permanent fashion; instead it is re-created anew for everyinstantiation.Daniel Tranel and Antonio R. Damasio, 2000The relationship between brain and behavior is exceedingly intricate andfrequently puzzling. Our understanding of this fundamental relationship isstill very limited, but the broad outlines and many details of the correlationsbetween brain and behavior have been sufficiently well explained to beclinically useful. Any given behavior is the product of a myriad of complexneurophysiological and biochemical interactions involving the whole brain.Complex acts, even as fundamental as swatting a fly or reading this page, arethe products of countless neural interactions involving many, often far-flungsites in the neural network; their neuroanatomical correlates are not confinedto any local area of the brain (Fuster, 2003; Luria, 1966; Sherrington, 1955).Yet discrete psychological activities such as the perception of a pure tone orthe movement of a finger can be disrupted by lesions (localized abnormaltissues changes) involving approximately the same anatomical structures inmost human brains. Additionally, one focal lesion may affect many functionswhen the damaged neural structure is either a pathway, nucleus, or regionthat is central in regulating or integrating a particular function or functions.These disruptions can produce a neurobehavioral syndrome, a cluster ofdeficits that tend to occur together with some regularity (Benton, 1977b[1985]; H. Damasio and Damasio, 1989; E. Goldberg, 1995).Disruptions of complex behavior by brain lesions occur with suchconsistent anatomical regularity that inability to understand speech, to recallrecent events, or to copy a design, for example, can often be predicted whenthe site of the lesion is known (Benton, 1981 [1985]; Filley, 1995, 2008;Geschwind, 1979). Knowledge of the localization of dysfunction, thecorrelation between damaged neuroanatomical structures and behavioralfunctions also enables neuropsychologists and neurologists to make educatedguesses about the site of a lesion on the basis of abnormal patterns ofbehavior. However, similar lesions may have quite dissimilar behavioraloutcomes (Bigler, 2001b). Markowitsch (1984) described the limits ofprediction: “[a] straightforward correlation between a particular brain lesionand observable functional deficits is … unlikely … as a lesioned structure isknown not to act on its own, but depends in its function on a network ofinput and output channels, and as the equilibrium of the brain will beinfluenced in many and up to now largely unpredictable ways by even arestricted lesion”(p. 40).Moreover, localization of dysfunction cannot imply a “push-button”relationship between local brain sites and specific behaviors as thebrain’s processing functions take place at multiple levels (e.g., encoding asingle modality of a percept, energizing memory search, recognition,attribution of meaning) within complex, integrated, interactive, and oftenwidely distributed systems. Thus lesions at many different brain sites mayalter or extinguish a single complex act (Luria, 1973b; Nichelli, Grafman, etal., 1994; Sergent, 1988), as can lesions interrupting the neural pathwaysconnecting areas of the brain involved in the act (Geschwind, 1965; Traneland Damasio, 2000). E. Miller (1972) reminded us:It is tempting to conclude that if by removing a particular part of the brain we can produce adeficit in behavior, e.g., a difficulty in verbal learning following removal of the left temporallobe in man, then that part of the brain must be responsible for the impaired function… .[T]his conclusion does not necessarily follow from the evidence as can be seen from thefollowing analogy. If we were to remove the fuel tank from a car we would not be surprisedto find that the car was incapable of moving itself forward. Nevertheless, it would be verymisleading to infer that the function of the fuel tank is to propel the car (pp. 19–20).THE CELLULAR SUBSTRATEThe nervous system makes behavior possible. It is involved in the reception,processing, storage, and transmission of information within the organismand in the organism’s exchanges with the outside world. It is a dynamicsystem in that its activity modifies its performance, its internal relationships,and its capacity to mediate stimuli from the outside. The basic cell of thebrain that gives rise to its complexity and ability to regulate behavior is theneuron. an overly simplified schematic of a neuron is shown in Figure 3.1.The neuron also has a supporting cast of cells, the glial cells. neuronsconduct electrochemical impulses that transmit information in the brain andthroughout the peripheral and central nervous system (CNS). a primaryfunction of the neuron is to provide a network of connectivity betweenneurons and different regions of the brain. Brain connectivity is key to brainfunctioning. one direct estimate suggests that the number of neurons in theneocortex alone is approximately 20 billion (pakkenberg and Gundersen,1997). estimates of all other structures in the CNS double or triple the totalnumber of neurons. At birth the full complement of neurons appears to bepresent (larsen et al., 2006), indicating an astonishing growth pattern fromconception to birth. At peak periods of development tens of thousands tohundreds of thousands of cells are created each minute to reach the ultimategoal of billions of brain cells (levitt, 2003; A.K. McAllister et al., 2008).Glial cells are supporting brain cells which come in several types. Whilethey do not transmit information (like neurons) (Carnevale and Knes, 2006;Kandel et al., 2010; levitan and Kaczmarek, 2002), glial cells, particularlyastrocytes, likely facilitate neural transmission and probably play a moredirect role in synaptic functioning and neural signaling than previouslythought (Araque and navarette, 2010; Fellin, 2009). Glial cells not only serveas structural supports, but they also appear to have nutritional and scavengerfunctions and to release growth factors. Astrocytes are a major type of glialcell that have an additional role as a component of the blood-brain barrierwhich prevents some substances in the blood from entering the CNS (P.A.Stewart, 1997). Another major type of glial cells are oligodendroglia, whichalso form myelin, the white fatty substance of axonal sheaths (see Fig. 3.1).Glia are substantially more numerous than neurons by a factor of two tothree (Pelvig et al., 2008). Thus the total number of individual cells withinthe CNS may be in excess of a hundred billion.Neurons vary in shape and function (Carnevale and Knes, 2006; levitanand Kaczmarek, 2002). Most have a well-defined nucleus within a cell bodyas seen in a photomicrograph taken of human thalamic neurons (blue insertin Fig. 3.1); they have multiple branching dendrites that receive stimulationfrom other neurons, and an axon that carries the electrical nerve impulses(action potentials). neural cells are very small, their size measured inmicrons (1/10,000 of a mm); the inset photomicrograph in Figure 3.1 showsthe cell body to be less than 10 microns. The typical length and diameter of aneuron cell body is approximately 30 microns (Carnevale and hines, 2006).neurons have only one initial segment, the axon, which may branch toproduce collateral segments; these can be very numerous in some neurons(Kandel et al., 2010; robber and Samuels, Mitochondrion 2009). Axons varyin length with the average estimated at approximately 1,000 microns.Coursing fasciculi (impulse transmitting axonal bundles), are comprised ofaxons from 10 to 15 centimeters in length to in excess of 30 centimeters(e.g., motor cortex to a synapse in the spine), depending on the size of theindividual. Long axons have myelin sheaths that provide insulation for high-speed neural conduction. The average axon diameter varies only fromapproximately one to a few microns. Neurons communicate via the synapse.FIGURE 3.1 Schematic of a neuron. photomicrograph from Bigler and Maxwell (2011) used withpermission from Springer publishing.The typical dendrite, which is the receptive process of the neuron thatinterfaces with other neurons, is also about the same diameter as an axon(see Fig. 3.1), but the typical dendritic field ranges from 200 to 600 microns.The surface of the dendrite may change in response to neural activityforming what is referred to as a spine; spine development is thought to beparticularly important in the formation of new memories and neuralplasticity (Kasai et al., 2010; Shepherd and Koch, 1998). At the tips of anaxon are synaptic vesicles that produce and house neurotransmitters which,when released, interface with dendrites on the postsynaptic neuron throughelectrochemical reactions.The many and differing interactions among excitatory and inhibitorypathways and neurotransmitters make the entire process of interneuralcommunication extremely complex (Connors and Long, 2004; D.E.Feldman, 2009). Given the brain’s primary activity of neural transmissionand connectivity and the billions of neural cells, a phenomenal level ofcomplexity is present in even the simplest cognitive, motor, or sensory task.Neural connectivity and effective neural transmission become even moreawesome when one considers the estimated rate of ionic changes that have tooccur via the cell membrane for a neural event to be passed on to the nextcell in line. During neural conduction a shift in ions through the cellmembrane occurs via ion channels (see Fig. 3.1). When an axon ispropagating an action potential, an estimated 100 million ions pass through asingle channel in one second (A.K. McAllister et al., 2008) . In addition, asingle neuron may have direct synaptic contact with thousands of otherneurons and thereby be involved in the almost unfathomable multiplicity andcomplexity of functioning synapses underlying behavior and cognition atany given moment. This also means that a few strategic CNS cells misfiringand/ or misconnecting can produce significant changes in brain function(Izhikevich and Edelman, 2008).The postsynaptic cell is constantly computing its excitatory andinhibitory inputs. It either maintains an excitatory or inhibitory valence orfires a neural impulse in the form of an action potential. Stimulation appliedto a neural pathway heightens that pathway’s sensitivity and increases theefficacy with which neuronal excitation may be transmitted through itssynapses (C. Koch and Segev, 2000; A.K. McAllister et al., 2008; Toni et al.,1999). Such alterations in spatial and temporal excitation patterns in thebrain’s circuitry can add considerably more to its dynamic potential. Long-lasting synaptic modifications are called l ong-term potentiation and long-term depression; these are critical neuro-physiological features of memoryand learning (Fuster, 1995; Korn et al., 1992; G. Lynch, 2000). Togetherthese mechanisms of synaptic modification provide the neural potential forthe variability and flexibility of human behavior (Carnevale and Hines,2006; Levitan and Kaczmarek, 2002; E.T. Rolls, 1998).Neurons do not touch one another at synapses (M.F.F. Bear et al., 2006;Cacioppo and Bernston, 2005; Kandel et al., 2010). Rather, communicationbetween neurons is made primarily through the medium of neurotransmitters—chemical agents generated within and secreted by stimulated neurons.These substances bridge synaptic gaps between neurons to activate receptorswithin the postsynaptic neurons (E.S. Levine and Black, 2000;D. A. McCormick, 1998; P.G. Nelson and Davenport, 1999) . Theidentification of more than 100 neurotransmitters (National Advisory MentalHealth Council, 1989) gives some idea of the possible range of selectiveactivation between neurons. Each neurotransmitter can bind to and thusactivate only those receptor sites with the corresponding molecularconformation, but a single neuron may produce and release more than one ofthese chemical messengers (Carnevale and Hines, 2006; Hokfelt et al., 1984;Levitan and Kaczmarek, 2002) . The key transmitters implicated inneurologic and psychiatric diseases are acetylcholine, dopamine,norepinephrine, serotonin, glutamate, and gammaaminobutyric acid(GABA) (Alagbe et al., 2008; A.K. McAllister et al., 2008; Wilcox andGonzales, 1995).When a neural cell is injured or diseased, it may stop functioning and thecircuits to which it contributed will then be disrupted. Some circuits mayeventually reactivate as damaged cells resume some functioning oralternative patterns involving different cell populations take over (see p. 356regarding brain injury and neuroplasticity). When a circuit loses asufficiently great number of neurons, the broken circuit can neither bereactivated nor replaced. As it is now known that neurogenesis does occur insome areas of the brain, investigations of its role in response to injury areongoing (T.C. Burns et al., 2009; A. Rolls et al., 2009). Probably mostpostinjury improvement comes from adaptation and the use and/ordevelopment of alternative pathways and synaptic modifications withinexisting pathways participating in functions for which they were notprimarily developed (M.V. Johnston, 2009).During development some neurons initiate apoptosis, which is,programmed cell death, which enhances the organization and efficiency ofspecific neuronal pathways in a process called pruning (Rakic, 2000; Yuanand yankner, 2000). While apoptosis occurs normally in the development ofthe nervous system and—over the lifespan—normal age-related apoptoticcellular changes occur, some nervous system diseases may result fromapoptotic processes gone awry or other forms of cell death which arenormally prevented by neurotrophic factors (Leist and Nicotera, 1997; A.K.McAllister et al., 2008; raff, 1998).THE STRUCTURE OF THE BRAINThe brain is an intricately patterned complex of small and delicate structuresthat form elaborate networks with identifiable anatomical landmarks. inembryological development, three major anatomical divisions of the brain,succeed one another: the hindbrain (pons, medulla, and cerebellum), themidbrain, and the forebrain (divided into the telencephalon anddiencephalon) (Fig. 3.2a); (for detailed graphic displays of braindevelopment and anatomy, see Hendelman, 2006; leichnetz, 2006;Montemurro and Bruni, 2009; netter, 1983). Structurally, the lowest braincenters are the most simply organized and mediate simpler, more primitivefunctions. The cerebral hemispheres mediate the highest levels of behavioraland cognitive function.A lateral view of the gross surface anatomy of the brain is shown inFigure 3.3 in which a postmortem brain on the left is compared to a similarview generated from an Mn of a living individual on the right. note howclosely the gross anatomy of the living brain as depicted by an Mn matchesthe postmortem specimen.FIGURE 3.2 (a) axial Mn of anatomical divisions of the brain. (b) Coronal Mn of anatomical divisionsof the brain. (c) Sagittal Mn of anatomical divisions of the brain.FIGURE 3.3 Lateral surface anatomy postmortem (left) with MRI of living brain (right).The sections of the brain in different planes (Fig. 3.2) are from the sameliving individual. The MRI depictions are sliced in the traditional planes:axial (Fig. 3.2a), coronal (Fig. 3.2b), and sagital (Fig. 3.2c).As shown in Figure 3.4, within the brain are four fluid-filled pouches, orventricles, through which cerebrospinal fluid (CSF) flows internally. Thesurface of the brain is also bathed in CSF circulating in the space betweenthe arachnoid membrane (the fine textured inner lining of the brain) and theundersurface of the dura mater (the leathery outer lining) (Blumenfeld,2010; see also Netter, 1983). Together these membranes are called themeninges. The most prominent of the pouches, the lateral ventricles, are apair of horn-shaped reservoirs situated inside the cerebral hemispheres,running from front to back and curving around and down into the temporallobe. The ventricles offer a number of landmark regions that are oftenexamined in viewing the integrity of such structures as the caudate nucleuswhich lies just lateral to the anterior horn of the lateral ventricle, theamygdala located just in front of the tip of the temporal horn, and thehippocampus in the floor of the temporal horn.The third ventricle is situated in the midline within the diencephalon(“between-brain”, see Figs. 3.2 and 3.4), dorsally (i.e., back of body)connected to the two lateral ventricles via a foramen (opening) with ventral(i.e., front of body) connections via the cerebral aqueduct with the fourthventricle. These connections permit CSF to flow freely throughout eachchamber. The fourth ventricle lies within the brain stem. Cerebrospinal fluidis produced within the choroid plexi, specialized structures located withinthe ventricles but mostly within the lateral ventricles. CSF is pressurizedwithin the ventricles, serving as a shock absorber and helping to maintain theshape of the soft nervous tissue of the brain by creating an outward pressuregradient that is held in check by the mass of the brain.FIGURE 3.4 Ventricle anatomy. (1) Anterior horn, (2) body, (3) atria, (4) posterior horn, and (5)temporal horn of the lateral ventricle, (6) III ventricle, (7) aqueduct, and (8) IV ventricle.Blockage somewhere within the ventricular system affects CSF flow,often in one of the foramen or the aqueduct, producing obstructivehydrocephalus; no obvious CFS flow obstruction is identified in normalpressure hydrocephalus (NPH) but the ventricles are nonetheless dilated (seep. 303–304). In disorders in which brain substance deteriorates, such as indegenerative diseases, the ventricles enlarge to fill the void. Sinceventricular size can be an important indicator of the brain’s status, it is oneof the common features examined in neuroimaging studies (see Figs. 7.12,7.21, and 7.22, pp. 198, 330, and 331).Almost as intricate and detailed as neural tissue is the incrediblyelaborate network of blood vessels (vasculature) that maintains a rich supplyof nutrients to brain tissue, which is very oxygen and glucose dependent(Festa and Lazar, 2009). Figure 3.5 shows the exquisite detail at the capillarylevel of the vasculature. These blood vessels have been impregnated withacrylic casting agent and then viewed with an electron microscope. Themicrovasculature interfaces with individual neurons and glial cells, feedingneurons through capillaries. When vascular pathology occurs its effects aretypically associated with one or a combination of the major blood vessels ofthe brain (Sokoloff, 1997; Tatu et al., 2001). However, it is in the intimateinteraction between individual capillaries and neurons that neural function ordysfunction occurs.How blood flow responds to the brain as it engages in a particularfunction—the basis of functional neuroimaging—is dependent on localautoregulation. The interface of oxygen and glucose-laden blood with neuralcells takes place at this microscopic level. The capillaries that deliver bloodto brain cells are not much bigger than the neural cells, creating a verydelicate microenvironment between blood and brain cells (see Fig. 3.5). Thisis a major reason why degenerative, neoplastic, and traumatic disordersaffect not only neural tissue but the vascular system as well. It is theinterplay between vascular damage and brain damage that gives rise toneuropsychological impairments.FIGURE 3.5 Scanning electron micrograph showing an overview of corrosion casts from the occipitalcortex in a control adult postmortem examination: (1) pial vessels, (2) long cortical artery, (3) middlecortical artery, (4) superficial capillary zone, (5) middle capillary zone, and (6) deep capillary zone.Scale bar = 0.86 mm. From Rodriguez-Baeza et al. (2003) reproduced with permission from Wiley-Liss.The three major blood vessels of the brain have distinctly differentdistributions (see Fig. 3.6). The anterior and middle cerebral arteries branchfrom the internal carotid artery. The anterior division supplies the anteriormedial (toward the midline) frontal lobe extending posteriorly to all of themedial parietal lobe. The middle cerebral artery feeds the lateral temporal,parietal, and posterior frontal lobes and sends branches deep into subcorticalregions. The posterior circulation originates from the vertebral arteries thatascend along the borders of the spinal column from the heart. They provideblood to the brain stem and cerebellum. The vertebral arteries join to formthe basilar artery which divides into the posterior cerebral arteries andsupplies the occipital cortex and medial and inferior regions of the temporallobe.Significant neuropathological effects occur from disruption of eitherarterial flow or venous return of deoxygenated blood and their byproducts(Rodriguez-Baeza et al., 2003). However, the most frequent vascular sourceof neuropsychological deficits is associated with the arterial side of bloodflow which is why only the arterial system is highlighted in Figure 3.6. Thesite of disease or damage to arterial circulation determines the area of thebrain cut off from its oxygen and nutrient supply and, to a large extent, theneuropathologic consequences of vascular disease (Lim and Alexander,2009; see pp. 229–239 for pathologies arising from cerebrovasculardisorders).The HindbrainThe medulla oblongataThe lowest part of the brain stem is the hindbrain, and its lowest section isthe medulla oblongata or bulb (see Fig. 3.2a). The corticospinal tract, whichruns down it, crosses the midline here so that each cerebral hemisphere hasmotor control over the opposite side of the body. The hindbrain is the site ofbasic life-maintainingcenters for neural control of respiration, bloodpressure, and heartbeat. Significant injury or pathology to the medullagenerally results in death or such profound disability that fine-grainedbehavioral assessments are irrelevant (Nicholls and Paton, 2009). Themedulla contains nuclei (clusters of functionally related nerve cells)involved in movements of mouth and throat structures necessary forswallowing, speech, and such related activities as gagging and control ofdrooling. Damage to lateral medullary structures can result in sensorydeficits (J.S. Kim, Lee, and Lee, 1997).The reticular formationRunning through the brainstem extending upward to forebrain structures (thediencephalon, see p. 53) is the reticular formation, a network of intertwinedand interconnecting nerve cell bodies and fibers that enter into or connectwith all major neural tracts going to and from the brain. The reticularformation is not a single functional unit but contains many nuclei. Thesenuclei mediate important and complex postural reflexes, contribute to thesmoothness of muscle activity, and maintain muscle tone. From about thelevel of the lower third of the pons, see below, up to and includingdiencephalic structures, the reticular formation is also the site of the reticularactivating system (RAS), the part of this network that controls wakefulnessand alerting mechanisms that ready the individual to react (S. Green, 1987;Mirsky and Duncan, 2005). The RAS modulates attention through its arousalof the cerebral cortex and its connections with the diffuse thalamicprojection system (E.G. Jones, 2009; Mirsky and Duncan, 2001;Parasuraman, Warm, and See, 1998). The intact functioning of this networkis a precondition for conscious behavior since it arouses the sleeping orinattentive organism (G. Roth, 2000; Tononi and Koch, 2008). Brain stemlesions involving the RAS give rise to sleep disturbances and to globaldisorders of consciousness and responsivity such as drowsiness, somnolence,stupor, or coma (A.R. Damasio, 2002; M.I. Posner et al., 2007).FIGURE 3.6 Major blood vessels schematic.The ponsThe pons is high in the hindbrain (Fig. 3.2a). It contains major pathways forfibers running between the cerebral cortex and the cerebellum. Together, thepons and cerebellum correlate postural and kinesthetic (muscle movementsense) information, refining and regulating motor impulses relayed from thecerebrum at the top of the brain stem. Lesions of the pons may cause motor,sensory, and coordination disorders including disruption of ocularmovements and alterations in consciousness (Felicio, Bichuetti, et al., 2009).The cerebellumThe cerebellum is attached to the brain stem at the posterior base of the brain(Fig. 3.2). In addition to reciprocal connections with vestibular (systeminvolved in balance and posture) and brain stem nuclei, the hypothalamus (p.52), and the spinal cord, it has strong connections with the motor cortex (p.58). It contributes to motor functions through influences on theprogramming and execution of actions and background motor control.Cerebellar damage is commonly known to produce problems of fine motorcontrol, coordination, and postural regulation, all of which require rapid andcomplex integration between the cerebellum and other brain regions (G.Koch et al., 2009). Dizziness (vertigo) and jerky eye movements may alsoaccompany cerebellar damage.The cerebellum has many nonmotor functions involving all aspects ofbehavior (Glickstein and Doron, 2008; Habas, 2009; Schmahmann,Weilburg, and Sherman, 2007; Strick et al., 2009). Highly organized neuralpathways project through the pons to the cerebellum from both lower andhigher areas of the brain (Koziol and Budding, 2009; Llinas and Walton,1998; Schmahmann and Sherman, 1998). Cerebellar projections also runthrough the thalamus to the same cortical areas from which it receives input,including frontal, parietal, and superior temporal cortices (Botez-Marquardet Lalonde, 2005; Middleton and Strick, 2000a; Schmahmann and Sherman,1998; Zacks, 2008).Through its connections with these cortical areas and with subcorticalsites, cerebellar lesions can disrupt abstract reasoning, verbal fluency,visuospatial abilities, attention, memory and emotional modulation (Botez-Marquard et Lalonde, 2005; Middleton and Strick, 2000a; Schmahmann,2010), along with planning and time judgment (Dow, 1988; Ivry and Fiez,2000). The cerebellum is also involved in linguistic processing (Leiner et al.,1989), word generation (Raichle, 2000), set shifting (Le et al., 1998),working memory and other types of memory and learning (Desmond et al.,1997; Manto, 2008)—especially habit formation (Eichenbaum and Cohen,2001; Leiner et al., 1986; R.F. Thompson, 1988) . Moreover, speed ofinformation processing slows with cerebellar lesions (Spanos et al., 2007).Some disruptions may be transient (Botez-Marquard, Leveille, and Botez,1994; Schmahmann and Sherman, 1998). Personality changes andpsychiatric disorders have also been linked to cerebellar dysfunction(Barlow, 2002; Gowen and Miall, 2007; Konarski et al., 2005; Parvizi,Anderson, et al., 2001).The MidbrainThe midbrain (mesencephalon), a small area just forward of the hindbrain,includes the major portion of the RAS. Its functioning may be a prerequisitefor conscious experience (Parvizi and Damasio, 2001). It also contains bothsensory and motor pathways and correlation centers (see Fig. 3.2). Auditoryand visual system processing that takes place in midbrain nuclei (superiorcolliculi for vision and inferior colliculi for audition) contribute to theintegration of reflex and automatic responses. The substantia nigra, adopamine-rich area of the brain that projects to the basal ganglia, is locatedat the level of the midbrain (for importance of the neurotransmitterdopamine, see p. 271). Midbrain lesions within the cerebral peduncle canproduce paralysis and may also be related to specific movement disabilitiessuch as certain types of tremor, rigidity, and extraneous movements of localmuscle groups. Even impaired memory retrieval has been associated withdamage to midbrain pathways projecting to structures in the memory system(E. Goldberg, Antin, et al., 1981; Hommel and Besson, 2001). Acquiredlesions in strategic motor areas at the level of the midbrain typically havedevastating effects on motor and sensory function with poor functionaloutcome (Bigler, Ryser, et al., 2006).The Forebrain: Diencephalic StructuresTwo subdivisions of the brain evolved at the anterior, or most forward, partof the brain stem. The diencephalon (“between-brain”) is composed mainlyof the thalamus, the site of correlation and relay centers that connectthroughout the brain; and the hypothalamus which connects with thepituitary body (the controlling endocrine gland). These structures are almostcompletely embedded within the two halves of the forebrain, thetelencephalon (see Fig. 3.2).The thalamusThe thalamus is a small, paired, somewhat oval structure lying along theright and left sides of the third ventricle (see Figs. 3.2, 3.7–3.9). Manysymmetric nuclei are located in each half of the thalamus and projectintrathalamically or to regions throughout the brain. The two halves arematched approximately in size, shape, and position to corresponding nucleiin the other half. Most of the anatomic interconnections formed by thesenuclei and many of their functional contributions involve widespreadprojections to the cerebral cortex. Figure 3.7 shows the extensive reciprocalconnections of thalamic nuclei with the cerebral cortex (see Johansen-Bergand Rushworth, 2009; S.M. Sherman and Koch, 1998). These thalamicprojections are topographically organized (see Fig. 3.7B). The thalamus isenmeshed in a complex of fine circuitry, feedback loops, and manyfunctional systems with continuous interplay between its neurophysiologicalprocesses, its neurotransmitters, and its structures. Moreover,as shown inFigure 3.7 (Plate V) C and D, thalamic projections feed into all areas of thecortex such that small thalamic lesions or even small lesions in the thalamictracks just outside the thalamus may have widespread disruptive effects oncerebral function.Sensory nuclei in the thalamus serve as major relay and processingcenters for all senses except smell and project to primary sensory cortices(see pp. 57–59). The thalamus may also play a role in olfaction, but quitedifferent than the relay functions for touch, vision, and hearing (Tham et al.,2009). Body sensations in particular may be degraded or lost with damage tospecific thalamic nuclei (L.R. Caplan, 1980; Graff-Radford, Damasio, et al.,1985) ; inability to make tactile discriminations and identification of what isfelt (tactile object agnosia) can occur as an associated impairment (Bauer,2011; Caselli, 1991). Although pain sensation typically remains intact or isonly mildly diminished, with some kinds of thalamic damage it may beheightened to an excruciating degree (A. Barth et al., 2001; Brodal, 1981;Clifford, 1990). Other thalamic nuclei are relay pathways for vision, hearing,and taste (J.S. Kim, 2001). Still other areas are relay nuclei for limbic systemstructures (see below and p. 54). Motor nuclei receive input from thecerebellum and the basal ganglia and project to the motor association cortexand also receive somatosensory feedback.As the termination site for the ascending RAS, it is not surprising that thethalamus has important arousal and sleep-producing functions (Llinas andSteriade, 2006) and that it alerts—activates and intensifies—specificprocessing and response systems via the diffuse thalamic projection system(Crosson, 1992; LaBerge, 2000; Mesulam, 2000b). Thalamic involvement inattention shows up in diminished awareness of stimuli impinging on the sideopposite the lesion (unilateral inattention) (Heilman, Watson, andValenstein, 2011; G.A. Ojemann, 1984; M.I. Posner, 1988).The thalamus plays a significant role in regulating higher level brainactivity (Tononi and Koch, 2008). The dorsomedial nucleus is of particularinterest because of its established role in memory and its extensivereciprocal connections with the prefrontal cortex (see Fig. 3.8) (Graff-Radford, 2003; Hampstead and Koffler, 2009; Mesulam, 2000b). It alsoreceives input from the temporal cortex, amygdala (see pp. 86–87),hypothalamus, and other thalamic nuclei (Afifi and Bergman, 1998). Thatthe dorsomedial nuclei of the thalamus participate in memory functions hasbeen known ever since lesions here were associated with the memory deficitof Korsakoff’s psychosis (von Cramon, et al., 1985; Victor, Adams, andCollins, 1971; see pp. 310–314). In most if not all cases of memoryimpairment associated with the thalamus, lesions have extended to themammillothalamic tract (Graff-Radford, 2003; Markowitsch, 2000;Verfaellie and Cermak, 1997). As viewed in Figure 3.8, this tract connectsthe mammillary bodies (small structures at the posterior part of thehypothalamus involved in information correlation and transmission [A.Brodal, 1981; Crosson, 1992]) to the thalamus which sends projections tothe prefrontal cortex and medial temporal lobe (Fuster, 1994; Markowitsch,2000).FIGURE 3.7 Thalamo-cortical topography demonstrated by DTI tractography. (a) On conventionalMRI it is not possible to visualize the intrinsic structure of the thalamus, yet we know from histologyin (b), the thalamus consists of cytoarchitectonically distinct nuclei. Cortical target regions areidentified in (c) and classified thalamic voxels according to the cortical region with which they had thehighest probability of connection are shown in (d). Compare (b) and (d) for specific thalamic nuclei.From Johansen-Berg and Rushworth (2009) used with permission from Annual Reviews.FIGURE 3.8 Memory and the limbic system. From Budson and Price, 2005. Reprinted courtesy ofNew England Journal of Medicine.Two kinds of memory impairments tend to accompany thalamic lesions:(1) Learning is compromised (anterograde amnesia), possibly by defectiveencoding which makes retrieval difficult if not impossible (N. Butters,1984a; Mayes, 1988; Ojemann, Hoyenga, and Ward, 1971); possibly by adiminished ability of learning processes to free up readily for succeedingexposures to new information (defective release from proactive inhibition)(N. Butters and Stuss, 1989; Parkin, 1984). A rapid loss of newly acquiredinformation may also occur (Stuss, Guberman, et al., 1988), although usuallywhen patients with thalamic memory impairment do learn they forget nofaster than intact persons (Parkin, 1984). (2) Recall of past information isdefective (retrograde amnesia), typically in a temporal gradient such thatrecall of the most recent (premorbid) events and new information is mostimpaired, and older memories are increasingly better retrieved (N. Buttersand Albert, 1982; Kopelman, 2002). Montaldi and Parkin (1989) suggestedthat these two kinds of memory impairment are different aspects of abreakdown in the use of context (encoding), as retrieval depends onestablishing and maintaining “contextual relations among existingmemories.” Errors made by an unlettered file clerk would provide ananalogy for these learning and retrieval deficits: Items filed randomly remainin the file cabinet but cannot be retrieved by directed search, yet they maypop up from time to time, unconnected to any intent to find them (see alsoHodges, 1995).Amnesic patients with bilateral diencephalic lesions, such as Korsakoffpatients, tend to show disturbances in time sense and in the ability to maketemporal discriminations; this may play a role in their prominent retrievaldeficits (Graff-Radford, Tranel, et al., 1990; Squire, Haist, and Shimamura,1989). Characteristically, memory impaired patients with thalamic or otherdiencephalic lesions lack appreciation of their deficits, in this differing frommany other memory impaired persons (Mesulam, 2000b; Parkin, 1984;Schacter, 1991). In a review of 61 cases of adults with thalamic lesions,mostly resulting from stroke, half had problems with concept formation,flexibility of thinking, or executive functions (Y.D. Van der Werf, Witter, etal., 2000). In advanced neuroimaging studies, Korsakoff patientsdemonstrated structural changes in the hippocampus, cerebellum, and ponsin addition to the bilateral diencephalic lesions characteristic of the disorder(E.V. Sullivan and Pfefferbaum, 2009). Discrete thalamic lesions mayproduce very specific memory deficits depending on which thalamic nucleiare affected (Y.D. Van der Werf, Jolles, et al., 2003).Differences in how the two halves of the brain process data, sopronounced at the highest cortical level, first appear in thalamic processingof sensory information (A. Barth, Bogousslavsky, and Caplan, 2001; J.W.Brown, 1975; J.A. Harris et al., 1996; D.M. Hermann et al., 2008). Thelateral asymmetry of thalamic organization parallels cortical organization inthat left thalamic structures are more implicated in verbal activity, and rightthalamic structures in nonverbal aspects of cognitive performance. Forexample, patients who have left thalamic lesions or who are undergoing leftthalamic electrostimulation have not lost the capacity for verbalcommunication but may experience dysnomia (defective verbal retrieval)and other language disruption (Crosson, 1992; Graff-Radford, Damasio, etal., 1985; M.D. Johnson and Ojemann, 2000). This disorder is notconsidered to be a true aphasia but rather has been described as a“withering”of language functioning that sometimes leads to mutism.Language deficits do not appear with very small thalamic lesions, suggestingthat observable language deficits at the thalamic level require destruction ofmore than one pathway or nucleus, as would happen with larger lesions(Wallesch, Kornhuber, et al., 1983). With larger thalamic lesions prominentlanguage disturbancescan occur (Carrera and Bogousslavsky, 2006; DeWitte et al., 2008; Perren et al., 2005). Apathy, confusion, and disorientationoften characterize this behavior pattern (J.W. Brown, 1974; see also D.Caplan, 1987; Mazaux and Orgogozo, 1982). Patients with left thalamiclesions may achieve lower scores on verbal tests than patients whosethalamic damage is limited to the right side (Graff-Radford et al., 1985;Vilkki, 1979). Attentional deficits may also occur with thalamic lesions,particularly posterior ones (J.C. Snow, Allen, et al., 2009).Neuroimaging studies have shown that right thalamic regions areinvolved in identifying shapes or locations (LaBerge, 2000). Patients whohave right thalamic lesions or who undergo electrostimulation of the rightthalamus can have difficulty with face or pattern recognition and patternmatching (Fedio and Van Buren, 1975; Vilkki and Laitinen, 1976), mazetracing (M.J. Meier and Story, 1967), and design reconstruction (Graff-Radford, Damasio, et al., 1985). Heilman, Valenstein, and Watson (2000)provided graphic evidence of patients with right thalamic lesions whodisplayed left-sided inattention characteristic of patients with right-sided—particularly right posterior—cortical lesions (the “visuospatial inattentionsyndrome"; see pp. 427–429). This phenomenon may also accompany leftthalamic lesions, although unilateral inattention occurs more often withright-sided damage (Formaglio et al., 2009; Velasco et al., 1986; Vilkki,1984). Although some studies have suggested that unilateral thalamic lesionslead to modality-specific memory deficits (Graff-Radford, Damasio, et al.,1985; M.D. Johnson and Ojemann, 2000; Stuss, Guberman, et al., 1988) ,conflicting data leave this question unresolved (N. Kapur, 1988b; Rousseauxet al., 1986).Alterations in emotional capacity and responsivity tend to accompanythalamic damage, typically manifesting as apathy, loss of spontaneity anddrive, and affective flattening, emotional characteristics that are integral tothe Korsakoff syndrome (M. O’Connor, Verfaillie, and Cermak, 1995; Schottet al., 1980; Stuss, Guberman, et al., 1988). Yet disinhibited behavior andemotions occasionally appear with bilateral thalamic lesions (Graff-Radford,Tranel, et al., 1990). Transient manic episodes may follow right thalamicinfarctions, with few such reactions—or strong emotional responses—seenwhen the lesion is on the left (Cummings and Mega, 2003; Starkstein,Robinson, et al., 1988). These emotional and personality changes indiencephalic amnesia patients reflect how intimately interlocked are theemotional and memory components of the limbic system (see pp. 311–313).Other limbic system structures with close connections to the thalamushave been specifically implicated in impaired recording and consolidationprocesses of memory. These are the mammillary bodies and the fornix (acentral forebrain structure that links the hippocampal and themammillothalamic areas of the limbic system, see Fig. 3.8) (N. Butters andStuss, 1989; Markowitsch, 2000; Tanaka et al., 1997). Massive anterogradeamnesia and some retrograde amnesia can result from diffuse lesionsinvolving the mammillary bodies and the thalamus (Graff-Radford, Tranel,et al., 1990; Kopelman, 2002; Squire, Haist, and Shimamura, 1989) .Recording of ongoing events may be impaired by lesions of the fornix(Grafman, Salazar, et al., 1985; R.J. Ojemann, 1966; D.F. Tate and Bigler,2000).The hypothalamusThe hypothalamus is located beneath the thalamus in the ventral wall of thethird ventricle. Although it takes up less than one-half of one percent of thebrain’s total weight, the hypothalamus regulates such importantphysiologically based drives as appetite, sexual arousal, and thirst (E.T.Rolls, 1999; C.B. Saper, 1990). It receives inputs from many brain regionsand coordinates autonomic and endocrine functions. It is one of the centersinvolved in regulating homeostasis and stress reactions for the rest of thebody (A. Levine, Zagoory-Sharon, et al., 2007). It may also participate in theneural processing of cognitive and social cues (Averbeck, 2010). Behaviorpatterns having to do with physical protection, such as rage and fearreactions, are also regulated by hypothalamic centers. Depending on the siteof the damage, lesions to hypothalamic nuclei can result in a variety ofsymptoms, including obesity, disorders of temperature control, fatigue, anddiminished drive states and responsivity (F.G. Flynn et al., 1988). Moodstates may also be affected by hypothalamic lesions (Cowles et al., 2008;Wolkowitz and Reus, 2001). Damage to the mammillary bodies locatedadjacent to the posterior extension of the hypothalamus disrupts memoryprocessing (Bigler, Nelson, et al., 1989; E.V. Sullivan, Lane, et al., 1999;Tanaka et al., 1997).The Forebrain: The CerebrumStructures within the cerebral hemispheres—the basal ganglia and the limbicareas of the cingulate cortex, amygdala and hippocampus—are of especialneuropsychological importance. Some of these structures have ratherirregular shapes. To help visualize their location and position within thebrain, see Figure 3.9, derived from the 3-D MRI used in Figure 3.2. It isoften helpful to visualize the position of these brain structures in reference tothe ventricular system which is also shown.The basal gangliaThe cerebrum, the most recently evolved, most elaborated, and by far thelargest brain structure, has two hemispheres which are almost but not quiteidentical mirror images of each other (see Figs. A1.x, x). Within eachcerebral hemisphere are situated a cluster of subcortical nuclear massesknown as the basal ganglia (“ganglion”is another term for “nucleus"; seeFigs. 3.2 and 3.9). These include the caudate, putamen, and globus pallidus.Some authorities also consider the amygdala, subthalamic nucleus,substantia nigra, and other subcortical structures to be part of the basalganglia (e.g., Koziol and Budding, 2009). Direct connections from thecerebral cortex to the caudate and putamen, and the globus pallidus andsubstantia nigra project back to the cerebral cortex through the thalamus.The caudate and gray matter bands, called striations, connect the caudateand putamen with the amygdala. These striations together with the caudateand putamen are referred to as the striatum or the neostriatum,“neo-”referring to the more recently evolved aspects of the caudate andputamen. The neostriatum is part of the system which translates cognitioninto action (Brunia and Van Boxtel, 2000; Divac, 1977; Grahn et al., 2009).FIGURE 3.9 Cut-away showing brain anatomy viewed from a left frontal perspective with the leftfrontal and parietal lobes removed. (A) Cingulate Gyrus, (B) Atrium of the Lateral Ventricle, (C)Posterior Horn of the Lateral Ventricle, (D) IV Ventricle, (E) Temporal Horn of the Lateral Ventricle,(F) Preoptic recess of the III ventricle, (G) Anterior Horn of the Lateral Ventricle, (H) MassaIntermedia and I-M Corpus Callosum, (I) Body, (J) Isthmus, (K) Splenium, (L) Rostrum and (M)Genu. Color code: aquamarine: Ventricular System, gray: Thalamus, blue: Globus Pallidus, purple:Putamen, yellow: Hippocampus, red: Amygdala.In addition to important connections to the motor cortex, the basalganglia have many reciprocal connections with other cortical areas,including subdivisions of the frontal lobes (Middleton and Strick, 2000a, b;E.T. Rolls, 1999). Somatotopic representation of specific body parts (e.g.,hand, foot, face) within basal ganglia structures overlap, are similar fordifferent individuals, and are unlike the pattern of cortical body partrepresentation (Maillard et al., 2000; see Fig. 3.14). The basal gangliainfluence all aspects of motor control. They are not motor nuclei in a strictsense, as damage to them gives rise to various motor disturbances but doesnot result in paralysis. What these nuclei contribute to the motor system,cognition, and behavior is less well understood(Haaland and Harrington,1990; J.M. Hamilton et al., 2003; Thach and Montgomery, 1990). Movementdisorders (particularly chorea, tremor and/ or dystonias) may be the mostcommon and obvious symptoms of basal ganglia damage (Crosson, Moore,et al., 2003; Tröster, 2010). In general, diseases of the basal ganglia arecharacterized by abnormal involuntary movements at rest.Much of the understanding of how the basal ganglia engage movementand other aspects of behavior has been obtained by studying patients withParkinson’s disease and Huntington’s disease (see pp. 271–286). Difficultiesin starting activities and in altering the course of ongoing activitiescharacterize both motor and mental aspects of Parkinson’s disease (R.G.Brown, 2003; Doyon, Bellec, et al., 2009). Huntington patients also appearto have trouble initiating cognitive processes (Brandt, Inscore, et al., 2008)along with impaired movements (De Diego-Balaguer et al., 2008; Richer andChouinard, 2003). In both conditions, many cognitive abilities may beimpaired and emotional disturbances are common.These nuclei also play an important role in the acquisition of habits andskills (Blazquez et al., 2002; Jog et al., 1999). The neostriatum appears to bea key component of the procedural memory system (Budson and Price,2005; Doyon et al., 2009), perhaps serving as a procedural memory bufferfor established skills and response patterns and participating in thedevelopment of new response strategies (skills) for novel situations (Saint-Cyr and Taylor, 1992). Damage to the basal ganglia reduces cognitiveflexibility—the ability to generate and shift ideas and responses (Lawrence,Sahakian, et al., 1999; Mendez, Adams, and Lewandowski, 1989).Hemispheric lateralization becomes apparent with unilateral lesions, bothin motor disturbances affecting the side of the body contralateral to thelesioned nuclei and in the nature of the concomitant cognitive disorders(L.R. Caplan, Schmahmann, et al., 1990). Several different types of aphasicand related communication disorders have been described in associationwith left-sided lesions (Crescentini et al., 2008; Cummings and Mega, 2003;De Diego-Balaguer et al., 2008). Symptoms tend to vary with the lesion sitein a fairly regular manner (Alexander, Naeser, and Palumbo, 1987; A. Basso,Della Sala, and Farabola, 1987; A.R. Damasio, H. Damasio, and Rizzo,1982; Tanridag and Kirshner, 1985), paralleling the cortical aphasia patternof reduced output with anterior lesions, reduced comprehension withposterior ones (Crosson, 1992; Naeser, Alexander, et al., 1982) . In somepatients, lesions in the left basal ganglia alone or in conjunction with leftcortical lesions have been associated with defective knowledge of the colorsof familiar objects (Varney and Risse, 1993). Left unilateral inattentionaccompanies some right-sided basal ganglia lesions (L.R. Caplan,Schmahmann, et al., 1990; Ferro, Kertesz, and Black, 1987).Alterations in basal ganglia circuits involved with nonmotor areas of thecortex have been implicated in a wide variety of neuropsychiatric disordersincluding schizophrenia, obsessive-compulsive disorder, depression,Tourette’s syndrome, autism, and attention deficit disorders (Chudasama andRobbins 2006; Koziol and Budding, 2009; Middleton and Strick, 2000b).Emotional flattening with loss of drive resulting in more or less severe statesof inertia can occur with bilateral basal ganglia damage (Bhatia andMarsden, 1994; Strub, 1989) . These anergic (unenergized, apathetic)conditions resemble those associated with some kinds of frontal damage,illuminating the interrelationships between the basal ganglia and the frontallobes. Mood alterations may trouble new stroke patients with lateralizedbasal ganglia lesions with depression more common in patients who haveleft-sided damage than in those with right-sided involvement (Starkstein,Robinson, et al., 1988).The nucleus basalis of Meynert is a small basal forebrain structure lyingpartly within and partly adjacent to the basal ganglia (N. Butters, 1985; H.Damasio and Damasio, 1989). It is an important source of the cholinergicneurotransmitters implicated in learning. Loss of neurons here occurs indegenerative dementing disorders in which memory impairment is aprominent feature (Hanyu et al., 2002; Teipel et al., 2005; N.M. Warren etal., 2005) and may also occur in traumatic brain injury (Arciniegas, 2003).The Limbic SystemThe limbic system includes the amygdala and two phylogenetically oldregions of cortex: the cingulate gyrus and the hippocampus (pp. 54, 83–87,94; Figs. 3.8 and 3.9, pp. 51, 53). Connecting pathways, most prominentlythe fornix, link the hippocampus with the mammillary bodies, themammillary bodies with the thalamus, and back to the cerebral cortex viaconnections through the cingulate gyrus as shown in Figure 3.8 (P. Andersenet al., 2007; Markowitsch, 2000; Papez, 1937). These connections form aloop, often referred to as the limbic loop. Its components are embedded instructures as far apart as the RAS in the brain stem and olfactory nucleiunderlying the forebrain. These structures play important roles in emotion,motivation, and memory (Markowitsch, 2000; Mesulam, 2000b; D.M.Tucker et al., 2000.)The intimate connection between memory and emotions is illustrated byKorsakoff patients with severe learning impairments who retain emotionallyladen words better than neutral ones (J. Kessler et al., 1987; Pincus andTucker, 2003; Wieser, 1986). Disturbances in emotional behavior also occurin association with seizure activity involving these structures (see p. 246).The cingulate cortexThe cingulate gyrus is located in the medial aspects of the hemispheresabove the corpus callosum (Figs. 3.2, 3.8, and 3.9). Within it lie theextensive white matter tracts that make up the cingulum, also referred to asthe cingulum bundle (see Fig. 3.10). It has important influences on attention,response selection, processing of pain, and emotional behavior (Brunia andVan Boxtel, 2000; J.S. Feinstein et al., 2009; E.T. Rolls, 1999) . Anterior andposterior portions differ in their projections and roles (p. 246).Intracerebral conduction pathwaysThe mind depends as much on white matter as on its gray counterpart.Christopher M. Filley, 2001Much of the bulk of the cerebral hemispheres is white matter, consistingof densely packed axons. These are conduction fibers that transmit neuralimpulses between cortical points within a hemisphere (association fibers),between the hemispheres (commissural fibers), or between the cerebralcortex and lower centers (projection fibers). The major tracts of the brain canbe readily identified with diffusion tensor imaging (DTI) (see Fig. 3.10).Lesions in cerebral white matter sever connections between lower and highercenters or between cortical areas within a hemisphere or betweenhemispheres (disconnection syndromes, see pp. 348–349). White matterlesions are common features of many neurological and neuropsychiatricdisorders and are often associated with slowed processing speed andattentional impairments (Libon, Price, et al., 2004; Schmahmann, Smith, etal., 2008).FIGURE 3.10 DTI (diffusion tensor imaging) of major tracts as shown from a dorsal view (left),frontal (middle) and right hemisphere (right). The colors reflect standardized fiber tract orientationwhere green indicates tract in the anterior-posterior or front-to-back direction, with warm colors(orange to red) indicating lateral or side-to-side direction and blue indicates vertical direction.The corpus callosum is the big band of commissural fibers connecting thetwo hemispheres (see Figs. 3.11 and 3.12). It can be readily imaged: DTImakes visible the aggregate tracts of the corpus callosum and where theyproject. Other interhemispheric connections are provided by some smallerbands of fibers, including the anterior and posterior commissures.Interhemispheric communication by the corpus callosumand othercommissural fibers maintains integration of cerebral activity between thetwo hemispheres (Bloom and Hynd, 2005; Zaidel, Iacoboni, et al., 2011). Itis organized with great regularity (J.M. Clarke et al., 1998). Studies ofwhether/ how differences in overall size of the corpus callosum might relateto cognitive abilities have produced inconsistent findings (Bishop andWahlsten, 1997; H.L. Burke and Yeo, 1994; Davatzikos and Resnick, 1998).Some studies have reported that the corpus callosum tends to be larger innonright-handers (Cowell et al., 1993; Habib, Gayraud, et al., 1991;Witelson, 1989).Surgical section of the corpus callosum cuts off direct interhemisphericcommunication (Baynes and Gazzaniga, 2000; Bogen, 1985; Seymour et al.,1994), which can be a successful treatment of otherwise intractablegeneralized epilepsy (Rahimi et al., 2007). When using examinationtechniques restricting stimulus input to one hemisphere (see E. Zaidel,Zaidel, and Bogen, 1990), patients who have undergone section ofcommissural fibers (commissurotomy) exhibit distinct behavioraldiscontinuities between perception, comprehension, and response, whichreflect significant functional differences between the hemispheres (see alsop. xx). Probably because direct communication between two cortical pointsoccurs far less frequently than indirect communication relayed throughlower brain centers, especially through the thalamus and the basal ganglia,these patients generally manage to perform everyday activities quite well.These include tasks involving interhemispheric information transfer (J.J.Myers and Sperry, 1985; Sergent, 1990, 1991b; E. Zaidel, Clarke, andSuyenobu, 1990) and emotional and conceptual information not dependenton language or complex visuospatial processes (Cronin-Golomb, 1986) . Innoting that alertness remains unaffected by commissurotomy and thatemotional tone is consistent between the hemispheres, Sperry (1990)suggested that both phenomena rely on bilateral projections through theintact brain stem.FIGURE 3.11 DTI of major tracts through the corpus callosum. Five major fasciculi involving thetemporal lobe are colorized simply to identify their position: these colors do not indicate fiber tractorientation as represented in diffusion tensor imaging (DTI) color maps. The following tracts areassociated with these colors: Green: cingulum bundle (CB), Purple: arcuate fasciculus (AF),Turquoise-Blue: uncinate fasciculus (UF), Chartreuse: inferior fronto-occipital fasciculus (IFOF), Red:inferior longitudinal fasciculus (ILF). The IFOF is mostly hidden in this illustration, but an outline ofits occipital-frontal projections can be visualized. Reproduced with permission from SpringerPublishing from Bigler, McCauley, Wu et al. (2010).FIGURE 3.12 (TOP) Representative commissural DTI “streamlines”showing cortical projections.Colors show the direction of projecting fibers: green reflects anterior-posterior orientation; warmcolors (red-orange) reflect lateral or back-and-forth projections; blue, a vertical orientation.(BOTTOM) Cortical termination of corpus callosum projections are shown on “Inflated”or“ballooned”appearing brains with the lateral surface shown in the middle view and the bottom viewreflects projections to the medial surface. Note the high specificity and organization of projectingfibers across the corpus callosum. From Pannek et al. (2010) used with permission from Elsevier.Some persons with agenesis of the corpus callosum (a rare congenitalcondition in which the corpus callosum is insufficiently developed or absentaltogether) are identified only when some other condition brings them to aneurologist’s attention. Normally they display no neurological orneuropsychological defects (L.K. Paul et al., 2007; Zaidel, Iacoboni,Berman, et al., 2011) other than slowed motor performances, particularly ofbimanual tasks (Lassonde et al., 1991). However, persons with congenitalagenesis of the corpus callosum also tend to be generally slowed onperceptual and language tasks involving interhemispheric communication,and some show specific linguistic and/or visuospatial deficits (Jeeves, 1990,1994; see also Zaidel and Iacoboni, 2003) . In some cases, problems withhigher order cognitive processes such as concept formation, reasoning, andproblem solving with limited social insight have been observed (W.S. Brownand Paul, 2000).The cerebral cortexThe cortex of the cerebral hemispheres (see Fig. 3.3, p. 46), the convolutedouter layer of gray matter composed of nerve cell bodies and their synapticconnections, is the most highly organized correlation center of the brain, butthe specificity of cortical structures in mediating behavior is neither clear-cutnor circumscribed (R.C. Collins, 1990; Frackowiak et al., 1997). Predictablyestablished relationships between cortical areas and behavior reflect thesystematic organization of the cortex and its interconnections (Fuster, 2008).Now modern visualizing techniques display what thoughtful clinicians hadsuspected: multiple cortical and subcortical areas are involved in complexinterrelationships in the mediation of even the simplest behaviors (Fuster,1995; Mesulam, 2009; Seeley et al., 2009) and specific brain regions aretypically multifunctional (Lloyd, 2000).While motor, sensory and certain receptive and expressive languagefunctions have relatively well-defined regions that subserve these functions,the boundaries of other functionally definable cortical areas, or zones, arevague. Cells subserving a specific function are highly concentrated in theprimary area of a zone, thin out, and overlap with other zones as theperimeter of the zone is approached (E. Goldberg, 1989, 1995; Polyakov,1966). Cortical activity at every level, from the cellular to the integratedsystem, is maintained and modulated by complex feedback loops that inthemselves constitute major subsystems, some within the cortex and othersinvolving subcortical centers and pathways. “Processing patterns take manyforms, including parallel, convergent [integrative], divergent [spreadingexcitation], nonlinear, recursive [feeding back onto itself] and iterative“ (H.Damasio and Damasio, 1989, p. 71). Even those functions that are subservedby cells located within relatively well-defined cortical areas have asignificant number of components distributed outside the local corticalcenter (A. Brodal, 1981; Paulesu et al., 1997) . Much of whatneuropsychological assessment techniques evaluate is the functioning of thecerebral cortex and its final control over behavior.THE CEREBRAL CORTEX AND BEHAVIORCortical involvement appears to be a prerequisite for awareness ofexperience (Changeux, 2004; Fuster, 2003). Patterns of functionallocalization in the cerebral cortex are organized broadly along two spatialplanes. The lateral plane refers to the left and right sides of the brain andthus cuts through homologous (in the corresponding position) areas of theleft and right hemispheres, with the point of demarcation being thelongitudinal fissure. The longitudinal plane runs from the front to the backof the cortex, with the demarcation point being the central sulcus (fissure ofRolando), roughly separating functions that are primarily localized in theanterior (or rostral) portion of the cortex and those that are primarilylocalized in the posterior (or caudal) portion of the cortex. Both of theseaxes—lateral and longitudinal— should be understood as constructs helpfulfor conceptualizing brain-behavior relations, and not as rigid rules thatdictate functional organization.Lateral OrganizationLateral symmetryAt a gross macroscopic level, the two cerebral hemispheres are roughlysymmetrical. For example, the primary sensory and motor centers arehomologously positioned within the cerebral cortex of each hemisphere in amirror-image relationship. Many afferent and efferent systems are crossed,so that the centers in each cerebral hemispherecolor Figure 7.13)FIGURE7.14This is a case of mild TBI where conventional imaging (upper left) shows no abnormalitybut the fractional anisotropy DTI map (top, middle image) does (See color Figure 7.14)FIGURE7.15The brain regions involved in TBI that overlap with PTSD are highlighted in this schematic(See color Figure 7.15)FIGURE7.16“The three neurodegenerative diseases classically evoked as subcortical dementia areHuntington’s chorea, Parkinson’s disease, and progressive supranuclear palsyFIGURE7.17Tracings of law professor’s Complex Figure copies (see text for description of hisperformance)FIGURE7.18Immediate (upper) and delayed (lower) recall of the Complex Figure by the law professorwith Huntington’s diseaseFIGURE7.19Pyramid diagram of HIV-Associated Neurocognitive Disorders (HAND)FIGURE7.20Schematic flow diagram showing a diagnostic decision tree for various neurocognitivedisorders associated with HiVFIGURE7.21Autopsy-proved HIV encephalitis in an AIDS patient with dementiaFIGURE7.22The devastating effects of structural damage from herpes simplex encephalitisFIGURE7.23Postmortem appearance of a glioblastoma multiformeFIGURE7.24Postmortem appearance of a mid-sagittal frontal meningioma (left) and a large inferiorfrontal meningioma (right)FIGURE7.25Postmortem appearance of malignant melanomaFIGURE7.26Postmortem appearance of pulmonary metastasis to the brain 335.FIGURE7.27The MRIs show bilateral ischemic hypoxic injury characteristic of anoxic brain injuryNeurobehavioral Variables and Diagnostic IssuesFIGURE8.1The handedness inventoryFIGURE8.2The target matrix for measuring manual speed and accuracyFIGURE8.3Tapley and Bryden’s (1985) dotting task for measuring manual speedOrientation and AttentionFIGURE9.1One of the five diagrams of the Personal Orientation TestFIGURE9.2Curtained box used by Benton to shield stimuli from the subject’s sight when testing fingerlocalizationFIGURE9.3Outline drawings of the right and left hands with fingers numbered for identificationFIGURE9.4aFloor plan of his home drawn by a 55-year-old mechanic injured in a traffic accidentFIGURE9.4bFloor plan of their home drawn by the mechanic’s spouseFIGURE9.5Topographical Localization responses by a 50-year-old engineer who had a ruptured rightanterior communicating arteryFIGURE9.6Corsi’s Block-tapping boardFIGURE9.7The symbol-substitution format of the WIS Digit Symbol TestFIGURE9.8The Symbol Digit Modalities Test (SDMT)FIGURE9.9Practice samples of the Trail Making TestPerceptionFIGURE10.1This sample from the Pair Cancellation test (Woodcock-Johnson III Tests of CognitiveAbilities)FIGURE10.2The Line Bisection testFIGURE10.3Performance of patient with left visuospatial inattention on the Test of Visual NeglectFIGURE10.4The Bells Test (reduced size)FIGURE10.5Letter Cancellation task: “Cancel C’s and E’s” (reduced size)FIGURE10.6Star Cancellation test (reduced size)FIGURE10.7Indented Paragraph Reading Test original format for copyingFIGURE10.8indented Paragraph Reading Test with errors made by the 45-year-old traumatically injuredpediatricianFIGURE10.9This attempt to copy an address was made by a 66-year-old retired paper mill worker twoyears after he had suffered a right frontal CVAFIGURE Flower drawn by patient with left visuospatial neglect10.10FIGURE10.11Judgment of Line OrientationFIGURE10.12Focal lesions associated with JLO failures. (See color Figure 10.12)FIGURE10.13Test of Facial RecognitionFIGURE10.14An item of the Visual Form Discrimination testFIGURE10.15Example of the subjective contour effectFIGURE10.16Closure Speed (Gestalt Completion)FIGURE10.17Two items from the Silhouettes subtest of the Visual Object and Space Perception TestFIGURE10.18Multiple-choice item from the Object Decision subtest of the Visual Object and SpacePerception TestFIGURE10.19Easy items of the Hooper Visual Organization TestFIGURE10.20Closure Flexibility (Concealed Figures)FIGURE10.21Example of a Poppelreuter-type overlapping figureFIGURE10.22Rey’s skin-writing proceduresMemory I: TestsFIGURE11.1Memory for Designs modelsFIGURE11.2Complex Figure Test performance of a 50-year-old hemiparetic engineer with severe rightfrontal damage of 14 years’ durationFIGURE11.3Two representative items of the Benton Visual Retention TestFIGURE11.4Ruff-Light Trail Learning Test (RuLiT) (reduced size)FIGURE11.5One of the several available versions of the Sequin-Goddard Formboard used in the TactualPerformance TestVerbal Functions and Language SkillsFIGURE13.1Alzheimer patient’s attempt to write (a) “boat” and (b) “America.”Construction and Motor PerformanceFIGURE14.1The Hutt adaptation of the Bender-Gestalt figuresFIGURE14.2Rey Complex Figure (actual size)FIGURE14.3Taylor Complex Figure (actual size)FIGURE Modified Taylor Figure14.4FIGURE14.5The four Medical College of Georgia (MCG) Complex Figures (actual size)FIGURE14.6An example of a Complex Figure Test Rey-Osterrieth copyFIGURE14.7Structural elements of the Rey Complex FigureFIGURE14.8Sample freehand drawings for copyingFIGURE14.9Freehand drawing of a clock by a 54-year-old man with a history of anoxia resulting inbilateral hippocampus damageFIGURE14.10Block Design testFIGURE14.11Voxel lesion-symptom mapping on 239 patients from the iowa Patient Registry projectedon the iowa template brainFIGURE14.12Example of a WIS-type Object Assembly puzzle itemFIGURE14.13Test of Three-Dimensional Constructional Praxis, Form A (A.L. Benton)FIGURE14.14Illustrations of defective performancesFIGURE14.15The Purdue Pegboard TestConcept Formation and ReasoningFIGURE15.1Identification of Common Objects stimulus card (reduced size)FIGURE15.2Examples of two levels of difficulty of Progressive Matrices-type itemsFIGURE15.3The Kasanin-Hanfmann Concept Formation TestFIGURE15.4The Wisconsin Card Sorting TestFIGURE15.5A simple method for recording the Wisconsin Card Sorting Test performanceFIGURE15.6WIS-type Picture Completion test itemFIGURE15.7WIS-type Picture Arrangement test itemFIGURE15.8Sample items from the Block Counting taskFIGURE15.9Example of a page of arithmetic problems laid out to provide space for written calculationsExecutive FunctionsFIGURE16.1Bender-Gestalt copy trial rendered by a 42-year-old interior designer a year after she hadsustained a mild anterior subarachnoid hemorrhageFIGURE16.2House and Person drawings by the interior designer whose Bender-Gestalt copy trial isgiven in Figure 16.1FIGURE16.3Two of the Porteus mazesFIGURE16.4Tower of London examplesFIGURE16.5A subject performing the Iowa Gambling Task on a computerFIGURE16.6Card selections on the Iowa Gambling Task as a function of group (Normal Control, Braindamaged Control, Ventromedial Prefrontal), deck type (disadvantageous v. advantageous),and trial blockFIGURE16.7A 23-year-old craftsman with a high school education made this Tinkertoy “spaceplatform”FIGURE16.8“Space vehicle” was constructed by a neuropsychologist unfamiliar with TinkertoysFIGURE16.9The creator of this “cannon” was a 60-year-old left-handed contractor who had had a smallleft parietal strokeFIGURE16.10This 40-year-old salesman was trying to make a “car” following a right-sided strokeFIGURE16.11Figural Fluency Test responses by 62-year-old man described on p. 698FIGURE16.12Ruff Figural Fluency Test (Parts I-V)FIGURE16.13Repetitive patterns which subject is asked to maintainFIGURE16.14Drawing of a clock, illustrating perseverationFIGURE16.15Signature of middle-aged man who had sustained a gunshot wound to the right frontal lobeNeuropsychological Assessment BatteriesFIGURE17.1This figurepredominantly mediate theactivities of the contralateral (other side) half of the body (see Fig. 3.13).Thus, an injury to the primary somatosensory (sensations on the body)cortex of the right hemisphere results in decreased or absent sensation in thecorresponding left-sided body part(s); similarly, an injury affecting the leftmotor cortex results in a right-sided weakness or paralysis (hemiplegia).FIGURE 3.13 Schematic diagram of visual fields, optic tracts, and the associated brain areas, showingleft and right lateralization in humans. (From Sperry, 1984)FIGURE 3.14 Diagram of a “motor homunculus”showing approximately relative sizes of specificregions of the motor cortex representing various parts of the body, based on electrical stimulation ofthe exposed human cortex. From Penfield, W. and Rasmussen, T. (1950). The cerebral cortex of man.NY: Macmillan. Used with permission of Cengage Group.Point-to-point representation on the cortex. The organization of both theprimary sensory and primary motor areas of the cortex provides for a point-to-point representation of the body. The amount of cortex associated witheach body portion or organ is roughly proportional to the number of sensoryor motor nerve endings in that part of the body, rather than to its size. Forexample, the areas concerned with sensation and movement of the tongue orfingers are much more extensive than the areas representing the elbow orback. This gives rise to the famous distorted-looking “homunculous,” the“little man”drawing which depicts the differential assignment of corticalareas to various body parts (Fig 3.14).The visual system is also organized on a contralateral plan, but it is one-half of each visual field (the entire view encompassed by the eye) that isprojected onto the contralateral visual cortex (see Fig. 3.13). Fibersoriginating in the right half of each retina, which regist er stimuli in the leftvisual field, project to the right visual cortex; fibers from the left half of eachretina convey the right visual field image to the left visual cortex. Thus,destruction of either eye leaves both halves of the visual field intact,although some aspects of depth perception will be impaired. Destruction ofthe right or the left primary visual cortex or of all the fibers leading to eitherside results in blindness for the opposite side of visual field (homonymoushemianopia).Lesions involving a portion of the visual projection fibers or visual cortexcan result in circumscribed field defects, such as areas of blindness(scotoma, pl. scotomata) within the visual field of one or both eyes,depending on whether the lesion involves the visual pathway before (oneeye) or after (both eyes) its fibers cross on their route from the retina of theeye to the visual cortex. The precise point-to-point arrangement of projectionfibers from the retina to the visual cortex permits especially accuratelocalization of lesions within the primary visual system (Sterling, 1998).Higher order visual processing is mediated by two primary systems, eachwith different pathways involving different parts of the cortex. A ventral or“what”system is specialized for pattern analysis and object recognition(“what”things are), and is differentiated from a dorsal or “where”systemwhich is specialized for spatial analysis and movement perception(“where”things are) (Goodale, 2000; Mendoza and Foundas, 2008;Ungerleider and Mishkin, 1982).Some patients with brain injuries that do not impair basic visual acuity orrecognition complain of blurred vision or degraded percepts, particularlywith sustained activity, such as reading, or when exposure is very brief(Hankey, 2001; Kapoor and Ciuffreda, 2005; Zihl, 1989). These problemsreflect the complexity of an interactive network system in which the effectsof lesions resonate throughout the network, slowing and distorting multipleaspects of cerebral processing with these resultant visual disturbances.A majority of the nerve fibers transmitting auditory stimulation fromeach ear are projected to the primary auditory centers in the oppositehemisphere; the remaining fibers go to the ipsilateral (same side) auditorycortex. Thus, the contralateral, crossed pattern is preserved to a large degreein the auditory system too. However, because the projections are not entirelycrossed, destruction of one of the primary auditory centers does not result incomplete loss of hearing in the contralateral ear. A point-to-pointrelationship between sense receptors and cortical cells is also laid out on theprimary auditory cortex, with cortical representation arranged according topitch, from high to low tones (Ceranic and Luxon, 2002; Mendoza andFoundas, 2008).Destruction of a primary cortical sensory or motor area results in specificsensory or motor deficits, but generally has little effect on the highercognitive functions. For instance, an adult-onset lesion limited to the primaryvisual cortex produces loss of visual awareness (cortical blindness), whilereasoning ability, emotional control, and even the ability for visualconceptualization may remain intact (Farah and Epstein, 2011; Guzeldere etal., 2000; Weiskrantz, 1986).Association areas of the cortex. Cortical representation of sensory ormotor nerve endings in the body takes place on a direct point-to-point basis,but stimulation of the primary cortical area gives rise only to vague,somewhat meaningless sensations or nonfunctional movements (Brodal,1981; Luria, 1966; Mesulam, 2000b). Complex functions involve the cortexadjacent to primary sensory and motor centers (E. Goldberg, 1989, 1990;Mendoza and Foundas, 2008; Paulesu et al., 1997). Neurons in thesesecondary cortical areas integrate and refine raw percepts or simple motorresponses. Tertiary association or overlap zones are areas peripheral tofunctional centers where the neuronal components of two or more differentfunctions or modalities are interspersed. The posterior association cortex, inwhich the most complex integration of perceptual functions takes place, hasalso been called the multimodal (Pandya and Yeterian, 1990), heteromodalMesulam, 2000b), or supramodal (Darby and Walsh, 2005) cortex.These processing areas are connected in a “stepwise”manner such thatinformation-bearing stimuli reach the cortex first in the primary sensorycenters. They then pass through the cortical association areas in order ofincreasing complexity, interconnecting with other cortical and subcorticalstructures along the way to frontal and limbic system association areas andfinally become manifest in action, thought, and feeling (Arciniegas andBeresford, 2001; Mesulam, 2000b; Pandya and Yeterian, 1990, 1998). Theseprojection systems have both forward and reciprocal connections at eachstep in the progression to the frontal lobes; and each sensory association areamakes specific frontal lobe connections which, too, have their reciprocalconnections back to the association areas of the posterior cortex (E.T. Rolls,1998) . “Anterior prefrontal cortex is bidirectionally interconnected withheteromodal association regions of the posterior cortex but not withmodality-specific regions”(E. Goldberg, 2009, p. 59).Unlike damage to primary cortical areas, a lesion involving associationareas and overlap zones typically does not result in specific sensory or motordefects. Rather, the behavioral effects of such damage will more likelyappear as various higher order neuropsychological deficits; e.g., lesions ofthe auditory association cortex do not interfere with hearing acuity but withthe appreciation or recognition of patterned sounds (see p. 24). In likemanner, lesions to visual association cortices may cause impairedrecognition of objects, while sparing visual acuity (see p. 21).Asymmetry between the hemispheresA second kind of organization across the lateral plane differentiates the twohemispheres with respect to the localization of primary cognitive functionsand to significant qualitative aspects of behavior processed by each of thehemispheres (Filley, 2008; E. Goldberg, 2009; Harel and Tranel, 2008).Although no two human brains are exactly alike in their structure, in mostpeople the right frontal area is wider than the left and the right frontal poleprotrudes beyond the left while the reverse is true of the occipital pole: theleft occipital pole is frequently wider and protrudes further posteriorly thanthe right but the central portion of the right hemisphere is frequently widerthan the left (A.R. Damasio and Geschwind, 1984; Janke and Steinmetz,2003). Men show greater degrees of frontal and occipital asymmetry thanwomen (D. Bear, Schiff, et al., 1986). These asymmetries begin in fetalbrains (de Lacoste et al., 1991; Witelson, 1995). The left Sylvian fissure, thefold between the temporal and frontal lobes, is larger than the right in mostpeople (Witelson, 1995), even in newborns (Seidenwurm et al., 1985). Theposterior portion of the superior surface of the temporal lobe, the planumtemporale, which is involved in auditory processing, is larger on the left sidein most right-handers (Beaton, 1997; E. Strauss, LaPointe, et al., 1985).Differences in the neurotransmitters serving each hemisphere have alsobeen associated with differences in hemisphere function (Berridge et al.,2003; Direnfeld et al., 1984; Glick et al., 1982) and sex (Arato et al., 1991).These differences may have an evolutionary foundation, for they have beenfound in primates and other animals (Corballis, 1991; Geschwind andGalaburda, 1985; Nottebohm, 1979). The lateralized size differential inprimates is paralleled in some species by left lateralization for vocalcommunication (MacNeilage, 1987). For example, studies have linkedintrahemispheric interconnections with this area to gestural capacity(possibly with communication potential) in macaque monkeys (Petrides,2006).Lateralized cerebral differences may also occur at the level of cellularorganization (Galuske et al., 2000; Gazzaniga, 2000; Peled et al., 1998). Along-standing hypothesis holds that the left and right hemispheres havedifferent degrees of specialization, with left greater than right. A half centuryago, Hecaen and Angelergues (1963) speculated that neural organizationmight be more closely knit and integrated on the left, more diffuse on theright. This idea is consistent with findings that patients with righthemisphere damage tend to have a reduced capacity for tactilediscrimination and sensorimotor tasks in both hands while those with lefthemisphere damage experience impaired tactile discrimination only in thecontralateral hand (Hom and Reitan, 1982; Semmes, 1968), althoughcontradictory data have been reported (Benton, 1972). Other support comesfrom findings that visuospatial and constructional disabilities of patientswith right hemisphere damage do not differ significantly regardless of theextensiveness of damage (Kertesz and Dobrowolski, 1981). Hammond(1982) reported that damage to the left hemisphere tends to reduce acuity oftime discrimination more than right-sided damage, suggesting that the lefthemisphere has a capacity for finer temporal resolution than the right. Also,the right hemisphere does not appear to be as discretely organized as the leftfor visuoperceptual and associated visual memory operations (Fried et al.,1982; Wasserstein, Zappula, Rosen, and Gerstman, 1984).Functional specialization of the hemispheres. Fundamental differences between the left and righthemispheres of the human brain constitute some of the bedrock principles of neuropsychology. Thefirst—stemming from the seminal observations of Broca (1861) and Wernicke (1874)—has to do withlanguage: in the vast majority of adults, the left side of the brain is specialized for language and forprocessing verbally coded information. This is true of most—usually estimated at upwards of 90%—right-handed individuals who constitute roughly 90% of the adult population and of the majority—usually estimated at around 70%—of left-handed persons (see pp. 365–366 for lateralization details).This lateralizing principle applies regardless of input modality; for example, in most people verbalinformation apprehended through either the auditory (e.g., speech) or visual (e.g., written text) channelis processed preferentially by the left hemisphere (Abutalebi and Cappa, 2008; M.P. Alexander, 2003;Bartels and Wallesch, 2010). The principle also applies to both the input and output aspects oflanguage, so not only does the left hemisphere play a major role in understanding language, it alsoproduces language (spoken and written). The principle even goes beyond spoken languages to includelanguages based on visuogestural signals (e.g., American Sign Language) (Bellugi et al., 1989; Hickoket al., 1996).The right hemisphere has a very different type of specialization (A.R.Damasio, Tranel, and Rizzo, 2000; Darby and Walsh, 2005). It processesnonverbal information such as complex visual patterns (e.g., faces) orauditory signals (e.g., music) that are not coded in verbal form. For example,structures in the right temporal and occipital regions are critical for learningand navigating geographical routes (Barrash, H. Damasio, et al., 2000) . Theright side of the brain is also the lead player in the cortical mapping of“feeling states,” that is, patterns of bodily sensations linked to emotions suchas anger and fear (A.R. Damasio, 1994). Another, related right hemispherecapacity concerns perceptions of the body in space, in both intrapersonal andextrapersonal terms—for example, understanding of where limbs are inrelationship to trunk, and where one’s body is in relationship to thesurrounding space. While not sufficient for basic language comprehensionand production, the right hemisphere contributes to appreciation of thecontext of verbal information and, thereby, to accuracy of languageprocessing and appropriateness of language usage (see p. 62).In early conceptualizations of left and right hemisphere differences, itwas common to see references to the left hemisphere as “major”or“dominant,” while the right hemisphere was considered “minor”or“nondominant.” This thinking came from a focus on language aspects ofhuman cognition and behavior. As a highly observable and unquestionablyimportant capacity, language received the most scientific and clinicalattention, and typically was considered the quintessential and most importanthuman faculty. For many decades the right hemisphere was thought tocontribute little to higher level cognitive functioning. Lesions to the righthemisphere typically did not produce immediately obvious languagedisturbances, and hence it was often concluded that a patient had lost little inthe way of higher order function after rightsided brain injury. Later, itbecame clear that each hemisphere was dedicated to specific, albeit different,cognitive functions and the notion of “dominance”gave way to the idea of“specialization"—that is, each hemisphere was specialized for certaincognitive functions (e.g., J. Levy, 1983).Many breakthroughs in the understanding of hemispheric specializationcame from studies of so-called “split-brain”patients, work led bypsychologist and Nobelist Roger Sperry (e.g., Sperry, 1968, 1982). Toprevent partial seizures from spreading from one side of the brain to theother, an operation severed the corpus callosum in these patients. Thus, theleft and right cerebral hemispheres were “split,” and no longer able tocommunicate with one another. Careful investigations of these patientsfound that each side of the brain had its own unique style of“consciousness,” with the left and right sides operating in verbal andnonverbal modalities, respectively. Sperry’s work and that of many others(e.g., Arvanitakis and Graff-Radford, 2004; Gazzaniga, 1987, 2000;Glickstein and Berlucchi, 2008; Zaidel, Iacoboni, et al., 2011) led to severalfundamentaldistinctions between the cognitive functions for which the leftand right hemispheres are specialized (Table 3.1).The nature of hemisphere specialization also shows up in processingdifferences. The left hemisphere is organized for “linear”processing ofsequentially presented stimuli such as verbal statements, mathematicalpropositions, and the programming of rapid motor sequences. The righthemisphere is superior for “configurational”processing required byinformation or experiences that cannot be described adequately in words orstrings of symbols, such as the appearance of a face or three-dimensionalspatial relationships. Moreover, the two hemispheres process global/local orwhole/detail information differently (L.C. Robertson and Rafal, 2000;Rossion et al., 2000). When asked to copy or read a large-scale stimulussuch as the shape of a letter or other common symbol composed of manydifferent symbols in small scale (see Fig. 3.15), patients with left hemispheredisease will tend to ignore the small bits and interpret the large-scale figure;those whose lesions are on the right are more likely to overlook the bigsymbol but respond to the small ones. This can be interpreted as indicatingleft hemisphere superiority in processing detailed information, and righthemisphere superiority for processing large-scale or global percepts.TABLE 3.1 Functional dichotomies of left and right hemispheric dominanceLeft RightVerbal NonverbalSerial HolisticAnalytic SyntheticLogical PictorialRational IntuitiveSource. Adapted from Benton, 1991.FIGURE 3.15 Example of global/local stimuli.In considering hemispheric specialization for verbal versus nonverbalmaterial, it should be kept in mind that absence of words does not make astimulus “nonverbal.” Pictorial, diagrammatic, or design stimuli— andsounds, sensations of touch and taste, etc.—may be more or less susceptibleto verbal labeling depending on their meaningfulness, complexity,familiarity, potential for affective arousal, and other characteristics such aspatterning or number. Thus, when classifying a wordless stimulus as verbalor nonverbal, it is important to take into account how readily it can beverbalized.The left-right dichotomies in hemispheric specialization should be takenas useful concepts and not iron-clad facts. Many variables come into play indetermining which hemisphere will take the lead in processing various typesof information (e.g., Beaumont, 1997; Sergent, 1990). These include thenature of the task (e.g., modality, speed factors, complexity), the subject’s setof expectancies, prior experiences with the task, previously developedperceptual or response strategies, and inherent subject (attribute) variablessuch as sex and handedness (Kuhl, 2000; Papadatou-Pastou et al., 2008;Tranel, H. Damasio, et al., 2005). The degree to which hemisphericspecialization occurs at any given time and under any given set of taskdemands is relative rather than absolute (Hellige, 1995; L.C. Robertson,1995; Sergent, 1991a).Moreover, it is important to recognize that normal behavior is a functionof the whole healthy brain with important contributions from bothhemispheres entering into virtually every activity, including the very notionof the self (Northoff et al., 2006). This phenomenon has been demonstratedperhaps even more compellingly in functional imaging studies in whichbilateral activations are observed for virtually any task, no matter itsapparent purity in terms of verbal vs. nonverbal demands, serial vs. holisticprocessing, or any of the other dichotomies enumerated in Table 3.1 (e.g.,Cabeza and Nyberg, 2000; D’Esposito, 2000; Mazziotta, 2000).Still, in most persons, the left hemisphere is the primary mediator ofverbal functions, including reading and writing, verbal comprehension andspeaking, verbal ideation, verbal memory, and even comprehension of verbalsymbols traced on the skin. The left hemisphere also mediates the numericalsymbol system. Moreover, left hemisphere lateralization extends to controlof posturing, sequencing hand and arm movements, and the bilateralmusculature of speech. Processing the linear and rapidly changing acousticinformation needed for speech comprehension is performed better by the leftcompared to the right hemisphere (Beeman and Chiarello, 1998; Howard,1997). In addition, it has been hypothesized but never fully proven thatmales have stronger left hemisphere lateralization for phonologicalprocessing than females (J. Levy and Heller, 1992; Shaywitz et al., 1995;Zaidel, Aboitiz, et al., 1995).An important contribution of the right hemisphere to language processingis the appreciation and integration of relationships in verbal discourse andnarrative materials (Beeman and Chiarello, 1998, passim; Jung-Beeman,2005; Kiehl et al., 1999), which includes the capacity for enjoying a goodjoke (Beeman, 1998; H. Gardner, 1994) . The right hemisphere also appearsto provide the possibility of alternative meanings, getting away from purelyliteral interpretations of verbal material (Bottini et al., 1994; Brownell andMartino, 1998; Fiore and Schooler, 1998). The right hemisphere has somesimple language comprehension capacity, as demonstrated by the findingthat following commissurotomy, when speech is directed to the righthemisphere, much of what is heard is comprehended so long as it remainssimple (Baynes and Eliassen, 1998; Searleman, 1977). That the righthemisphere has a language capacity can also be inferred in aphasic patientswith left-sided lesions who show improvement from their immediate post-stroke deficits accompanied by measurably heightened right hemisphereactivity (B.T. Gold and Kertesz, 2000; Heiss et al., 1999; Papanicolaou,Moore, et al., 1988).The right hemisphere is sensitive to speech intonations (Borod, Bloom,and Santschi-Haywood, 1998; Ivry and Lebby, 1998) and is important formeaningfully expressive speech intonation (prosody) (Borod, Bloom, andSantschi-Haywood, 1998; Filley, 1995; E.D. Ross, 2000). It takes the lead infamiliar voice recognition (Van Lancker, Kreiman, and Cummings, 1989),plays a role in organizing verbal production conceptually (Brownell andMartino, 1998; Joanette, Goulet, and Hannequin, 1990), and contributes tothe maintenance of context-appropriate and emotionally appropriate verbalbehavior (Brownell and Martino, 1998; Joanette, Goulet, and Hannequin,1990). Specific right hemisphere temporal and prefrontal areas contribute tocomprehending story meanings (Nichelli, Grafman, et al., 1995). The righthemisphere’s characteristic contributions are not limited to communicationsbut extend to all behavior domains (Lezak, 1994a).Examples of right hemisphere specialization for nonverbal informationinclude the perception of spatial orientation and perspective, tactile andvisual recognition of shapes and forms, reception and storage ofnonverbalizable visual data, and copying and drawing geometric andrepresentational designs and pictures. The left hemisphere seems topredominate in metric distance judgments (Hellige, 1988; McCarthy andWarrington, 1990), while the right hemisphere has superiority in metricangle judgments (Benton, Sivan, et al., 1994; Mehta and Newcombe, 1996;Tranel, Vianna, et al., 2009) . Many aspects of arithmetic calculations—forexample, those involving spatial organization of problem elements asdistinct from left hemisphere-mediated linear arithmetic problems, have asignificant right hemisphere component (Denburg and Tranel, 2011). Someaspects of musical ability are also localized on the right (Peretz and Zatorre,2003), as are the recognition and discrimination of nonverbal sounds (Bauerand McDonald, 2003).Data from a variety of sources suggest right hemisphere dominance forspatial attention specifically, if not attention generally. Patients withcompromised right hemisphere functioning tend to have diminishedawareness of or responsiveness to stimuli presented to their left side,reactiontimes mediated by the right hemisphere are faster than thosemediated by the left, and the right hemisphere is activated equally by stimulifrom either side in contrast to more exclusively contralateral left hemisphereactivation (Heilman, Watson, and Valenstein, 2011; Meador, Loring, Lee, etal., 1988; Mesulam, 2000b). Moreover, the right hemisphere predominates indirecting attention to far space while the left hemisphere directs attention tonear space (Heilman, Chatterjee, and Doty, 1995). The appearance of righthemisphere superiority for attention in some situations may stem from itsability to integrate complex, nonlinear information rapidly.Facial recognition studies exemplify the processing differences underlying many aspects ofhemisphere specialization. When pictured faces are presented in the upright position to eachfield separately they are processed more rapidly when presented to the left field/righthemisphere than to the right field/left hemisphere; but no right hemisphere advantageappears when faces are inverted. “It seems that, in the right hemisphere, upright faces areprocessed in terms of their feature configuration, whereas inverted faces are processed in apiecemeal manner, feature by feature… . In the left hemisphere, both upright and invertedfaces seem to be processed in a piecemeal manner.” (Tovee, 1996, pp. 134–135).As illustrated in Figure 3.15 (p. 61), the distinctive processing qualities ofeach hemisphere become evident in the mediation of spatial relations. Lefthemisphere processing tends to break the visual percept into details that canbe identified and conceptualized verbally in terms of number or length oflines, size and direction of angles, and so on. In the right hemisphere thetendency is to deal with the same visual stimuli as spatially related wholes.Thus, for most people, the ability to perform such complex visual tasks asthe formation of complete impressions from fragmented percepts (theclosure function), the appreciation of differences in patterns, and therecognition and remembering of faces depends on the functioning of theright hemisphere. Together the two processing systems provide recognition,storage, and comprehension of discrete and continuous, serial andsimultaneous, detailed and holistic aspects of experience across at least themajor sensory modalities of vision, audition, and touch.Cognitive alterations with lateralized lesions. In keeping with the robust principles of hemisphericspecialization, the most obvious cognitive defect associated with left hemisphere damage is aphasia(Benson and Ardila, 1996; D. Caplan, 2011; Grodzinsky and Amunts, 2006). Otherneuropsychological manifestations of left hemisphere dysfunction include impaired verbal memory,verbal fluency deficits, concrete thinking, specific impairments in reading or writing, and impairedarithmetic ability characterized by defects or loss of basic mathematical concepts of operations andeven of number. Patients with left hemisphere damage can also lose their ability to perform complexmanual—as well as oral—motor sequences (i.e., apraxias) (Harrington and Haaland, 1992; Meador,Loring, Lee, et al., 1999; Schluter et al., 2001).The diversity of behavioral disorders associated with right hemispheredamage continues to thwart any neat or simple classification system (S.Clarke, 2001; Feinberg and Farah, 2003b; Filley, 1995). No attempt toinclude every kind of impairment reported in the literature will be madehere. Rather, the most prominent features of right hemisphere dysfunctionare described.Patients with right hemisphere damage may be quite fluent, even verbose(Mendoza and Foundas, 2008; Rivers and Love, 1980; E.D. Ross, 2000), butillogical and given to loose generalizations and bad judgment (Stemmer andJoanette, 1998). They are apt to have difficulty ordering, organizing, andmaking sense out of complex stimuli or situations. These organizationaldeficits can impair appreciation of complex verbal information so that verbalcomprehension may be compromised by confusion of the elements of whatis heard, by personalized intrusions, by literal interpretations, and by ageneralized loss of gist in a morass of details (Beeman and Chiarello, 1998,passim). Their speech may be uninflected and aprosodic, paralleling theirdifficulty in comprehending speech intonations (E.D. Ross, 2003).FIGURE 3.16 Example of spatial dyscalculia by the traumatically injured pediatrician described on p.438 whose reading inattention is shown in Figure 10.8 (p. 438). Note omission of the 6 on the left ofthe problem in the upper left corner; errors on the left side of bottom problem which appear to be dueto more than simple inattention; labored but finally correct working out of problem in middle rightside of page. The test was taken with no time limit.Perceptual deficits, particularly left-sided inattention phenomena anddeficits in comprehending degraded stimuli or unusual presentations, are notuncommon (Kartsounis, 2010; McCarthy and Warrington, 1990). Thevisuospatial perceptual deficits that trouble many patients with right-lateralized damage affect different cognitive activities. Arithmetic failuresare most likely to appear in written calculations that require spatialorganization of the problems’ elements (Denburg and Tranel, 2011; see Fig.3.16). Visuospatial and other perceptual deficits show up in these patients’difficulty in copying designs, making constructions, and matching ordiscriminating patterns or faces (e.g., Tranel, Vianna, et al., 2009). Patientswith right hemisphere damage may have particular problems with spatialorientation and visuospatial memory such that they get lost, even in familiarsurroundings, and can be slow to learn their way around a new area. Theirconstructional disabilities may reflect both their spatial disorientation anddefective capacity for perceptual or conceptual organization (e.g., Tranel,Rudrauf, et al., 2008).The painful efforts of a right hemisphere stroke patient to arrange plain and diagonallycolored blocks according to a pictured pattern (Fig. 3.17a [a-e]) illustrate the kind ofsolutions available to a person in whom only the left hemisphere is fully intact. This glib 51-year-old retired salesman constructed several simple 2 × 2 block design patterns correctly byverbalizing the relations. “The red one (block) on the right goes above the white one; there’sanother red one to the left of the white one.” This method worked so long as therelationships of each block to the others in the pattern remained obvious. When thediagonality of a design obscured the relative placement of the blocks, he could neitherperceive how each block fit into the design nor guide himself with verbal cues. He continuedto use verbal cues, but at this level of complexity his verbalizations only served to confusehim further. He attempted to reproduce diagonally oriented designs by lining up the blocksdiagonally (e.g., “to the side,” “in back of”) without regard for the squared (2 × 2 or 3 × 3)format. He could not orient any one block to more than another single block at a time, andhe was unable to maintain a center of focus to the design he was constructing.On the same task, a 31-year-old former logger who had had left hemisphere surgeryinvolving the visual association area had no difficulty until he came to a 3 × 3 design (Fig.3.17b [f, g]). On this design he reproduced the overall pattern immediately but oriented onecorner block erroneously. He attempted to reorient it but then turned a correctly orientedblock into a 180° error. Though dissatisfied with this solution, he was unable to localize hiserror or define the simple angulation pattern.FIGURE 3.17a Attempts of a 51-year-old right hemisphere stroke patient to copy pictured designswith colored blocks. (a) First stage in the construction of a 2 × 2 chevron design. (b) Second stage: thepatient does not see the 2 × 2 format and gives up after four minutes.(c) First stage in construction ofa 3 × 3 pinwheel pattern (see below). (d) Second stage. (e) Third and final stage. This patient later toldhis wife that he believed the examiner was preparing him for “architect school.”FIGURE 3.17b Attempts of a 31-year-old patient with a surgical lesion of the left visual associationarea to copy the 3 x 3 pinwheel design with colored blocks. (f) Initial solution: 180° rotation of upperleft corner block. (g) “Corrected”solution: upper left corner block rotated to correct position and lowerright corner rotated 180° to an incorrect position.Although hemispheric asymmetry and lateralization of function arerelative and hypothesis-driven concepts, they have considerable clinicalvalue. Loss of tissue in a hemisphere tends to impair its particular processingcapacity. When a lesion has rendered lateralized areas essentiallynonfunctional, the intact hemisphere may process activities normallyhandled by the damaged hemisphere (W.H. Moore, 1984; Papanicolaou etal., 1988; Fig. 3.17a is an example of this phenomenon). Moreover, adiminished contribution from one hemisphere may be accompanied byaugmented or exaggerated activity of the other when released from theinhibitory or competitive constraints of normal hemispheric interactions.This phenomenon appears in the verbosity and overwriting of many righthemisphere damaged patients (Lezak and Newman, 1979; see Fig. 3.18). Inan analogous manner, patients with left hemisphere disease tend toreproduce the essential configuration but leave out details (see Fig. 3.19).The functional difference between hemispheres also appears in the tendencyfor patients with left-sided damage to be more accurate in remembering largevisually presented forms than the small details making up those forms; butwhen the lesion is on the right, recall of the details is more accurate thanrecall of the whole composed figure (Delis, Robertson, and Efron, 1986).Learning and memory are also strongly influenced by the generalprinciples of hemispheric specialization. Thus, relationships between theside of the lesion and the type of learning impairment are fairly consistent.For example, damage to the left hippocampal system produces an amnesicsyndrome that affects verbal material (e.g., spoken words, written material)but spares nonverbal material and, in contrast, damage to the righthippocampal system affects nonverbal material (e.g., complex visual andauditory patterns) but spares verbal material (e.g., B. Milner, 1968, 1972;R.G. Morris, Abrahams, and Polkey, 1995; Pillon, Bazin, Deweer, et al.,1999). After damage to the left hippocampus, a patient may lose the abilityto learn new names but remain capable of learning new faces and spatialarrangements (Tranel, 1991). With surgical resection of the left temporallobe, verbal memory— episodic (both short-term and learning), semantic,and remote—may be impaired (Frisk and Milner, 1990; Loring and Meador,2003b; Seidenberg, Hermann, et al., 1998) . Nonverbal (auditory, tactile,visual) memory disturbances, including disturbances such as impaired routelearning (Barrash, H. Damasio, et al., 2000), tend to accompany righttemporal lobe damage.FIGURE 3.18 Overwriting (hypergraphia) by a 48-year-old college-educated retired policeinvestigator suffering right temporal lobe atrophy secondary to a local right temporal lobe stroke.FIGURE 3.19 Simplification and distortions of four Bender-Gestalt designs by a 45-year-old assemblyline worker with a high school education. These drawing were made four years after he had incurredleft frontal damage in an industrial accident.Emotional alterations with lateralized lesions. The complementarymodes of processing that distinguish the cognitive activities of the twohemispheres extend to emotional behavior as well (D.M. Bear, 1983;Heilman, Blonder, et al., 2011; Gainotti, 2003). The configurationalprocessing of the right hemisphere lends itself most readily to the handlingof the multidimensional and alogical stimuli that convey emotional tone,such as facial expressions (Adolphs, Damasio, and Tranel, 2000; Borod,Haywood, and Koff, 1997; Ivry and Lebby, 1998) and voice quality(Adolphs, Damasio, and Tranel, 2002; Joanette, Goulet, and Hannequin,1990; Ley and Bryden, 1982). The analytic, bit-by-bit style of the lefthemisphere is better suited for processing the words of emotion. A facedistorted by fear and the exclamation “I’m scared to death”both conveyaffective meaning, but the meaning of each is normally processed well byonly one hemisphere, the right and left, respectively. Thus, patients withright hemisphere damage tend to experience relative difficulty in discerningthe emotional features of stimuli, whether visual or auditory, withcorresponding diminution in their emotional responsivity (Adolphs andTranel, 2004; Borod, Cicero, et al., 1998; Van Lancker and Sidtis, 1992).Impairments in emotional recognition may affect all or only somemodalities. Defects in recognizing different kinds of emotionalcommunication (e.g., facial expressions, gestures, prosody [the stresses andintonations that infuse speech with emotional meaning]) can occurindependently of one another (Adolphs and Tranel, 2004; Bowers et al.,1993). Left hemisphere lesions typically do not impair processing of facialemotional expressions and emotional prosody. Selfrecognition and self-awareness are associated with predominantly right hemisphere involvement(J.P. Keenan et al., 2000), although both hemispheres contribute toprocessing of self-relevant information (Northoff et al., 2006). Prefrontalstructures, most notably the medial prefrontal cortices regardless of side,play an important role in self-referential processing (Gusnard et al., 2001;Macrae et al., 2004) and in the capacity for introspection (S.M. Fleming etal., 2010).Differences in emotional expression can also distinguish patients withlateralized lesions (Borod, 1993; Etcoff, 1986). Right hemisphere-lesionedpatients’ range and intensity of affective intonation are frequentlyinappropriate (Borod, Koff, Lorch, and Nicholas, 1985; Joanette Goulet, andHannequin, 1990; B.E. Shapiro and Danly, 1985). Some investigators havefound that the facial behavior of right hemisphere damaged patients is lessexpressive than that of persons with left hemisphere damage or of normalcomparison subjects (e.g., Brozgold et al., 1998; Montreys and Borod, 1998;see Pizzamiglio and Mammucari, 1989, for a different conclusion). Thepreponderance of research on normal subjects indicates heightenedexpressiveness on the left side of the face (Borod, Haywood, and Koff,1997). These findings are generally interpreted as indicating righthemisphere superiority for affective expression.There is disagreement as to whether right hemisphere impaired patientsexperience emotions any less than other people. Some studies have foundreduced autonomic responses to emotional stimuli in right hemispheredamaged patients (Gainotti, Caltagirone, and Zoccolotti, 1993; Tranel and H.Damasio, 1994). However, given that such patients typically have impairedappreciation of emotionally charged stimuli, it is not entirely clear what isthe fundamental deficit here; it could be that emotional experiences in suchpatients would not be impaired if the patients could apprehend emotionalstimuli properly in the first place. Many clinicians have observed strong—but not necessarily appropriate—emotional reactions in patients with right-lateralized damage, leading to the hypothesis that their experience ofemotional communications and their capacity to transmit the nuances andsubtleties of their own feeling states differ from normal affective processing,leaving them out of joint with those around them (Lezak, 1994; Morrow,Vrtunski, et al., 1981; E.D. Ross and Rush, 1981).Other hemispheric differences have been reported for some of theemotional and personality changes that occur with lateralized brain injury(Adolphs andTranel, 2004; Gainotti, 2003; Sackeim, Greenburg, et al.,1982). Some patients with left hemisphere lesions exhibit a catastrophicreaction (extreme and disruptive transient emotional disturbance) which mayappear as acute—often disorganizing—anxiety, agitation, or tearfulness,disrupting the activity that provoked it. Typically, it occurs when patients areconfronted with their limitations, as when taking a test (R.G. Robinson andStarkstein, 2002), and they tend to regain their composure as soon as thesource of frustration is removed. Although it has been associated withaphasia (Jorge and Robinson, 2002), one study found that more nonaphasicthan aphasic patients exhibited this problem (Starkstein, Federoff, et al.,1993). Anxiety is also a common feature of left hemisphere involvement(Gainotti, 1972; Galin, 1974). It may show up as undue cautiousness (Jones-Gotman and Milner, 1977) or oversensitivity to impairments and a tendencyto exaggerate disabilities (Keppel and Crowe, 2000). Yet, despite tendenciesto be overly sensitive to their disabilities, many patients with left hemispherelesions ultimately compensate for them well enough to make a satisfactoryadaptation to their disabilities and living situations (Tellier et al., 1990).Ben-Yishay and Diller (2011) point out that—regardless of injury site—acatastrophic reaction can occur when patients feel acutely threatened byfailure or by a situation which, due to their disability, is perceived asdangerous. It may be that diminished awareness of their limitations is whatprotects many patients with right hemisphere lesions from this acuteemotional disturbance and why some authorities have associated it with lefthemisphere damage.In contrast, patients whose injuries involve the right hemisphere are lesslikely to be dissatisfied with themselves or their performances than are thosewith left hemisphere lesions (Keppel and Crowe, 2000) and less likely to beaware of their mistakes (McGlynn and Schacter, 1989). They are more likelyto be apathetic (Andersson et al., 1999), to be risk takers (L. Miller andMilner, 1985), and to have poorer social functioning (Brozgold et al., 1998).At least in the acute or early stages of their condition, they may display anindifference reaction, denying or making light of the extent of theirdisabilities (Darby and Walsh, 2005; Gainotti, 1972). In extreme cases,patients are unaware of such seemingly obvious defects as crippling left-sided paralysis or slurred and poorly articulated speech. In the long run thesepatients tend to have difficulty making satisfactory psychosocial adaptations(Cummings and Mega, 2003), with those whose lesions are anterior beingmost maladjusted in all areas of psychosocial functioning (Tellier et al.,1990).The Wada technique for identifying lateralization of function beforesurgical treatment of epilepsy provided an experimental model of thesechanges (Jones-Gotman, 1987; Wada and Rasmussen, 1960). The emotionalreactions of patients undergoing Wada testing tend to differ depending onwhich side of the brain is inactivated (Ahern et al., 1994; R.J. Davidson andHenriques, 2000; G.P. Lee, Loring, et al., 1990). Patients whose lefthemisphere has been inactivated are tearful and report feelings of depressionmore often than their right hemisphere counterparts who are more apt tolaugh and appear euphoric. Since the emotional alterations seen with somestroke patients and in lateralized pharmacological inactivation have beeninterpreted as representing the tendencies of the disinhibited intacthemisphere, some investigators have hypothesized that each hemisphere isspecialized for positive (the left) or negative (the right) emotions (e.g., Rootet al., 2006). These positive/negative tendencies have suggestedrelationships between the lateralized affective phenomena and psychiatricdisorders (e.g., Flor-Henry, 1986; G.P. Lee, Loring, et al., 1990).Gainotti, Caltagirone, and Zoccolotti (1993) hypothesized that theemotional processing tendencies of the two hemispheres are complementary:“The right hemisphere seems to be involved preferentially in functions ofemotional arousal, intimately linked to the generation of the autonomiccomponents of the emotional response, whereas the left hemisphere seems toplay a more important role in functions of intentional control of theemotional expressive apparatus”(pp. 86–87). They hypothesized further thatlanguage development tends to override the left hemisphere’s capacity foremotional immediacy while, in contrast, the more spontaneous andpronounced affective display characteristic of right hemisphere emotionalitygives that hemisphere the appearance of superior emotional endowment.These ideas have held up reasonably well with the test of time. For example,a study using EEG and self-report of normal participants’ emotionalresponses to film clips, supported this model of lateralized emotionprocessing (Hagemann et al., 2005). Thus, these basic characterizations ofthe emotional “styles”of the two cerebral hemispheres are mostly accurate intheir essence.Although studies of depression in stroke patients seem to have producedinconsistent findings (A.J. Carson et al., 2000; Koenigs and Grafman, 2009a;Singh et al., 2000) , when these patients are also studied long after the acuteevent, a pattern appears in which depression tends to evolve—and worsen—in right hemisphere stroke patients and diminishes in those with left-sidedlesions. Shimoda and Robinson (1999) found that hospitalized strokepatients with the greatest incidence of depression were those with leftanterior hemisphere lesions. At short-term follow-up (3–6 months),proximity of the lesion to the frontal pole and lesion volume correlated withdepression in both right and left hemisphere stroke patients. At long-termfollow-up (1–2 years), depression was significantly associated with righthemisphere lesion volume and proximity of the lesion to the occipital pole.Moreover, the incidence of depression in patients with left hemispheredisease dropped over the course of the first year (R.G. Robinson and Manes,2000). Impaired social functioning was most evident in those patients whoremained depressed. Women are more likely to be depressed in the acutestages of a left hemisphere stroke than men (Paradiso and Robinson, 1998).The differences in presentation of depression in right and left hemispheredamaged patients are consistent with what is known about hemisphereprocessing differences. With left hemisphere damaged patients, depressionseems to reflect awareness of deficit: the more severe the deficit and acutethe patient’s capacity for awareness, the more likely it is that the patient willbe depressed. Yet over time, many patients with residual right-sidedmotor/sensory defects and speech/language deficits make a kind of peacewith their disabilities.In right hemisphere damaged patients, awareness of deficit is often mutedor even absent (K. Carpenter et al., 1995; Meador, Loring, Feinberg, et al.,2000; Pedersen et al., 1996). These patients tend to be spared the agony ofsevere depression, particularly early in the course of their condition. Whenthe lesion is on the right, the emotional disturbance does not seem to arisefrom awareness of defects so much as from the secondary effects of thepatient’s diminished self-awareness and social insensitivity. Patients withright hemisphere lesions who do not appreciate the nature or extent of theirdisability tend to set unrealistic goals for themselves or to maintain previousgoals without taking their new limitations into account. As a result, theyfrequently fail to realize their expectations. Their diminished capacity forself-awareness and for emotional spontaneity and sensitivity can make themunpleasant to live with and thus more likely to be rejected by family andfriends than are patients with left hemisphere lesions. Depression in patientswith right-sided damage may take longer to developthan it does in patientswith left hemisphere involvement since it is less likely to be an emotionalresponse to immediately perceived disabilities than a more slowly evolvingreaction to the development of these secondary consequences. Whendepression does develop in patients with right-sided disease, however, it canbe more chronic, more debilitating, and more resistant to intervention.These descriptions of differences in the emotional behavior of right andleft hemisphere damaged patients reflect observed tendencies that are notnecessary consequences of unilateral brain disease (Gainotti, 2003). Nor arethe emotional reactions reported here associated only with unilateral brainlesions. Mourning reactions naturally follow the experience of personal lossof a capacity whether it be due to brain injury, a lesion lower down in thenervous system, or amputation of a body part. Inappropriate euphoria andself-satisfaction may accompany lesions involving brain areas other than theright hemisphere (McGlynn and Schacter, 1989). Depression in patients withbilateral lesions may be predicated on small anatomical differences as theincidence of depression is higher with lesions in the dorsolateral prefrontalarea, in contrast to a lower incidence of depression with bilateralventromedial prefrontal lesions, and relative to lesions outside the frontallobes (Koenigs, Huey, et al., 2008; also see Koenigs and Grafman, 2009b).Further, psychological stressors associated with stroke (Fang and Cheng,2009) and/or premorbid personality (R.G. Robinson and Starkstein, 2005)can affect the quality of patients’ responses to their disabilities. Thus, theclinician should never be tempted to predict the site of damage from thepatient’s mood alone.While knowledge of the asymmetrical, lateralized pattern of cerebralorganization adds to the understanding of many cognitive and emotionalphenomena associated with unilateral lesions or demonstrated incommissurotomized patients or laboratory studies of normal subjects, it isimportant not to generalize these findings to the behavior of persons whosebrains are intact. In normal persons, the functioning of the two hemispheresis tightly yoked by the corpus callosum so that neither can be engagedwithout significant activation of the other (Lezak, 1982b). As much ascognitive styles and personal tastes and habits might seem to reflect theprocessing characteristics of one or the other hemisphere, these qualitiesappear to be integral to both hemispheres (Arndt and Berger, 1978; Sperry etal., 1979). We cannot emphasize enough that, “In the normal intact state, theconscious activity is typically a unified and coherent bilateral process thatspans both hemispheres through the commissures“ (Sperry, 1976).Advantages of hemisphere interaction. Simple tasks in which theprocessing capacity of one hemisphere is sufficient, may be performed fasterand more accurately than if both hemispheres are engaged (Belger andBanich, 1998; Ringo et al., 1994). However, the reality is that very few tasksrely exclusively on one cerebral hemisphere. Interaction between thehemispheres also has important mutually enhancing effects. Complex mentaltasks such as reading, arithmetic, and word and object learning areperformed best when both hemispheres can be actively engaged (Belger andBanich, 1998; Huettner et al., 1989; Weissman and Banich, 2000). Othermutually enhancing effects of bilateral processing show up in the superiormemorizing and retrieval of both verbal and configurational material whensimultaneously processed (encoded) by the verbal and configurationalsystems (B. Milner, 1978; Moscovitch, 1979: A. Rey, 1959; see also pp.849–850 on use of double encoded stimuli for testing memory effort); inenhanced cognitive efficiency of normal subjects when hemisphericactivation is bilateral rather than unilateral (J.-M. Berger, Perret, andZimmermann, 1987: Tamietto et al., 2007); and in better performances ofvisual tasks by commissurotomized patients when both hemispheresparticipate than when vision is restricted to either hemisphere (Sergent,1991a, b; E. Zaidel, 1979). Moreover, functional imaging studies in healthyparticipants exhibit bilateral activation, no matter the task, making itabundantly clear that both hemispheres contribute to almost every task withany degree of cognitive complexity (Cabeza and Nyberg, 2000). {g}The cerebral processing of music illuminates the differences in what eachhemisphere contributes, the complexities of hemispheric interactions, andhow experience can alter hemispheric roles (Peretz and Zatorre, 2003) . Theleft hemisphere tends to predominate in the processing of sequential anddiscrete tonal components of music (M.I. Botez and Botez, 1996; Breitling etal., 1987; Gaede et al., 1978). Inability to use both hands to play a musicalinstrument (bimanual instrument apraxia) has been reported with lefthemisphere lesions that spare motor functions (Benton, 1977a). The righthemisphere predominates in melody recognition and in melodic singing(H.W. Gordon and Bogen, 1974; Samson and Zatorre, 1988; Yamadori et al.,1977). Its involvement with chord analysis is generally greatest formusically untrained persons (Gaede et al., 1978). Training can alter thesehemispheric biases so that, for musicians, the left hemisphere predominatesfor melody recognition (Bever and Chiarello, 1974; Messerli, Pegna, andSordet, 1995), tone discrimination (Mazziota et al., 1982; Shanon, 1980),and musical judgments (Shanon, 1980, 1984). Moreover, intact, untrainedpersons tend not to show lateralized effects for tone discrimination ormusical judgments (Shanon, 1980, 1984).Taken altogether, these findings suggest that while cerebral processing ofdifferent components of music is lateralized with each hemispherepredominating in certain aspects, both hemispheres are needed for musicalappreciation and performance (Bauer and McDonald, 2003) . This point wasemphatically demonstrated in a longitudinal study which found that when itcomes to “real music,” as opposed to laboratory experiments, musicalcompetence is highly individualized and appears to rely on widelydistributed neuronal networks in both hemispheres (Altenmuller, 2003).Given these many studies, it is interesting to note that strong, reliablerelationships between focal brain lesions and impaired music processinghave been surprisingly elusive (E. Johnsen, Tranel, et al., 2009).The bilateral integration of cerebral function is also highlighted bycreative artists, who typically have intact brains. Making music, for example,is nearly always a two-handed activity. For instruments such as guitars andthe entire violin family, the right hand performs those aspects of the musicthat are mediated predominantly by the right hemisphere, such as expressionand tonality, while the left hand interprets the linear sequence of notes bestdeciphered by the left hemisphere. Right-handed artists do their drawing,painting, sculpting, and modeling with the right hand, with perhaps anoccasional assist from the left. Thus, by its very nature, the artist’sperformance involves the smoothly integrated activity of both hemispheres.The contributions of each hemisphere are indistinguishable and inseparableas are the artist’s two eyes and two ears guiding the two hands or thebisymmetrical speech and singing structures that together render the artisticproduction.Longitudinal OrganizationAlthough no two human brains are exactly alike in their structure, allnormally developed brains tend to share the same major distinguishingfeatures (see Fig. 3.20). The external surface of each half of the cerebralcortex is wrinkled into a complex of ridges or convolutions called gyri(sing., gyrus), which are separated by two deep fissures and many shallowclefts, the sulci (sing., sulcus). The two prominent fissures and certain of themajor sulci divide each hemisphere into four lobes: occipital, parietal,temporal,and frontal. For detailed delineations of cortical features andlandmarks, the reader is referred to basic neuroanatomy textbooks, such asBlumenfeld (2010) or Montemurro and Bruni (2009); Mendoza and Foundas(2008) relate detailed anatomic features to brain function.The central sulcus divides the cerebral hemispheres into anterior andposterior regions. Immediately in front of the central sulcus lies theprecentral gyrus which contains much of the primary motor or motorprojection area. The entire area forward of the central sulcus is known as theprecentral or prerolandic area, while the entire area forward of the precentralgyrus is known as the prefrontal cortex. The bulk of the primary somestheticor somatosensory projection area is located in the gyrus just behind thecentral sulcus, called the postcentral gyrus. The area behind the centralsulcus is also known as the retrorolandic or postcentral area.Certain functional systems have primary or significant representation onthe cerebral cortex with sufficient regularity that the identified lobes of thebrain provide a useful anatomical frame of reference for functionallocalization, much as a continent provides a geographical frame of referencefor a country. Nonetheless, the lobes were originally defined solely on thebasis of their gross, macroscopic appearance, and thus many functionallydefinable areas overlap two or even three lobes. For example, the boundarybetween the parietal and occipital lobes is arbitrarily defined to be in thevicinity of a minor, fairly irregular sulcus, the parieto-occipital sulcus, lyingin an overlap zone for visual, auditory, and somatosensory functions. Theparieto-occipital sulcus is usually better seen on the mesial aspect of thehemisphere, where it more clearly provides a demarcation between theparietal and occipital lobes.FIGURE 3.20 The lobe-based divisions of the human brain and their functional anatomy. (FromStrange, 1992.)A two-dimensional—longitudinal, in this case—organization of corticalfunctions lends itself to a schema that offers a framework forconceptualizing cortical organization. In general, the posterior regions of thebrain, behind the central sulcus, are dedicated to input systems: sensation andperception. The primary sensory cortices for vision, audition, andsomatosensory perception are located in the posterior sectors of the brain inoccipital, temporal, and parietal regions, respectively. Thus, in general,apprehension of sensory data from the world outside is mediated byposteriorly situated brain structures. Note that the “world outside”is actuallytwo distinct domains: (1) The world that is outside the body and brain; and(2) the world that is outside the brain but inside the body. The latter, thesoma, includes the smooth muscle, the viscera, and other bodily structuresinnervated by the central nervous system.The anterior brain regions, in front of the central sulcus, generallyfunction as output systems, specialized for the execution of behavior. Thusthe primary motor cortices are located immediately anterior to the rolandicsulcus. The motor area for speech, known as Broca’s area, is located in theleft frontal operculum (Latin: lid-like structure). The right hemispherecounterpart of Broca’s area, in the right frontal operculum, is important formaintenance of prosody. Perhaps most important, a variety of higher-orderexecutive functions, such as judgment, decision making, and the capacity toconstruct and implement various plans of action are associated withstructures in the anterior frontal lobes. Overall, this longitudinal frameworkcan be helpful in conceptualizing specialization of brain functions.FUNCTIONAL ORGANIZATION OF THE POSTERIOR CORTEXThree primary sensory areas—for vision, hearing, and touch—are located inthe posterior cortex. The occipital lobes at the most posterior portion of thecerebral hemisphere constitute the site of the primary visual cortex (see Fig.3.20, p. 69). The postcentral gyrus, at the most forward part of the parietallobe, contains the primary sensory (somatosensory) projection area. Theprimary auditory cortex is located on the uppermost fold of the temporallobe close to where it joins the parietal lobe. Kinesthetic and vestibularfunctions are mediated by areas low on the parietal lobe near the occipitaland temporal lobe boundary regions. Sensory information undergoesextensive associative elaboration through reciprocal connections with othercortical and subcortical areas. Although the primary centers of the majorfunctions served by the posterior cerebral regions are relatively distant fromone another, secondary association areas gradually fade into tertiary overlap,or heteromodal, zones in which auditory, visual, and body-sensingcomponents commingle.As a general rule, the character of the defects arising from lesions of theassociation areas of the posterior cortex varies according to the extent towhich the lesion involves each of the sense modalities. Any disorder with avisual component, for example, may implicate some occipital lobeinvolvement. If a patient with visual agnosia also has difficulty estimatingclose distances or feels confused in familiar surroundings, then parietal lobeareas serving spatially related functions may also be affected. Knowledge ofthe sites of the primary sensory centers and of the behavioral correlates oflesions to these sites and to the intermediate association areas enables theclinician to infer the approximate location of a lesion from the patient’sbehavioral symptoms (see E. Goldberg, 1989, 1990, for a detailedelaboration of this functional schema). However, the clinician must alwayskeep in mind that, in different brains, different cognitive functions may usethe same or closely related circuits, and that similar functions may beorganized by different circuits (Fuster, 2003).The Occipital Lobes and Their DisordersThe visual pathway travels from the retina through the lateral geniculatenucleus of the thalamus to the primary visual cortex. A lesion anywhere inthe path between the lateral geniculate nucleus and primary visual cortex canproduce a homonymous hemianopia (see p. 58). Lesions of the primaryvisual cortex result in discrete blind spots in the corresponding parts of thevisual fields, but typically do not alter the comprehension of visual stimuli orthe ability to make a proper response to what is seen.Blindness and associated problemsThe nature of the blindness that accompanies total loss of function of theprimary visual cortex varies with the extent of involvement of subcortical orassociated cortical areas. Some visual discrimination may take place at thethalamic level, but the cortex is generally thought to be necessary for theconscious awareness of visual phenomena (Celesia and Brigell, 2005; Kochand Crick, 2000; Weiskrantz, 1986). When damage is restricted to theprimary visual cortex bilaterally (a fairly rare condition), the patient appearsto have lost the capacity to distinguish forms or patterns while remainingresponsive to light and dark, a condition called cortical blindness (Bartonand Caplan, 2001; Luria, 1966). Patients may exhibit blindsight, a form ofvisually responsive behavior without experiencing vision (Danckert andRossetti, 2005; Stoerig and Cowey, 2007; Weiskrantz, 1996) . Thisphenomenon suggests that limited information in the blind visual field mayproject through alternate pathways to visual association areas.Total blindness due to brain damage appears to require large bilateraloccipital cortex lesions (Barton and Caplan, 2001). In some patients,blindness due to cerebral damage may result from destruction of thalamicareas as well as the visual cortex or the pathways leading to it. In denial ofblindness due to brain damage, patients lack appreciation that they are blindand attempt to behave as if sighted, giving elaborate explanations andrationalizations for difficulties in getting around,handling objects, and othermanifestly visually dependent behaviors (Celesia and Brigell, 2005;Feinberg, 2003). This denial of blindness, sometimes called Anton’ssyndrome, may occur with several different lesion patterns, but typically thelesions are bilateral and involve the occipital lobe (Goldenberg, Mullbacher,and Nowak, 1995; McGlynn and Schacter, 1989; Prigatano and Wolf, 2010).Such denial may be associated with disruption of corticothalamicconnections and breakdown of sensory feedback loops; there are manytheories about the etiology of this and other related conditions (Adair andBarrett, 2011).Visual agnosia and related disordersLesions involving the visual association areas give rise to several types ofvisual agnosia and other related disturbances of visual recognition and visualperception (Benson, 1989; A.R. Damasio, Tranel, and Rizzo, 2000; E.Goldberg, 1990). Such lesions are strategically situated so that basic visionis spared: the primary visual cortex is mostly or wholly intact, and thepatient is not blind. The common sites of damage associated with visualagnosia include the ventral sector of the visual association cortices in thelower part of Brodmann areas 18/19 and extending into the occipitotemporaltransition zone in Brodmann area 37, and include the fusiform gyrus (seeFig. 3.21). Damage to the upper sector of the visual association cortices, thedorsal part of Brodmann areas 18/19 and transitioning into theoccipitoparietal region in Brodmann areas 7 and 39, produces visuallyrelated disturbances in spatial orientation and movement perception.Visual agnosia refers to a variety of relatively rare visual disturbances inwhich visual recognition is defective in persons who can see and who arenormally knowledgeable about information coming through other perceptualchannels (A.R. Damasio, Tranel, and H. Damasio, 1989; Farah, 1999;Lissauer, [1888] 1988). Most visual agnosias are associated with bilaterallesions to the occipital, occipitotemporal, or occipitoparietal regions (Tranel,Feinstein, and Manzel, 2008).FIGURE 3.21 Brodmann’s cytoarchitectural map of the human brain, depicting different areas(marked by symbols and numbers) defined on the basis of small differences in cortical cell structureand organization. This figure shows lateral left hemisphere (upper) and mesial right hemisphere(lower) views. The Brodmann areas are comparable on the left and right sides of the brain, althoughspecific areas can differ notably in size and configuration. (From Heilman and Valenstein, 2011).Lissauer (1890) divided visual agnosia into two basic forms, apperceptiveand associative. Associative agnosia refers to a failure of recognition due todefective retrieval of knowledge pertinent to a given stimulus. The problemis due to faulty sensory-specific memory: the patient is unable to recognize astimulus (i.e., to know its meaning) despite being able to perceive thestimulus normally (e.g., to see shape, color, texture). Patients withassociative visual agnosia can perceive the whole of a visual stimulus, suchas a familiar object, but cannot recognize it although they may be able toidentify it by touch, sound, or smell (A.R. Damasio, Tranel, and H. Damasio,1989). Apperceptive agnosia refers to defective integration of otherwisenormally perceived components of a stimulus. This problem is more a failureof perception: these patients fail to recognize a stimulus because they cannotintegrate the perceptual elements of the stimulus, even though individualelements are perceived normally (M. Grossman, Galetta, and D’Esposito,1997; see Humphreys, 1999, for case examples). They may indicateawareness of discrete parts of a printed word or a phrase, or recognizeelements of an object without organizing the discrete percepts into aperceptual whole. Drawings by these patients are fragmented: bits and piecesare recognizable but not joined. They cannot recognize an object presentedin unconventional views, such as identifying a teapot usually seen from theside but now viewed from the top (Davidoff and Warrington, 1999; for teststimuli see Warrington, 1984; also see p. 44).The terms associative and apperceptive agnosia have remained usefuleven if the two conditions have some overlap. Clinically, it is usuallypossible to classify an agnosic patient as having primarily a disturbance ofmemory (associative agnosia) or primarily a disturbance of perception(apperceptive agnosia) (Riddoch and Humphreys, 2003). This classificationhas important implications for the management and rehabilitation of thesepatients (M.S. Burns, 2004; Groh-Bordin and Kerkhoff, 2010). It also mapsonto different sites of neural dysfunction. For example, associative visualagnosia is strongly associated with bilateral damage to higher orderassociation cortices in the ventral and mesial occipitotemporal regions,whereas apperceptive visual agnosia is associated with unilateral or bilateraldamage to earlier, more primary visual cortices.To diagnose agnosia, it is also critical to establish that the patient’s defectis not one of naming. Naming and recognition are two different capacities,and they are separable both cognitively and neurally. Although recognitionof an entity under normal circumstances is frequently indicated by naming,there is a basic difference between knowing and retrieving the meaning of aconcept (its functions, features, characteristics, relationships to otherconcepts), and knowing and retrieving the name of that concept (what it iscalled). It is important to maintain the distinction between recognition,which can be indicated by responses signifying that the patient understandsthe meaning of a particular stimulus, and naming, which may not—and neednot—accompany accurate recognition. The examiner can distinguish visualobject agnosia from a naming impairment by asking the patient who cannotname the object to give any identifying information, such as how it is used(see also Kartsounis, 2010). Moreover, the discovery of deficits for specificcategories (e.g., animals vs. plants; living things vs. nonliving things) hasmade apparent the highly detailed and discrete organization of that part ofthe cortex essential for semantic processing (Mahon and Caramazza, 2009;Warrington and Shallice, 1984; see visual object agnosia, below).Simultaneous agnosia, or simultanagnosia, is a component of Balint’s syndrome. Simultanagnosia(also known as visual disorientation) appears as an inability to perceive more than one object or pointin space at a time (Coslett and Lie, 2008; A.R. Damasio, Tranel, and Rizzo, 2000; Rafal, 1997a). Thisextreme perceptual limitation impairs these patients’ ability to move about: they get lost easily; evenreaching for something in their field of vision becomes difficult (L.C. Robertson and Rafal, 2000). Inaddition to simultanagnosia, fullblown Balint’s syndrome includes defects in volitional eyemovements (ocular apraxia, also known as psychic gaze paralysis) and impaired visually guidedreaching (optic ataxia). These abnormalities in control of eye movements result in difficulty in shiftingvisual attention from one point in the visual field to another (Pierrot-Deseilligny, 2011; Striemer et al.,2007; Tranel and Damasio, 2000). This problem has also been characterized as reduced access to“spatial representations that normally guide attention from one object to another in a clutteredfield”(L.R. Robertson and Rafal, 2000).Left hemisphere lesions have been associated with a variety of visualagnosias. Color agnosia is loss of the ability to retrieve color knowledge thatis not due to faulty perception or impaired naming. Patients with coloragnosia cannot remember the characteristic colors of various entities, recallentities that appear in certain colors, choose the correct color for an entity,and retrieve basic knowledge about color (e.g., know that mixing red andyellow will make orange). As color agnosia is rare, only a fewwell-studiedcases have been reported (see Tranel, 2003, for review). Theneuroanatomical correlates of color agnosia include the occipitotemporalregion, either unilaterally on the left or bilaterally. It is not entirely clear howthis pattern differs from central achromatopsia (acquired color blindness;e.g., see Tranel, 2003), although color agnosia is probably associated withlesions that are somewhat anterior to those responsible for centralachromatopsia. Functional imaging studies have shown activations in the leftinferior temporal region, bilateral fusiform gyrus, and right lingual gyrusduring a condition in which subjects were asked to retrieve previouslyacquired color knowledge (Chao and Martin, 1999; A. Martin, Haxby, et al.,1995). A. Martin and colleagues noted that these regions are not activated bycolor perception per se, and thus functional imaging supports the sameconclusion hinted at by lesion studies: that the neural substrates for colorperception and color knowledge are at least partially separable.Inability to comprehend pantomimes (pantomime agnosia), even whenthe ability to copy them remains intact, has been reported with lesionsconfined to the occipital lobes (Goodale, 2000; Rothi, Mack, and Heilman,1986). Another disorder of visual perception associated mainly with lesionsto the left inferior occipital cortex and its subcortical connections is purealexia, a reading problem that stems from defects of visual recognition,organization, and scanning rather than from defective comprehension ofwritten material. The latter problem usually occurs only with parietaldamage or in aphasia (Coslett, 2011; Kohler and Moscovitch, 1997). Purealexia is frequently accompanied by defects in color processing, especiallycolor anomia (impaired color naming) (Benson, 1989; A.R. Damasio and H.Damasio, 1983). One form of acalculia (literally, “no counting”), a disorderthat Grewel (1952) considered a primary type of impaired arithmetic abilityin which the calculation process itself is affected, may result from visualdisturbances of symbol perception associated with left occipital cortexlesions (Denburg and Tranel, 2011).Some visual agnosias are particularly associated with unilateral damage(see Chaves and Caplan, 2001). Associative visual agnosia usually occurswith lesions of the left occipitotemporal region (De Renzi, 2000). Visualobject agnosia can develop for specific categories of stimuli at a basicsemantic level which accounts for its predominance with left posteriorlesions (Capitani et al., 2009). Because this condition usually affects thedifferent stimulus categories selectively (Farah and McClelland 1991; Fordeand Humphreys 1999; Warrington and Shallice, 1984), it has been termedcategory specific semantic impairment (see Mahon and Caramazza, 2009).Patients with this condition experience major defects in the recognition ofcategories of living things, especially animals, with relative or evencomplete sparing of categories of artifactual entities (e.g., tools and utensils).Less commonly, the profile is reversed, and the patient cannot recognizetools/utensils but performs normally for animals (Tranel, H. Damasio, andDamasio, 1997; Warrington and McCarthy 1994). Lesions in the right mesialoccipital/ventral temporal region, and in the left mesial occipital region, havebeen associated with defective recognition of animals; for lesions in the leftoccipital-temporal-parietal junction the association appears to be withdefective recognition of tools/utensils (Tranel, H. Damasio, and Damasio,1997).Other visuoperceptual anomalies that can occur with occipital lesionsinclude achromatopsia (loss of color vision in one or both visual half-fields,or in a quadrant of vision), astereopsis (loss of stereoscopic vision),metamorphopsias (visual distortions), monocular polyopsias (double, triple,or more vision in one eye), optic allesthesia (misplacement of percepts inspace), and palinopsia (perseverated visual percept) (Barton and Caplan,2001; Morland and Kennard, 2002; Zihl, 1989). These are very rareconditions but of theoretical interest as they may provide clues to corticalorganization and function. Lesions associated with these conditions tend toinvolve the parietal cortex as well as the occipital cortex.ProsopagnosiaProsopagnosia (face agnosia), the inability to recognize familiar faces, is themost frequently identified and well-studied of the visual agnosias (A.R.Damasio, Tranel, and H. Damasio, 1990). Undoubtedly this owes in largemeasure to the fact that faces are such an important and intriguing class ofvisual stimuli. Millions of faces are visually similar, yet many people learnto recognize thousands of distinct faces. Moreover, faces are recognizableunder many different conditions, such as from obscure angles (e.g., frombehind, from the side), adorned with various artifacts (e.g., hat, hockeyhelmet), and after aging has radically altered the physiognomy. Faces alsoconvey important social and emotional information, providing clues aboutthe affective state of a person or about potential courses of social behavior(e.g., approach or avoidance: Darwin, 1872/1955; Adolphs, Tranel, andDamasio, 1998). The remarkable cross-cultural and cross-speciesconsistencies in face processing provide further proof of the fundamentalimportance of this class of stimuli (cf. Ekman, 1973; Fridlund, 1994).Patients with prosopagnosia typically can no longer recognize the facesof previously known individuals and are also unable to learn new faces—hence, the impairment covers both the retrograde and anterograde aspects ofmemory. These patients are unable to recognize the faces of familymembers, close friends, and—in the most severe cases—even their own face(e.g., in photographs or in a mirror). The impairment is modality-specific inthat it is confined to vision; thus, for example, a prosopagnosic patient canreadily identify familiar persons from hearing their voices. Even withinvision, the disorder is highly specific, and may not affect recognition fromgait or other movement cues.The classic neural correlate of prosopagnosia is bilateral occipitotemporaldamage in the cortex and underlying white matter of the ventral occipitalassociation regions and the transition zone between occipital lobe andtemporal lobe (A.R. Damasio, H. Damasio, and Rizzo, 1982; A.R. Damasio,Tranel, and H. Damasio, 1990) . However, prosopagnosia has occasionallybeen reported with lesions restricted to the right hemisphere (De Renzi,Perani, Carlesimo, et al., 1994; Landis, Cummings, Christen, et al., 1986;Vuilleumier, 2001). Characteristic hemisphere processing differences showup in face recognition performances of patients with unilateral occipital lobelesions (A.R. Damasio, Tranel, and Rizzo, 2000). Left occipital lesionedpatients using right hemisphere processing strategies form their impressionsquickly but may make semantic (i.e., naming) errors. With right occipitallesions, recognition proceeds slowly and laboriously in a piecemeal manner,but may ultimately be successful.Oliver Sacks richly described the extraordinary condition ofprosopagnosia in his book The Man who Mistook His Wife for a Hat (1987).His patient suffered visual agnosia on a broader scale, with inability torecognize faces as just one of many recognition deficits. In patients withprosopagnosia the problem with faces is usually the most striking, but therecognition defect is often not confined to faces. Careful investigation mayuncover impaired recognition of other visual entities at the normal level ofspecificity. The key factors that make other categories vulnerable todefective recognition are whether stimuli are relatively numerous andvisually similar, and whether the demands of the situation call for specificidentification. Thus, for example, prosopagnosic patients may not be able toidentify a unique car or a unique house, even if they are able to recognizesuch entitiessummarizes the lesion mapping of cognitive abilities showing whereabnormally low WAIS-III Index Scores are most often associated with focal lesionsFIGURE17.2The Peabody Individual Achievement TestFIGURE17.3Histograms illustrating the distribution of scores for each measure in the ADC UDSNeuropsychological Test BatteryObservational Methods, Rating Scales, and InventoriesFIGURE18.1Partial items from the Montreal Cognitive AssessmentFIGURE18.2Galveston Orientation and Amnesia Test (GOAT) record formTests of Personal Adjustment and Emotional FunctioningFIGURE19.1Mean MMPI profile for patients with diagnosed brain diseaseFIGURE19.2MMPI-2 profile in a patient with medically unexplained “spells” and significantpsychosocial stressorsFIGURE19.3Illustration of the ventromedial prefrontal regionAPPENDIX A: Neuroimaging PrimerFIGUREA1With computerized tomography (CT) and magnetic resonance imaging (MRI), gross brainanatomy can be readily visualized. (See color Figure A1)FIGUREA2This scan, taken several months after a severe traumatic brain injury, shows how an oldright frontal contusion appears on the different imaging sequencesFIGUREA3These horizontal scan images are from a patient with a severe TBIFIGUREA4The postmortem coronal section in the center of this figure shows the normal symmetry ofthe brain and the typically white appearance of normal white matter, and gray matter (Seecolor Figure A4)FIGUREA5Diffusion tensor imagining (DTI) tractography is depicted in these images of the brain (Seecolor Figure A5)FIGUREA6DTI tractography of a patient who sustained a severe TBI showing loss of certain tracts inthe frontal and isthmus region (See color Figure A6)FIGUREA7This figure shows how structural 3-D MRI may be integrated with 3-D DTI tractography.(See color Figure A7)FIGUREA8The MRI image on the left is at approximately the same level as the positron emissioncomputed tomogram or PET scan on the right of a 58-year-old patient (See color FigureA8)FIGUREA9In plotting functional MRI (fMRI) activation, the regions of statistically significantactivation are mapped onto a universal brain model. (See color Figure A9)List of TablesBasic ConceptsTABLE 2.1 Most Commonly Defined Aphasic SyndromesThe Behavioral Geography of the BrainTABLE 3.1 Functional dichotomies of left and right hemispheric dominanceThe Rationale of Deficit MeasurementTABLE 4.1 North American Adult Reading Test (NAART): Word ListThe Neuropsychological Examination: ProceduresTABLE 5.1 Classification of Ability LevelsThe Neuropsychological Examination: InterpretationTABLE 6.1 Standard Score Equivalents for 21 Percentile Scores Ranging from 1 to 99TABLE 6.2 Behavior Changes that are Possible Indicators of a Pathological Brain ProcessThe Neuropsychological Examination: InterpretationTABLE 7.1 Diagnostic Criteria for Mild TBI by the American Congress of Rehabilitation MedicineTABLE 7.2 Selected Signs and Symptoms of a ConcussionTABLE 7.3 Estimates of Injury Severity Based on Posttraumatic Amnesia (PTA) DurationTABLE 7.4 Test Completion CodesTABLE 7.5 Exclusion Criteria for Diagnosis of Alzheimer’s DiseaseTABLE 7.6 Uniform Data Set of the National Alzheimer’s Coordination Center NeuropsychologicalTest BatteryTABLE 7.7 Memory in Alzheimer’s DiseaseTABLE 7.8 A Comparison of Neuropsychological Features of AD, FTLD, LBD, PDD, HD, PSP,and VaDNeuropathology for NeuropsychologistsTABLE 8.1 Some Lateral Preference Inventories and Their Item CharacteristicsOrientation and AttentionTABLE 9.1 Temporal Orientation Test Scores for Control and Brain Damaged PatientsTABLE 9.2 Sentence Repetition: Form 1TABLE 9.3 Sentence Repetition (MAE): Demographic Adjustments for Raw ScoresTABLE 9.4 Example of Consonant Trigrams FormatTABLE 9.5 Symbol Digit Modalities Test Norms for Ages 18 to 74perceptionTABLE10.1The Bells Test: Omissions by Age and EducationTABLE10.2Judgment of Line Orientation: Score CorrectionsTABLE Facial Recognition Score Corrections10.3TABLE10.4The Face-Hand TestTABLE10.5Skin-Writing Test Errors Made by Four Adult GroupsMemory I: TestsTABLE11.1Telephone Test Scores for Two Age GroupsTABLE11.2Benson Bedside Memory TestTABLE11.3Rey Auditory-Verbal Learning Test Word ListsTABLE11.4Word Lists for Testing AVLT Recognition, Lists A-BTABLE11.5Multiple-Choice and Cued-Recall Items for Forms 1–4 of SRTTABLE11.6Norms for the Most Used SR Scores for Age Groups with 30 or More SubjectsTABLE11.7WMS-III Logical Memory Recognition Scores as a Function of Age or LM II ScoresTABLE11.8Expected Scores for Immediate and Delayed Recall Trials of the Babcock Story RecallTestTABLE11.9Percentiles for Adult Accuracy Scores on Memory Trials of the Complex Figure Test(Rey-O)TABLE11.10Medical College of Georgia Complex Figure (MCGCF) Data for Two Older AgeGroupsTABLE11.11BVRT Norms for Administration A: Adults Expected Number Correct ScoresVerbal Functions and Language SkillsTABLE13.1The Most Frequent Alternative Responses to Boston Naming Test ItemsTABLE13.2Normal Boston Naming Test Score Gain with Phonemic CueingTABLE13.3The Token TestTABLE13.4A Summary of Scores Obtained by the Four Experimental Groups on The Token TestTABLE13.5Adjusted Scores and Grading Scheme for the “Short Version” of the Token TestTABLE13.6The National Adult Reading TestConstruction and Motor PerformanceTABLE14.1Scoring System for the Rey Complex FigureTABLE14.2Scoring System for the Taylor Complex FigureTABLE Modified Taylor Figure14.3TABLE14.4Scoring Systems for the MCG Complex FiguresTABLE14.5Scoring System of Qualitative ErrorsTABLE14.6Complex Figure Organizational Quality ScoringTABLE14.7Scoring System for Bicycle DrawingsTABLE14.8Bicycle Drawing Means and Standard Deviations for 141 Blue Collar WorkersTABLE14.9Scoring System for House DrawingTABLE14.10WAIS-IV Block Design Score Changes with AgeTABLE14.11Activities for Examining Practic FunctionsConcept Formation and ReasoningTABLE15.1Matrix Reasoning and Vocabulary are Age-corrected Scaled ScoresTABLE15.2First Series of Uncued Arithmetic Word ProblemsTABLE15.3Benton’s Battery of Arithmetic TestsExecutive FunctionsTABLE16.1Items Used in the Tinkertoy TestTABLE16.2Tinkertoy Test: Scoring for ComplexityTABLE16.3Comparisons Between Groups on np and Complexity ScoresTABLE16.4Verbal Associative Frequencies for the 14 Easiest LettersTABLE16.5Controlled Oral Word Association Test: Adjustment Formula for Males (M) andFemales (F)TABLE16.6Controlled Oral Word Association Test: Summary TableNeuropsychological Assessment BatteriesTABLE17.1Rapid Semantic Retrieval Mean Scores for 1-min TrialTABLE17.2CDEs: Traumatic Brain Injury Outcome MeasuresTABLE17.3Repeatable Battery for the Assessment of Neuropsychological Status Test MeansObservational Methods, Rating Scales, and InventoriesTABLE18.1Dementia ScoreTABLE18.2Glasgow Coma ScaleTABLE18.3Severity Classification Criteria for the Glasgow Coma Scale (GCS)TABLE18.4Frequency of “Bad” and “Good” Outcomes Associated with the Glasgow Coma ScaleTABLE18.5The Eight Levels of Cognitive Functioning of the “Rancho Scale”TABLE18.6Disability Rating ScaleTABLE18.7Item Clusters and Factors from Part 1 of the Katz Adjustment ScaleTABLE18.8Mayo-Portland Adaptability Inventory (MPAI) Items by SubscalesTABLE18.9Satisfaction With Life Scale (SWLS)Tests of Personal Adjustment and Emotional FunctioningTABLE19.1MMPI-2 RC Scales and corresponding Clinical Scales from MMPI-2TABLE19.2Sickness Impact Profile (SIP) Categories and Composite ScalesTABLE19.3Major Response Variables Appearing in Every Rorschach Scoring SystemTesting for Effort, Response Bias, and MalingeringTABLE20.1Malingering Criteria ChecklistTABLEgenerically; e.g., cars as cars and houses as houses. Thesefindings demonstrate that the core defect in prosopagnosia is the inability todisambiguate individual visual stimuli. In fact, cases have been reported inwhich the most troubling problem for the patient was in classes of visualstimuli other than human faces—for example, a farmer who lost his abilityto recognize his individual dairy cows, and a bird-watcher who becameunable to tell apart various subtypes of birds (Assal et al., 1984; B. Bornsteinet al., 1969).Another interesting dissociation is that most prosopagnosics canrecognize facial expressions of emotion (e.g., happy, angry), and can makeaccurate determinations of gender and age based on face information(Humphreys et al., 1993; Tranel, Damasio, and H. Damasio, 1988). Withregard to emotional expressions, the reverse dissociation can occur; forexample, bilateral damage to the amygdala produces an impairment inrecognizing facial expressions such as fear and surprise, but spares theability to recognize facial identity (Adolphs, Tranel, and Damasio, 1995).An especially intriguing finding is “covert”or “non-conscious”facerecognition in prosopagnosic patients. Despite a profound inability torecognize familiar faces consciously, prosopagnosic patients often haveaccurate, above-chance discrimination of familiar faces when tested withcovert or implicit measures. For example, when prosopagnosics werepresented with either correct or incorrect face-name pairs, the patientsproduced larger amplitude skin conductance responses (SCRs) to the correctpairs (Bauer, 1984; Bauer and Verfaellie, 1988). Rizzo and coworkers (1987)reported that prosopagnosic patients produced different patterns of eyemovement scanpaths for familiar faces, compared to unfamiliar ones. DeHaan and his colleagues (1987a,b) used a reaction time paradigm in whichprosopagnosic patients had to decide whether two photographs were of thesame or different individuals. They found that reaction time wassystematically faster for familiar faces compared to unfamiliar ones. In otherstudies, SCRs were recorded while prosopagnosic patients viewed well-known sets of faces randomly mixed with new faces (Tranel and Damasio,1985; Tranel, Damasio, and H. Damasio, 1988). The patients producedsignificantly larger SCRs to familiar faces compared to unfamiliar ones.Covert face recognition has also been reported in developmental (congenital)prosopagnosia (R.D. Jones and Tranel, 2001).Oliver Sacks (2010) estimated that up to 10% of normal persons haveweak face recognition, often occurring on a familial basis. In this it is similarto established distributions of other biologically related cognitive skills.While patients with prosopagnosia can often recognize familiar personsupon seeing their distinctive gait, patients with lesions in more dorsaloccipitoparietal regions, who typically have intact recognition of faceidentity, often have defective motion perception and impaired recognition ofmovement. These findings make evident the separable and distinctivefunctions of the “dorsal”and “ventral”visual systems (see below).Two visuoperceptual systemsA basic anatomic dimension that differentiates visual functions has to dowith a dorsal (top side of the cerebrum)- ventral (bottom) distinction (seeFig. 3.22). Within this dorsal-ventral distinction are two well-establishedfunctional pathways in the visual system (Goodale, 2000; Mesulam, 2000b;Ungerleider and Mishkin, 1982). One runs dorsally from the occipital to theparietal lobe. This occipital-parietal pathway is involved with spatialanalysis and spatial orientation. It is specialized for visual “where”types ofinformation, and hence is known as the dorsal “where”pathway. Theoccipital-temporal pathway, which takes a ventral route from the occipitallobe to the temporal lobe, conveys information about shapes and patterns, Itsspecialization is visual “what”types of information, and hence it is known asthe ventral “what”pathway. This basic distinction between the “what”and“where”visual pathways provides a useful context for understanding theclassic visual syndromes, such as prosopagnosia (what), achromatopsia(what), and Balint’s syndrome (where).FIGURE 3.22 Lateral view of the left hemisphere, showing the ventral “what”and dorsal“where”visual pathways in the occipital-temporal and occipital-parietal regions, respectively. Thepathways are roughly homologous in left and right hemispheres. Figure courtesy of:http://en.wikipedia.org/wiki/File:Ventral-dorsal_streams.svg.The Posterior Association Cortices and Their DisordersAssociation areas in the parieto-temporo-occipital region are situated just infront of the visual association areas and behind the primary sensory strip (seeFig. 3.20, p. 69). These higher order association cortices include significantparts of the parietal and occipital lobes and some temporal association areas.Functionally, higher order association cortices (secondary, tertiary) are thesite of cortical integration for all behavior involving vision, touch, bodyawareness and spatial orientation, verbal comprehension, localization inspace, abstract and complex cognitive functions of mathematical reasoning,and the formulation of logical propositions that have their conceptual rootsin basic visuospatial experiences such as “inside,” “bigger,” “and,” or“instead of.” As it is within these areas that intermodal sensory integrationtakes place, this region has been deemed “an association area of associationareas”(Geschwind, 1965), “heteromodal association cortex”(Mesulam,2000b), and “multimodal sensory convergence areas”(Heilman, 2002).A variety of apraxias (inability to perform previously learned purposefulmovements) and agnosias have been associated with parieto-temporo-occipital lesions. Most of them have to do with verbal or with nonverbalstimuli but not with both, and thus are asymmetrically localized. A fewoccur with lesions in either hemisphere. Constructional disorders are amongthe most common disabilities associated with lesions to the posteriorassociation cortices in either hemisphere (Benton and Tranel, 1993; F.W.Black and Bernard, 1984; De Renzi, 1997b), reflecting the involvement ofboth hemispheres in the multifaceted demands of such tasks (see Chapter14). They are impairments of the “capacity to draw or construct two- orthree-dimensional figures or shapes from one- and two-dimensionalunits”(Strub and Black, 2000) and seem to be closely associated withperceptual defects (Sohlberg and Mateer, 2001) . Constructional disorderstake different forms depending on the hemispheric side of the lesion (Laeng,2006).Left-sided lesions are apt to disrupt the programming or ordering ofmovements necessary for constructional activity (Darby and Walsh, 2005;Hecaen and Albert, 1978) . Defects in design copies drawn by patients withleft hemisphere lesions appear as simplification and difficulty in makinghttp://http//en.wikipedia.org/wiki/File:Ventral-dorsal_streams.svgangles. Visuospatial defects associated with impaired understanding ofspatial relationships or defective spatial imagery tend to underlie righthemisphere constructional disorders (Pillon, 1979) . Diagonality in a designor construction can be particularly disorienting to patients with righthemisphere lesions (B. Milner, 1971; Warrington, James, and Kinsbourne,1966). The drawings of patients with right-sided involvement suffer from atendency to a counterclockwise tilt (rotation), fragmented percepts,irrelevant overelaborativeness, and inattention to the left half of the page orthe left half of elements on the page (Diller and Weinberg, 1965; Ducarneand Pillon, 1974; Warrington, James, and Kinsbourne, 1966; see Fig. 3.23aand b for freehand drawings produced by left and right hemisphere damagedpatients showing typical hemispheric defects). Assembling puzzles in two-and three-dimensional space may be affected by both right and20.2Confidence Intervals (CIs) for Random Responses for Several Halstead-Reitan BatteryTestsTABLE20.3D.E. Hartman (2002) Criteria for Evaluating Stand-alone Malingering and SymptomValidity Tests …TABLE20.4Percentile Norms for Time (in Seconds)Taken to Count Ungrouped DotsTABLE20.5Percentile Norms for Time (in Seconds) Taken to Count Grouped DotsTABLE20.6Autobiographical Memory InterviewI Theory and Practice ofNeuropsychological Assessment1 The Practice of NeuropsychologicalAssessmentImaging is not enough.Mortimer Mishkin, 1988Clinical neuropsychology is an applied science concerned with thebehavioral expression of brain dysfunction. It owes its primordial—andoften fanciful—concepts to those who, since earliest historic times, puzzledabout what made people do what they did and how. These were thephilosophers, physicians, scientists, artists, tinkerers, and dreamers whofirst called attention to what seemed to be linkages between body—notnecessarily brain—structures and people’s common responses to commonsituations as well as their behavioral anomalies (Castro-Caldas andGrafman, 2000; Finger, 1994, 2000; C.G. Gross, 1998; L.H. Marshall andMagoun, 1998). In the 19th century the idea of controlled observationsbecame generally accepted, thus providing the conceptual tool with whichthe first generation of neuroscientists laid out the basic schema of brain-behavior relationships that hold today (Benton, 2000; Boring, 1950; M.Critchley and Critchley, 1998; Hécaen et Lanteri-Laura, 1977; N.J. Wadeand Brozek, 2001).In the first half of the 20th century, war-damaged brains gave the chiefimpetus to the development of clinical neuropsychology. The need forscreening and diagnosis of brain injured and behaviorally disturbedservicemen during the first World War and for their rehabilitationafterwards created large-scale demands for neuropsychology programs(e.g., K. Goldstein, 1995 [1939]; Homskaya, 2001; see references in Luria,1973b; Poppelreuter, 1990 [1917]; W.R. Russell [see references inNewcombe, 1969]). The second World War and then the wars in east Asiaand the Mideast promoted the development of many talentedneuropsychologists and of increasingly sophisticated examination andtreatment techniques.While clinical neuropsychology can trace its lineage directly to theclinical neurosciences, psychology contributed the two other domains ofknowledge and skill that are integral to the scientific discipline and clinicalpractices of neuropsychology today. Educational psychologists, beginningwith Binet (with Simon, 1908) and Spearman (1904), initially developedtests to capture that elusive concept “intelligence.” Following thesepioneers, mental measurement specialists produced a multitude ofexamination techniques to screen recruits for the military and to assist ineducational evaluations. Some of these techniques—such as Raven’sProgressive Matrices, the Wechsler Intelligence Scales, and the Wide RangeAchievement Tests—have been incorporated into the neuropsychologicaltest canon (W. Barr, 2008; Boake, 2002).Society’s acceptance of educational testing led to a proliferation oflarge-scale, statistics-dependent testing programs that providedneuropsychology with an understanding of the nature and varieties ofmental abilities from a normative perspective. Educational testing has alsobeen the source of ever more reliable measurement techniques andstatistical tools for test standardization and the development of normativedata, analysis of research findings, and validation studies (Mayrhauser,1992; McFall and Townsend, 1998; Urbina, 2004). Clinical psychologistsand psychologists specializing in personality and social behavior researchborrowed from and further elaborated the principles and techniques ofeducational testing, giving neuropsychology this important assessmentdimension (Cripe, 1997; G.J. Meyer et al., 2001).Psychology’s other critical contribution to neuropsychologicalassessment comes primarily from experimental studies of cognitivefunctions in both humans and other animals. In its early development,human studies of cognition mainly dealt with normal subjects—predominantly college students who sometimes earned course credits fortheir cooperation. Animal studies and clinical reports of brain injuredpersons, especially soldiers with localized wounds and stroke patients,generated much of what was known about the alterations and limitations ofspecific cognitive functions when one part of the brain is missing orcompromised. In the latter half of the 20th century, many experimentalpsychologists became aware of the wealth of information about cognitivefunctions to be gained from studying brain injured persons, especially thosewith localized lesions (e.g., G. Cohen et al., 2000; Gazzaniga, 2009, passim;Tulving and Craik, 2000, passim).Similarly, neuroscientists discovered the usefulness of cognitiveconstructs and psychological techniques when studying brain-behaviorrelationships (Bilder, 2011; Fuster, 1995; Luria, 1966, 1973b). Now in the21st century, dynamic imaging techniques permit viewing functioning brainstructures, further refining understanding of the neural foundations ofbehavior (Friston, 2009) . Functional neuroimaging gives psychologicalconstructs the neurological bases supporting analysis and comprehension ofthe always unique and often anomalous multifaceted behavioralpresentations of brain injured patients.When doing assessments, clinical neuropsychologists typically address avariety of questions of both neurological and psychological import. Thediversity of problems and persons presents an unending challenge toexaminers who want to satisfy the purposes for which the examination wasundertaken and still evaluate patients at levels suited to their capacities andlimitations. In this complex and expanding field, few facts or principles canbe taken for granted, few techniques would not benefit from modifications,and few procedures will not be bent or broken as knowledge and experienceaccumulate. The practice of neuropsychology calls for flexibility, curiosity,inventiveness, and empathy even in the seemingly most routine situations(B. Caplan and Shechter, 1995; Lezak, 2002). Each neuropsychologicalevaluation holds the promise of new insights into the workings of the brainand the excitement of discovery.The rapid evolution of neuropsychological assessment in recent yearsreflects a growing sensitivity among clinicians generally to the practicalproblems of identification, assessment, care, and treatment of brainimpaired patients. Psychologists, psychiatrists, and counselors ask forneuropsychological assistance in identifying those candidates for theirservices who may have underlying neurological disorders. Neurologists andneurosurgeons request behavioral evaluations to aid in diagnosis and todocument the course of brain disorders or the effects of treatment.Rehabilitation specialists request neuropsychological assessments to assistin rehabilitation planning and management of a neurological condition(Malec, 2009) . A fruitful interaction is taking place betweenneuropsychology and gerontology that enhances the knowledge and clinicalapplications of each discipline with the worldwide increase in longevity andthe neurological problems that are associated with aging (see Chapter 8, pp.354–361).Child neuropsychology has developed hand in hand with advances in thestudy of mental retardation, neurodevelopmental disorders includinglearning disabilities, and children’s behavior problems. As this textconcerns neuropsychological issues relevant for adults, we refer theinterested reader to the current child neuropsychology literature (e.g.,Baron, 2004; Hunter and Donders, 2007; Semrud-Clikeman and TeeterEllison, 2009; Yeates, Ris, et al., 2010).Adults whose cognitive and behavioral problems stem fromdevelopmental disorders or childhood onset conditions may also needneuropsychologicalattention. These persons are more likely to be seen inclinics or by neuropsychologists specializing in the care of adults. However,the preponderance of the literature on their problems is in books and articlesdealing with developmental conditions such as attention deficithyperactivity disorder, spina bifida, or hydrocephalus arising from aperinatal incident, or with the residuals of premature birth or childhoodmeningitis, or the effects of cancer treatment in childhood.When this book first appeared, much of the emphasis in clinicalneuropsychology was on assessing behavioral change. In part this occurredbecause much of the need had been for assistance with diagnostic problems.Moreover, since many patients seen by neuropsychologists were consideredtoo limited in their capacity to benefit from behavioral training programsand counseling, these kinds of treatment did not seem to offer practicaloptions for their care. Yet, as one of the clinical sciences, neuropsychologyhas been evolving naturally: assessment tends to play a predominant rolewhile these sciences are relatively young; treatment techniques develop asdiagnostic categories and etiological relationships are defined and clarified,and the nature of the patients’ disorders become better understood. Today,treatment planning and evaluation have become not merely commonplacebut often necessary considerations for neuropsychologists performingassessments.EXAMINATION PURPOSESAny of six different purposes may prompt a neuropsychologicalexamination: diagnosis; patient care—including questions aboutmanagement and planning; treatment-1: identifying treatment needs,individualizing treatment programs, and keeping abreast of patients’changing treatment requirements; treatment-2: evaluating treatmentefficacy; research, both theoretical and applied; and now in the UnitedStates and to a lesser extent elsewhere, forensic questions are frequentlyreferred to neuropsychologists. Each purpose calls for some differences inassessment strategies. Yet many assessments serve two or more purposes,requiring the examiner to integrate the strategies in order to gain the neededinformation about the patient in the most focused and succinct mannerpossible.1. Diagnosis. Neuropsychological assessment can be useful fordiscriminating between psychiatric and neurological symptoms, identifyinga possible neurological disorder in a nonpsychiatric patient, helping todistinguish between different neurological conditions, and providingbehavioral data for localizing the site—or at least the hemisphere side—of alesion. However, the use of neuropsychological assessment as a diagnostictool has diminished while its contributions to patient care and treatment andto understanding behavioral phenomena and brain function have grown.This shift is due at least in part to the development of highly sensitive andreliable noninvasive neurodiagnostic techniques (pp. 864–870, AppendixA). Today, accurate diagnosis and lesion localization are often achieved bymeans of the neurological examination and laboratory data.Still, conditions remain in which even the most sensitive laboratoryanalyses may not be diagnostically enlightening, such as toxicencephalopathies (e.g., L.A. Morrow, 1998; Rohlman et al., 2008; B. Weiss,2010), Alzheimer’s disease and related dementing processes (e.g., Y.L.Chang et al., 2010; Derrer et al., 2001; Welsh-Bohmer et al., 2003), or someautoimmune disorders which present with psychiatric symptoms (E.K.Geary et al., 2010; Nowicka-Sauer et al., 2011; Ponsford Cameron et al.,2011). In these conditions the neuropsychological findings can bediagnostically crucial.Even when the site and extent of a brain lesion have been shown onimaging, the image will not identify the nature of residual behavioralstrengths and the accompanying deficits: for this, neuropsychologicalassessment is needed. It has been known for decades that despite generalsimilarities in the pattern of brain function sites, these patterns will differmore or less between people. These kinds of differences were demonstratedin three cases with localized frontal lesions that appeared quite similar onneuroimaging yet each had a distinctively different psychosocial outcome(Bigler, 2001a). Moreover, cognitive assessment can document mentalabilities that are inconsistent with anatomic findings, such as the 101-year-old nun whose test scores were high but whose autopsy showed “abundantneurofibrillary tangles and senile plaques, the classic lesions of Alzheimer’sdisease” (Snowdon, 1997) . Markowitsch and Calabrese (1996), too,discussed instances in which patients’ level of functioning exceededexpectations based on neuroimaging. In another example, adults who hadshunts to treat childhood hydrocephalus may exhibit very abnormalneuroradiological findings yet perform adequately and sometimes atsuperior levels on cognitive tasks (Feuillet et al., 2007; Lindquist et al.,2011).Thus, neuropsychological techniques will continue to be an essentialpart of the neurodiagnostic apparatus.Although limited in its applications as a primary diagnostic tool,neuropsychological assessment can aid in prodromal or early detection andprediction of dementing disorders or outcome (Seidman et al., 2010). Theearliest detection of cognitive impairments during the prodrome as well asconversion to Alzheimer’s disease often comes in neuropsychologicalassessments (R.M. Chapman et al., 2011; Duara et al., 2011; Ewers et al.,2010). For identified carriers of the Huntington’s disease gene, the earliestimpairments can show up as cognitive deficits identified inneuropsychological assessments, even before the onset of motorabnormalities (Peavy et al., 2010; Stout et al., 2011). Pharmacologicresearch may engage neuropsychological assessment to assist in predictingresponders and best psychopharmacological treatments in mood disorders(Gudayol-Ferre et al., 2010). In patients with intractable epilepsy,neuropsychological evaluations are critical for identifying candidates forsurgery as well as for implementing postsurgical programs (Baxendale andThompson, 2010; Jones-Gotman, Smith, et al., 2010).Screening is another aspect of diagnosis. Until quite recently, screeningwas a rather crudely conceived affair, typically dedicated to separating out“brain damaged” patients from among a diagnostically mixed populationsuch as might be found in long-term psychiatric care facilities. Littleattention was paid to either base rate issues or the prevalence of conditionsin which psychiatric and neurologic contributions were mixed andinteractive (e.g., Mapou, 1988; A. Smith, 1983; C.G. Watson and Plemel,1978; discussed this issue). Yet screening has a place in neuropsychologicalassessment when used in a more refined manner to identify persons mostlikely at risk for some specified condition or in need of further diagnosticstudy, and where brevity is required—whether because of the press ofpatients who may benefit from neuropsychological assessment (D.N. Allenet al., 1998) or because the patient’s condition may preclude a lengthyassessment (S. Walker, 1992) (also see Chapter 6, p. 175). In the last decadescreening tests have been developed for identifying neurocognitive andneurobehavioral changes in TBI (traumatic brain injury) patients (Donnellyet al., 2011).2. Patient care and planning. Whether or not diagnosis is an issue, manypatients are referred for detailed information about their cognitive status,behavioral alterations, and personality characteristics—often with questionsabout their adjustment to their disabilities—so that they and the peopleresponsible for their well-being may know how the neurological conditionhas affected their behavior. At the very least the neuropsychologist has aresponsibility to describe the patient as fully as necessary for intelligentunderstanding and care.Descriptive evaluations may be employed in many ways in the care andtreatmentof brain injured patients. Precise descriptive information aboutcognitive and emotional status is essential for careful management of manyneurological disorders. Rational planning usually depends on anunderstanding of patients’ capabilities and limitations, the kinds ofpsychological change they are undergoing, and the impact of these changeson their experiences of themselves and on their behavior.A 55-year-old right-handed management expert with a bachelor’s degree in economics washospitalized with a stroke involving the left frontoparietal cortex three months after takingover as chief executive of a foundering firm. He had been an effective troubleshooter whodevoted most of his waking hours to work. In this new post, his first as chief, hisresponsibilities called for abilities to analyze and integrate large amounts of information,including complex financial records and sales and manufacturing reports; creative thinking;good judgment; and rebuilding the employees’ faltering morale. Although acutely he haddisplayed right-sided weakness and diminished sensation involving both his arm and leg,motor and sensory functions rapidly returned to near normal levels and he was dischargedfrom the hospital after ten days. Within five months he was walking 3 1/2 miles daily, he wasusing his right hand for an estimated 75% of activities, and he felt fit and ready to return towork. In questioning the wisdom of this decision, his neurologist referred him for aneuropsychological examination.This bright man achieved test scores in the high average to superior ability ranges yet hisperformance was punctuated by lapses of judgment (e.g., when asked what he would do if hewas the first to see smoke and fire in a movie theater he said, “If you’re the first—if it’s not adangerous fire try to put it out by yourself. However, if it’s a large fire beyond your controlyou should immediately alert the audience by yelling and screaming and capturing theirattention.”). When directed to write what was wrong with a picture portraying two personssitting comfortably out in the rain, he listed seven different answers such as, “Right-hand sideof rain drops moves [sic] to right on right side of pict. [sic],” but completely overlooked thecentral problem. Impaired self-monitoring appeared in his rapid performance of a taskrequiring the subject to work quickly while keeping track of what has already been done(Figural Fluency Test)—he worked faster than most but left a trail of errors; in assigningnumbers to symbols from memory (Symbol Digit Modalities Test) without noting that he gavethe same number to two different symbols only inches apart; and in allowing two small errorsto remain on a page of arithmetic calculations done without a time limit. Not surprisingly, hehad word finding difficulties which showed up in his need for phonetic cueing to retrieve sixwords on the Boston Naming Test while not recalling two even with cueing. This problemalso appeared in discourse; for example, he stated that a dog and a lion were alike in being“both members of the animal factory, I mean animal life.” On self-report of his emotionalstatus (Beck Depression Inventory, Symptom Check List-90-R) he portrayed himself as havingno qualms, suffering no emotional or psychiatric symptoms.In interview the patient assured me [mdl] that he was ready to return to a job that herelished. As his work has been his life, he had no “extracurricular” interests or activities. Hedenied fatigue or that his temperament had changed, insisting he was fully capable ofresuming all of his managerial duties.It was concluded that the performance defects, though subtle, could be seriousimpediments at this occupational level. Moreover, lack of appreciation of these deficits plusthe great extent to which this man’s life—and sense of dignity and self-worth—were boundup in his work suggested that he would have difficulty in understanding and accepting hiscondition and adapting to it in a constructive manner. His potential for serious depressionseemed high.The patient was seen with his wife for a report of the examination findings withrecommendations, and to evaluate his emotional situation in the light of both his wife’sreports and her capacity to understand and support him. With her present, he could no longerdeny fatigue since it undermined both his efficiency and his good nature, as evident in herexamples of how his efficiency and disposition were better in the morning than later in theday. She welcomed learning about fatigue as his late-day untypical irritability and cognitivelapses had puzzled her. With his neurologist’s permission, he made practical plans to return towork—for half-days only, and with an “assistant” who would review his actions anddecisions. His need for this help became apparent to him after he was shown some of hisfailures in self-monitoring. At the same time he was given encouraging information regardinghis many well-preserved abilities.Judgmental errors were not pointed out: While he could comprehend the concreteevidence of self-monitoring errors, it would require more extensive counseling for a man withan impaired capacity for complex abstractions to grasp the complex and abstract issuesinvolved in evaluating judgments. Moreover, learning that his stroke had rendered himcareless and susceptible to fatigue was enough bad news for the patient to hear in one hour; tohave given more discouraging information than was practically needed at this time wouldhave been cruel and probably counterproductive.An interesting solution was worked out for the problem of how to get this self-acknowledged workaholic to accept a four-hour work day: If he went to work in the morning,his wife was sure he would soon begin stretching his time limit to five and six or more hours.He therefore agreed to go to work after his morning walk or a golf game and a midday restperiod so that, arriving at the office after 1 PM, he was much less likely to exceed his half-daywork limit.Ten months after the stroke the patient reported that he was on the job about 60 hours perweek and had been told he “was doing excellent work.” He described a mild naming problemand other minor confusions. He also acknowledged some feelings of depression in theevening and a sleep disturbance for which his neurologist began medication.In many cases the neuropsychological examination can answer questionsconcerning patients’ capacity for self-care, reliability in following atherapeutic regimen (Galski et al., 2000), not merely the ability to drive acar but to handle traffic emergencies (J.D. Dawson et al., 2010; MarcotteRosenthal et al., 2008; Michels et al., 2010) , or appreciation of money andof their financial situation (Cahn, Sullivan, et al., 1998; Marson et al.,2000). With all the data of a comprehensive neuropsychologicalexamination taken together—the patient’s history, background, and presentsituation; the qualitative observations; and the quantitative scores—theexaminer should have a realistic appreciation of how the patient reacts todeficits and can best compensate for them, and whether and how retrainingcould be profitably undertaken (A.-L. Christensen and Caetano, 1996;Diller, 2000; Sohlberg and Mateer, 2001).The relative sensitivity and precision of neuropsychologicalmeasurements make them well-suited for following the course of manyneurological diseases and neuropsychiatric conditions (M.F. Green et al.,2004; Heaton, Grant, Butters, et al., 1995; Wild and Kaye, 1998) .Neuropsychological assessment plays a key role in monitoring cognitiveand neurobehavioral status following a TBI (I.H. Robertson, 2008; E.A.Wilde, Whiteneck, et al., 2010). Data from successive neuropsychologicalexaminations repeated at regular intervals can provide reliable indicationsof whether the underlying neurological condition is changing, and if so,how rapidly and in what ways (e.g., Salmon, Heindel, and Lange, 1999) as,forinstance, monitoring cognitive decline in dementia patients (Josephs etal., 2011; Tierney et al., 2010), since deterioration on repeated testing canidentify a dementing process early in its course (J.C. Morris, McKeel,Storandt, et al., 1991; Paque and Warrington, 1995). Parenté and Anderson(1984) used repeated testing to ascertain whether brain injured candidatesfor rehabilitation could learn well enough to warrant cognitive retraining.Freides (1985) recommended repeated testing to evaluate performanceinconsistencies in patients complaining of attentional deficits. Repeatedtesting may also be used to measure the effects of surgical procedures,medical treatment, or retraining.A single, 27-year-old, highly skilled logger with no history of psychiatric disturbanceunderwent surgical removal of a right frontotemporal subdural hematoma resulting from a caraccident. Twenty months later his mother brought him, protesting but docile, to the hospital.This alert, oriented, but poorly groomed man complained of voices that came from his teeth,explaining that he received radio waves and could “communicate to their source.” He wasemotionally flat with sparse speech and frequent 20- to 30-sec response latencies thatoccasionally disrupted his train of thought. He denied depression and sleeping or eatingdisturbances. He also denied delusions or hallucinations, but during an interview pointed outIchabod Crane’s headless horseman while looking across the hospital lawn. As he becamecomfortable, he talked more freely and revealed that he was continually troubled bydelusional ideation. His mother complained that he was almost completely reclusive, withoutinitiative, and indifferent to his surroundings. He had some concern about being watched, andonce she had heard him muttering, “I would like my mind back.”Most of his neuropsychological test scores were below those he had obtained whenexamined six and a half months after the injury. His only scores above average were on twotests of well-learned verbal material: background information and reading vocabulary. Hereceived scores in the low average to borderline defective ranges on oral arithmetic,visuomotor tracking, and all visual reasoning and visuoconstructive—including drawing—tests. Although his verbal learning curve was considerably below average, immediate verbalspan and verbal retention were within the average range. Immediate recall of designs wasdefective.Shortly after he was hospitalized and had completed a scheduled 20-month examination,he was put on trifluoperazine (Stelazine), 15 mg h.s., continuing this treatment for a monthwhile remaining under observation. He was then reexamined. The patient was still poorlygroomed, alert, and oriented. His reaction times were well within normal limits. Speech andthinking were unremarkable. While not expressing strong emotions, he smiled, complained,and displayed irritation appropriately. He reported what hallucinating had been like andrelated the content of some of his hallucinations. He talked about doing physical activitieswhen he returned home but felt he was not yet ready to work.His test scores 21 months after the injury were mostly in the high average to superiorranges. Much of his gain came from faster response times which enabled him to get full creditrather than partial or no credit on timed items he had completed perfectly but slowly theprevious month. Although puzzle constructions (both geometric designs and objects) wereperformed at a high average level, his drawing continued to be of low average quality (butbetter than at 20 months). All verbal memory tests were performed at average to high averagelevels; his visual memory test response was without error, gaining him a superior rating. Hedid simple visuomotor tracking tasks without error and at an average rate of speed; his scoreon a complex visuomotor tracking task was at the 90 th percentile.In this case, repeated testing provided documentation of both thecognitive repercussions of his psychiatric disturbance and the effects ofpsychotropic medication on his cognitive functioning. This casedemonstrates the value of repeated testing, particularly when one or anotheraspect of the patient’s behavior appears to be in flux. Had testing been doneonly at the time of the second examination, a very distorted impression ofthe patient’s cognitive status would have been gained. Fortunately, since thepatient was in a research project, the first examination data were availableto cast doubt on the validity of the second set of tests, performed when hewas acutely psychotic, and therefore the third examination was given aswell.Brain impaired patients must have factual information about theirfunctioning to understand themselves and to set realistic goals, yet theirneed for this information is often overlooked. Most people who sustainbrain injury or disease experience changes in their selfawareness andemotional functioning; but because they are on the inside, so to speak, theymay have difficulty appreciating how their behavior has changed and whatabout them is still the same (Prigatano and Schacter, 1991, passim).Neurological impairment may diminish a patient’s capacity for empathy(De Sousa et al., 2010) , especially when damage occurs in prefrontalregions (Bramham et al., 2009). These misperceptions tend to heightenwhat mental confusion may already be present as a result of altered patternsof neural activity.Distrust of their experiences, particularly their memory and perceptions,is a problem shared by many brain damaged persons, probably as a result ofeven very slight disruptions and alterations of the exceedingly complexneural pathways that mediate cognitive and other behavioral functions. Thisself-distrust seems to reflect feelings of strangeness and confusionaccompanying previously familiar habits, thoughts, and sensations that arenow experienced differently, and from newly acquired tendencies to makeerrors (T.L. Bennett and Raymond, 1997; Lezak, 1978b; see also Skloot,2003, for a poet’s account of this experience). The selfdoubt of the braininjured person, often referred to as perplexity, is usually distinguishablefrom neurotic selfdoubts about life goals, values, principles, and so on, butit can be just as painful and emotionally crippling. Three years afterundergoing a left frontal craniotomy for a parasagittal meningioma, a 45-year-old primary school teacher described this problem most tellingly:Perplexity, the not knowing for sure if you’re right, is difficult to cope with. Before mysurgery I could repeat conversations verbatim. I knew what was said and who said it… . Sincemy surgery I don’t have that capability anymore. Not being able to remember for sure whatwas said makes me feel very insecure.Careful reporting and explanation of psychological findings can domuch to allay the patient’s anxieties and dispel confusion. The followingcase exemplifies both patients’ needs for information about theirpsychological status and how disruptive even mild experiences ofperplexity can be.An attractive, unmarried 24-year-old bank teller sustained a concussion in a car accidentwhile on a skiing trip in Europe. She appeared to have improved almost completely, with onlya little residual facial numbness. When she came home, she returned to her old job but wasunable to perform acceptably although she seemed capable of doing each part of it well. Shelost interest in outdoor sports although her coordination and strength were essentiallyunimpaired. She became socially withdrawn, moody, morose, and dependent. A psychiatristdiagnosed depression, and when her unhappiness was not diminished by counseling orantidepressant drugs, he administered electroshock treatment, which gave only temporaryrelief.While waiting to begin a second course of shock treatment, she was given aneuropsychological examination at the request of the insurer responsible for awardingmonetary compensation