“Probing” the nature of CPT deficits in schizophrenia with blink modification

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plitude of P3 to A's and B's, to Y's following A's and B's, or to X's following A's. There was a significantdifference in the peak amplitude of P3 to X's following B's: schizophrenic patients showed a significantly larger P3 ampliinde than controls to X's following B's when the IS! was 5 sec. but not when the IS! was 0.85 sec. The role of the invalid cue (B) is to set up an inhibitory set to targets (X). These data therefore suggest that at longer ISis schizophrenics have a weakened inhibitory set. This may be due to the premature decay of an inhibitory trace to the invalid cue. The shorter ISi of 0.85 see is of insufficient duration to allow the inhibitory trace to decay, which accounts for the lack of difference hetween patients and controls.

213. SMOOTH PURSUIT AND PREDICTIVE SACCADIC TRACKING IN PATIENTS WITH OCD B.A. Clementz, M.N. Lam, & N.R. Swerdlow

FRIDAY, M AY 20

finding of a similar increased incidence of eye tracking abnormality in first degree relatives of schizophrenics implicates this disorder as a potential biological marker for schizophrenia. To test the assumption that the eye tracking dysfunction of schizophrenics is genetically related, left versus right pursuit gain and phase shift were obtained for 38 schizophrenics (20 familial and 18 sporadic) and for 18 normal controls. Family history status was determined through interviews with family members. Subjects • tracked pendular targets on an LED light bar moving at frequencies of.2 and .7 Hz. Their horizontal eye movements were recorded using DC-electro-oculography. Also, schizophrenic subjects were administered the Wisconsin Card Sorting Test. Perseveration scores were used to identify potential differential relationships between frontal lobe function and eye tracking dysfunction for the two clinical groups. Results indicate that schizophrenics with a positive family history had significantly reduced right gain compared with controls, while right gain for negative family history schizophrenics did not differ from either group. Further, linear regression by groups analysis reveal that Wisconsin Card Sort perseveration scores significantly predicted right gain to slower targets (.2 Hz) for the positive family history group, but not for negative family history schizophrenics. The contribution of genetic and laterality variables on smooth pursuit eye movements in schizophrenics is discussed.

Departments of Psychology and Psychiatry, University of California, San Diego, CA Obsessive-compulsive disorder (OCD) is associated with dysregulation of a fronto-striato-thalamo-frontal loop. Studies of ocular motor performance have been useful for investigating the effects of specific neuropa. thologies on behavior. This study was conducted to determine if OCD patients have particular and characteristic patterns of ocular motor response. Twelve patients with OCD (Age M -32.7, SD - 10.4; 42% Fe. male) and 12 nonpsychiatric comparison (Age M - 37.0, S D - 15.3; 58% Female) subjects participated. Based on previous studies and neurophysiological considerations, subjects were administered: (i) smooth pursuit (unpredictable 9 and 27 deg/sec targets); and (2) three variations (regular, 250 msec gap, and overlap) of a predictive saccadic ("square wave") tracking (0.4 Hz; +/-15 dug of visual angle) task. OCD patients had norreal steady-state pursuit gain to both target velocities (OED overall M -0.88, SD-.08; nonpsychiatric overall M-0.86, SD-. 12), but had significantly more frequent (events/see: OCD overall M-0.60, SD-.33; nonpsyehiatric overall M-0.44, SD-.24) and smaller (dug/event: OCD overall M-2.1, SD-.70; nonpsychiatric overall M-2.8, SD-.60) "catch-up" saccades during smooth pursuit than nonpsychiatric subjects (perhaps a type of position "checking" behavior). There were no differences in he. queney of "back-up" saecades or steady-state gain variability between. groups. During the gap version only, OCD patients were significantly slower to develop a predictive saecadic tracking strategy (similar to Parkinson's disease patients). The groups did not differ on any other ocular motor variable. These findings demonstrate that ocular motor studies could be helpful for addressing the behavioral consequences of OCD patients' neuropathology.

214. FAMILIAL STATUS DIFFERENTIATES SMOOTH PURSUIT EYE MOVEMENTS OF SCHIZOPHRENICS

215. NEUROLEPTIC EFFECTS ON CPT AND EYE TRACKING IN SCHIZOPHRENIA J.l. Epstein, R.S.E. Keefe, S.E. Lees Roitman, P.D. Harvey, M. Davidson, L.J. Siever, & R.C. Mohs Psychiatry Service (I 16A), Mount Sinai School of Medicine, VAMC, 130 West Kingsbridge Rd., Bronx, NY 10468 The effects of antipsychotie medication on visual attention and eye tracking in schizophrenia are poorly understood. Previous attempts to investigate this question have been limited by cross-sectional design, small sample size, and a failure to define precisely which neurocognitive function is affected. We have analyzed data on 23 DSM-Ill-R schizophrenics, tested within a three month period both on and off medication (minimum of 2 weeks in each condition) on two sets of cognitive tasks hypothesized to be markers of vulnerability to schizophrenia: continuous performance test (CPT) and eye Iraeking. On the CPT (3-7 version), a trend toward a decrease in mean errors of commission was seen in the medicated state (unmed-6.87+ 10.62, med=3.78:l:5.05, n-23, p<0.10). No significant difference in mean errors of omiss,:on was detected across states (unmed 6. ! 7:£-6.5I, mud - 7.87:£-9.38, n=23, p<0.18). Similarly, no significant differences in mean levels of performance across medicated and unmedicated conditions were seen for eye tracking measures, including total number of saccades, large saecades both toward and away from the target, small saecades both toward and away from the target, and gain (n- 18, all ps>0.25). These results suggest that neuroleptic status may have a minor effect on CPT errors of commission, but no significant effect on CFF errors of omission or on eye tracking.

B. Schwartz1,2, B. O'Brien 2,3, W. Evans i,2,3, F. Sautteri, & D. Winstead 1~

216. "PROBING" THE NATURE OF CPT DEFICITS IN SCHIZOPHRENIA WITH BLINK MODIFICATION

Thlane University School of Medicine, Department of Psychiatry and Neurology, New Orleans, LA; 2 Veterans Administration Medical Center, New Orleans, LA; 3 Tulane University, Department of Psychology, New Orleans, LA.

E.A. Hazlett I, M.E. Dawson 2, K.H. Nuechterlein 3, & D.L. Filion 2

Disrupted smooth pursuit eye tracking characterizes a greater proportion of individualswith schizophrenia than that of the normal population. The

~The Mount Sinai School of Medicine, New York, NY 10029; 2University of Southern California; SUniversity of California, Los Angeles, CA

FRIDAI~, MAY 20

The Continuous Performance Test (CPT) has been used extensively in studies concerned with attentional deficits in schizophrenia, however, the cognitive subprocesses underlying CPT performance are poorly understood. Startle eyeblink modification (gEM) is a psychophysiological measure which has the potential to separately evaluate discrete stages of information processing. When a nonstartling prepulse precedes a startleeliciting stimulus by a short interval (250 ms or less), the startle reflex is reliably inhibited. This prepuise inhibition is thought to reflect the early stages of information processing associated with sensory gating. When the interval is longer (1000 ms or greater), gEM is thought to reflect later stages of information processing. This study employed the gEM technique to index early and later stages of attentional processing during a visual memory-load version of the CPT with auditory (tone) distractors. Relatively remitted schizophrenic outpatients (n-20) and matched normal controls (n-18) viewed a series of single digits some of which served as prepulses for a startle.eliciting noise burst. Subjects were instructed to press a button after the digit "7" of each 3-7 sequence. The noise burst was presented either 120 or 1200 ms following the onset of preselected Target (i.e., "Y'), Nontarget (non-3, non-7 digits), and Target plus Distractor ("Y' and simultaneous tone distractor) prepuises, as well as in the absence of a prepulse (baseline). Primary results indicate that for control subjects the Target prepulse produced significantly greater inhibition than the Nontarget prepulse at the 120 ms lead-interval, suggesting early stimulus discrimination and selective attention. Also, significant but nondifferential prepulse inhibition was observed following the Target prepulse and the Target plus Distraetor prepulse, suggesting that the controls effectively ignot~l the distractor. In contrast, the patients failed to show differential prepulse inhibition to the Target and Nontarget prepulses. However, they did show attentional modulation of gEM as they exhibited significantly greater prepulse inhibition following the Target plus Distractor prepulse. These findings suggest that CPT deficits in schizophrenia are associated with inefficient early controlled attentional processes. Together with animal models of prepulse inhibition, gEM offers a unique way to delineate the neural basis of information processing deficits in schizophrenia.

217. EVOKED POTENTIAL MEASURES OF LANGUAGE PROCESSING IN SCHIZOPHRENIA M.A. Niznikiewicz, B.F. O'Donnell, & R.W. McCarley

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electrode p<.06) in the schizophrenic group suggesting a larger impairment in this modality. Smaller P600 amplitudes were recorded in the schizophrenic group in both modalities (group x condition x electrode p<.003) suggesting impaired processes of meaning integration. Significantly slower peak latencies of both the N400 (p<.0001) and the 1:'600 (group X modality p<.07) in Sz suggest the slowing of language processing in schizophrenics.

218. ABNORMAL P3 TOPOGRAPHY IN SCHIZOTYPAL PERSONALITY DISORDER D.F. Salisbury; M.M. Voglmaier, R.W. McCarley, & L.J. Seidman Harvard Medical School, Department of Psychiatry at Massachusetts Mental Health Center, Boston, MA 02115 Schizotypal personality disorder (SPD), a schizophrenia-spectrum disorder, is of interest in that schizotypes possess many of the same phenomenoiogical traits as schizophrenics, albeit in milder form, without the po. tential confounding effects of chronic neuroleptic treatment, hospitalization or debilitating illness. Eleven right-handed DSM-IliR diagnosed schizotypes and eleven age-, sex- and handedness-matcbed controls were measured on event-related potential (ERP) measures aberrant in schizophrenia, namely P3 amplitude from sagittal midline and lateral sites overlying temporal lobe. Unlike in schizophrenia, P3 amplitudes in SPD were not significantly different from those of controls along the sagittal midline, although there was a trend for reduced amplitudes at central and posterior sites. Like P3 in schizophrenia, lateralized P3 amplitude deficits were present in SPD, resulting in an asymmetrical P3 topography fGro,p x Side: Ft~-4.36, p -.05). Schizotypes showed a left-sided deficit, with amplitudes smaller on the left (!"3:2.18 try) than the right (T4:3.01 try). Controls showed the opposite pattern, with larger amplitudes on the left (4.73 Ixv)than the right (4.33 try). Groups showed greater statistical separation on the left side of the head 020 "!.96, p -.032) than on the right 020 -I.17, p -.129). These results are the first to demonstrate topographic abnormalities in P3 in SPD. SPD shares similarities in electrophysiological profiles with schizophrenia. Left-lateralized deficits in P3 voltage topography may be associated with the schizophrenia-spectrum diathesis and thus be a viable biological marker of a schizophrenia-related 'gene-complex'.

Harvard Medical School and Brocton VAMC, Brockton, MA 02401 Language problems are a prominent feature of schizophreniayet their biological basis remains unknown. We used a semantic incongruity Evoked Potential (EP) paradigm to explore electrophysiological correlates of schizophrenic language. The two waveform components sensitive to language processes are the N400, peaking at 400 msec, sensitive to the activation of the lexical memory network, and the Pt00, peaking about 600 msec after stimulus presentation, thought to be sensitive to further meaning processing. Two hundred sentences were presented one word at a time in both the visual and auditory modalities. Half of the sentences made sense, e.g., Jane has never been to Boston and another half were nonsensical, e.g., John wanted to eat one more sleeve (incongruent last word). Larger group differences were predicted in the auditory sentence condition, given the previous EP and clinical findings of larger auditory than the visual impairment in schizophrenics. Ten male, right handed, chronic medicated schizophrenics (Sz) and twelve nomcd, age matched males were asked to judge if the sentences made sense. Schizophrenics had more negative N400 amplitude to both congruent and incongruent sentence completions in both modalities which suggests excessive activation of lexical networks. This result corroborates earlier findings where smaller N400 amplitude in Sz was reported for the difference waveform (incongruent minus congruent condition). Larger N400 amplitudes were recorded in the auditory than in the visual modality ( group x modality x

219. RELATIONSHIP BETWEEN DST FINDINGS AND POLYSOMNOGRAPHIC ABNORMALITIES IN SCHIZOPHRENIA R. Tandon, S. Taylor, C. Lewis, J.E. Shipley, J.F. Greden, A. Douglass, J.R. DeQuardo, & ]. Goodson SchizophreniaProgram, Universityof Michigan Medical Center, Ann Arbor, MI 48109-0116 Although nonsuppression of cortisoi following dexamethasone administration (DST nonsuppression) and short REM latency were originally considered to be "biological markers" of major depressive disorder (MDD), several recent studies have documented these abnormalities in a substantial number of schizophrenic patients, in MDD, a strong association between these findings has been observed in both correlational and categorical analyses; this suggests that a common pathophysiological mechanism or process may underlie the findings of short REM latency and DST nonsuppression in MDD. The relationship between DST nonsuppression and REM latency in schizophrenia has not been studied;