185

SPATIAL PROPERTIES OF COGNITIVE INHIBITION IN SCHIZOPHRENICS, RELATIVES OF SCHIZOPHRENICS AND NORMAL CONTROLS; A NEGATIVE PRIMING STUDY

Sohee Park*, Philip S. Holzman

Dept. of Psychology, Harvard University, 33 Kirkland St, Cambridge, MA 02138, USA

We investigated the spatial properties of cognitive inhibition in

schizophrenics, unaffected relatives of schizophrenics and normal

controls. Cognitive disinhibition, assessed by negalive priming tasks in schizophrenics and schizotypal subjects (e.g. Beech &

Claridge,l989), may be state-dependent and dopaminergically

mediated. In this study, we compared cognitive inhibition within

one hemisphere and between the two hemispheres. The effect of

distance on spatial negative priming was also examined.

Normals and schizophrenics showed significant spatial negative

priming, indicating the presence of cognitive inhibition during a

selective attention task. All schizophrenics were receiving

neuroleptics and were not acutely ill. The relatives, however, were

significantly disinhibited. All relatives were medication-free. It

is likely that neuroleptics restored inhibition to a normal level in

schizophrenics.

Although inhibition was restored in schizophrenics, the spatial

structure of inhibition was different from that seen in normals.

Normals showed equal inhibition within and behveen the two

hemispheres. But in schizophrenics, negative priming occured

only between the two hemispheres and there was no cognitive

inhibition within a hemisphere. In addition, for schizophrenics and

normals, the inhibition decreased with increasing distance from the

target stimulus. These results suggest that the spatial structure of cognitive

inhibition is altered in schizophrenics even if overall inhibition is

restored with neuroleptics. Studying the healthy relatives of

schizphrenics may reveal subtle attentional deficits that are masked

by medication in the patient population.

SPATIAL WORKING MEMORY DEFICIT IN THE RELATIVES OF SCHIZOPHRENIC PATIENTS IS ASSOCIATED WITH THEIR SMOOTH PURSUIT EYE TRACKINC

PERFORMANCE

Sohee Park*, Philip S. Holzman, Deborah L. Levy

Dept. of Psychology, Harvard University, 33 Kirkland St, Cambridge, MA 02138, USA

Evidence implicates the role of prefrontal cortex in working

memory deficits and smooth pursuit eye movement (SPEM) dys- function of schizophrenic patients. In previous studies, we re-

ported that schizophrenics show working memory deficit and that

this deficit is associated with SPEM dysfunction. Using the ocu- lomotor delayed response paradigm, working memory function was

examined in unaffected, medication-free relatives of schizophrenic

patients. The relatives showed significant deficits in working

memory compared with the normal controls but they were better

than the schizophrenic patients.

We grouped the relatives into “good” and “bad” eye trackers

and hypothesized that the good trackers would be unimpaired on

the oculomotor delayed response whereas the bad trackers would

show deficits in working memory. There was no significant dif-

ference between the good tracking relatives and the normals on

the oculomotor delayed response tasks. But the bad tracking

relatives were significantly less accurate and slower than the nor-

mal control group. Also, the good tracking relatives were sig-

nificantly more accurate and faster than the schizophrenics

whereas there was no significant difference between the bad

tracking relatives and the schizophrenic patients. These results

implicate possible prefrontal pathology in some relatives of

schizophrenic patients and suggest that the oculomotor delayed

response paradigm may be useful in broadening the concept of

the phenotype of schizophrenia.

A SIMPLE CHOICE TASK AND COMPLEX DYNAMICAL METHODS REVEAL A FUNDAMENTAL DISORGANIZATION OF RESPONSE SEQUENCES IN SCHIZIOPHRENICS

M.P. Paulus*, M.A. Geyer, D.L. Braff

Department of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, UC. San Diego, LA Jolla CA, 92093- 0804, USA

Schizophrenia is a complex disorder with deficiencies and

dysregulation in attention and information processing and certain

executive functions. Clinically, schizophrenia is characterized by

thought disorder, autism, disturbance of affect, ambivalence, and

association. The anatomical substrate of neuropsychological and

neurophysiological dysfunctions in schizophrenia has been hy-

pothesized to involve reverberating cortico-striato-pallido-thalamic

(CSPT) neural circuits. To test the functional implications of

dysfunctions in this circuitry we have further developed a simple,

computerized, binary choice task paradigm that is thought to probe

thought-contingent responses (TCR) by utilizing a strategy of not

imposing an a-priori right or wrong choice alternative. Specifi-

cally, it was hypothesized that response organization consisting of

response selection, ordering, and sequencing differs significantly

between controls and schizophrenic subjects. We have developed

a detailed analytic method based on complexity theory derived

from mathematical approaches for nonlinear dynamical systems that quantifies the complexity and predictability of subsequences

within a response sequence. The results of this study demonstrate

that both controls (n=16) and schizophrenics (n=22) do not ran-

domly select response alternatives. Moreover, they differ in the

contribution of response subsequences characterized by different local complexities. In particular, the bifurcation in high and low

complexity subsequences indicate a fundamental disorganization of TCR in schizophrenia that may relate to specific dysfunctions in

the CSPT neural circuitry.