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P300 amplitude in schizophrenia is inversely related to duration of illness
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volumes were quantified from 5 mm axial spin-echo MR images and corrected for overall cranial volume. A correlation between left temporal brain volume and 1/s P1 amplitudes was obtained (r = 0.43, p < 0.05). Greater P 1 abnormality (reduced amplitude at this stimulus rate) was associated with reduced brain volume. When patients were classified as deficit (n= 10) or nondeficit (n= 18), negative correlations were obtained in deficit patients between 10/s P1 amplitudes and left (r= -0.67, p<0.05) and right ( r = - 0 . 7 8 , p<0.01) frontal brain volumes. Greater P1 abnormality (increased amplitude at this rate) was associated with reduced brain volumes in these regions. No significant correlations were obtained in controls. These findings suggest that abnormal P1 amplitudes in schizophrenia may be related to structural abnormalities.
ADDITIONAL REDUCTION OF P300 AMPLITUDE IN PATIENTS WITH A DUAL DIAGNOSIS OF SCHIZOPHRENIA AND ALCOHOLISM J . M Ford*, B.G. Isaacks, D. Jackson, M.J. R o s e n b l o o m , A. Pfefferbaum
Department of Psychiatry and Behavioral Science, Stanford School of Medicine, Stanford, CA 94305, USA
To address the question of whether electrophysiological deficits are progressive with duration of schizophrenia, we investigated relationships between the P300 component of the event-related brain potential (ERP) and duration of disease. Thirty-nine male veterans with schizophrenia (DSM-III-R) were tested. Mean age of onset of schizophrenic symptoms was 26 years (18 55), mean age at testing was 39 years (27 63), and mean duration of disease was 14 years (0-43). ERPs were collected during auditory and visual paradigms in which frequent events occurred on 80% of the trials, and rare events on 20%. Subjects pressed a button to rare events. Because older patients had longer duration of disease, and because age often affects P300, age effects were removed with multiple linear regression analyses. Independent of age, P300 was smaller in patients with longer duration of disease in auditory (partial F = 7.71, p <0.01) but not visual paradigms (partial F=2.08, p<0.20). Latencies of both auditory and visual P300s tended to be later with longer duration of illness, but not significantly. Clinical symptomatology was not related to duration of disease. The contribution of medication duration to this effect must also be considered. Supported by NIMH (MH30854) & Department of Veterans Affairs.
In a classical auditory oddball ERP paradigm, P300 is reduced in schizophrenics and alcoholics; N1 is reduced in schizophrenics, but not necessarily in alcoholics. We studied patients comorbid for schizophrenia and alcoholism to determine if ERP amplitude deficits are additive. We predicted P300 reduction would be compounded in comorbids but N1 reduction would not. We compared 35 normal control subjects (no schizophrenia, no alcoholism), 32 alcoholics (no schizophrenia), 25 schizophrenics (no alcoholism) and 18 comorbid patients (schizophrenia and alcoholism). Four schizophrenics and 5 comorbid patients were stabilized on antipsychotic medication. All others were not taking antipsychotic medication. ERPs were collected during an auditory paradigm in which rare tones occurred on 20% of the trials. Subjects pressed a button to rare tones. P300 amplitude was reduced in both schizophrenics and alcoholics, with additional reduction in the comorbid patients. Subjects with schizophrenia (schizophrenics and comorbids) had smaller Nls than subjects without schizophrenia (normal controls and alcoholics), with no additional N1 amplitude reduction in comorbids. There was no difference in clinical severity between schizophrenics and comorbids. Supported by NIMH (MH30854), AA05965 & Department of Veterans Affairs.
P300 AMPLITUDE IN SCHIZOPHRENIA INVERSELY RELATED TO DURATION ILLNESS
Department of Psychiatry and Behavioral Science, Stanford School of Medicine, Stanford, CA 94305, USA
IS OF
J.M. Ford*, B.G. Isaacks, K.O. Lim, A. Pfefferbaum
MODELING SACCADIC EYE MOVEMENTS IN SCHIZOPHRENIA: INSIGHTS INTO MEMORY MECHANISMS Steven D. F o r m a n * , J o n a t h a n D. C o h e n
Clinical Cognitive Neuroscience Laboratory, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical School, 3811 O'Hara Street, Pittsburgh, PA 15213, USA We have used the asymmetric diffusion learning algorithm (Movellan, 1993) to model visually and non-visually guided saccadic eye movements. A growing body of evidence from primate experiments indicates a role for frontal cortex in the maintenance of memory representations needed to support non-visually guided responses. The system is clinically interesting because schizophrenic patients show deficits in non-visually guided but not visually-guided eye movements. Specific neural modeling achievements include single- and multiple-hidden layer models of the oculomotor delayed-response and antisaccade task. These models produce qualitatively similar behavior to primate experiments both under control conditions and under putative catecholaminergic manipulations in the prefrontal cortex. In addition this modeling effort has led to a new conceptualization for how working memory representations could be developed and sustained in the prefrontal cortex. The key result is the manner by which memory representations are chosen and maintained as the result of sequential input through circuits. Unlike earlier models requiring specific recurrent cir-
volumes were quantified from 5 mm axial spin-echo MR images and corrected for overall cranial volume. A correlation between left temporal brain volume and 1/s P1 amplitudes was obtained (r = 0.43, p < 0.05). Greater P 1 abnormality (reduced amplitude at this stimulus rate) was associated with reduced brain volume. When patients were classified as deficit (n= 10) or nondeficit (n= 18), negative correlations were obtained in deficit patients between 10/s P1 amplitudes and left (r= -0.67, p<0.05) and right ( r = - 0 . 7 8 , p<0.01) frontal brain volumes. Greater P1 abnormality (increased amplitude at this rate) was associated with reduced brain volumes in these regions. No significant correlations were obtained in controls. These findings suggest that abnormal P1 amplitudes in schizophrenia may be related to structural abnormalities.
ADDITIONAL REDUCTION OF P300 AMPLITUDE IN PATIENTS WITH A DUAL DIAGNOSIS OF SCHIZOPHRENIA AND ALCOHOLISM J . M Ford*, B.G. Isaacks, D. Jackson, M.J. R o s e n b l o o m , A. Pfefferbaum
Department of Psychiatry and Behavioral Science, Stanford School of Medicine, Stanford, CA 94305, USA
To address the question of whether electrophysiological deficits are progressive with duration of schizophrenia, we investigated relationships between the P300 component of the event-related brain potential (ERP) and duration of disease. Thirty-nine male veterans with schizophrenia (DSM-III-R) were tested. Mean age of onset of schizophrenic symptoms was 26 years (18 55), mean age at testing was 39 years (27 63), and mean duration of disease was 14 years (0-43). ERPs were collected during auditory and visual paradigms in which frequent events occurred on 80% of the trials, and rare events on 20%. Subjects pressed a button to rare events. Because older patients had longer duration of disease, and because age often affects P300, age effects were removed with multiple linear regression analyses. Independent of age, P300 was smaller in patients with longer duration of disease in auditory (partial F = 7.71, p <0.01) but not visual paradigms (partial F=2.08, p<0.20). Latencies of both auditory and visual P300s tended to be later with longer duration of illness, but not significantly. Clinical symptomatology was not related to duration of disease. The contribution of medication duration to this effect must also be considered. Supported by NIMH (MH30854) & Department of Veterans Affairs.
In a classical auditory oddball ERP paradigm, P300 is reduced in schizophrenics and alcoholics; N1 is reduced in schizophrenics, but not necessarily in alcoholics. We studied patients comorbid for schizophrenia and alcoholism to determine if ERP amplitude deficits are additive. We predicted P300 reduction would be compounded in comorbids but N1 reduction would not. We compared 35 normal control subjects (no schizophrenia, no alcoholism), 32 alcoholics (no schizophrenia), 25 schizophrenics (no alcoholism) and 18 comorbid patients (schizophrenia and alcoholism). Four schizophrenics and 5 comorbid patients were stabilized on antipsychotic medication. All others were not taking antipsychotic medication. ERPs were collected during an auditory paradigm in which rare tones occurred on 20% of the trials. Subjects pressed a button to rare tones. P300 amplitude was reduced in both schizophrenics and alcoholics, with additional reduction in the comorbid patients. Subjects with schizophrenia (schizophrenics and comorbids) had smaller Nls than subjects without schizophrenia (normal controls and alcoholics), with no additional N1 amplitude reduction in comorbids. There was no difference in clinical severity between schizophrenics and comorbids. Supported by NIMH (MH30854), AA05965 & Department of Veterans Affairs.
P300 AMPLITUDE IN SCHIZOPHRENIA INVERSELY RELATED TO DURATION ILLNESS
Department of Psychiatry and Behavioral Science, Stanford School of Medicine, Stanford, CA 94305, USA
IS OF
J.M. Ford*, B.G. Isaacks, K.O. Lim, A. Pfefferbaum
MODELING SACCADIC EYE MOVEMENTS IN SCHIZOPHRENIA: INSIGHTS INTO MEMORY MECHANISMS Steven D. F o r m a n * , J o n a t h a n D. C o h e n
Clinical Cognitive Neuroscience Laboratory, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical School, 3811 O'Hara Street, Pittsburgh, PA 15213, USA We have used the asymmetric diffusion learning algorithm (Movellan, 1993) to model visually and non-visually guided saccadic eye movements. A growing body of evidence from primate experiments indicates a role for frontal cortex in the maintenance of memory representations needed to support non-visually guided responses. The system is clinically interesting because schizophrenic patients show deficits in non-visually guided but not visually-guided eye movements. Specific neural modeling achievements include single- and multiple-hidden layer models of the oculomotor delayed-response and antisaccade task. These models produce qualitatively similar behavior to primate experiments both under control conditions and under putative catecholaminergic manipulations in the prefrontal cortex. In addition this modeling effort has led to a new conceptualization for how working memory representations could be developed and sustained in the prefrontal cortex. The key result is the manner by which memory representations are chosen and maintained as the result of sequential input through circuits. Unlike earlier models requiring specific recurrent cir-