ANPA Abstracts, Poster Sessions I and II

POSTER SESSION 1—SUNDAY, FEBRUARY 25

ABBREVIATIONS

The abbreviations defined below are used frequently within the abstracts.

AD=Alzheimer's disease; ADHD=Attention-deficit/hyperactivity disorder; ANCOVA=analysis of covariance; ANOVA= analysis of variance; CNS=central nervous system; CT=computed tomography; fMRI=functional magnetic resonance imaging; FSIQ=Full Scale IQ; Ham-D=Hamilton Rating Scale for Depression; MANOVA=multivariate analysis of variance; MMPI=Minnesota Multiphasic Personality Inventory; MMSE=Mini-Mental State Examination; MR= magnetic resonance; MRI=magnetic resonance imaging; NARSAD=National Alliance for Research on Schizophrenia and Depression; NIA=National Institute on Aging; NIMH= National Institute of Mental Health; NIH=National Institutes of Health; OCD=obsessive-compulsive disorder; PET=positron emission tomography; PIQ=Performance IQ; rCBF= regional cerebral blood flow; SD=standard deviation; SPECT=single-photon emission computed tomography; SSRI=selective serotonin reuptake inhibitor; TBI=traumatic brain injury; VAMC=Veterans Affairs Medical Center; VIQ=Verbal IQ.

*Corresponding author (if other than the author listed first).

An overview of the poster sessions begins on page 119.

Epilepsy

P1. Do frontal behaviors change following surgery for temporal lobe epilepsy?Linda Mah, Sheldon Benjamin, Joan Swearer, Catherine Phillips, John Weaver (Departments of Psychiatry, Neurology, and Neurosurgery, University of Massachusetts Medical School, Worcester, MA)

Background: Behavioral changes following temporal lobe resection for medically intractable epilepsy have been described but not studied systematically (Stevens, Psychol Med 1990; 20:529–545). Patients with refractory seizures frequently report greater assertiveness as well as verbal and behavioral disinhibition after surgical intervention. We studied these changes in inhibitory control and other frontal behaviors in postoperative epilepsy patients by using the Frontal Lobe Personality Scale (FLOPS; Grace et al, Assessment 1999; 6:269– 284). Methods: Patient and family versions of the FLOPS were mailed to patients who had been treated surgically for refractory epilepsy. Retrospective ratings of frontal behaviors (pre- and postoperative) were obtained. 28 subjects participated. Mean number of months following surgery was 36.5. Results: Scores on the executive subscale of the self-rated FLOPS showed a trend toward improvement following surgery (P= 0.054). Patients whose seizures lateralized to the right tended to rate themselves as having greater changes in level of disinhibition (P=0.087). Patients with pathological diagnoses of mesial temporal sclerosis involving the right side tended to be perceived by family members as showing the greatest degree of worsening inhibitory control (P=0.063). Conclusions: Changes in frontal behaviors occur following surgical intervention for temporal lobe epilepsy. These changes may be mediated by disruption of frontal circuits via the extended amygdala.

P2. Psychiatric and psychosocial characteristics of a sample of epilepsy patients in South Florida: a prospective studyGustavo J. Rey, L. Campos, Rafael Rivas-Vazquez, G. Garaycoa, E. Carrazana (Neurologic Center of South Florida and Department of Neurology, University of Miami School of Medicine, Miami, FL)

Background: There are limited data regarding the demographic, clinical, and psychosocial correlates of depression and anxiety in epilepsy. Methods: 119 consecutive epilepsy patients were examined, using the Beck Depression Inventory II (BDI-II) and the Beck Anxiety Inventory (BAI). Quality of life was assessed with the Schwartz Outcome Scale (SOS). Results: The sample was heterogeneous in regard to age (mean=41.8 years, SD=15.7) and education (mean=12.9 years, SD=4.4). There was an approximate 2:1 gender ratio (female:male). For the BDI-II the sample had a mean score of 10.1 (SD=11.3), with 15% of subjects endorsing mild-moderate depression and 19% endorsing severe levels of depression. The mean BAI score was 8.8 (SD=10.8), with similar percentages for severity of symptoms. The mean SOS score was 46.4, indicating significantly lower levels of satisfaction relative to normative data. Basic demographic variables were not related to severity of psychopathology, but there was a significantly inverse relation between quality of life and the presence of affective disturbance. Inconsistent seizure control was inversely related to levels of depression and anxiety. Conclusions: There is a high prevalence of depression and anxiety in our epilepsy patient sample. Inconsistent seizure control is an important determinant of the severity of affective disorder in this neurological condition.

P3. Affective disorders in the primary generalized epilepsiesRafael Rivas-Vazquez, G. Garaycoa, L. Campos, G. Rey, E. Carrazana (Neurologic Center of South Florida and Department of Neurology, University of Miami School of Medicine, Miami, FL)

Background: Although affective and personality disorders are well documented in generalized epilepsies, differences between generalized epilepsy subtypes remain controversial. Methods: 20 juvenile myoclonic epilepsy (JME) patients and 20 grand mal or awakening (GMA) patients completed the Beck Depression Inventory II, the Beck Anxiety Inventory, and the Schwartz Outcome Scale quality of life questionnaire. Results: Patient groups did not differ in regard to age, education, gender, age at onset, or seizure control. The JME group endorsed significantly higher levels of depression and anxiety, as well as lower quality of life scores. Conclusions: In our generalized epilepsy sample, patients with JME showed higher levels of depression and anxiety than patients with GMA. JME patients also reported lower satisfaction with their current quality of life. These differences do not appear to be a reactive response, since the two groups evidenced similar seizure control. Although antiepileptic drugs (AEDs) may be contributory, this is unlikely because patients with JME are primarily on AEDs with mood modulation effects. The previously reported “personality traits” of JME patients may be a reflection of an underlying affective disorder. These findings have important implications in the management of JME patients.

Neuropsychology

P4. Neuropsychological profile of two sisters with familial Creutzfeldt-Jakob diseaseAmarilis Acevedo, Gloria White, Ranjan Duara, David Loewenstein, Raymond Ownby (Wien Center for Alzheimer's Disease and Memory Disorders; Mount Sinai Medical Center, Miami Beach; Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, FL)

Background: Creutzfeldt-Jakob disease (CJD) is an uncommon, progressive, and invariably fatal prion disease characterized by cognitive, psychiatric, and motor disturbance. About 5% to 15% of cases are familial and show an autosomal dominant pattern of inheritance. To our knowledge, this is the first report of comparative serial neuropsychological evaluations on two family members affected with familial CJD. Methods: Neuropsychological evaluations were conducted on the younger of the two affected sisters, who first showed cognitive changes at age 39. Records were reviewed on five neuropsychological evaluations conducted on the older sister, who died at age 46, 10 years after initial symptoms and a few months before the onset of symptoms in the younger sister. Results: The two sisters showed remarkably similar neuropsychological profiles, with severe impairment on tasks that assess calculation, visuospatial and constructional skills, memory, cognitive flexibility, and ability to manipulate information mentally. Presence and degree of impairment varied on tasks that assess attention, confrontation naming, verbal fluency, and word knowledge and reading. Conclusions: Familial CJD presents with similar cognitive changes among members of the same kindred. However, individual differences seem to exist in the expression of deficits in specific areas of cognition, especially language.

P5. Hemispheric asymmetry of facial processing: an examination of spatial frequency and processing durationKim Curyto, Douglas Whitman* (Wayne State University, Detroit, MI)

Background: One of the best-documented demonstrations of asymmetrically lateralized information processing in normal subjects is the left visual field superiority for facial recognition. Whitman and colleagues have been able to show hemispheric differences with direct manipulation of spatial frequency information by masking and filtering spatial frequencies representing different bandwidths, demonstrating that the left hemisphere is biased towards the processing of high spatial frequency information and the right hemisphere toward low spatial frequency information. Methods: Neutral faces (Ekman) were presented to the right or left visual field of 40 right-handed subjects (20 male, 20 female) and were followed by one of three visual gratings masking three different fundamental spatial frequencies: 1 c/deg, 6 c/deg, and 24 c/deg, at a delay of either 0 ms, 20 ms, or 40 ms. Subjects then had to identify the face from a six-face array. Results: The right visual field was more accurate at face recognition for both male and female subjects. Recognition accuracy was significantly reduced by the low spatial frequency mask. Although the right hemisphere showed a superiority in facial recognition, the low spatial frequency mask caused proportionally greater loss in identification accuracy than did the high spatial frequency mask.

P6. False recognition and misidentification in face processing: left hemisphere contributionsTannahill Glen (Walton Rehabilitation Hospital, Augusta, GA)

Background: False recognition of unfamiliar faces without prosopagnosia (inability to recognize familiar faces) is relatively rare in literature on facial processing. Existing research focuses on the right hemisphere (RH) role in facial processing and alludes to left hemisphere (LH) input in responding to facial features or biographic information. The authors of this case study conceptualize false recognition in terms of positive and negative signs of neurologic injury. Methods: L.F., a 61-year-old right-handed white female with recent large frontotemporal infarct, was administered a battery of neuropsychological tests 1 week and 7 weeks after cerebrovascular accident. Results: L.F. showed significant impairment in all areas except right-side motor functions and verbal comprehension. On a measure of facial recognition, she endorsed each face as one she knew. Behavior was marked by left neglect, rightward head/eye deviation, visual grasp reflex, perseveration, motor impulsivity, and poor initiation, suggestive of left frontal disinhibition. Results will be described in detail. Conclusions: The positive sign or productive error in L.F.'s false recognition was a strong sense of familiarity with new faces. The negative sign was inability to critically evaluate her sense of familiarity with contextual input from the damaged RH. The disinhibited LH is forced to make sense of the situation by using stored biographic information to confabulate a story. The delusional sense of certainty reflects L.F.'s resistance to counterarguments in the absence of RH critical evaluation.

P7. Cognitive behavior rating scales reflect severity of impairment in patients with cerebral neoplasmSamuel T. Gontkovsky, William D. Ruwe, Russell L. Adams, James G. Scott (University of Oklahoma Health Sciences Center, Oklahoma City, OK)

Background: The clinical interview is regarded as a fundamental tool in obtaining information regarding a patient's functional abilities. However, patients with cortical dysfunction may show impaired awareness of their deficits (Sherer et al, J Int Neuropsychol Soc 1998; 4:380–387). Thus, relying solely on their reports may lead to inaccurate conclusions regarding specific strengths or weaknesses. Based on observations of family members or caregivers, the Cognitive Behavior Rating Scales (CBRS) provide a quantitative profile of a patient's functional abilities. In the present study, the degree of impairment as indicated by CBRS scores was examined in comparison to a normative sample. Methods: Subjects were 22 patients with diagnoses of cerebral neoplasm who had been referred for neuropsychological assessment. Family members of each patient completed CBRS questionnaires. Descriptive statistics for these subjects were generated and compared with those for an age-equated control group. Results: Patients with neoplasms showed greater impairment than the normative sample on the nine scales of the CBRS. Six scales differed by more than 1¼ SD, and two of the six differed by more than 2½ SD. Conclusions: The CBRS are sensitive to neurocognitive sequelae secondary to cerebral neoplasms. Language deficits and apraxias are the most robust indicators of cortical dysfunction.

P8. Validation of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Figure Copy and Figure Recall subtestsSamuel T. Gontkovsky, Michael T. Ropacki, Frank G. Hillary, Elliott D. Ross, James G. Scott (University of Oklahoma Health Sciences Center, Oklahoma City, OK)

Background: The Repeatable Battery for the Assessment of Neuropsychological Status was recently developed to evaluate functioning across multiple domains of neurocognitive status (Randolph et al, J Clin Exp Neuropsychol 1998; 20:310–319). However, validation of the RBANS and its individual subtests with empirically established neuropsychological measures has yet to be demonstrated. This study investigated the sensitivity of the RBANS Figure Copy and Figure Recall subtests in comparison to the Rey-Osterrieth Complex Figure Test. Methods: Subjects were selected from patients referred for routine neuropsychological assessment. 10 patients were classified as cognitively impaired, based on MMSE performances at or below the cutoff score of 23. The remaining 18 patients scored above 23 on the MMSE and served as a cognitively intact neurological control group. The RBANS and Rey-Osterrieth Complex Figure Test were administered a part of a comprehensive neuropsychological evaluation. Results: Analyses yielded data indicating that the RBANS Figure Copy and Figure Recall subtests were nearly as sensitive to cognitive dysfunction as was the Rey-Osterrieth Complex Figure Test. Conclusions: Results served to validate the efficacy of the RBANS Figure Copy and Figure Recall measures in detecting deficits in both visuospatial constructional abilities and visual memory.

P9. Monocular facial recognition, laterality, and genderJonathan L. Hess, Michael Smith (University of Illinois, Springfield, IL)

Background: A right-handed stroke patient complained that “things don't look right out of the left eye” but was unable to characterize this phenomenologically. Each eye was tested on a number of visual perceptual tests. All yielded roughly equal performance except for facial recognition, where he was only 50% as efficient with his left eye as with his right eye. Virtually all of the literature we found was for binocular facial recognition. We wondered if comparable differences are common in the unimpaired population. Methods: A 2×2×2 factorial design was used with right/left eye, order in which eyes were tested, and gender. Subjects were upper-division college students. Results: 1) All subjects were nearly equal when each eye was compared for facial recognition skills, establishing that inferior left-sided facial recognition indeed is abnormal. 2) The statistical interaction was significant. Males did better with their left eye; females did better with the eye that they used second in the order. Although statistically significant, the effect size was small. Conclusions: A laterality hypothesis is consistent with the male data. A learning hypothesis is consistent with the female data. Perhaps, in a paternalistic culture, females historically had to gain access to power by being better at learning facial expressions and other cues to establish the dominance not otherwise given to them.

P10. Employing the new diagnostic criteria for malingering in neuropsychological assessmentGrant L. Iverson, Daniel J. Slick (University of British Columbia and Riverview Hospital, Vancouver, BC, Canada)

Background: In the 1990s, there was an explosion of research on the detection of malingering in neuropsychology. These widespread and concerted efforts gave rise to increasingly sophisticated, efficient methodologies and specific tests and procedures. Despite these advances, the clinical process of diagnosing malingering remains challenging and idiosyncratic. Recently published diagnostic criteria (Slick et al, Clin Neuropsychol 1999; 13:545–561) should facilitate the diagnostic process in both clinical practice and research. The purpose of this study is to present a series of cases that illustrate the use of these new diagnostic criteria and clinical formulations for the diagnosis and differential diagnoses of malingering. Methods and Results: Three cases will be presented that illustrate the diagnostic categories of definite, probable, and possible malingering. A fourth case will illustrate the differential diagnostic process. These four individuals were involved in mild head injury litigation. Conclusions: The case studies presented illustrate the difficulty and complexity of the differential diagnosis of malingering and show how the application of standardized criteria makes the diagnostic process easier. Widespread adoption of standardized criteria should facilitate research and clinical communication in this area.

P11. Effects of stimulant treatment for adult ADHD on executive functioningMelissa Jenkins, Stephen Salloway, Paul Malloy, Joseph Hong, Kristen McKiernan (Brown University, Providence, RI)

Background: Recent studies demonstrate that empirical evidence of both attentional and executive dysfunction is found in adults with residual symptoms of childhood ADHD (Jenkins et al, The Clinical Neuropsychologist 1998; 12:74–83) and that stimulant treatment results in enhanced performance on neuropsychological tests of attention and memory (Riordan et al, Arch Clin Neuropsychol 1999; 14:217–233). Methods: Pre- and post-treatment evaluation was conducted, using a variety of attention, executive, learning, and memory tasks to determine which aspects of cognition are most affected by stimulants. 12 adults with ADHD and 11 control subjects completed testing; patients were treated with methylphenidate or pemoline at clinically titrated dosages and were retested after 8 weeks at a stable dosage. Results: Pre-treatment testing showed group differences in mood state, Continuous Performance Test (CPT) performance, Stroop Interference test, and verbal memory. Differential improvement (patients>untreated control subjects) was seen on tests of memory, CPT performance, and self-rated confusion and tension. Improvement was not seen on cognitive interference on the Stroop test or in self-rated depression. Increased intrusion errors and “ false alarms” were made by patients taking stimulant medications. Conclusions: Vigilance, reaction time, and memory efficiency improve with stimulant treatment in adults with ADHD. However, executive functioning does not improve, and some measures of impulsivity worsen with stimulant treatment.

P12. The influence of cognitive reserve on memory following electroconvulsive therapySusan A. Legendre, Robert A. Stern,* David A. Solomon, Martin J. Furman, Kristin E. Smith (Neuropsychology Program, Rhode Island Hospital, Providence, RI)

Background: Memory is negatively affected in many patients who receive electroconvulsive therapy (ECT). However, the degree and consistency of this impairment is variable (Sackeim et al, N Engl J Med 1993; 328:839–846). Research in the fields of Alzheimer's disease (Y Stern et al, JAMA 1994, 271:1004– 1010; Snowdon et al, JAMA 1996, 275:528–532) and HIV (Satz et al, J AIDS 1993, 6:503–511; R Stern et al, Arch Neurol 1996; 53:148–153) suggests that some aspects of cognitive reserve, such as educational attainment, may help explain the differential impact of various assaults to the central nervous system. We examined whether greater cognitive reserve (e.g., higher educational attainment) may protect against memory dysfunction among individuals treated with ECT. Methods: 40 depressed patients treated with bilateral ECT were placed in high (n=18) or low (n=22) cognitive reserve groups based on a variety of factors, including years of education, socioeconomic status, and estimated IQ. All were administered a measure of verbal memory (Randt Stories) at baseline and after every third ECT treatment. Results: There were no significant differences between the groups at baseline or after three treatments. After six ECT treatments, however, preliminary data on a subgroup of participants indicate significant differences in verbal learning and recall (Randt percentage retained, P< 0.05), with the high cognitive reserve group showing better memory performance. Conclusions: These data suggest that cognitive reserve may be a factor underlying differential memory loss in ECT, and that higher education level and other related variables may protect against memory loss at later points during the course of ECT.

P13. Exploring attention and eye movement control in obsessive-compulsive disorder with a cued saccade paradigmChiang-shan Ray Li (Chang Gung Memorial Hospital and Chang Gung University, Tao-yuan, Taiwan)

Background: Previous work revealed abnormalities in the corticostriatal circuitry and in executive control in patients with OCD. The present study examined the coordination of attention and oculomotor processes in OCD by studying the effect of spatial cueing on saccade latency. Methods: 6 OCD patients (4 medication-free) and 6 matched control subjects participated in reaction time experiments involving visual and cued saccades. The fixation light was straight ahead and the peripheral target 6 degrees to the left or right of the fixation in all experiments. One of the three trials was visual and two were cued saccades, in which a brief cue preceded the target by a variable-onset asynchrony. The cue was nonpredictive of target location in experiment 1 and predictive in experiment 2. In experiment 3 the cue was a change of the fixation light color: red (green) signaling the target to appear at left (right) in 75% of the trials; blue not predictive. Latencies of the cued and visual saccades were compared. Results: We obtained robust results that patients with OCD showed a different time course of inhibition of return in oculomotor programming. Conclusions: The findings suggest that corticostriatal circuitry might play a role in orchestrating eye movement and attentional shifting.Supported by CMRP 792 from the Chang Gung Memorial Hospital.

P14. Item reaction time as a function of response dissimulationRichard I. Naugle, Gordon J. Chelune, Tara T. Lineweaver, Julie A. Zone (Cleveland Clinic Foundation, Cleveland, OH)

Background: The Victoria Symptom Validity Test (VSVT) is a forced-choice measure that was designed to detect attempts to feign or exaggerate memory compromise; it includes items that appear easy or hard. Error rates that exceed chance performance are regarded to be attributable to malingering. It was hypothesized that attempts to malinger would affect response latency, since dissimulation requires that the subject determine the correct response and make a decision about whether to respond accurately or feign compromise. Methods: To examine differences in response latency, mean reaction times of malingerers (n=4) and age- and education-matched control subjects (n=6) were compared. Individual subjects' mean response latencies were then reviewed to determine the optimal cutoff to distinguish malingerers from control subjects. Results: ANOVA revealed that those subjects who were thought to be exaggerating their memory compromise responded significantly more slowly to the “hard” items of the VSVT than the control group (F=8.02, df=1,7, P<0.05); this effect was apparent only for those items to which the malingerers responded correctly, however. Using a reaction time of 4,000 ms as a cutoff correctly classified all malingerers and misclassified only one control subject among the sample of this pilot study.

P15. Differences on executive function measurements in Colombian university studentsDavid A. Pineda, Vilma Merchán (University of San Buenaventura and University of Antioquia, Medellín, Colombia)

Background: Several studies have found differences on executive function test scores among different populations (Boone et al, Arch Clin Neuropsychol 1998; 13:585–595).The aim of this study was to compare executive function tests scores among university students from different careers. Methods: 100 participants of both sexes, ages 16 to 21 years and high normal on WAIS Full Scale IQ (112.1±8.1) were selected in a randomized and representative approach from private universities of Medellín, Colombia. They were sorted into those pursuing verbal, visuoperceptual, and mathematical careers. An executive function assessment battery was applied, which included the Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) parts A and B, verbal fluency test (FAS) by phonologic and semantic guidance, and Word-Color Stroop test. Results: No differences were found on WAIS VIQ, PIQ, and FSIQ among groups. Mathematical students obtained significantly higher scores on several WCST variables than students from verbal and visuoperceptual careers (ANOVA, P< 0.02). Students from verbal careers obtained higher scores on verbal semantic fluency test than students from visuoperceptual careers (ANOVA, P<0.05). Conclusions: Mathematical university students showed higher algorithm organization, and verbal university students showed higher verbal semantic organization, which is not dependent on FSIQ.

P16. Neuropsychological assessment of Colombian adolescent offendersDavid A. Pineda, Ana Isabel Isaza, Isabel Cristina Puerta, Silvia Mejía (University of San Buenaventura and University of Antioquia, Medellín, Colombia)

Background: Brain frontotemporal dysfunction interacts with social variables to form a complex matrix of antisocial behavior (Blake et al, Neurology 1995; 45:1641–1647). Low VIQ and early drug use predicted conduct disorder in adolescent students (Pineda et al, Int J Neurosci 2000; 101:133–155). Our objective in this study was to define neuropsychological characteristics of a group of adolescent offenders with conduct disorder (CD). Methods: A sample of 138 male participants, ages 12 to 16 years, was selected. The 68 control subjects were attending regular schools and the 70 cases were attending institutions of reeducative training for offenders. Groups were matched by age, socioeconomic status, and habitual place of residence. As was expected, cases had significantly lower FSIQ and significantly lower school achievement. Results: ANCOVA, controlling for the effect of FSIQ on cognitive scores, showed significant differences between the groups (P<0.05) on Wechsler Memory Scale verbal logic memory scores and a number of trials of the verbal learning curve. Control subjects performed better than cases. Conclusions: Some specific alterations on cognition tests related to verbal memory were found in adolescent offenders, which could be related to left temporal lobe dysfunction.

P17. Gaze deviation: frequency, anatomy, and relationship to hemispatial neglect in a large stroke cohortJohn M. Ringman, Jeffrey Saver, Harold Adams, R.F. Woolson, and W.R. Clarke, for the TOAST Investigators (University of California, Irvine, CA)

Background: The frequency, neuroanatomic substrate, and relationship to the neglect syndrome of conjugate gaze deviation in ischemic stroke have not been well characterized. Methods: Serial examinations for gaze deviation and hemispatial neglect, employing the NIH Stroke Scale, were performed at presentation and at 3 months on 1,281 acute stroke patients. CT scans were obtained at 1 week. Results: At presentation, in right-handed patients (n=1,161), gaze deviation was present in 60% with complete neglect and in 14% with no or partial neglect. Similar frequencies were noted in non–right-handed patients (n=64; 57% and 14%, respectively). By 3 months, only 15% of right-handers with complete neglect exhibited gaze deviation. Neuroanatomic analysis included 330 patients with discrete lesions in regions of interest. At presentation, gaze deviation was more common with lesions of the right (RHL) than left (LHL) hemisphere (P=0.017). Gaze deviation was most frequent with lesions involving both frontal and parietal lobes (33% for RHL, 11% for LHL) followed by frontal (23%, 13%), thalamus (22%, 0%), parietal (17%, 7%), and basal ganglia/internal capsule (11%, 8%). At 3 months, gaze deviation frequency decreased to 8% for right frontal-parietal lesions, 7% for right frontal, 5% for right parietal, and 0% for all other lesions. Conclusions: Functionally and anatomically related neural networks subserve gaze deviation and hemispatial attention.Support from NIH Grant R01 N527863.

P18. Tests of a brief measure of veracityRichard D. Sanders, Douglas L. Mossman (University of Pittsburgh, Pittsburgh, PA; Wright State University, Dayton, OH)

Background: Clinical and research assessments are frequently obscured by uncertainty as to the subject's honesty. Clinical patients and research subjects deliberately mislead examiners for profit, to avoid punishment, and to manipulate treatment decisions. Although examiners could and should consider their subjects' veracity, there is no convenient means of quantifying this. We have written a two-item scale, intended for appending to psychiatric rating scales, for assessing veracity. Methods: “Global Assessment of Honesty” (GAH) is based on the examination. “Global Incentive to Mislead” (GIM) is based on the subject's circumstances, requiring familiarity with his or her social history. Both are 7-point bivalent Likert-type scales, similar in format to the Global Improvement Scale. We have piloted the reliability of the GAH during interrater reliability sessions by appending it to other similarly constructed psychopathological rating scales. Validity has been explored by comparing ratings on both items with MMPI validity scales. Ratings were recorded within 1 week of administering the MMPI, without knowledge of its results. Results: Despite very limited training, raters consistently achieve ICC> 0.6. Ratings significantly correlate with MMPI validity scales. Conclusions: This scale shows potential as an efficient, valid, and reliable means of rating apparent veracity.

P19. The face-hand test in neuropsychiatryRichard D. Sanders, Matcheri S. Keshavan, Gerald Goldstein (University of Pittsburgh, Pittsburgh, PA)

Background: The face-hand test probes for tactile extinction during asymmetric double simultaneous stimulation. In its long history, it has been forwarded as an ancillary test in the diagnoses of dementia, pediatric behavioral and cognitive syndromes, and neuromedical (organic) etiologies for psychiatric syndromes. Various mechanisms have been proposed, but there is little psychological or physiological data relevant to the nature of impairment on the face-hand test. We review the literature on this test and present our own data. Methods: Using an abbreviated version (from the Neurological Evaluation Scale) in treatment-naive patients, we compared those with schizophrenia versus other idiopathic psychotic disorders. Using a longer version (from the Halstead-Reitan battery) in previously treated patients, we compared those with schizophrenia versus other (generally nonpsychotic) psychiatric disorders. Results: In both studies, hand extinctions were more common in schizophrenia than in patient comparison groups. We find no relationships with demographic variables, general intelligence, premorbid functioning, or current symptoms. The test is statistically associated with neurological exam abnormalities on tasks that are relatively cognitively demanding and require integration of sensory input. Conclusions: The face-hand test may be useful in the diagnosis of schizophrenia and may hold clues to the specific nature of schizophrenia among the psychoses.Support from Department of Veterans Affairs and NIH grants.

P20. Qualitative analysis of errors on the Paced Auditory Serial Addition Task (PASAT)Choun M. Sourathathone, Holly James Westervelt, Robert A. Stern, Geoffrey Tremont (Rhode Island Hospital, Providence, RI)

Background: The PASAT is a calculation task requiring both sustained attention and speeded processing. Although the task is frequently used in both clinical practice and research, interpretation of PASAT results may be limited by reliance on scores representing a quantitative computation of the total number of errors. Methods: We examined the qualitative aspects of PASAT performance by conducting a retrospective review of the type and frequency of errors in a mixed neurologic sample (N=98). Results: The most prevalent errors were omissions (86%). Of non-omissions, errors included adding to the previous target (35%), adding to one's previous answer (31%), unclear non-omissions (Other; 28%), and other rare error types (6%). The use of omission errors as a strategy was further examined. 9% of participants used the strategy of responding to every other item at least once. The prevalence of non-omission errors in a patient's performance may reflect more pervasive difficulties (e.g., perseveration, loss of set), and certain groups may be prone to making particular errors; in our group, psychiatric patients (n=17) committed the most errors of adding to the previous target and adding to one's answer, whereas the TBI group (n=13) committed the most “Other” errors. Conclusions: A qualitative analysis of PASAT performance revealed several different error types. Future research analyzing the differences between diagnostic groups and the relationship of error types to performance on other neuropsychological measures may further define the significance of the errors made on the PASAT and thereby improve on the clinical utility of this commonly used neuropsychological instrument.

P21. Verbal fluency and quantitative EEG in Spanish-English bilingualsK. Stringer, A. McCabe, B. Lenis, M. Rosselli,* A. Ardila (Division of Psychology, College of Liberal Arts, Florida Atlantic University, Davie, FL)

Background: Differences in brain organization of language between bilingual and monolingual individuals have been suggested. Methods: This study analyzed the patterns of cerebral cortical activation (quantitative electroencephalogram) underlying letter and semantic fluency in 8 Spanish-English bilingual and 8 English monolingual individuals. All subjects were right-handed college students with no history of neurological or psychiatric problems (mean age=26.6). The frequency bands investigated were alpha (8–12 Hz), beta 1 (12–20 Hz), and beta 2 (20–30 Hz). There were three counterbalanced conditions each consisting of two trails (60 seconds each): letter fluency (generating English words when cued with the letter F), semantic fluency (generating names of animals in English), and a silent control condition. The bilingual group received two additional verbal fluency conditions: Spanish letter fluency and Spanish semantic fluency. Results: Despite some heterogeneity in the pattern of activation, left temporal beta activation predominated in most subjects. No evident differences were observed between letter and semantic verbal fluency. With regard to monolinguals, bilinguals presented more diffuse brain activation. In some but not all bilinguals, a similar pattern of activation was observed when performance was either in English or in Spanish. Conclusions: Results suggest both similarities and differences in brain organization of the two languages.

P22. Neuropsychological and SPECT findings in Lyme diseaseJeanette Wasserstein, Marianne N. Findler, Kenneth B. Liegner (Mount Sinai Medical Center and Columbia-Presbyterian Medical Center, New York, NY)

Background: Vague cognitive complaints are reported in Lyme disease (LD), typically including forgetfulness, impaired concentration, and fatigue. Psychiatric complaints, most notably depression and irritability, are also common. Neuropsychological consequences of LD are poorly understood, with inconsistent results in empirical studies to date. Methods: We present 6 case studies with extensive neuropsychological batteries, interfaced with SPECT results. Subjects were highly educated adults without significant premorbid neuropathology. Participants met rigorous criteria for LD, reported multiple neurocognitive problems, by history had long disease duration, and were either unmedicated or in early antibiotic treatment. SPECT scans were performed and interpreted at the same teaching hospital. Results: Both the neuropsychological and the SPECT profiles showed deficits but were remarkably variable. Diffuse and focal findings existed in each, typically having some interrelationship within cases. Neuropsychological deficits were most consistently detected by noting a wide range between WAIS-III Indexes. Counterintuitively, processing speed and working memory were not always low. Conclusions: Like the other well-known spirochetal illness, syphilis, LD may be a “great pretender” with protean patterns. Not all patients have neurological LD. Even those with neurological LD may have different neurocognitive, neuroanatomical, and physiological manifestations. This may partially account for inconsistent findings in the literature.

Dementia

P23. Cognition and behavior in pallido-ponto-nigral degenerationZoe Arvanitakis, Cynthia A. McRae, Neill R. Graff-Radford, Zbigniew K. Wszolek (Mayo Clinic, Jacksonville, FL; University of Denver, Denver, CO)

Background: Investigators have linked many kindreds with frontotemporal dementia (FTD) and parkinsonism to mutations of the tau gene on chromosome 17, One such family has pallido-ponto-nigral degeneration (PPND), associated with the exon 10 N279K mutation. This study focuses on the associated cognitive and personality changes, which are not well described. Methods: 5 affected individuals (mean age at disease onset 46 years), and 5 nonaffected at-risk individuals (mean age 32 years), underwent standardized testing (neurologic, cognitive, autonomic, and sleep assessments), brain MRI, and PET scans. Results: At-risk individuals had normal cognition and an MMSE of 29/30. Affected individuals invariably present with parkinsonism. The mean MMSE score was 20/30. Cognition and behavior may or not be involved at onset but are altered with progression of the disease: 2 individuals late in the course met published criteria for FTD, and 2 others had changes in keeping with FTD. 3 patients performed poorly on the Frontal Assessment Short Test, and 3 had abnormal speech. Only 1 had visuospatial difficulties. Conclusions: Cognition and behavior are affected in the later stages of PPND, and these changes are in keeping with sporadic forms of FTD. A longitudinal study is under way to define the evolution of these features further.

P24. Physical exam indicators of dementiaGregory A. Charlton, John C. Adair (University of New Mexico Department of Neurology and VAMC, Albuquerque, NM)

Background: It has been observed that paratonia can strongly predict cognitive performance in patients with dementia, and that the modified Kral procedure (a clinical maneuver to test facilitatory paratonia) can predict performance on frontal lobe tests. (Beversdorf, Neurology 1998; 51:968–971). Our objective was to determine if certain motor signs (paratonia, frontal release signs) can help differentiate between different types of dementing illness. Methods: Patients from the memory disorders clinic were divided into two groups: probable Alzheimer's disease and frontal/subcortical dementia. Paratonia was assessed by using subjective impression of opposition or assistance to passive arm movement as well as the modified Kral procedure. A “frontal release” (FR) score was derived as the summary of multiple component signs (e.g., grasp). Findings were also sought in an age-matched control group. All patients underwent detailed cognitive testing. Results: Compared with AD patients and control subjects, the “other” dementia group showed significantly greater paratonia and higher FR and Kral scores. Only paratonic rigidity showed a significant inverse correlation with dementia severity. Motor signs failed to correlate with most measures of executive function. Conclusions: Exam signs that may indicate executive dysfunction were more consistently detected in frontal/subcortical dementia patients. Measures of paratonia provided more information than FR score.

P25. Posterior cortical atrophy versus early-onset Alzheimer's disease: clinical and neuroimaging differencesMehdi Ghajarnia, Mario F. Mendez (University of California at Los Angeles, Los Angeles, CA)

Background: Posterior cortical atrophy (PCA) is a rare, early-onset dementing illness that in clinicopathological studies is most commonly attributed to Alzheimer's disease. No study has systematically evaluated clinical differences between PCA and presenile AD. Methods: We retrospectively compared 12 clinically diagnosed PCA patients with 24 early-onset AD patients who met NINCDS-ADRDA criteria for clinically probable AD. PCA and AD patients were matched by gender, age, and duration of dementia. We evaluated differences in epidemiological, clinical, and neuroimaging variables between groups. Results: The PCA patients were 8 men and 4 women with a mean age of 64.2±6.3 years and mean dementia duration of 4.3±2.6 years. Compared with the matched AD patients, PCA patients had significantly greater visuospatial deficits, depression, and insight into illness. Functional neuroimaging in the PCA patients showed prominent occipitoparietal hypoperfusion or hypometabolism, in contrast to frontal and temporoparietal in the AD patients. Predominant visuospatial disturbances in the PCA patients included alexia, visual agnosia, prosopagnosia, and Balint's syndrome. Conclusions: These results demonstrate significant differences between the clinical syndromes of PCA and early-onset AD. In addition to showing PCA to be clinically distinguishable from AD, these findings suggest the possibility of specific interventions such as antidepressant medication or the use of visual assistance for patients with PCA.Support from an American Federation on Aging Research/Heartford Geriatric Fellowship (M.G.).

P26. Apolipoprotein E and cognitive functioning in community-residing middle-aged and older adults without evidence of dementiaFelicia C. Goldstein, Vicki J. Roberts, Joanne Green, Angela V. Ashley, Marla Gearing, Allan I. Levey (Department of Neurology, Emory University School of Medicine, Atlanta, GA)

Background: Previous research has investigated whether the apolipoprotein E (APOE) E4 allele, a genetic risk factor for Alzheimer's disease, is associated with poorer cognitive functioning in asymptomatic adults without evidence of dementia. However, studies have yielded inconsistent findings. The current investigation simultaneously considered the possible roles of age and education in moderating this relationship. Methods: The sample included 92 community-residing middle-aged and older adults (age range 42–81 years, education range 7–20 years) enrolled in the Emory Alzheimer's Disease Center. Subjects underwent genotyping and received comprehensive neuropsychological evaluations examining multiple cognitive domains. They were classified as normal control subjects on the basis of consensual agreement of a group of physicians and neuropsychologists who were unaware of their genotype results. Hierarchical regression analyses examined the extent to which APOE status, age, and education predicted neuropsychological performance indices. Predicted values were generated to aid in the interpretation of significant (P< 0.05) interactions. Results: In general, predicted values indicated that among those individuals who were positive, but not negative, for the E4 allele, higher age, lower education, or both factors in combination were associated with poorer performance on measures of memory, attention, and design copying. Conclusions: Advanced age and lower education are vulnerability factors for poorer cognitive functioning in carriers versus noncarriers of the APOE E4 allele. Future research should examine whether additional risk factors such as a positive family history of AD modify the influence of the E4 allele on cognitive performance.Support from NIA Grant P30 AG10130.

P27. Circadian sleep and neuropsychiatric disturbances in Alzheimer's diseaseDaniel I. Kaufer, Patrick Ketchel, Oscar L. Lopez, Charles F. Reynolds III, Steven T. DeKosky (University of Pittsburgh, Pittsburgh, PA)

Background: The objective of this study was to examine the relationship between neuropsychiatric and circadian sleep disturbances in Alzheimer's disease. Sleep disturbances are common in AD and may contribute significantly to clinical morbidity. Neuropsychiatric symptoms in AD are likely influenced by alterations in the sleep–wake cycle, yet these relationships have not been systematically investigated. Methods: 50 Probable AD subjects were evaluated by caregiver-based scales assessing neuropsychiatric symptoms (Neuropsychiatric Inventory–Questionnaire; NPIQ) and circadian sleep disturbances (Circadian Sleep Inventory for Normal and Pathological States; CSINAPS). The latter is a 14-item measure comprising two main subscales: Sleep–Wake Disturbances (SWD; 10 items) and Circadian Behavioral Disturbances (CBD; 4 items). Pearson correlations were performed between the total and individual symptom measures on the NPI-Q and subscales from the CSINAPS. Results: SWD and CBD were both significantly correlated to total NPI-Q score (r=0.34 and r= 0.43, respectively). Among individual NPI-Q symptoms, apathy was most strongly correlated to SWD (r=0.50), and delusions were most strongly correlated to CBD (r=0.43). Conclusions: These findings suggest that neuropsychiatric and sleep disturbances in AD tend to occur together, and that specific interrelationships between these clinical manifestations may reflect overlapping pathophysiological mechanisms.Support from NIA.

P28. Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in patients with Alzheimer's dementiaJohn S. Kennedy, Jamie S. Street, W. Scott Clark, Beth E. Juliar, Peter D. Feldman, Deborah L. Kadam (Eli Lilly and Company, Indianapolis, IN)

Background: A multicenter study was conducted to determine long-term efficacy and safety of olanzapine in treating psychotic symptoms and behavioral disturbances associated with Alzheimer's disease. Methods: Elderly nursing home patients (mean age 83.1 years) with dementia (n=137) who successfully completed a 6-week double-blind study entered an open-label phase of up to 18 weeks during which they received olanzapine (dose range: 5, 10, or 15 mg/day). Mean change in the sum of the Agitation, Delusions, and Hallucinations items of the Neuropsychiatric Inventory–Nursing Home Version (NPI-NH) was used as the primary efficacy measure (Core Total). Results: Following treatment with olanzapine, patients' scores improved significantly on the Core Total (mean=−7.55, SD= 8.53, P<0.001), the Total (mean=−17.85, SD=23.72, P< 0.001), and 10 of the 13 individual item scores of the NPI-NH, including Occupational Disruptiveness (mean=−2.84, SD= 3.24, P<0.001). Barnes Akathisia scores improved significantly from baseline (mean=−0.22, SD=0.80, P=0.002). Simpson-Angus and AIMS scores were not significantly changed. No significant changes occurred in patient ECGs, including QT_c interval, nor in any other vital sign or in weight. Treatment-emergent symptoms included somnolence (26%), accidental injury (25%), and rash (22%). Conclusions: These data suggest that olanzapine is an effective, generally safe, and well tolerated long-term treatment for psychotic symptoms and behavioral disturbances in elderly patients with Alzheimer's dementia.

P29. Reduction of psychotic symptoms by olanzapine in patients with possible Lewy body dementiaJohn S. Kennedy, W. Scott Clark, Jamie S. Street, Todd M. Sanger (Eli Lilly and Company, Indianapolis, IN)

Background: A post hoc analysis was performed on the results of a double-blind, 6-week study of 206 nursing home patients with dementia to determine the efficacy and safety of olanzapine in reducing psychosis and behavioral disturbances. Methods: The effects of 5, 10, and 15 mg/day of olanzapine were assessed relative to placebo in patients who had possible Lewy body dementia (N=29), determined by a nonzero score on the Simpson-Angus Scale and a nonzero score on the Hallucinations item of the Neuropsychiatric Inventory–Nursing Home Version (NPI-NH). All data are reported as mean changes. Results: Patients receiving 5 mg/day of olanzapine improved by 82.9% on the NPI-NH Delusions and Hallucinations combined score, compared with 17.4% for placebo (P=0.015). On the Delusions item, olanzapine-treated patients improved by 77.8%, compared with 29.0% for placebo (P= 0.012). Olanzapine-treated patients showed 85.7% improvement in Occupational Disruptiveness related to the NPI Delusions and Hallucinations items. Placebo-treated patients showed only 14.0% improvement (P=0.002). Significant improvement (P=0.042) was also found on the MMSE for olanzapine-treated patients (2.4-point improvement) compared with placebo (0.1-point worsening). Changes in extrapyramidal side effects were not statistically or clinically significantly different for patients treated with olanzapine. Conclusions: Compared with placebo, 5 mg/day of olanzapine significantly improved psychotic symptoms and behavioral disturbances in patients with possible DLB. Additional well-controlled studies are needed to confirm these results.

P30. Compulsive and repetitive behaviors in Alzheimer's disease: case report and review of the literatureFadi Massoud, Jean Charbonneau, Ngoc-Tram Nguyen (Centre Hospitalier de l'Universitéde Montréal, Montréal, Québec, Canada)

Background: Compulsive and repetitive behaviors are described in dementing disorders, especially frontal lobe dementia (FLD). Case Report: A 69-year-old woman was admitted to our acute geriatrics care unit after being found wandering the streets of the neighborhood. The patient's daughter reported the woman had a 3-year history of paranoid delusions and a 1-year history of global cognitive decline, including short-term memory decline, disorientation, and executive dysfunction. She also reported episodes of repetitive and vigorous scratching of the scalp, with secondary alopecia. Other abnormal behaviors included cleaning rituals and repetitive digging in her garden without obvious reason. On physical examination, the patient was disoriented and had attention and short-term memory deficits as well as visuoconstructive apraxia and executive dysfunction, all consistent with the diagnosis of probable Alzheimer's disease. On examination of her head, a homogeneous area of alopecia was noted, particularly in the bitemporal regions. A SPECT scan showed bitemporal and biparietal hypoperfusion consistent with the clinical diagnosis. She was treated with sertraline 25 mg po qd, with partial response of the compulsive behavior. Literature Review: A MEDLINE (1966–2000) review of the literature was conducted using the terms dementia, Alzheimer's disease, obsessive-compulsive behavior (OCB), and stereotypia. Several papers and their bibliographies were reviewed. Obsessive-compulsive and repetitive behaviors are encountered less frequently in AD (10%–14%) than in FLD (38%–80%). These behaviors take different forms. One paper reports a significant response of OCB in FLD to SSRIs. Conclusions: Obsessive-compulsive behavior is a rare but established entity associated with Alzheimer's disease.Support from Berthiaume–Du Tremblay Foundation.

P31. Individual differences in aging: correlates of depression among older adultsSilvia Mejía, Luz María Hoyos, Gloria Cecilia Henao, David Pineda* (University of San Buenaventura, Medellín, Colombia)

Background: Depression occurs in 15% to 20% of older adults (Gallo and Lebowitz, Psychiatr Serv 1999; 50:1158–1166). The heterogeneous etiology reported in several studies emphasizes the low impact of inheritance in depression (Gottfries, Int Clin Psychopharmacol 1998; 13[suppl 5]:S13–S18). The occurrence of depression in later life has been associated with psychosociogenic factors such as stress processes, cognitive impairment, lack of social support, early losses, premorbid psychopathology, and lower levels of education (Steffens et al, Am J Geriatr Psychiatry 1999, 7:34–40; Kivel et al, Int J Geriatr Psychiatry 1998, 13:527–530; Kubzansky et al, Psychosom Med 1998, 60:578–585) and with physical aging factors like smoking, alcohol abuse, poor general physical health, and functional decline (Vaillant et al, Psychol Med 1998, 28:1159–1168; Roberts et al, J Gerontol B Psychol Sci Soc Sci 1997, 52:S253– S258). Methods: Participants included 34 depressive and 40 nondepressive institutionalized older adults. Retrospective information concerning educational and occupational attainment, medical record, affective history, stressful events during life, and functional decline was gathered through interview. Results: Depressive elders showed greater correlation with psychological factors than nondepressive subjects. Conclusions: Individual differences in psychological history constitute important correlates of depression among elderly persons.

P32. Progressive prosopagnosia: a presenting manifestation of posterior cortical atrophyMario F. Mendez, Mehdi Ghajarnia (University of California at Los Angeles, Los Angeles, CA)

Background: Posterior cortical atrophy (PCA), a dementia syndrome often attributed to Alzheimer's disease, is associated with occipitoparietal atrophy. PCA can result in prosopagnosia, the inability to recognize familiar faces. Methods: We studied a 53-year-old man with progressive facial recognition difficulty of 1 year's duration. He also had difficulty visually recognizing foods and reading. Examination disclosed problems with word-finding, auditory comprehension, reading, and verbal learning. Visual acuity, neurologic examination, and electroencephalography were normal. Structural neuroimaging showed atrophy, and functional neuroimaging showed hypoperfusion in the right temporal lobe and both parieto-occipital areas. Results: Specialized testing was normal for drawings; color naming; visual localization; Benton Line Orientation and Facial Discrimination tests; and Gollin, Street, and overlapping figures. He was unable to recognize pictures of familiar faces, e.g., his wife or well-known politicians or entertainers, but could recognize faces with salient features, e.g., a beard or glasses. When presented with 20 visual objects, he misidentified 5 but matched and describe them visually. Conclusions: PCA may differentially involve the dorsal “where” (occipitoparietal) pathway for spatial perception or the ventral “what” (occipitotemporal) pathway for object perception. Disproportionate disturbance of the right ventral pathway in this patient produced prominent and progressive prosopagnosia with mild associative visual agnosia.

P33. Functional status of elderly adults at various levels of cognitive impairmentRaymond L. Ownby, Lilian Scheinkman, David Loewenstein (University of Miami School of Medicine, Miami, FL)

Background: The importance of assessing functional abilities in elderly persons is evident in the way that functional status is related to the burden of dementing illnesses. Loewenstein and colleagues developed a standardized behavioral measure of functional abilities in the elderly, the Direct Assessment of Functional Status (DAFS; Loewenstein et al, J Gerontol 1989; 44:P114–121). The DAFS includes subtests that assess basic and instrumental activities of daily living. The purpose of this study was to evaluate the relationship of scores on DAFS subtests to various levels of cognitive impairment as assessed by the MMSE. Methods: 542 elderly patients who presented with complaints of memory problems were evaluated with the DAFS, MMSE, and a broad battery of neuropsychological measures. Patients were classified according to MMSE scores into mildly, moderately, and severely impaired groups. We used MANOVA to study the relationships among cognitive function on the MMSE and functional status as measured by DAFS subtests. Results: Overall MANOVA results indicated between-group differences. Univariate ANOVAs showed that scores on each subtest of the DAFS differed significantly among groups. Post hoc tests showed that 12 of 15 DAFS subtests differed among each group. Conclusions: These results show that functional status as assessed by the DAFS is related to general level of cognitive function as evaluated by the MMSE. 12 of the DAFS subtests differentiated patients in each ability domain. These results provide further evidence of the validity of the DAFS in these patients and confirm its usefulness in evaluating patients with memory complaints.

P34. Neuropsychological correlates of functional status in elderly adultsLilian Scheinkman, Raymond L. Ownby,* David Loewenstein (University of Miami School of Medicine, Miami, FL)

Background: The relationship of functional status to diagnosis and disease-related morbidity in elderly persons has long been recognized (Rowe & Katzman, Principles of Geriatric Neurology, 1992). There is thus a need for data regarding functional status in older adults. Loewenstein and colleagues developed a standardized behavioral measure of functional abilities in the elderly, the Direct Assessment of Functional Status (DAFS; Loewenstein et al, J Gerontol 1989; 44:P114–121). In this study we evaluated the relationships among functional skills and cognitive abilities in elderly adults. Methods: 565 elderly patients seen for complaints of memory problems were evaluated with the DAFS, and a broad battery of neuropsychological measures assessed verbal, visuospatial, and memory skills. We used principal factor analysis to study the relationships among ability domains and functional status. Results: The factor analysis showed that DAFS subtests made up an ability domain that was in many respects independent of cognitive abilities assessed by neuropsychological measures. One DAFS subtest that required patients to remember a grocery list was closely related to a memory factor. Several DAFS subtests, including identifying transportation alternatives, writing a check, and making change, showed modest relationships to verbal skills. Conclusions: Results show that functional status as assessed by the DAFS is an independent ability domain that at the same time shows some relationships to cognitive ability measures. These findings support the validity of the DAFS in this group of patients and underscore the importance of a separate assessment of functional abilities in elderly patients evaluated for memory problems.

P35. Neuropsychiatric manifestations of superficial siderosisRodney A. Short, Neill R. Graff-Radford (Mayo Clinic, Jacksonville, FL)

Background: Superficial siderosis is a rare neurologic disorder in which deposition of hemosiderin occurs in the subpial and subependymal margins of the CNS. The cause is most likely chronic subarachnoid hemorrhage. The majority of patients present with sensorineural deafness, cerebellar ataxia, and pyramidal signs (Feamley et al, Brain 1995; 118:1051–1066). Methods: 2 cases are reported with neuropsychiatric manifestations that had the classic neuroimaging findings of superficial siderosis. Results: Case 1 is a 73-year-old man who first developed paresthesias in the lower extremities. Several months later he became manic, exhibiting nonstop talking, insomnia, and obsessive-compulsive behaviors. He developed gait ataxia a few months later. Case 2 is a 79-year-old woman with slowly progressive gait and memory problems who had also become much more argumentative and irritable. She had a decreased appetite with considerable weight loss and excessive sleeping. Neurologic exam revealed a cerebellar ataxia, mild hearing loss, and moderate dementia with severely impaired anterograde memory. The neuroimaging findings of superficial siderosis will be presented in each case. Conclusions: These cases illustrate the diverse presentation, and especially the behavioral and cognitive problems, that can occur in superficial siderosis. If appropriate neuroimaging is not performed in such cases, the diagnosis could easily be missed.

P36. Effects of donepezil on aphasia, agnosia, and apraxia in patients with cerebrovascular lesionsChow Tsz-Ming, Daniel I. Kaufer* (University of Pittsburgh, Pittsburgh, PA)

Background: Disturbances of higher cortical functions are common sequelae of cerebrovascular insults. Pharmacological treatments in this context have generally been unsuccessful. We report 2 patients with multifocal cerebrovascular lesions and higher cortical dysfunction whose symptoms were significantly improved with cholinesterase-inhibitor therapy. Case 1: A 67-year-old male with a history of transient neurological symptoms and diffuse subcortical white matter ischemic changes on MRI imaging suffered a left parieto-occipital hemorrhage. Acute changes included visual agnosia, alexia, acalculia, and anomia. After partial recovery 6 months later, he was started on donepezil 5 mg/day. Follow-up exam 5 weeks later revealed marked improvement in language (speech, reading and writing), awareness, recognition, mood, and general functioning. Case 2: A 55-year-old female with no preexisting deficits developed a left homonymous hemianopia and Balint's syndrome from bilateral parieto-occipital infarctions. 10 months later her residual deficits included severe praxis and visuomotor dysfunction. After 3 months of treatment with donepezil, her praxis deficits had improved markedly and her husband noted robust improvement in her daily functional abilities. Conclusions: Cholinesterase inhibitor therapy may help remediate higher cortical deficits and other dementia symptoms attributable to cerebrovascular lesions in the absence of Alzheimer's disease.Support from NIA.

Traumatic Brain Injury

P37. Normalization of P50 physiology by donepezil hydrochloride in traumatic brain injury patientsDavid B. Arciniegas, Jeannie L. Topkoff, C. Alan Anderson, Christopher M. Filley, Lawrence E. Adler (Denver VAMC, Denver, CO)

Background: Traumatic brain injury may produce hippocampal cholinergic dysfunction. We previously reported that such dysfunction may be reflected by abnormal suppression of the P50 evoked waveform to paired auditory stimuli (Arciniegas et al, Brain Inj 1999; 13:1–13). The present study was performed to determine whether cholinergic augmentation would transiently normalize abnormal P50 suppression. Methods: 10 subjects with remote (>l year) TBI of mild or greater severity (American Congress of Rehabilitation Medicine criteria; J Head Trauma Rehabil 1993; 8:86–87) and persistently impaired auditory gating, attention, and memory were recruited for the study. All subjects demonstrated abnormally large P50 ratios (mean=107, SD=50.1) as determined by our previously described methods (Arciniegas et al, J Neuropsychiatry Clin Neurosci 2000; 12:77–85), and all were naive to procholinergic treatment. Subjects were treated with donepezil HCl 5 mg daily for 6 weeks, at the end of which P50 responses were reassessed. Results: P50 ratios were significantly reduced following treatment with donepezil HCl (mean=45.8, SD=44.1; t=3.95, P=0.004). 80% of subjects showed a reduction in P50 ratio of at least 35%; all subjects with normalized P50 physiology reported subjective improvement in auditory gating. Conclusions: Normalization of P50 nonsuppression and improvement of impaired auditory gating by donepezil supports the hypothesis that cholinergic dysfunction may contribute to the development of persistent cognitive impairments following TBI. The present findings suggest that cholinergic augmentation may benefit persistently symptomatic TBI patients similar to those included in this study.Support from Department of Veterans Affairs and Pfizer, Inc.

P38. Valproic acid in the management of behavioral and psychiatric complications of acquired brain injuryTeresa J. Humaran, Edward Kim (Robert Wood Johnson Medical School, Piscataway, NJ)

Background: Acquired brain injury (ABI) may be complicated by behavioral and psychiatric symptoms (McAllister, Community Ment Health J 1997; 33:341–364). Divalproex sodium has been demonstrated to be effective in reducing agitation related to ABI (Wroblewski et al, Brain Inj 1997; 11:37–47). Methods: A retrospective chart review study was performed for 11 patients referred to an acute psychiatric inpatient/partial hospital program or neuropsychiatry clinic with a history of ABI. All patients received divalproex sodium alone or in combination with other psychotropic medications. Results: Mean serum valproic acid level was 85.6 ng/l (SD=29.6). Mean Clinical Global Impression (CGI) improvement score was 1.9 (SD=0.54). Patients with serum levels above 100 ng/ l (n=5) achieved CGI improvement scores of 1 (extremely improved; n=2) or 2 (much improved; n=3). Patients with levels below 100 (n=6) achieved CGI improvement scores of 2 (n=5) or 3 (minimally improved; n=l). This trend was independent of concomitant medications. Conclusions: Divalproex sodium, either alone or in combination with other psychotropic medications, appears to be effective in reducing neurobehavioral complications of ABI. Serum levels above 100 ng/dl appear to be more effective than lower serum levels.

P39. SPECT imaging in behavioral and psychiatric complications of acquired brain injuryEdward Kim, Teresa J. Humaran (Robert Wood Johnson Medical School, Piscataway, NJ)

Background: SPECT is useful in assessing acquired brain injury (ABI; Masdeu et al, J Neuroimaging 1994; 4:177–181). Patients with ABI may experience significant behavioral dyscontrol and other psychiatric symptoms (McAllister, Community Ment Health J 1997; 33:341–364), although the mechanism of ABI-induced behavioral disorders has not been clearly delineated. Methods: A retrospective chart review study was performed on 13 patients referred to an acute psychiatric inpatient/partial hospital program or neuropsychiatry clinic with a history of ABI. All patients had also undergone SPECT scans as part of their workup. Patient demographics, psychiatric diagnoses, and injury parameters were reviewed. Results: All patients had left orbitofrontal hypoperfusion, and 12 (92%) had bilateral orbitofrontal hypoperfusion. 5 (38%) had right temporal hypoperfusion, 7 (54%) had left temporal hypoperfusion, and 4 (31%) had bitemporal hypoperfusion. 5 (38%) had basal ganglia–thalamic hypoperfusion. This pattern differs from those in previous studies that included patients without neurobehavioral complications (Abdel-Dayan et al, Clin Nucl Med 1998; 23:309–317). Conclusions: Brain-injured patients with neuropsychiatric complications show a pattern of cerebral hypoperfusion different from that of the general brain-injured population.

P40. Reduction in episodic memory fMRI circuitry activation is related to traumatic brain injury severityThomas W. McAllister, Molly B. Sparling, Laura A. Flashman, Stephen J. Guerin, James C. Ford, Alexander C. Mamourian, Andrew J. Saykin (Dartmouth Medical School, Lebanon, NH; New Hampshire Hospital, Concord, NH)

Background: Individuals with traumatic brain injury frequently report problems with encoding and retrieving new information. Particularly with mild TBI, complaints of memory dysfunction can appear out of proportion to measurable deficits. We hypothesized that abnormalities in activation of the circuitry of encoding and retrieval underlie these complaints and thus would be more evident with increasing injury severity. Methods: 23 individuals with mild TBI and 8 with moderate TBI were studied within 1 month of their injury and compared with 15 healthy control subjects. Each group completed symptom checklists, a neuropsychological assessment, and structural and functional MRI (1.5 T). Participants learned a 10-item word list and passively listened to the learned words interspersed with 38 novel words during fMRI acquisition (see Brain 1999; 122:1963–1971 for task details). Results: In all groups, familiar words activated right prefrontal cortex primarily, whereas novel words activated medial temporal structures, particularly parahippocampal gyrus. However, TBI was associated with significant reductions in activation of memory circuitry. This reduction was most apparent in the group with more severe injuries. Conclusions: These results provide evidence of reduced brain activation associated with memory encoding and retrieval processes shortly after mild and moderate TBI. The relationship between activation abnormality and injury severity suggests that these patterns may play a pathophysiological role in memory complaints after TBI.Support from National Institute on Disability and Rehabilitation Research.

P41. A follow-up study of neuropsychiatric sequelae in patients with varying degrees of mild traumatic brain injuryScott McCullagh, Donna Ouchterlony, Andrea Protzner, Nancy Blair, Anthony Feinstein (University of Toronto, Toronto, Ontario, Canada). Will not be presented.

Background: A wide range of neuropsychiatric sequelae may occur following mild TBI, although the relationship between early indices of severity and outcome is unclear. This study examines the potential of the initial Glasgow Coma Scale (GCS) score to predict neuropsychiatric differences at follow-up. Methods: 57 consecutive subjects with mild TBI who were attending a follow-up clinic were grouped according to initial GSC score (15 vs. 13–14) and contrasted at about 160 days post injury. Results: As expected, those with GCS 13–14 had longer posttraumatic amnesia (PTA; P<0.001) and a higher rate of abnormal brain CT scans (P<0.005). However, no significant differences emerged for indices of neuropsychiatric status, including measures of neurobehavioral symptoms/ signs, overall psychological distress, psychiatric “caseness,” functional and psychosocial outcome, frequency of common somatic complaints, and rate of return to work. Subsidiary analyses based on the presence/absence of CT abnormalities and the duration of PTA (<1 hour vs. 1–24 hrs) also failed to yield significant differences. A trend was observed associating longer PTA with reduced functional outcome. Conclusions: Despite clear neurosurgical differences, this study demonstrates that initial GCS scores do not clearly translate into neuropsychiatric heterogeneity at follow-up within the spectrum of mild TBI. Whether this holds for neurocognitive performance is the subject of ongoing work.Support from Medical Research Council of Canada, Ontario Neurotrauma Foundation, and Physicians' Services Incorporated.

P42. Chronic sequelae of minor traumatic brain injury on mouse performance in the Morris water mazeShaul Schreiber, V. Getslev, C.G. Pick (Department of Psychiatry C, Sheba Medical Center, Tel Hashomer; Department of Anatomy and Anthropology, Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel)

Background: Minor traumatic brain injuries (mTBI) commonly present as a number of imprecise perceptual symptoms without objective structural brain alterations. After mTBI, headaches, dizziness, difficulty in concentrating, various degrees of cognitive difficulties, variable amnesia, depression, apathy, and anxiety are common, more so than after severe head injuries. We developed a novel mouse model of minor traumatic brain injury to reproduce long-lasting cognitive and behavioral deficits in mice similar to the persistent deficits in human mTBI syndrome. Methods: Following 20-g, 25-g, or 30-g glide mode injury, brain nMRI and neurological status of the experimental animals was assessed in each group at 1 hour and 24 hours. Preliminary nMRI study demonstrated absence of any morphological changes in the brains of injured mice compared with the control mice 24 hours after a sustained 20-g glide mode injury. Only animals with no neurological score were permitted for future experiments. All groups were trained at Morris water maze at the different intervals following the injury according to the standard protocol. Results: Control mice learned to find an invisible escape platform located in a fixed position relative to environmental cues more rapidly than did injured mice. Escape latencies of animals that sustained mTBI were significantly increased compared with control subjects (P<0.01). Control mice also displayed better knowledge of the platform location during a probe trial conducted in the absence of the escape platform on day 5 by crossing the platform field about 30% more often than did injured animals (P<0.001). Conclusions: These results show clear long-term effect of mTBI on learning behavior in mice that is similar to the persistent deficit of cognitive learning abilities in human mTBI syndrome.

P43. Combined clinical and neuroSPECT guidance of drug treatment choice in minor traumatic brain injuryShaul Schreiber, E. Goshen, T. Gur-Hartman, E. Klag, S.T. Zwas, C.G. Pick (Departments of Psychiatry C and Nuclear Medicine, Sheba Medical Center, Tel-Hashomer; Department of Anatomy and Anthropology, Tel-Aviv University Sackler School of Medicine, Tel-Aviv; Neuropsychiatry Unit for Treatment and Rehabilitation, Tel-Aviv, Israel)

Background: Various drugs are available for treatment of chronic sequelae following minor traumatic brain injuries (mTBI), including mood stabilizers, reversible inhibitors of monoamine oxidase, and SSRIs. Choosing the drug can be challenging, in face of the often nonspecific clinical findings. The aim of this study was to guide treatment choice by combined NeuroSPECT and neuropsychological evaluation in a group of mTBI patients. Methods: 10 consecutive male patients, ages 20 to 52 years (mean=22), 6 months to 28 years post mTBI, with normal brain CT/MRI studies, were included. All underwent a standardized battery of neuropsychological tests. NeuroSPECT was performed following intravenous injection of 30 mCi [^99mTc]-ethyl cysteinate dimer, using a dual-head gamma camera equipped with fan-beam collimators. Results: The NeuroSPECT and neuropsychological data revealed local or diffuse hypoperfusion changes in frontotemporal regions (bilaterally in 6/10 patients, unilaterally in 4/10); in parietal regions in 5/10 patients; and in basal ganglia in 1/10. Neuropsychological results were less localized regionally but correlated well with NeuroSPECT findings, demonstrating frontal disturbances without clear lateralizations. Combined findings defined localization and extent of injury with corresponding neurocognitive dysfunction and served as the basis for treatment choice. According to clinical follow-up results, all 10 patients benefited from their individually specified treatments. A follow-up SPECT showed improvement that warranted altering treatment. Conclusions: Combined evaluations may have significant impact on mTBI drug treatment choice, but more studies are needed for further evaluation of this approach.

P44. Presence of postconcussion syndrome symptoms in chronic pain versus head injury patientsLaura Smith-Seemiller, Neil R. Fow, Michael D. Franzen, Ravi Kant (HealthSouth Rehabilitation Hospital of Sewickley, PA)

Background: Many people who experience mild head injuries (HI) experience prolonged symptomatology, which has been termed postconcussion syndrome (PCS). This syndrome includes affective, cognitive, and somatic symptoms. The etiology of PCS has been debated, with both neurological and psychosocial factors suggested. It has been noted that people with chronic pain (CP) have many of the features of PCS; however, direct comparisons between CP and HI patients have been limited. In this study we compared chronic pain patients with mild head injury patients on a questionnaire that assesses PCS symptoms. Methods: Subjects included 47 CP patients with no history of neurological problems and 31 people with HI (74% classified as mild HI). Subjects completed the Rivermeade Post-Concussion Questionnaire (RPCQ). Differences between the two groups on RPCQ scores were analyzed by using the Mann-Whitney U-test. Results: There was no difference between groups for the RPCQ total score. Among individual items, however, CP patients had higher scores (endorsed worse symptomatology) on five items: sleep disturbance, fatigue, depression, frustration, and restlessness. Conclusions: Symptoms of postconcussion syndrome symptoms are not unique to mild head injury and may be seen in other diagnostic groups such as chronic pain. This suggests that factors other than neurological impairment (e.g., psychological distress) may be causally related to prolonged PCS.

P45. Persistent alteration of Simple Reaction Time and Continuous Performance Test in grade 1 boxing concussions after resolution of symptomsDeborah Warden, Joseph Bleiberg, Ken Cameron, Winston Punch, James Ecklund (Walter Reed Defense and Veterans Head Injury Program, Washington, DC)

Background: Existing sports concussion guidelines have been based largely on expert clinical judgment. We hypothesized that an onsite, brief, computerized assessment of cognitive function (National Rehabilitation Hospital Automated Neuropsychological Metrics; NRH-ANAM) could aid assessment of the recovery process. Methods: 430 West Point cadets were baselined prior to boxing. Concussed students were retested by sports trainers within 1 hour of injury, 24 hours later, and at day 4. Scores of the concussed group were compared with baselines of the same group by using t-tests. Results: 19 cadets received a grade 1 concussion and were asymptomatic by the expiration of their 4-day pass. Simple Reaction Time (SRT) and Continuous Performance Test (CPT) score were significantly slower at all time periods (P=0.001 and P=0.044, respectively, at day 4 compared with baseline). Math subtest was slower at 1 and 24 hours but normalized by day 4. Memory tests (Sternberg and Code Substitution Delayed) showed no decrement at any testing. Conclusions: In grade 1 concussion, tests requiring complex mental processing are less sensitive to concussion than SRT and CPT. All subjects were asymptomatic by day 4, at which time they still tested slower on SRT and CPT.Support from the Department of Defense.

POSTER SESSION II—TUESDAY, FEBRUARY 27

Schizophrenia

P46. Visual processing disturbances in schizophrenia: nature and specificityStéphane Ertlé, Christine Rebourg (FORENAP, Rouffach, France)

Background: Most neuropsychological research in schizophrenia has focused on attention, executive function, and memory. In this study, we attempt to evaluate the nature of the visual gnosis impairment in schizophrenia. Methods: Subjects were 30 schizophrenic patients according to DSM-IV criteria. All were under neuroleptic treatment. The tasks were also given to age- and sex-matched control subjects. Three tasks were used: the Progressive Enrichment of Visual Information Test, the Boston Naming Test, and the Benton Facial Recognition Test. Results: Statistically significant differences suggest that in schizophrenic patients, more cues are requested in order to recognize an object; there is inadequate generalization from a partial arbitrary detail; and images of an object presented in different spatial positions are not recognized as being similar (i.e., face seen from different angles). Conclusions: We notice specific perceptual disturbances in schizophrenic patients. These impairments are discontinuous within and between tasks. The gestalt of an object is not apprehended as a whole but as the sum of different elements. All information regarding the object is not synthesized. Interactions with attention abilities and visual scanning are taken into consideration.

P47. The dimensions of schizotypia: a confirmatory factor analytic explorationRudy Hatfield, Douglas Whitman* (Wayne State University, Detroit, MI)

Background: Results from prior exploratory factor analyses (EFA) of scales designed to measure schizotypal personality disorder report two-, three-, and four-factor solutions for schizotypia. These studies failed to investigate the proposed structure of contributory schizotypia components such as perceptual aberration, magical thinking, and physical anhedonia and often used insufficient sample sizes. Methods: The current research used confirmatory factor analysis (CFA) to investigate the components and structure of the most commonly used schizotypia scales, using 1,478 subjects. Results: Results indicate that perceptual aberration, magical thinking, and physical anhedonia each comprise different components and may not represent unitary constructs. The components of these schizotypal dimensions were subjected to CFA. Several models were compared for fit, and the three-factor model was supported. In the current study, this solution includes a positive or perceptual distortions factor (both Perceptual Aberration Scale components and the STA Unusual Perceptual Experiences component study loaded on this factor), an anhedonia component (all three anhedonia components loaded on this factor), and a nonconformity or atypical belief factor (the two Magical Ideation components and the STA Magical Thinking and Paranoid Suspiciousness components loaded on this factor ).Support from the Ethyl and James Flinn Family Foundation.

P48. Abstract withdrawn.

P49. Laterality differences in mental rotation in psychosis-prone individualsDouglas Whitman, Robert Kotasek, Robin Hanks (Wayne State University and Rehabilitation Institute of Michigan, Detroit, MI)

Methods: 20 psychosis-prone individuals and 20 matched control subjects were administered a battery of tests sensitive to attention, plus line orientation, the National Adult Reading Test, and a mental rotation task. The central presentation of the initial figure (a three-dimensional matrix pattern) was followed by a 30-ms rotated comparison figure in either the right or left visual field. Results: No differences were found on self-reported depression, anxiety, attention span, visual-motor scanning, or sustained selective attention. The psychosis-prone group was more accurate at line orientation, took less time inspecting the initial figure, and was more accurate on the mental rotation task overall. Only control subjects showed a reduction in accuracy with right visual field–left hemisphere presentations of the rotated stimulus. Subjects slower on the numerical subtraction task had longer inspection times of the initial rotation stimulus and were less accurate with right visual field presentations of the test stimulus. Conclusions: These results suggest that verbal mediation may contribute to greater difficulties in left hemisphere mental rotation, particularly for the control subjects, and are viewed as further evidence that psychosis-prone and schizophrenic individuals show deficits in left hemisphere information processing, or hyperarousal of the right hemisphere, and show deficits in visual working memory.Support from the Ethyl and James Flinn Family Foundation.

P50. Glucose intolerance with atypical antipsychoticsD.R. Wilson, L. D'Souza, L. Johansen, N. Sarkar (Creighton University, Omaha, NE)

Background: The authors have previously reported diabetes and ketosis associated with atypical antipsychotics in a state hospital cohort and now report preliminary findings from their more systematic evaluation of the statewide Ohio Department of Mental Health database. Methods: The Ohio central pharmacy and laboratory computerized records of all adult patients were retrospectively reviewed for a 60-month period (May 1995 to May 2000) to identify patients either treated with novel antipsychotics or evaluated for diabetes. The full charts of patients on both lists were hand reviewed as to age, sex, diagnosis, prescription history, diabetic risks, and clinical association of glucose intolerance and treatment with atypical antipsychotics. Results: Preliminary analysis confirms the previous case-series association of new-onset diabetes with use of some atypical antipsychotics. A more extensive analysis of the database continues to ascertain whether: 1) hyperglycemic effects are compound-specific, 2) more assertive treatment monitoring is warranted, 3) unique patient factors influence risk for new-onset diabetes, and 4) informed-consent issues can be clarified. Conclusions: At least some antipsychotics appear to be dangerously diabetogenic. More systematic study data are urgently needed.Support from the Ohio Department of Mental Health and Janssen Research Foundation.

P51. Reciprocal hemispheric integration of semantic networks: relationship to creativity and schizophreniaJason Zanes, Adele Hutchinson, Douglas Whitman* (Wayne State University, Detroit, MI), Bradley Axelrod (Detroit, MI)

Background: Priming the right hemisphere, by the presentation of a prime stimulus (e.g., a word) to the left visual temporal half field arouses both close and remote associations; in contrast, priming the left hemisphere arouses only closely related words. These findings are supported by studies using positron emission tomography. Methods: We showed the effect of priming each hemisphere upon the contralateral hemisphere by contrasting target priming in the contralateral hemisphere at two different prime-target offsets (stimulus onset asynchrony of 50 ms and 750 ms). Results: We demonstrated symmetrical priming results in activating neural networks in both hemispheres. There was a narrow spread of activation in the left hemisphere, a broad activation of neural networks in the right hemisphere, and a reciprocal, topographically similar activation of fundamentally different neural networks in the hemisphere contralateral to the one originally activated. Further, when subjects were divided on the basis of performance on a battery of creativity measures, highly creative subjects showed greater priming and they showed a broader spread of activation, particularly in the right hemisphere. These differences in semantic priming are discussed in reference to asymmetries in cognitive processing, schizotypic and schizophrenic individuals, individuals with Alzheimer's disease, and individuals scoring high on creativity.Support from the Ethyl and James Flinn Family Foundation.

P52. Neuropsychological differentiation of late-life schizophrenia and frontotemporal dementiaKonstantine K. Zakzanis, Donald A. Young, Mark Boulas (University of Toronto at Scarborough, Toronto, Ontario, Canada)

Background: Frontal-temporal dementia (FTD) and schizophrenia are characterized by disturbances in cognition, personality, behavior, and social functioning often leading to a decline in activities of daily living. Deterioration of comportment and disturbances in attention are typical in both disorders and manifest behaviorally in terms of withdrawal, isolation, lack of volition, emotional unresponsiveness, and poverty of speech. Accordingly, the considerable overlap in behavioral expression between patients with schizophrenia and those with FTD makes a differential diagnosis difficult. This differential diagnosis is especially difficult when the age at onset of schizophrenia is late (i.e., age 45 or older). The purpose of this study was to identify which neuropsychological tests best differentiate patients with late-onset schizophrenia from patients with FTD. Methods: Neurocognitive test results from a total of 12 patients with FTD and 32 patients with schizophrenia were analyzed by using test sensitivity statistics (i.e., Cohen's U2 percent overlap). Results: The results support a test battery composed of the WAIS-R Vocabulary, Information, Digit Span, and Comprehension subtests and the Hooper Visual Organization Test as being the most sensitive measures to diagnostic differentiation between patients with FTD and those with late-onset schizophrenia.

Pediatric Neuropsychiatry

P53. Suspected mitochondrial disorders in pediatric mood disordersL. Jarrett Barnhill (University of North Carolina, Chapel Hill, NC)

Background: Variants of childhood-onset bipolar affective disorder (BPAD) are relatively common among selected populations with ADHD, irritability, explosive behaviors, hypersexual behavior, and other disruptive behaviors. Migraine headaches and cyclical vomiting are also reported at increased rates among children with BPAD. Cyclical changes in metabolic function and encephalopathy are common in mitochondrial disorders, especially following physiological challenges and febrile illness. Mood and behavioral changes associated with mitochondrial disorders may be overlooked in some forms of treatment-resistant BPAD. Methods: Case studies will be presented of treatment-refractory mood disorders that responded to carnitine, riboflavin, and coenzyme Q. Results: Although probably rare, treatment-refractory mood disorders or other cyclical disorders in children may reflect underlying metabolic disorders. A history of recurring vomiting, migraine headaches, periods of lethargy and excitement, and either failure to respond to mood stabilizers or an apparent worsening with valproic acid may be indicators. Conclusions: Mitochondrial disorders are a complex group of maternally transmitted disorders that should be considered in treatment-refractory mood disorders.

P54. Cerebral magnetic resonance relaxometry in developmental right hemisphere learning disabilitiesYitzchak Frank, P. B. Kingsley, S. G. Pavlakis (North Shore Hospital, Manhasset, NY; NYU School of Medicine, New York, NY). Not presented.

Background: Nonverbal learning disabilities (NVLD) are developmental syndromes characterized by a significant verbal–performance IQ discrepancy, deficits in visuospatial and visuoconstructive ability, social-emotional disability, and impaired academic achievements. NVLD are similar to clinical abnormalities seen after right hemisphere damage and may be caused by a developmental right hemisphere abnormality, possibly in the white matter (WM). MRI relaxometry is a quantitative imaging method to measure T₁ relaxation times, which can be affected by water/protein ratio, myelination, and iron content. It may be useful for characterization of tissues and pathologic states. Methods: We investigated the relationship between IQ scores (FSIQ, VIQ, and PIQ) and WM T₁, measured on both sides in the centrum semiovale (RCS and LCS) and at the basal ganglia level (RBG and LBG), in 20 children with NVLD, other LDs, or no LD. Results: IQ scores generally increased as WM T₁ decreased, and the correlation strengths were VIQ>(VIQ−PIQ)∼FSIQ>PIQ and RCS>(RCS+ LCS)>(RBG−LBG). Strongest correlations were found between VIQ and RCS (P=0.009), VIQ and RCS+LCS (P= 0.011), and VIQ and RBG−LBG (P=0.018); between VIQ− PIQ and RBG−LBG (P=0.013); and between FSIQ and RCS (P=0.015). Conclusions: Quantitative MRI measurements may increase our understanding of the brain properties that contribute to cognitive performance.

P55. Trends in the use of alternative therapies in a pediatric neuropsychiatry clinicJoseph P. Horrigan, L. Jarrett Barnhill (University of North Carolina, Chapel Hill, NC)

Background: Complementary and alternative medicine (CAM) has grown in popularity over the past decade. However, there is a lack of systematic data concerning CAM consumption patterns in neuropsychiatric populations. Methods: A survey addressing CAM usage (including antioxidants, herbs, nutritional supplements, and homeopathy) was conducted at a university-based pediatric neuropsychiatry clinic in March 1998 and March 2000. Results: There were 180 responses in 1998 and 201 in 2000 (age range 3–17 years). The current use of any type of CAM treatment was 56% in 1998 and 51% in 2000 (P=0.059). For both years, only 43% informed the clinic physician of the concurrent use of CAM therapies. A downward trend was noted for all types of CAM consumption; this was statistically significant for antioxidant use (51% to 41%, P=0.045) and botanical (herbs) use (11% to 4%, P=0.025). The percentage of families that desired further knowledge about CAM therapies declined (66% to 47%, P< 0.001). There were no definitive cases of adverse interactions between psychotropic medications and CAM therapies. Conclusions: The attraction to these alternative therapies appears to be lessening, at least in this clinic population. Various reasons may account for this negative trend, including a lack of efficacy.

P56. Genetic correlates of impulsive/explosive aggression in juvenilesDaniel T. Matthews, Larry Fisher, Kenneth Blum (Comprehensive Neurobehavioral Systems, Cedar Park, TX)

Methods: The “behavioral phenotype”under study was the pathologically aggressive juvenile whose violent behaviors were impulsive/explosive, as opposed to premeditated, as determined by history and structured interview. The 11 subjects, ages 12 to 19 years, were in residential treatment for this type of pathological aggression and showed abnormalities in their long-latency evoked responses. Using standard procedures, we genotyped these 11 subjects for DRD2 and DAT1 gene polymorphisms. Results: The results show that 11 of 11 subjects (100%) showed polymorphisms of the DAT1 (vent 10) gene. A significant association was found for the DAT1 10 gene and pathological aggression when compared with literature controls, in whom 34 of 91 (37.4%) showed this polymorphism (χ²=15.6, df=l, P<0.00006), Additionally, 6 of the 11 subjects (56%) showed polymorphisms of the DRD2 A1 allele. All 6 had absent P300 responses. Compared with literature controls, of whom 1 out of 30 (3.3%) showed this polymorphism, a significant association for the DRD2 A1 gene and pathological aggression was observed (χ²=14.9, df=l, P< 0.00006). Conclusions: If these associations can be replicated, this genotype/phenotype relationship may allow for early identification of children at risk. It may also be possible to target treatment more effectively.

P57. Predictive factors in the use of valproic acid in children and adolescentsSamuel O. Okpaku, K. Elizabeth Spivey (Vanderbilt University, Nashville, TN)

Background: (See Jensen et al, Psychoactive medication prescribing practice for U.S. children: gaps between research and clinical practice. J Am Acad Child Adolesc Psychiatry 1999; 38:557–565.) There is limited research data on the clinical psychopharmacology for children and adolescents with psychiatric problems. Many psychotropic medications do not have FDA approval for use in this population. Clinicians therefore are forced to extrapolate their experience with adult patients in prescribing for this group. This off-label practice is quite common in adolescent patients for whom nonpsychotropic means of treatment have failed. The present study attempts to predict use of valproic acid in this population. Methods: This study is based on a chart review of 132 consecutive children and adolescent patients admitted to a university psychiatric hospital. Data on demographics, symptom profile, diagnosis, and medications were abstracted and analyzed. Results: Valproic use in this population was independent of age, gender, and diagnosis. However, the use of valproic for bipolar disorder appeared more apparent than in any other groups. Grandiosity (β=2.68, P=0.008), Homicidal Ideation (β= 1.50, P=0.006), and Fire Setting (β=1.88, P=0.04) were significant predictors for the population receiving valproic acid. Conclusions: The use of valproic acid in this population in whom the classical psychiatric syndromes are yet not fully expressed requires further studies.Support from Abbott Laboratories.

P58. Pathological antecedents of Colombian adolescent offendersDavid A. Pineda, Ana Isabel Isaza, Isabel Cristina Puerta (University of San Buenaventura and University of Antioquia, Medellín, Colombia)

Background: Physical and peer conflict relationships have been related to conduct disorder in children and adolescents (Gortmaker et al, Pediatrics 1990, 85:267–276; Cadoret et al, Arch Gen Psychiatry 1995, 52:916–924). The objective of this study was to determine if adolescent offenders with conduct disorder (CD) have different physical and psychological antecedents than control adolescents. Methods: A sample of 138 male participants, ages 12 to 16 years, was selected. 68 control subjects were attending regular schools and 70 cases were attending institutions of reeducative training for offenders. Groups were matched by age, socioeconomic status, and habitual place of residence. Results: Cases had more pathological antecedents during pregnancy (P<0.02), higher scores in conflictive relationships with peers during childhood (P<0.001), and higher scores in ADHD antecedents.(P<0.05) than control subjects. Conclusions: Offender adolescents have more physical and psychological abnormal antecedents than control subjects, which would represent risk factors for developing conduct disorder during adolescence.

P59. Examination of minor neurological signs in children, IP.S.B. Sarma (FUHS/The Chicago Medical School, Department of Psychiatry, North Chicago, IL)

Background: Right-handed males have more markedly lateralized cerebral hemispheres than left-handed males. They generally use the same hand for writing and throwing. If there is a dissociation of hand preference for writing and throwing in boys who write with the right hand, it might be due to some noxious effect on the development of the brain. If so, it should affect their academic functioning. Methods and Results: In a preliminary test of this hypothesis, the author surveyed the total population of third- and fourth-graders in an urban school district. The boys who wrote with the right hand (RHW) but threw with the left scored significantly lower on study skills on the California Achievement Test than the comparison group who wrote with the left (LHW) but threw with the right (P<0.05). In the second study, a new sample of mixed-handed boys in grades six to eight were compared. The RHW group obtained spelling scores more than one standard deviation below the mean significantly more frequently than the LHW group (χ²=6.53, df=1, P=0.025). 62% of the RHW group scored below 30 in reading, language or spelling, whereas only 35% of the LHW group did so. Conclusions: Mixed handedness as defined above (seen in less than 5% of males) is an appropriate item for an examination of minor neurological signs in boys.Support from NIH Grant BRSG S07 RR05366.

P60. Long-term memory associated with processing of words in high-functioning autismMotomi Toichi (Case Western Reserve University, Cleveland, OH)

Background: Semantic processing of verbal materials facilitates long-term memory (LTM) better than “shallow” (phonological or perceptual) processing both in normal and amnesic subjects, which is known as the levels-of-processing effect (Craik and Tulving, J Exp Psychol 1975; 104:268–294). Although a parallel between autism and amnesia has long been suggested, there have been no studies that examined this effect in autism. Methods: In Study 1, a levels-of-processing task was conducted on 48 healthy volunteers. In Study 2, the same task was conducted on 20 autistic subjects with mild or no mental retardation and 20 ability-matched control subjects. Results: Study 1 confirmed the levels-of-processing effect with our task. In Study 2, although the levels-of-processing effect was confirmed in the control group, it was not found in the autistic group. Conclusions: The lack of the levels-of-processing effect in the autistic subjects indicates that autism is different from amnesia with medial temporal pathology. The failure to use semantic information in remembering suggests similarities in LTM between autism and frontal lobe dysfunction.

Imaging

P61. Effects of aging on a nonverbal recognition task: an H₂¹⁵O PET studyKaren E. Anderson, Katherine Lynch, Aileen Park, Bridget Pierpont, Joseph Flynn, Ronald Van Heertum, Harold Sackeim, Yaakov Stern (Columbia University, New York, NY)

Background: To help understand how normal aging affects nonverbal memory, positron emission tomography was used to obtain regional cerebral blood flow measurements in 12 normal elders and 20 young subjects during performance of an abstract shape recognition task. Methods: Subjects were studied during Titrated Demand, with study list size (SLS) adjusted in a staircase manner so that each subject performed at 75% recognition accuracy. A control condition with SLS=1 was also used. Activation patterns were analyzed by using Statistical Parametric Mapping (SPM96). Results: SLS averaged 7.3±4.3 shapes for elders and 13.2±6.6 for young subjects. Compared with the control condition, Titrated Demand was associated with right prefrontal cortex activation in elders (corrected P=0.030), and left medial temporal lobe deactivation (P=0.038). Young subjects demonstrated right inferior frontal and left superior occipital cortical activation (P=0.059 and P=0.006, respectively), and left medial temporal and lingual gyrus deactivation (P=0.021 and P=0.054, respectively). Conclusions: Elderly subjects attained a lower list length during a Titrated Demand shape recognition condition than young subjects. Compared with the control condition, elders activated prefrontal cortical areas, associated with working memory, during Titrated task performance. Young subjects activated inferior frontal and left occipital regions, which perhaps enabled them to automate and maximize task performance.Support from the Dana Foundation.

P62. Multisubject 3D template images for neuroimaging studies in baboonKevin J. Black, Abraham Z. Snyder, Jonathan M. Koller, Mokhtar H. Gado, Joel S. Perlmutter (Washington University School of Medicine, St. Louis, MO)

Background: Human functional neuroimaging studies are often interpreted after registration to a high-quality 3D template image easily referable to a published atlas. Such a template was not available for baboons, limiting analysis of neuroimaging studies. Methods: We formed a T₁-weighted structural MR template image from 9 baboons and an H₂¹⁵O PET template from 7 baboons, forcing them to fit the 1968 Davis and Huffman photomicrographic atlas. Custom software aligns individual MR images to the MRI template; human supervision is needed only to initially estimate any gross rotational misalignment. Results: In aligned individual images, internal subcortical fiducial points correspond closely to the printed atlas, with an average error of 1.53 mm. Cortical test points showed a mean error of 1.99 mm. A multisubject PET template was formed, and individual PET images were aligned directly to this template. The result was tested by comparison to a two-step alignment process, via each subject's MR image, and was identical within 0.41 mm, 0.54 degrees, and 1.0 percent (translation, rotation, and linear stretch; average), providing a check on the validity of the alignment software as well as of the template images. Conclusions: The baboon templates are accurate and can be used as targets for any image registration software.Support from the National Institute of Neurological Disorders and Stroke, NARSAD, the Tourette Syndrome Association, the American Parkinson Disease Association, and the Dana Foundation.

P63. Brain regions involved in deception: an fMRI study in healthy volunteersF. Andrew Kozel, Letty Revell, Jeffrey P. Lorberbaum, Ananda Shastri, Ziad Nahas, Michael D. Horner, Diana J. Vincent, Mikhail Lomarev, Daryl E. Bohning, Mark S. George (Functional Neuroimaging Division, Medical University of South Carolina, Charleston, SC)

Background: Deception is ubiquitous in medicine and in our culture. The polygraph is presently used extensively to evaluate for deception despite its poor predictive power (Brett et al, Lancet 1986; i,8480:544). Blood-oxygenation-level-dependent (BOLD)-fMRI has been shown to be a useful tool to probe neuronal circuitry involved in emotion, memory, and other cognitive functions (George et al, Neuroimaging Approaches to the Study of Emotion: The Neuropsychology of Emotion, ed. Borod, 2000, pp 106–134). We hypothesized that deception would correlate with increased regional cerebral blood flow in the anterior cingulate gyrus, orbitofrontal region, and amygdala. Methods: 10 right-handed healthy adults (2 females) were consented, screened, and given personality questionnaires (MMPI-2, TCI). Subjects were asked to find money hidden under objects. In the MRI scanner (Picker 1.5 T), subjects gave truthful and deceptive answers regarding the location of the money. While they were being scanned, electrodermal and electrocardiac data were also acquired. Results: Statistical parametric analysis (using MedX 3.2/SPM96) will be performed comparing brain changes during truthful and deceptive answers (P<0.001; cluster probability threshold P<0.05). Group and individual analysis are under way. In addition, electrodermal activity and personality scores on MMPI and TCI will be correlated with rCBF changes across the paradigm. Conclusions: BOLD-fMRI appears to be a feasible tool to investigate deception. Further analysis will help better qualify the underlying mechanism of deception and may lead to future investigations into neuropsychiatric conditions such as sociopathy, conversion disorder, factitious disorder, and malingering.

P64. Increased frontal and parietal activation in a schizophrenic mother and her schizophrenic son after treatment with olanzapine: a longitudinal fMRI studyAnders Lund, K. Stordal, R. Kroken, T. Thomsen, L. Ersland, A.I. Smievoll, R. Barndon, A. Lundervold, H. Sundberg, K. Hugdahl (Dept. of Psychiatry, U. of Bergen, (Norway). Will not be presented.

Background: Schizophrenia is associated with impaired cognitive functioning related to the frontal and temporal brain regions. This is found in behavioral tests and also in functional imaging studies. These impairments are often thought to be irreversible, or even show worsening over time. Methods: A young drug-naive schizophrenic patient and his unmedicated schizophrenic mother were tested with a working memory/ mental arithmetic test during fMRI before and after treatment with the new atypical antipsychotic drug olanzapine for several months. Results: A normalization of activation in both the prefrontal and the parietal regions was observed after treatment with olanzapine for several months. An improvement in cognitive functions and a dramatic decrease in psychiatric symptoms paralleled this increased activation in fMRI. Conclusions: This study points to the possible restoration of neuronal activation in brain regions that are critical for cognitive functioning after olanzapine treatment, even in a patient who has suffered from schizophrenia for several years.Support from the Norwegian Research Council.

P65. rCBF changes related to the processing of increasing monetary rewardChantal Martin-Soelch, Wolfram Schultz, John Missimer, Klaus L. Leenders (Paul Scherrer Institut, Villigen, Switzerland)

Background: Reward, a major determinant of goal-directed behavior, seems to be processed by the mesolimbic dopamine system (Berridge and Robinson, Brain Res Rev 1998; 28:309– 369). A previous PET study (Künig et al, NeuroReport, in press) showed that dopaminergic regions respond in a comparison between monetary reward and neutral feedback. Our purpose is the investigation of regions activated in processing the amount of monetary reward. Methods: We measured regional cerebral blood flow in healthy subjects with H₂¹⁵O PET while they performed a pattern recognition task. Subjects received three different amounts of money as reward. Each amount defined a different task condition. Results: Regions showing increasing activation with increasing monetary reward were located in the right and left frontal cortex, right and left parietal lobule, right and left superior temporal cortex, right and left occipital cortex, left cingulate gyrus, left midbrain, right fornix, and left cerebellum. Conclusions: Attribution of the value of reward seems to involve principally associative and limbic cortical regions. Typical dopaminergic regions like the striatum are not involved. This suggests that these regions participate in the processing of qualitative rather than quantitative aspects of reward.Support from Swiss National Science Foundation NFP38 and European Science Commission BIODED2.

P66. Brainstem serotonin transporter availability is reduced in poststroke pathological cryingToshiya Murai, Henryk Barthel, Jörg Berrouschot, Dietlind Sorger, D. Yves von Cramon, Ulrich Müller (Max Planck Institute of Cognitive Neuroscience, Leipzig, Germany)

Background: Pathological crying (PC) is a neuropsychiatric disorder characterized by an excessive tendency toward crying after brain damage. SSRIs are very effective in treating this condition, suggesting that altered serotonin (5-HT) neurotransmission is involved in the pathogenesis of PC. To elucidate the role of 5-HT neurotransmission for PC, the authors estimated central 5-HT transporter (5-HTT) availability in stroke patients either with PC or without. Methods: 6 patients with PC and 9 patients without PC after unilateral cerebral infarction underwent SPECT using the 5-HTT ligand [¹²³I]β-CIT. Specific-to-nonspecific binding ratios (a measure of regional 5-HTT density) were calculated for midbrain/pons and thalamus/hypothalamus. Results: In the PC group, midbrain/ pons binding ratios were significantly lower than those of the non-PC group (1.26±0.51 vs. 1.93±0.59, P=0.025). There was no significant difference in the thalamus/hypothalamus binding ratios between these two groups. Conclusions: These preliminary results support the idea that pathological crying would be caused by the combination of damaged limbic-cortical networks and reduced raphe 5-HTT availability. The findings also have implications for understanding the neural basis of normal sadness and crying.Support from DAAD, Bonn, Germany.

P67. Brain systems of anhedonia in schizophrenia: an H₂¹⁵O PET study of unpleasant stimuliSergio Paradiso, Benedicto C. Facorro, Nancy C. Andreasen, Debra L. Johnson, Daniel S. O'Leary, Leonard G. Watkins, Laura L. Boles Ponto, Richard D. Hichwa (University of Iowa, Iowa City, IA).

Background: Anhedonia, a core symptom of schizophrenia, has rarely been studied at the neural level. We examined neural correlates of anhedonia in schizophrenia, using visual valence attribution probe to assess functioning of the frontal lobe and limbic system, regions shown to be involved in hedonic capacity in healthy volunteers (Paradiso et al, Am J Psychiatry 1999; 156:1618–1629). Methods: 18 drug-free patients (6 drug-naive, 12 for >3 weeks) with schizophrenia (16 male, mean age 30 years, SD=8.9, mean education 14.5 years, SD=3.3) and 17 healthy control subjects (10 female, mean age 31.2, SD=8.7, mean education 14.5 years, SD=1.6) were shown two sets of emotionally laden pictures carrying pleasant and unpleasant content (Lang et al, International Affective Picture System: Technical Manual, 1995). Subjects were asked to evaluate the visual stimuli for emotional valence while rCBF was measured with the use of H₂¹⁵O PET (Andreasen et al, Proc Natl Acad Sci USA 1995; 92:5111–5115). Subjects' ratings of emotional valence were recorded on a verbal analog scale ranging from –7 (very unpleasant) to 7 (very pleasant). Data were analyzed by comparing PET data acquired during the unpleasant and pleasant image sets in patients and control subjects, using a randomization nonparametric analysis unaffected by the difference in variance across groups (Arndt et al, J Cereb Blood Flow Metab 1996; 16:1271–1279). Results: Patients rated unpleasant pictures similarly to control subjects (patients: –4.37, SD=4.48; control subjects: –4.87, SD=4.09; F=0.10, df=1,30, P=0.7) but showed inability to attribute the correct hedonic value to pleasant stimuli (patients: 3.62, SD=4.04; control subjects: 6.11, SD=1.11; F=5.97, df=1,31, P=0.02, two-tailed). During appraisal of unpleasant stimuli, patients showed increased blood flow in orbital and medial frontal regions but abnormally decreased activity in limbic regions (i.e., orbital frontal cortex, amygdala, hippocampus, and thalamus), cerebellum, and extrastriate cortex compared with control subjects. Patients' evaluation of pleasant stimuli resulted in a small area of increased blood flow in ventral prefrontal cortex and several activation defects in sectors of prefrontal cortex, of right anterior and posterior insula, and of tertiary association cortex in the parietal lobe. Conclusions: Prefrontal activation deficit is perhaps responsible for patients' inability to attribute correct hedonic value to pleasant pictures. Attributing correct valence to unpleasant stimuli (an evolutionarily more relevant task) is associated with failure to recruit limbic/cerebellar territories but with compensatory engagement of prefrontal circuitry. Complex abnormalities of cerebellar, mesolimbic, and frontal functional interactions may be at the core of anhedonia in schizophrenia.Support from NIMH Grants MH31593, MH40856, MHCRC43271, and Research Scientist Award MH00625, and from an Established Investigator Award from NARSAD.

P68. Impairment of negative emotion processing in patients with lesions of the right basal ganglia: a study of the mechanisms using PETSergio Paradiso, Robert G. Robinson, G. Leonard Watkins, Laura L. Boles Ponto, Richard D. Hichwa (University of Iowa, Iowa City, IA)

Background: Emotion processing is impaired after cortical right hemisphere damage (Heilman and Gilmore, J Clin Neurophysiol 1998; 15:409–423). Effects of right basal ganglia (RBG) lesions on emotion have rarely been studied. We hypothesized that RBG damage would be associated with impairment in emotion appraisal and experience and examined the neural basis of the phenomenon by using PET. Methods: Emotional experience and recognition of emotionally laden visual stimuli were measured in 16 healthy subjects (7 F, 9 M, mean age 64 years, SD=7.1) and 8 patients with RBG damage (3 F, 5 M, mean age 65, SD=5.4). Visual stimuli consisted of sets of happy, frightening, sad, and neutral pictures (Lang et al, International Affective Picture System: Technical Manual, 1995) including either nonfamiliar human faces or inanimate objects and scenery. Subjects were instructed to “take in” the emotional content of the stimuli while rCBF was measured with H₂¹⁵O PET (Andreasen et al, Proc Natl Acad Sci USA 1995; 92:5111–5115). After each set of stimuli, subjects rated the intensity of the elicited emotions on 0–10 analog scales (experiential component). After completion of PET study, subjects viewed the stimuli again and performed a valence recognition task (appraisal component). PET data acquired during emotionally laden conditions, minus the neutral conditions, in RBG patients and in control subjects were compared by using a randomization analysis (Arndt et al, J Cereb Blood Flow Metab 1996; 16:1271–1279). Results: Severe impairment in experience of sadness (defined as <3 on the analog scale) occurred in 37.5% of RBG subjects and 5.8% of control subjects (χ²=4.04, df=1, P<0.05). Impairment in experiencing fear delivered through frightening human faces was exhibited by 87.5% of RBG subjects and 41.2% of control subjects, consistent with our unpublished data in healthy older subjects (χ²=5.2, df=1, P<0.03). The RBG subjects showed no impairment in the response to positive emotion and negative emotion delivered through inanimate objects compared with control subjects. Similar results were obtained on valence recognition. Impairment in experience of sadness and fear delivered through human faces in the RBG group was associated with decreases in rCBF in ventral prefrontal cortex and thalamus contralateral to the lesion side. In the RBG patients, processing of pleasant stimuli was associated with increased activity in left dorsal lateral prefrontal and visual cortices. Conclusions: Failure to activate prefrontal and subcortical limbic circuitry may contribute to the impairment in recognition and experience of negative emotion presented through human facial features associated with right basal ganglia damage. Patients with right basal ganglia lesions preserve the ability to activate prefrontal isocortical circuitry to appraise and experience positive emotion (Paradiso et al, Am J Psychiatry 1999; 156:1618–1629).Support from NIMH Research Scientist Award MH00163 and NIMH Grant MH52879.

P69. Change in regional cerebral blood flow on recovery from depression: comparison of vascular depression and nonvascular depressionKengo Shimoda, Mahito Kimura, Yuichi Murata, Amane Tateno, Aya Tanabe, Sunao Mizumura, Shunkichi Endo (Nippon Medical School, Tokyo, Japan)

Background: Cerebrovascular change is frequent in elderly depressed patients. The concept of vascular depression has been a topic of interest in neuropsychiatry. Functional neuroimaging studies have reported that recovery from depression was associated with increased regional blood flow in specific regions. However, the majority of studies have been confined to depression without cerebrovascular changes. Few reports were focused on comparison of vascular with nonvascular depression. Methods: rCBF was measured with [¹²³I] IMP SPECT in 20 patients with late-life depression when ill and after recovery. Each subject also underwent MRI evaluation. Subjects were divided into groups of 9 patients with vascular depression and 11 patients with nonvascular depression, based on the concept of MRI-defined vascular depression (Krishnan, Am J Psychiatry 1997; 154:497–501). Results: Patients with vascular depression showed relatively decreased left frontal rCBF compared with nonvascular depressed patients when presenting with clinical recovery. On the other hand, recovery from depression was associated with increases in rCBF in left anterior temporal, regardless of existing cerebrovascular changes. Conclusions: These data suggest that changes in left temporal function play an important role in the recovery from depressive episodes. These data also suggest that vascular depression and nonvascular depression may be based at least partly on different mechanisms.

General Clinical Neuropsychiatry

P70. The use of topiramate among patients with mental retardation and severe developmental disabilitiesL. Jarrett Barnhill, John Kraus, David Janowsky, John M. Davis (University of North Carolina, Chapel Hill, NC; The Psychiatric Institute, University of Illinois-Chicago, Chicago, IL)

Background: Topiramate is a modified glucosamine that is currently used as an add-on anticonvulsant for complex partial and simple partial seizures. The use of topiramate in neuropsychiatry includes adjunct treatment of bipolar affective disorder, weight gain for atypical neuroleptics, and treatment-refractory anxiety and obsessive-compulsive disorders. Methods: This study involves a review of 20 patients selected from a residential center for mental retardation and developmental disorder. Data will be drawn from individual behavioral data, mood ratings, and side effect profiles. Results: Topiramate is beneficial for selected bipolar patients, but side effects may limit the usefulness of this drug for mood disorders. The majority of side effects appear to be neurological, with delirium, ataxia, and lethargy most commonly reported. Conclusions: Although topiramate can be useful for bipolar illness, side effects may limit efficacy among patients with severe developmental disorders. We speculate that the effects on NMDA/ glutamate neurotransmission or carbonic anhydrase inhibition may contribute to dose-independent neuropsychiatric side effects. Other pharmacodynamic and pharmacokinetic issues will be discussed.

P71. A neurobiological taxonomy of psychiatric disordersDeborah N. Black (University of Vermont, Burlington, VT)

Background: A premise of neuropsychiatry is that normal and abnormal behavior are related to brain structure and activity. Disorders with similar manifestations reflect disturbance in shared brain circuits. A valid diagnostic system should advance understanding of disease by grouping under a common heading diseases that are functionally related. Diverse brain lesions can result in similar outcomes by affecting functionally linked circuits (e.g., depression in Parkinson's disease, Huntington's chorea, and multiple sclerosis; mesial temporal dysfunction in schizophrenia and the schizophreniform psychosis of temporal lobe epilepsy; endogenous and poststroke mania). Methods and Conclusions: We propose a neurobiologically based multiaxial classification of psychiatric disorders. This system acknowledges that 1) clinical phenotypes converge on common neuroanatomical and neurochemical circuits, and 2) successful therapy may result in similar brain changes. A neurobiologically based taxonomy can account for comorbidities, e.g., Tourette's-OCD; ADHD-tic; or frontal dysfunction in acquired sociopathy. The overlap among diagnoses reflects the activity of distributed neural systems and has implications for treatment based on biological similarities, e.g., the use of psychostimulants in depression, TBI, and multi-infarct dementia; ECT for depression and Parkinson's disease; and anticonvulsants for mood disorders, migraine, and epilepsy.

P72. A common pathogenesis of the serotonin syndrome, catatonia, and neuroleptic malignant syndromeBrendan T. Carroll, Kevin T. Graham, Arthur J. Thalassinos (VAMC, Chillicothe, OH)

Background: The serotonin syndrome, the neuroleptic malignant syndrome (NMS), and catatonia appear to share many clinical similarities—namely, cognitive, behavioral, neuromuscular, and autonomic nervous system dysfunction, with variable hyperthermia. The pathogenesis of the serotonin syndrome is reported to involve serotonin hyperactivity at the 5-HT_1A receptor (Sternbach, Am J Psychiatry 1991; 148:705–713). Methods: Review of recent literature as well as clinical reports from the Neuroleptic Malignant Syndrome Information Service demonstrate the consolidation of the three disorders into variants of a single entity (Fricchione et al, Psychiatric Annals 2000; 30:347–355). Furthermore, the differential diagnosis of the serotonin syndrome includes NMS (Keck et al, Psychiatric Annals 2000; 30:333–343). Results: Serotonin hyperactivity at the 5-HT_1A receptor was found to have a significant role in the etiologies of the serotonin syndrome, NMS, and catatonia (Buckley et al, new manuscript). Conclusions: Based on the commonality of the proposed 5-HT_1A hyperactivity in the pathogenesis of the three disorders, the serotonin syndrome, NMS, and catatonia may be considered as allied conditions.

P73. Improved recovery in activities of daily living associated with remission of poststroke depressionEran Chemerinski, Robert G. Robinson, James T. Kosier (Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA)

Background: Poststroke depression is associated with impaired recovery of activities of daily living (ADL) function in affected patients compared with similar nondepressed patients. We examined the differences in recovery of ADL functions among poststroke depressed patients with remission of their depression compared with poststroke depressed patients without mood recovery over the first 3 to 6 months following stroke. Methods: On the basis of a semistructured psychiatric exam and DSM-IV diagnostic criteria, a consecutive series of patients with poststroke major or minor depression (N=55) was selected. Their impairment in ADL function was assessed with the John Hopkins Functioning Exam during acute hospitalization and either 3 or 6 months later. Results: Patients whose mood improved at follow-up (n=21) had significantly greater recovery in ADL functions at follow-up than patients whose mood did not improve (n=34). There were no differences in demographics variables, lesion characteristics, and neurological symptoms between the two groups. Furthermore, patients with either major or minor depression at the initial evaluation showed the same amount of recovery in ADL function if they improved at follow-up. Conclusions: Our findings suggest that remission of poststroke depression over the first few months after stroke is associated with greater recovery in ADL function than continued depression. Early effective treatment of depression may have a positive effect on the rehabilitation outcome of stroke patients.

P74. Explaining the differential effects of bilateral temporolimbic injury on feeding, sexual, and aggressive behavior: an appetitive versus instrumental drive hypothesisElizabeth Crabtree, Jeffrey Saver (University of California, Los Angeles, CA)

Background: Bilateral temporolimbic lesions produce the Klüver-Bucy syndrome (KBS)—psychic blindness, hyperorality, hypermetamorphopsia, hypersexuality, and loss of aggressive/ fearful responses. No detailed account has explained the discrepancy between the alterations in feeding and sexual behaviors (increase and broadening of targets) and aggressive behavior (decrease and narrowing of targets). Methods: We reviewed the experimental literature on temporolimbic lesions in rodents and nonhuman primates; clinical literature on human KBS; studies of imaging, psychophysiology, and electrophysiology of normal and abnormal temporolimbic function; and experimental studies in ethology, evolutionary biology, and behavioral biology. Results: The ethological distinction between appetitive and instrumental drives affords an explanation of differential drive-related behavioral alterations in KBS, in which lesions disrupt the association of emotional-limbic responses and appropriate targets in the external world. Fundamentally appetitive drives such as feeding and reproduction, driven by internal, visceral signals, will continue to impel behavior and be released onto inappropriate targets. Conversely, instrumental drives such as aggression, requiring an identified target for their trigger, will no longer be elicited, because of the suppression of past, learned associations. Conclusions: The seemingly paradoxical disinhibition of feeding and reproductive behaviors and inhibition of aggressive behavior in KBS is explained by domain-specific variations in the regulation of appetitive and instrumental drives.

P75. Relationship of neurocognitive impairment to quality of life in malignant brain tumor patientsElena Farace, Mark E. Shaffrey (Department of Neurosurgery, University of Virginia, Charlottesville, VA)

Background: Family caregivers of patients with malignant brain tumors sustain all the stress of caring for a loved one with cancer in addition to the stress of caring for a patient with neurocognitive deficits. Malignant brain tumor patients are less able to take advantage of standard cancer resources because of cognitive impairment, which increases caregiver burden. In this unique population, intervention with family caregivers may improve patient and family quality of life (QOL) and reduce caregiver burden. Methods: 24 patients with a biopsy-proven malignant brain tumor were given baseline QOL and neuropsychological assessments. Family caregivers were given measures of QOL and caregiver burden upon enrollment. A subset of caregivers (n=12, currently) was enrolled in a randomized single-blind trial of a family caregiver–based problem-solving skills intervention in caregivers of malignant brain tumor patients. These caregivers were selected only by availability for a weekly hour-long individual intervention for a 10-week period. Half were randomized to treatment and half were randomized to the control condition (placed on a waitlist for the same period). Results: Caregiver strain was significantly correlated with patient's expressive language deficits measured by the Neurobehavioral Rating Scale (r=0.73), the Boston Naming Test (BNT; r=0.44), or the Controlled Oral Word Association verbal fluency test (r=0.544; which, in a stepwise regression, explained 44% of variance in caregiver strain). Memory scores (California Verbal Learning Test, r= 0.583 to 0.853), naming (BNT, r=0.472), and ability to maintain set (Stroop, r=0.560) were also associated with poor family QOL. Interestingly, there were no significant correlations of patient or caregiver QOL with any of the motor scales. A significant reduction in caregiver burden for the intervention treatment group was found, suggesting that this intervention can significantly improve family caregiver QOL. Conclusions: Cognitive impairment is clearly related to patient and caregiver QOL. The findings suggest that intervening with the family, when appropriate, may result in an improvement in QOL for patients with malignant brain tumors and their families.Support from NIH and the National Cancer Institute.

P76. Lack of efficacy of thiamine treatment for chemosensory disordersAlan R. Hirsch, Jamal Baker (The Smell and Taste Treatment and Research Foundation, Chicago, IL)

Background: Even though olfactory loss affects approximately 17 million people in the United States, no treatment has been found to be consistently effective for this condition. Thiamine is a necessary coenzyme in the olfactory pathway, and its deficiency, as manifest in the Wernicke-Korsakoff syndrome, is associated with olfactory loss. Methods: To assess the efficacy of thiamine as a treatment of olfactory loss not due to Wernicke-Korsakoff syndrome, 31 patients with olfactory dysfunction who were treated daily with oral thiamine 100 mg for 3 months were retrospectively assessed for their olfactory abilities before and after treatment. Results: In 23% there was improvement, in 48% there was no effect, and in 29% there was actual worsening of olfactory ability. Conclusions: At this time we cannot recommend that thiamine be used as a primary treatment option in olfactory loss not due to Wernicke-Korsakoff syndrome.

P77. Frontal network syndromes in young stroke patients: frequency, topography, and etiologyMichael Hoffmann, Ann Watts (Department of Neurology, University of Kentucky, Lexington KY; Neurology Department, University of Natal, South Africa)

Background: Frontal network control subjects and integrates all other cognitive activities. Despite this metacognitive role, frontal network syndromes (FNS) are not featured in any stroke scales or drug trials. We evaluated frequencies and topographical subtypes of FNS in acute and subacute young (ages 15 to 49) stroke patients and their relationship to stroke etiology. Methods: The population was alert, first-ever, young stroke patients devoid of concomitant neurodegenerative disease. Patients were derived from a cognitive stroke registry (N=1,352). All patients underwent a CT or MRI brain scan, a neurological deficit scale (CNS), and etiological (TOAST) classification. A hierarchical semiquantitative cognitive battery including FNS tests was applied to all alert patients on admission. Neuropsychological testing, as a gold-standard comparison, was performed in those with mild or subtle cognitive deficits and where neuroimaging defined an appropriate lesion with normal cognitive screening. Results: For alert young stroke patients (n=307/352;87%) with FNS (52; 17%), infarct location was in the cortical (13; 25%), subcortical (19; 37%), and subtentorial regions (5; 10% brainstem, 3.6% cerebellar), or there were multiple lesions (12; 23%). Those with cortical versus subcortical and subtentorial locations differed significantly when compared (P=0.008). Etiological subtypes included large vessel (LV; n=2), small vessel (SV; 9), cardioembolic (5), other (22; leading causes were dissection, vasculitis, and prothrombotic states), and unknown (11). Comparison of the atherosclerotic group (SV+LV) against “other” differed significantly (P=0.03). Conclusions: 1) Topographically, subcortical stroke is the most common lesion site for frontal network syndromes, with only one-quarter due to isolated cortical lesions; 2) isolated subtentorial stroke may manifest with an FNS; and 3) the “other” stroke etiological group was the most common cause of FNS.

P78. Treatment of poststroke generalized anxiety disorder: a double-blind trial of nortriptylineMahito Kimura, Robert G. Robinson (Department of Psychiatry, University of Iowa College of Medicine, Iowa City, IA)

Background: Generalized anxiety disorder (GAD) has been shown to have a negative influence on recovery in activities, recovery of social function, and duration of accompanying depression following stroke. There have been, however, no systematic studies of the treatment of GAD in patients with stroke. Methods: 27 patients with comorbid GAD and depression participated in a double-blind treatment study comparing nortriptyline (n=13) and placebo (n=14). The outcome measures included the Hamilton Rating Scale for Anxiety (Ham-A), the Hamilton Rating Scale for Depression (Ham-D), and the Johns Hopkins Functioning Inventory (JHFI) for assessment of activities of daily living. Results: Repeated-measures ANOVA demonstrated significantly greater improvement on the Ham-A (P<0.005), Ham-D (P<0.05) and JHFI (P<0.05) among patients treated with nortriptyline compared with placebo. The anxiety symptoms show earlier improvement at 50 mg dose of nortriptyline compared with depressive symptoms. Conclusions: These findings demonstrate for the first time that poststroke GAD can be effectively treated with nortriptyline and that anxiety symptoms respond sooner than depressive symptoms.Support from NIMH Grants MH40355, MH52879, MH53592, and Research Scientist Award MH00163 (R.G.R.) and a grant from Nippon Medical School, Tokyo, Japan (M.K.).

P79. Psychiatric symptoms and cognitive impairment in cerebellar degenerationIracema Leroi, Elizabeth O'Hearn, Kathleen Tracy, Christopher A. Ross, Jason Brandt, Russell L. Margolis* (Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD)

Background: Recent evidence (e.g., Schmahmann and Sherman, Brain 1998; 1:561–579) suggests that cerebellar pathology may result in cognitive deficits and psychiatric symptoms. To explore this possibility, we compared the cognitive and psychiatric symptoms in subjects with cerebellar degeneration (CD) versus neurologic and normal control subjects. Methods: 25 subjects with CD, 20 subjects with Huntington's disease (HD), and 22 disease-free control subjects were assessed with neuropsychological, psychiatric, and neurological rating instruments and a semistructured psychiatric interview (SCID). Results: The prevalence of DSM-IV Axis I diagnoses was higher in the CD (80%) and HD (88%, from a subset of 9 subjects) groups than in the disease-free group (41%), reflecting high rates of mood disorder, personality change, and psychotic disorders in the CD subjects. The groups also differed on ratings of irritability, apathy, and emotionality. Cognitive testing revealed significant group differences on 13 of 15 measures, including tests of learning and memory, constructional praxis, attention, concentration, letter and semantic fluency, and psychomotor speed and dexterity. On the majority of cognitive measures, CD and HD subjects performed comparably and more poorly than disease-free control subjects. However, the CD subjects performed worse than the HD and disease-free subjects on measures with high executive demand. Conclusions: These findings suggest that cerebellar degeneration is associated with significant cognitive impairment and psychiatric symptoms.Support from NARSAD and from NIH Grant 5M01 RR00052.

P80. Extreme dissociation of cognitive functions over time in a case of intractable OCD: the heterogeneity of putative “frontal lobe” functionsJoel E. Morgan, Robert Adams, Danielle Barry, Elise Caccappolo (VAMC, East Orange, NJ; Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ)

Background: Numerous functions are ascribed to the frontal lobes and many neuropsychiatric conditions to frontal dysfunction. However, the many frontal/executive functions appear independent of one another. We present the case of C.K., a 70-year-old retired professor with a history of chronic anxiety-OCD. He was self-referred to Neuropsychology with memory complaints and was evaluated twice over 2 years. Despite extensive treatment, he remained refractory. Past medical history was noncontributory, with normal neuroimaging. At first, he was taking fluoxetine 30 mg; on retesting, he was on paroxetine 60 mg. Methods: Comprehensive neuropsychological testing occurred twice, 2 years apart, with full batteries emphasizing frontal/executive measures. Results: A striking dissociation of function was noted, with significant improvement in IQ, memory, and attention, but dramatic worsening of higher reasoning/executive functioning on the Wisconsin Card Sorting Test and Category Test, on which he was extremely perseverative. Very unusually, however, performance on difficult tests of attention, working memory, and speed of processing was very superior (>3 SD on the difficult Paced Auditory Serial Addition and Auditory Consonant Trigrams tests). Conclusions: This extraordinary dissociation of functions all ostensibly subserved by frontal systems suggests heterogeneity of “frontal/executive” processes. Improvement of some (memory, general intellect, attention) but worsening of others (higher reasoning and executive functions) perhaps suggests a medication effect with concomitant chronicity of OCD. OCD appears associated with dysfunction of particular frontal systems that appear to be implicated in, and likely mediate, executive processes.

P81. A two-year longitudinal study of poststroke nondepressed patients: outcome and “rebound” effect of nortriptylineKenji Narushima, Robert G. Robinson* (University of Iowa, Iowa City, IA)

Background: This study examined the preventive effect of nortriptyline versus fluoxetine or placebo on the development of depression during the first 3 months after stroke and the outcome for 2 years in poststroke nondepressed patients. Methods: Subjects included 50 poststroke nondepressed patients. Patients were randomly assigned to fluoxetine, nortriptyline, or placebo for 12 weeks. They were examined at enrollment and at 3, 6, 9, 12, 18, and 24 months' follow-up. Diagnosis was by DSM-IV, and depression severity was evaluated with Ham-D. Activities of daily living were measured with the Functional Independence Measure (FIM) and cognitive function with the MMSE. Results: During the treatment period, no patient in the nortriptyline group developed depression. In contrast, 16.7% of the fluoxetine and 25.0% of the placebo patients developed depression during the treatment period. At 9 and 12 months, however, the nortriptyline-treated group had a greater percentage of depressed patients than the other two groups. Through the treatment period, improvement in Ham-D and FIM was seen only in the nortriptyline group. However, the nortriptyline group had significantly worse Ham-D scores compared with the other two groups at 6- and 9-month follow-ups. Conclusions: On the basis of diagnoses and depression severity, nortriptyline-treated patients did better than the fluoxetine or placebo group during the treatment. However, after treatment they were significantly more likely to develop depression, and they had more severe depression symptoms during the next 6 months. This might suggest a “rebound” effect of nortriptyline.Support from NIMH Grants MH40355, MH52879, and MH53592.

P82. Anticonvulsants in psychiatry as illustrated by an inpatient data baseSamuel O. Okpaku, K. Elizabeth Spivey (Vanderbilt University, Nashville, TN)

Background: (See Freeman and Stoll, Mood stabilizer combinations: a review of safety and efficiency, Am J Psychiatry 1998; 155:12–21). The adoption of anticonvulsants in the treatment of psychiatric syndromes is expanding. This study examines their uses with respect to diagnosis, symptom clusters, and their associated combinations. Methods: The charts of 425 consecutive patients admitted to an inpatient psychiatric setting were reviewed. Data on diagnosis, symptom profiles, psychotropic medications, and severity of illness were extracted and analyzed. Results: The use of anticonvulsants is not independent of diagnosis. Polytherapy (combination with antidepressants and antipsychotics) seems to be the rule. Conclusions: As the use of these agents expands, studies to refine their specific indications, safety, and efficiency in combination strategies will be necessary.Support from Abbott Laboratories.

P83. Syndromic use versus symptomatic use of valproic acid in psychiatric patientsSamuel O. Okpaku, K. Elizabeth Spivey (Vanderbilt University, Nashville, TN)

Background: (See Celabrese et al, Predictors of mood stabilizers, J Clin Psychol Pharmacol 1996; 16:245–315.) There is increasing interest in the use of anticonvulsants for treating psychiatric disorders. In the United States, 50% of prescriptions for valproic acid are by psychiatrists. This drug is approved for the treatment of bipolar disorder. However, there are reports of its use for treating symptoms such as hostility and aggression irrespective of diagnosis. This study examines the syndromatic and the symptomatic use of valproic acid in an inpatient setting. Methods: The charts of 425 consecutive patients admitted to an inpatient psychiatric setting were reviewed. Data on the demographics, symptoms, and psychotropic medications were extracted and analyzed. Results: The prescription of valproic acid is not independent of diagnosis. Bipolar patients were prescribed valproic acid (53% on admission and 55% at discharge) more frequently than patients with other diagnoses. Of 29 symptom variables, 4 were predictors for the prescription of valproic acid. These were Pressured Speech (β=1.64, P=0.0001), Fire Setting (β=1.96, P=0.005), Mood Swings (β=0.84, P=0.008), and Suicide Attempt (β= −0.74, P=0.4). Conclusions: Further research to predict the symptomatic use of valproic acid across diagnostic categories is required, especially as attempts are being made to expand the diagnosis of bipolar disorder and its spectrum.Support from Abbott Laboratories.

P84. Depression and Huntington's disease: prevalence, clinical manifestations, and treatmentJames R. Slaughter, Matthew P. Martens, Kathleen A. Slaughter (University of Missouri-Columbia, Columbia, MO)

Background: Huntington's disease (HD), first described by George Huntington in 1872, is a neurodegenerative disorder characterized by chorea, oculomotor abnormalities, ataxia, and dementia, as well as altered mood, personality, and behavior. HD is often complicated by psychiatric symptoms, which take the form of personality alterations, aggressive behavior, manic behavior, abnormal sexual behavior, and depression (Cummings, Behav Pharmacol 1995; 65:179–186). Methods: 16 HD depression studies, encompassing 1,558 HD patients assessed for depression, were analyzed for this study. This analysis included every published English-language study that assessed the prevalence of HD depression. Results: The prevalence of depression is approximately 30% for all HD patients (461/1,558). When assessed with DSM criteria, however, the prevalence rate is approximately 37% (160/429). Clinical manifestations of HD depression include a markedly increased risk for suicide. Case reports and case series support the efficacy of standard antidepressant interventions in resolving symptoms of depression. Conclusions: Depression is a common occurrence in HD patients and should be routinely assessed by physicians treating those with HD. Although several types of treatment have been shown to be somewhat effective in treating HD depression, our experience indicates that sertraline may be the most efficacious pharmacological treatment.The salary of M.P.M. was funded by an unrestricted grant from Pfizer, Inc.

P85. Functional anatomy of central painKatherine H. Taber, Anis Rashid, L. Anne Hayman, Robin A. Hurley (Baylor College of Medicine, Houston, TX)

Background: Approximately 30% of the U.S. population suffers from chronic pain. It is the number two cause of work loss in the United States and is the third greatest health care problem after cardiac disease and cancer. In 1999 the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) approved revised standards for more aggressive pain management and treatment. Methods and Results: Clinical literature relevant to the functional anatomy and pathophysiology of central pain was reviewed. A summary and synthesis of the peripheral and central nervous system anatomy, neurochemistry, physiology, and treatment of central pain were created. The relevant information was color coded onto anatomic diagrams and human brain sections. Conclusions: Central pain, the most difficult type of chronic pain to manage, results from damage to the ascending pain pathways and associated structures, the most important of which is the thalamus. To manage these patients effectively, it is very important to diagnose central pain acutely. A better understanding of these mechanisms will aid the clinician in recognizing central pain and will help in choosing treatments customized to specific patients. Aggressive treatment of central pain also complies with the recommendations made by the JCAHO.Support from the Mike Hogg Foundation.

P86. Delirium phenomenology using the Delirium Rating Scale-Revised-98 (DRS-R-98)Paula T. Trzepacz, Dinesh Mittal, Rafael Torres, Kim Kanary, John Norton, Nita Jimerson (University of Mississippi Medical Center, Jackson, MS; Lilly Neuroscience Research, Indianapolis, IN)

Background: Inconsistent use of standardized delirium rating instruments contributes to poor knowledge about delirium symptoms (Sx). It has been hypothesized that certain Sx are “ core” while others occur less often and may be considered “ associated” symptoms. Identification of core Sx, implying involvement of certain brain pathways or regions in their production, could lead to better understanding of neuroanatomical underpinnings of delirium. Methods: We studied 24 (DSM-IV) delirium patients using the DRS-R-98, Clinical Global Impression, and Cognitive Test for Delirium (CTD) as part of another Institutional Review Board–approved study with five diagnostic groups. Researchers were blind to diagnosis during the ratings. Results: Mean age was 64 years (range 18–89), 87% were male, and 63% were white. Incidence of “core” Sx was as follows: attentional deficits, 100%; short-term memory impairment, 92%; disorientation, long-term memory impairment, and visuospatial problems, each 96%; physical disorientation, 100%; acute Sx onset, 92%; fluctuation of Sx, 88%; sleep– wake cycle disturbances, 92%; thought process abnormality and motor agitation, each 79%; language impairment, 67%. Perceptual disturbances, delusions, and affective lability occurred in fewer cases and may be “associated” Sx, consistent with previous literature. Item correlations for DRS-R-98 and CTD showed that psychotic Sx correlated together; attention correlated with both language and other cognitive Sx; and visuospatial Sx correlated with orientation. Conclusions: The DRS-R-98, designed to assess delirium phenomenology, found “core” Sx of delirium when used cross-sectionally across a range of case severity. Less common Sx may be more related to certain etiologies or to individual brain differences, whereas core Sx may signify that certain neural circuits are affected irrespective of the etiology. Larger samples are needed in future studies.Support from the Mental Illness Research Education and Clinical Center, Veterans Integrated Service Network 16 (MIRECC-VISN 16), Department of Veterans Affairs.