339. Posterior cortical white matter anomalies in velocardiofacial syndrome

102S

Friday Abstracts

BIOL PSYCHIATRY 2000;47:1S–173S

338. L-DOPA EFFECT ON CONNECTIVITY WITHIN MOTOR CSPTC LOOP IN PARKINSON’S DISEASE M.J. Mentis, A. Feigin, A.R. McIntosh, P. Spetsieris, D. Eidelberg PET Laboratory North Shore University Hospital, Manhasset, N.Y. 11030 In Parkinson’s Disease (PD), reduced nigrostriatal dopamine is believed to alter function of regions within the motor cortico-striatopallidal-thalamocortical (CSPTC) loop resulting in increased pallidal-thalamic inhibition. Motor symptoms result from decreased thalamocortical feedback. Dopamine replacement (L-dopa administration) should increase thalamocortical activity. Structural Equation Modeling (SEM) of PET data is an ideal tool for testing such a well formulated functional anatomy theory. Five right handed PD patients (4M, 1F; 60.8 years ⫾ 4.3 S.D.; Hoehn and Yahr stage 2.2 ⫾ 0.6) underwent H2150 PET scans while performing a reaching task with their right hand under two drug conditions: a) Off all medications for at least 12 hours, and b) on an individually titrated continuous infusion of L-dopa (mean dose 72 mg/kg ⫾ 29.5) that improved performance on the motor component of the Unified Parkinson’s Disease Rating Scale by 38% ⫾ 11.5 (p ⫽ 0.001). Regions of interest (ROI) were placed over components of the left motor CSPTC loop. The effects of supplementary motor area proper (SMAp), on Motor Cortex, Motor Cortex on Putamen, Putamen on Pallidum, Pallidum on Thalamus, and Thalamus feedback onto SMAp were evaluated by SEM. Off drug, the effect of each region on the next from SMAp through Thalamus was large (coefficients 0.65 to 0.90), but the Thalamo-SMAp feedback was inhibited (coefficient 0.05). During L-dopa infusion, Thalamo-SMAp feedback was significantly increased (coefficient 0.90). The greatest change in regional connectivity within the motor CSPTC loop, associated with L-Dopa induced improved motor function, was increased thalamic feedback on SMAp.

339. POSTERIOR CORTICAL WHITE MATTER ANOMALIES IN VELOCARDIOFACIAL SYNDROME W.R. Kates (1,2), C.P. Burnette (1)

from 13.9% in the left parietal lobe to 19.3% in the left occipital lobe. Posterior gray matter loss followed a similar pattern to white matter loss, but was of a smaller magnitude. These data point toward possible dysfunction in the posterior myelination process in VCFS, and suggest potential hypotheses of the neuroanatomic pathways through psychiatric disorder is produced in these patients.

340. IMPLICIT VERSUS EXPLICIT CATEGORY LEARNING: AN EVENTRELATED FUNCTIONAL MRI STUDY H.J. Aizenstein, A.W. MacDonald, V.A. Stenger, J.K. Larson, S. Ursu, R.D. Nebes, C.S. Carter Clinical Cognitive Neuroscience Laboratory, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213 Previous studies have shown that category learning is associated with decreased posterior activation and increased frontal activation. The increases are thought to result from explicit processes (i.e., with awareness) and the decreases are associated with implicit learning (without awareness). However, the specific neural circuitry underlying the different category learning systems remains uncertain, and the interaction between these systems is also unclear. To directly compare the neural systems involved during learning with and without awareness, we performed an event-related fMRI study. Ten healthy young subjects participated. Black and white dot patterns were displayed on a screen and then quickly turned red, yellow or green. The subject was to press a button corresponding to the color. Subjects first performed this implicitly; they were not told that whenever the pattern was a distortion of a prototype, then the dots turned red. The explicit condition was the same except subjects were instructed to look for a pattern. Behavioral data showed learning in both conditions. With implicit learning there was decreased activation in extrastriate region V3 and in the inferotemporal region. Increased medial frontal activity was found with a switch to a different association (i.e., when expectancy was violated). Increases in V1, V2, V3, and inferior frontal cortical regions occurred throughout explicit learning. Also, the inferotemporal region showed decreased activation with explicit learning. These results support the theory that implicit and explicit learning utilize dissociable complementary neural systems. The medial frontal activation with the implicit rule switch may result from an expectancy violation when the previous rule no longer applies. Supported by ADRC Grant #P50-AG05133.

(1) Kennedy Krieger Institute, Baltimore, MD 21205 (2) Department of Psychiatry, Johns Hopkins University School of Medicine Certain genetic conditions associated with the development of schizophrenia and mood disorders serve as powerful models for understanding the pathogenesis of severe psychiatric disorder. Velocardiofacial syndrome (VCFS), caused by a microdeletion on chromosome 22q.11, is such a genetic disorder, affecting 1:4000 individuals, and leading to bipolar disorder or schizophrenia in up to 30% of its patients. We know very little about the ways in which the 22q.11 deletion affects brain development, ultimately producing the neuropsychiatric phenotype that is characteristic of VCFS patients. In an initial effort to answer this question, we used anatomic MRI to compare the gray and white lobar tissue volumes of a sample of 10 children with VCFS (8 girls, 2 boys; overall mean age, 10.1 years) and an age- and gender-matched sample of controls. Statistical comparisons with the Mann-Whitney U test revealed that children with VCFS had significantly reduced volumes in posterior (p ⬍ .01), but not anterior, lobar regions of the brain. Volume loss appeared to affect posterior white matter to a greater extent than posterior gray matter. Whereas white matter loss in the frontal lobe was under 5% for children with VCFS relative to controls, white matter loss in posterior lobar regions ranged

341. SPECIFICITY OF REDUCED CORTICAL GRAY MATTER TO FIRST EPISODE SCHIZOPHRENIC PSYCHOSIS Y. Hirayasu (1), M.E. Shenton (1,2), S. Tanaka (1), D.F. Salisbury (1,2), A. Nagy (1), C.C. Dickey (1), A. Kricun (1), D.A. Yurgelun-Todd (2), C. Zarate, Jr. (2), R.W. McCarley (1,2) (1) Brockton VA Medical Center, Brockton, MA 02401, (2) McLean Hospital, Belmont, MA 02178 Department of Psychiatry, Harvard Medical School and (3) Kyorin University School of Medicine, Mitaka, Tokyo, Japan 181-8611 Magnetic resonance (MR) measures have shown anatomical abnormalities in first episode schizophrenia, including reduced volumes in both