Frontal Lobe Influences on Delusions: A Clinical Perspective

Transcription

1 VOL. 16, NO. 3, 1990 Frontal Lobe Influences on Delusions: A Clinical Perspective by D. Frank Benson and Donald T. Stuss Abstract The presence of delusions, a significant feature of many schizophrenic patients, implies a disturbance of reality testing. Through descriptions of a number of organic delusion syndromes featuring frontal damage, and a theory of prefrontal functions, a correlation of schizophrenic delusions and prefrontal malfunction is postulated. Of all of the findings used to characterize schizophrenia, delusions are among the most dramatic and generally best known. Although many other causes of delusions are recognized, for many physicians they represent true schizophrenia and their presence invariably raises this diagnostic possibility. Delusions readily fulfill the definition of psychosis as a loss of reality testing such that affected individuals cannot evaluate the accuracy of their perceptions or thought and make incorrect inferences about external reality (American Psychiatric Association 1987). Reality testing is a key human competency but has proved difficult to define. One characteristic is the ability to be self-critical; disturbed reality testing indicates disordered self-analysis. Clinically, disturbances in self-criticism/selfanalysis are most frequently correlated with frontal lobe damage. The role of the frontal lobes in the positive symptomatology of schizophrenia is discussed through review of pertinent clinical examples. Reduplicative Paramnesla her home has been called reduplicative paramnesia. First described by Pick (1903) in a demented patient, the disorder is infrequently reported. Paterson and Zangwill (1944) described two braininjured soldiers who could tell the name of the hospital in which they were recuperating but insisted that it was located in their respective home towns. Weinstein and his associates (Weinstein et al. 1952; Weinstein and Kahn 1955; Weinstein 1969) recorded a number of such cases. Reduplicative paramnesia has always been reported with coarse brain disease and in recent years has been correlated with frontal lobe injury (Benson et al. 1976; Ruff and \folpe 1981; Hakim et al. 1988). Casel. A 28-year-old man sustained a head injury in a one-vehicle traffic accident. He was unconscious for several days and had a stormy post-traumatic recovery that included frightening visual hallucinations. There were no basic neurologic deficits but mental status testing demonstrated a post-traumatic amnesia that cleared over a period of about six weeks. He became oriented to time and learned and recited the details of his accident. He consistently misplaced the hospital (which he correctly named) to a distant army base where he had been stationed a few years earlier. The mandatory reduplication of the hospital remained after he learned much information such as his doctors' names, current sports results and family activities and persisted despite many explanations of the true location of the hospital. Even after several A tendency for a brain-injured patient to identify and name the hospital correctly but demand that it is located at a site closer to his or Reprint requests should be sent to Dr. D.F. Benson, Dept. of Neurology, UCLA, 710 Westwood Plaza, Los Angeles, CA

2 404 SCHIZOPHRENIA BULLETIN weekend leaves at his own home he continued to relocate the hospital to the distant army base. The reduplicative paramnesia remained for almost six weeks after the clearing of the amnesia although the strengtn of the belief slowly decreased. Imaging studies revealed bilateral frontal intracerebral hematomas plus right frontal contusion. When seen at follow-up several months following discharge, there was no hint of reduplicative paramnesia. [Benson et al. 1976, p. 148] All reported cases of reduplicative paramnesia have evidence of brain damage. Some show right parietal damage, but all cases with demonstrated pathology have had frontal structural damage. Ruff and \blpe (1981) suggest that unilateral right frontal pathology may be sufficient but most show bifrontal damage. In addition to the striking reduplication of place, these individuals show altered emotional behavior including an indifferent, unconcerned attitude, a tendency toward apathy, and some degree of euphoria or inappropriate contentment with their current status. The full syndrome includes some impairment of memory function (improved), disturbance in topographical orientation (improving), decreased drive and foresight, plus disturbed awareness and selfcriticism, the key problem in reduplication. Reduplicative paramnesia follows damage or dysfunction involving several brain sites, one of which is frontal. Capgras Syndrome Declaring that a close relative, a spouse or child, is an imposter (reduplication of person), the Capgras syndrome, has been recognized for many years (Capgras and Reboul-Lachaux 1923). The patient with the Capgras syndrome is adamant that a person, almost always a close relative, is a substitute who closely resembles but is not the original individual. Case 2. A 44-year-old man sustained a serious head injury, including a large frontal subdural hematoma, when struck by a moving vehicle. There was a prolonged recovery from post-traumatic amnesia. At the time his memory function was beginning to dear, his wife came to the hospital to take him home for a weekend visit in a newly purchased automobile. From that date the patient was convinced that the lady who picked him up was not his wife but was a substitute who resembled his first wife, had the same name and had the same number of children, each of whom had the same names as his own children. He believed that the house he visited was either his own house or a similar house built on the same property. When evaluated some 5 years after the onset, he remained totally convinced that the lady who picked him up each weekend was not his true wife. He was satisfied with the situation, believed his wife had found this person to take her place and that there must be an important reason why his wife was no longer able to live with him. Despite constant arguments to the contrary, the delusion remained fixed. Localizing studies demonstrated bifrontal and right temporal hypodensities consistent with old brain injuries (figure 1), [Alexander et al. 1979, pp ] The Capgras syndrome has been reported with modest frequency, usually as an unusual psychiatric syndrome (Freedman et al. 1975; Lehmann 1975; Enoch and Trethowan 1979; Rudnick 1982). Most individuals with the Capgras syndrome have been called schizophrenic, with the diagnosis at least partially based on the firmly held delusion of reduplication (Enoch 1963; Ball and Kidson 1968; Merrin and Silberfarb 1976; Quinn 1981). Other evidence such as positive family history, Schneiderian firstrank symptoms (Schneider 1930), and other schizophrenic phenomenology is absent in most reported cases. Alexander et al. (1979) reviewed all cases of Capgras syndrome reported to that time and noted that more than half had evidence of some organic brain abnormality, and it has been suggested that organic brain defects, either structural or metabolic, may play a crucial role in the genesis of the syndrome (MacCallum 1973; Christodoulou 1977; Waziri 1978; Lewis 1987). In the Capgras syndrome, just as it was in reduplicative paramnesia, the patient demonstrates awareness of correct data (the name and appearance of the family member) but can neither accept nor act on these data. The delusions are firmly held, even in the face of absolute evidence of their falseness. The possibility that sufficient frontal malfunction to produce a disturbance in reality testing plays a role in the Capgras syndrome appears rational. Confabulation Confabulation is characterized by bizarre, incorrect responses given to routine questions. The disorder is most often associated with loss of memory (amnesia) and, in fact, the Korsakoff syndrome was once officially termed the amnesticconfabulatory syndrome (American Psychiatric Association 1952). Confabulations range from mild elaborations to wildly bizarre fabrications (Bonhoffer 1904; Berlyne 1972). Most

3 405 VOL 16, NO. 3, 1990 treated by surgery with no evidence of physical residua. He did not recover normal mental function, however, and had to be institutionalized. When examined about 5 years after the surgery, he was disoriented as to time and place and manifested an inability to learn new material, but he showed no other significant cognitive deficit. His affect was one of persistent euphoria, an inappropriate satisfaction with his limited status. Wild, bizarre confabulations would be presented spontaneously or in the midst of a conversation totally unrelated to the material in the confabulation. The occurrences described by the patient were wildly fantastic, usually featuring sadism and violence including mutilation or death of members of his family. Despite the violence of the presentations, they were stated with a detached, bemused, 'Isn't that a strange thing that happened?" attitude. X-ray computed tomography (CT) demonstrated marked ventricular enlargement, much greater in the frontal lobes than elsewhere (figure 2). Normalpressure hydrocephalus was diagnosed and a ventriculopentoneal shunt performed. The shunt decreased the size of the ventricles but did not alter the memory loss or confabulations. Case 4. From Alexander et aj. (1979), with permission. Copyright Edgell Communications, Inc, confabulatory replies are based on old memories (Talland 1965; Benson and Blumer 1982); they occur in a patient who cannot remember that he cannot remember (Barbizet 1963) and, when questioned, produces the best available information from his old store of memories. Different degrees of confabulation can be appreciated. Case 3. A 47-year-old man suffered a rupturea anterior communicating artery that was successfully A 53-year-old attorney who had become a severe alcoholic was admitted to the hospital in a cachectic state with severe peripheral neuropathy, marginal fiver functions, and alcoholic gastritis. Appropriate medical measures improved the cachexia, liver, and gastrointestinal function, and the peripheral neuropathy slowly improved. The patient was left, however, with a severe Korsakoffs amnesia. He was disoriented to time and place, and he was unable to remember the examiner's name or any other information for as little as 30 seconds. During this time, he readily offered information concerning the distant past Figure 1. Computed tomographic scan of case 2 demonstrating blfrontal and right temporal lucencles1

4 406 SCHIZOPHRENIA BULLETIN 1 From Stuss et al. (1978), with permission. Copyright Edgell Communications, Inc., 197a (his military experience, his experience in law school). When asked questions such as, "What did you do yesterday?", he presented wildly bizarre tales of traveling across the country, visiting with dignitaries, etc. Careful evaluation of his past revealed that these were true incidents that had occurred 15 to 20 years previously. Over a period of many months, he slowly became aware of problems with his own memory; as this progressed, there was a concomitant decrease in the freedom and quantity of con- fabulation. At discharge, he remained strongly amnesic but without confabulation. Confabulation has been discussed for many years (Bonhoffer 1904; Berlyne 1972), most often as a distinctive feature of the Korsakoff syndrome (Victor et al. 1971, 1989), but only in recent years have attempts been made to probe the mechanisms of the disorder. Mercer et al. (1977) evaluated patients who were confabulating and demonstrated that the degree of confabulation did not correlate with either the severity of the memory disturbance or the suggestibility of the individual. Instead, a close correlation was demonstrated between the degree of confabulation and the subject's ability to self-monitor and be self-corrective. This phenomenon can be noted in case 4; the amnesia improved only slightly, but confabulation disappeared. Conversely, the amnesia may recover even though confabulations persist (Stuss et al. 1978). Mercer et al. (1977) suggested that it was the inability to self-correct and an unawareness of how inappropriate the responses were that characterized confabulation; frontal malfunction was suggested. Several studies (Stuss et al. 1978; Kapur and Coughlan 1980) have reported patients who spontaneously produced fantastic, bizarre confabulations (e.g., case 3). These individuals had significant frontal lobe structural damage, and Kapur and Coughlan (1980) demonstrated that the quantity of confabulation decreased commensurate with improvement in the patient's performance on neuropsychological tests of frontal lobe function. Shapiro et al. (1981) verified the presence of confabulation in patients with frontal damage. Figure 2. Computed tomographic scan demonstrating bifrontal damage in case 41

5 VOL. 16, NO. 3, The key feature of confabulation appears to be an inability to monitor and correct erroneous responses, a disturbance of self-analysis/selfcontrol consistent with frontal deficiency. Some cases in the literature demonstrate actual frontal lobe damage in patients who confabulate; but even in those without evidence of structural damage, malfunction is probable. Organic Delusions Many different organic brain disorders are associated with delusions (Cummings 1985a, 1985b). Paranoid delusions, ideas of reference, and persecutory thoughts are most common, but morbid jealousy, delusions of infestation (parasitophobia), agoraphobia, or delusional belief of an unpleasant body odor or significant disfigurement are not uncommon. While all have been reported in patients who are called schizophrenic, many other disorders such as posttrauma, neoplasms, encephalitis, Addison's disease, drug intoxications, nutritional disturbances, and general paresis have produced significant delusions. Case 5. A 67-year-old man was hospitalized with a complaint of crawling sensations that he insisted were worms that were constantly moving under his skin. He was unswayed by medical examinations and other evaluations that failed to demonstrate abnormality. A full examination revealed only minimal neurologic disturbances and his Mini-Mental scale score was above the cutoff point for dementia; memory testing, language testing and cognitive testing all showed that he performed adequately. Routine laboratory studies including electrocardiogram and electroencephalogram were normal. A CT [scan] of the brain, however, revealed bilateral periventricular lucencies, and an MRI [magnetic resonance imaging scan] demonstrated high-signal periventricular lesions bilaterally, most prominent in the frontal white matter bilaterally. Attempts at management with a variety of antidepressants and psychotropic medications were unsuccessful. [Flynn et al. 1989, pp ] In case 5, leukoaraiosis (Hachinski et al. 1987), with particular involvement of the frontal periventricular region, was considered the source of the delusions. Miller et al. (1986) and Cummings (1985b) have reported late-life onset of delusions based on cerebrovascular disease. Silent vascular disease was present in 20 percent of cases with a late-life paraphrenia (Miller and Lesser 1988). Cummings et al. (1987) demonstrated onset of delusions in almost 40 percent of patients with a multiinfarct dementia syndrome. Despite the demonstration of delusions based on cerebrovascular disease, it is difficult to pinpoint an anatomical locus because the vascular disturbance is widespread in most such patients. Figure 3 shows typical bilateral lucencies, particularly notable in the frontal lobes and anterior to the frontal horns. The inability to be self-critical is a notable abnormality in cases of organic delusion. Discussion To postulate a position for frontal dysfunction in the genesis of delusions, some newer concepts of frontal behavioral functions can be reviewed. Over the past 30 years, a slow but persistent accumulation of data has characterized prefrontal functions. Stuss and Benson (1986) summarized these changes, emphasizing the supramodal, controlling aspects of the prefrontal lobes. Their frontal control theory is illustrated in a schematic diagram (figure 4) that shows self-analysis to be supramodal to executive control functions that operate through both drive and sequencing competencies. All are supramodal to the nine basic behavioral functions. Self-analysis, executive control, sequencing, and drive are functions of the prefrontal cortex. Self-analysis is the prefrontal function of utmost importance for monitoring and reality testing, and it would thus appear to be highly significant for both delusions and hallucinations. The ability to selfmonitor and to be self-critical must be functional for recognition of the inappropriateness of delusional misinterpretation or the incorrectness of an imagined sensory perception. The tenacity of organic delusions is at least partially explained by the serious inability to be self-critical. Each of the cases presented here demonstrated deficient ability to monitor reality and to be critical of the responses. In the cases of reduplicative paramnesia, Capgras syndrome, and bizarre confabulations, these dysfunctions were associated with significant bilateral structural damage involving the frontal lobes. The dramatic differences in symptomatology can be postulated as effects of differing areas of additional brain damageright parietal, right temporal, and bilateral temporal, respectively. Similar bifrontal damage was present in the case of parasitic delusion. In contrast, the Korsakoff confabulation case did not have

6 408 SCHIZOPHRENIA BULLETIN recognized frontal structural damage. It can be assumed that frontal dysfunction was present by the similarity of the confabulatory symptomatology to that in the case with structural frontal damage. The major difference was the temporary nature of the confabulation in the alcoholic Korsakoff patient. Disturbance in awareness can be reviewed as a disruption in monitoring, an interruption in a feedback loop. A review of the neurological/ neuropsychological literature suggests the existence of at least three monitoring systems at different levels of mental processes, two of which are related to the frontal lobes (Stuss, in press a, in press b). Each level has an input (specific type of information for this level of processing), a comparator to analyze the input based on previous experience or knowledge, and an output channel leading to action or demand for additional information. Damage to the system results in deficiencies in monitoring specific to the level affected (see figure 5). Monitoring at one level is related to the posterior/basal functional systems. Input monitored at this level is a specific fact or binding of groups of facts about the basic external sensory or internal visceral environment, or their immediate representations. Each functional system has its own feedback loop. Damage in a particular loop results in a deficit in self-monitoring of a particular fact; the patient will appear to have lost knowledge of the deficit. Clinical syndromes compatible with this description include Wernicke's aphasia (Heilman, in press) and hemineglect (Weinstein and Friedland 1977; Heilman et al. 1985). In the disturbances of awareness related to the frontal lobes, basic information is intact. The interpretation or handling of the knowledge, however, is impaired. The second level of awareness involves the executive control functions of the frontal lobes. The neural input is information of the sensory/perceptual level with the executive (comparator) function providing initiation, judgment, and planning. The third level represents an even higher level of the monitoring of behavior, an ability to be selfreflective. In cases of impairment, factual knowledge would be intact and executive control abilities would also be reasonably sound. It is the awareness of the implications of behavior that would be deficient, Figure 3. Computed tomographic scan demonstrating modestly enlarged frontal horns with distinct lucencies in frontal periventricular white matter bilaterally

7 VOL. 16, NO. 3, Figure 4. Schematic presentation of the major prefrontal cognitive activities emphasizing their mode of action through the more basic brain functions 1 Prefrontal Self-Analysis Prefrontal Prefrontal Medial/Lateral Posterior/ Basal 'Modified from Stuss and Benson (1986), with permission. Memory Motor Alertness Executive (Cognitive) Control Language Sensory Attention Sequencing Cognition Visual-Spatial Emotion Figure 5. Three proposed levels of feedback/feedforward loops related to awareness 1 SENSATION, BASIC KNOWLEDGE *"" OUTPUT HESEMSATOMPERCEPTlON INPUT EXECUTIVE FUNCTIONS f"" OUTPUT f INTERACTION Of MULTIPLE MODULES N ORGANIZED I OUTPUT COMPARATOR COMPARATOR INPUT ASSOCIATIONS. COMPLEX PATTERNS FACTUAL REFERENCE SELF-REFLECTIVENESS, METACOGNVTION PRINCIPLES OF ORGANIZATION JUDGEMENT COMPARATOR VALUES. PHINCPLES INTERNAL\EXTERNAL ENVIRONMENT The terms are descriptive and not necessarily related to independent psychological or anatomical entities. 'From Stuss (in press 6), with permission. Copyright Springer-Verlag, in press b.

8 410 SCHIZOPHRENIA BULLETIN a true impairment of monitoring of the total self. While circumstantial, the evidence cited here implies that reality testing is, to a great degree, dependent upon competent frontal lobe function. Failure to be self-critical and to perform reality testing in the face of correct knowledge suggests highlevel prefrontal malfunction. In this concept, the occurrence of delusions in schizophrenic patients implies prefrontal malfunction. While all schizophrenic symptomatology cannot be explained by this theory, prefrontal system disorder appears to be a significant component and this hypothesis appears consistent with current investigations of the underlying pathophysiology of schizophrenia (Weinberger 1988). References Alexander, M.P.; Stuss, D.T.; and Benson, D.F. Capgras syndrome: A reduplicative phenomenon. Neurology, 29: , American Psychiatric Association. DSM-I: Diagnostic and Statistical Manual of Mental Disorders. Washington, DC: The Association, American Psychiatric Association. DSM-UI-R: Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., revised. Washington, DC: The Association, Ball, J.R.B., and Kidson, M.A. The Capgras syndrome: A rarity? Australian and New Zealand Journal of Psychiatry, 2:44-45, Barbizet, J. Defect of memorizing of hippocampal-mamillary origin: A review. Journal of Neurology, Neurosurgery and Psychiatry, 26: , Benson, D.F., and Blumer, D. Amnesia: A clinical approach to memory. In: Benson, D.F., and Blumer, D., eds. Psychiatric Aspects of Neurologic Disease. Vo\. 2. New York: Grune & Stratton, Inc., pp Benson, D.F.; Gardner, H.; and Meadows, J.C. Reduplicative paramnesia. Neurology, 26: , Berlyne, N. Confabulation. British Journal of Psychiatry, 120:31-39, Bonhoffer, K. Die Korsakowsche symptomenkomplex in Seinen bezeikungen zu den verscheidenen Krankheitsformen. Allgemeine Zeitschrift fur Psychiatrie, 61: , Capgras, J., and Reboul-Lachaux, J. L'illusion des soises dans un delire systematise chronique. Bulletin de la Societe Clinique de Medicine Mentale, 11:6-16, Christodoulou, G.N. The syndrome of Capgras. British Journal of Psychiatry, 130: , Cummings, J.L. Oinical Neuropsychiatry. Orlando, FL: Grune & Stratton, Inc., 1985a. Cummings, J.L. Organic delusions: Phenomenology, anatomic correlations and review. British Journal of Psychiatry, 46: , 1985b. Cummings, J.L.; Miller, B.; Hill, M.A.; and Neshkes, R. Neuropsychiatric aspects of multi-infarct dementia and dementia of the Alzheimer type. Archives of Neurology, 44: , Enoch, M.D. The Capgras syndrome. Ada Psychiatrica Scandinavica, 39: , Enoch, M.D., and Trethowan, W.H. Uncommon Psychiatric Syndromes. Bristol: Wright, Flynn, F.; Cummings, J.L.; Scheibel, J.; and Wirshing, W. Monosymptomatic delusions of parasitosis associated with ischemic cerebrovascular disease. Journal of Geriatric Psychiatry and Neurology, 2: , Freedman, A.M.; Kaplan, H.I.; and Sadock, B.J., eds. Comprehensive Textbook of PsychiatryIII. 2nd ed. Baltimore: Williams & Wilkins Company, Hachinski, V.C.; Potter, P.; and Merskey, H. Leuko-araiosis. Archives of Neurology, 44:21-23, Hakim, H.; \ferma, N.P.; and Greiffenstein, M.F. Pathogenesis of reduplicative paramnesia. Journal of Neurology, Neurosurgery and Psychiatry, 51: , Heilman, K.M. Anosognosia: Possible neuropsychological mechanisms. In: Prigatano, G.P., and Schacter, D.L., eds. Awareness of Deficit After Bruin Injury. New York: Oxford University Press, in press. Heilman, K.M.; Watson, R.T.; and Valenstein, E. Neglect and related disorders. In: Heilman, K.M., and Vdenstein, E., eds. Clinical Neuropsychology. 2nd ed. New York: Oxford University Press, pp Kapur, N., and Coughlan, A.K. Confabulation and frontal lobe dysfunction. Journal of Neurology, Neurosurgery and Psychiatry, 43: , Lehmann, H.E. Unusual psychiatric disorders and atypical psychoses. In: Freedman, A.M.; Kaplan, H.I.; and Sadock, B.J., eds. Comprehensive Textbook of Psychiatry III. 2nd ed. Baltimore: Williams & Wilkins Company, pp Lewis, S. Brain imaging in a case of Capgras syndrome. British Journal of Psychiatry, 150: , 1987.

9 VOL. 16, NO. 3, MacCallum, W.A.G. Capgras symptoms with an organic basis. British Journal of Psychiatry, 123: , Mercer, B.; Wepner, W.; Gardner, H.; and Benson, D.F. A study of confabulation. Archives of Neurology, 34: , Merrin, E.L., and Silberfarb, P.M. The Capgras phenomenon. Archives of General Psychiatry, 33: , Miller, B.L.; Benson, D.E; Cummings, J.L.; and Neshkes, R. Late-life paraphrenia: An organic delusional syndrome. Journal of Clinical Psychiatry, 47: , Miller, B.L., and Lesser, I.M. Latelife psychosis and modern neuroimaging. Psychiatric Ginks of North America, 11:33-46, 198a Paterson, A., and Zangwill, O.L. Recovery of spatial orientation in the post-traumatic confusional state. Brain, 67:54-68, Pick, A. On reduplicative paramnesia. Brain, 26: , Quinn, D. The Capgras syndrome: Two cases and a review. Canadian Journal of Psychiatry, 26: , Rudnick, F.D. The paranoid-erotic syndromes. In: Friedman, C.T.H., and Faguet, R.A., eds. Extraordinary Disorders of Human Behavior. New York: Plenum Press, pp Ruff, R.L., and Volpe, B.T. Environmental reduplication associated with right frontal and parietal lobe injury. Journal of Neurology, Neurosurgery and Psychiatry, 44: , Schneider, C. Psychologie der Schizophrenen. [Psychology of Schizophrenics.] Leipzig: Thieme, Shapiro, B.E.; Alexander, M.P.; Gardner, H.; and Mercer, B. Mechanisms of confabulation. Neurology, 31: , Stuss, D.T. Disturbance of selfawareness after frontal system damage. In: Prigatano, G.P., and Schacter, D.L., eds. Awareness of Deficit After Brain Injury. New York: Oxford University Press, in press a. Stuss, D.T. Self, awareness and the frontal lobes: A neuropsychological perspective. In: Goethals, G.R., and Strauss, ]., eds. The Self: An Interdisciplinary Approach. New York: Springer-Verlag, in press b. Stuss, D.T.; Alexander, M.P.; Lieberman, A.; and Levine, H. An extraordinary form of confabulation. Neurology, 28: , Stuss, D.T., and Benson, D.F. The Frontal Lobes. New York: Raven Press, Talland, G.A. Deranged Memory A Psychonomic Study of the Amnesic Syndrome. New York: Academic Press, Victor, M.; Adams, R.D.; and Collins, G.H. The Wemicke-Korsakoff Syndrome. Philadelphia: F.A. Davis Company, Victor, M.; Adams, R.D.; and Collins, G.H. The Wemicke-Korsakoff Syndrome. 2nd ed. Philadelphia: F.A. Davis Company, Waziri, R. The Capgras phenomenon: Cerebral dysfunction with psychosis. Neuropsychobiology, 4: , Weinberger, D.R. Schizophrenia and the frontal lobe. Trends in Neurosciences, 11: , Weinstein, E.A. Patterns of reduplication in organic brain disorder. In: Vinken, P.J., and Bruyn, G.W., eds. Handbook of Clinical Neurology. Vol. 3. Amsterdam: North-Holland Publishing Company, pp Weinstein, E.A., and Friedland, R.P., eds. Advances in Neurology. Vol. 18. Hemi-Inattention and Hemisphere Specialization. New York: Raven Press, Weinstein, E.A., and Kahn, R.L. Denial of Illness: Symbolic and Physiologic Aspects. Springfield, IL: Charles C Thomas, Publisher, Weinstein, E.A.; Kahn, R.L.; and Sugarman, L.A. Phenomenon of reduplication. Archives of Neurology and Psychiatry, 67: , The Authors D. Frank Benson, M.D., is the Augustus S. Rose Professor of Neurology, UCLA School of Medicine, Los Angeles, CA. Donald T. Stuss, Ph.D., is Director of Research, Rotman Research Institute of Baycrest Centre, North York, and Professor of Psychology and Medicine, University of Toronto, Toronto, Ontario, Canada.