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Temporal P300 asymmetry in schizophrenia vs. Manic psychosis and controls
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In the neuropsychological approach to psychopathology event-related brain potentials (ERPs) are examined to uncover electrocortical correlates of cognitive or behavioral characteristics in schizophrenic patients. While smaller amplitudes of several ERP-components have been repeatedly reported for schizophrenic patients versus control groups, a larger slow surface-negative potential following the completion of a forewarned (motor or cognitive) response, called postimperative negative variation (PINY), has been reliably found in schizophrenic patients by several authors, but only rarely in healthy subjects. In a series of studies we examined contributions to the PINY by varying task-related features in visual and auditory delayed-matching-to-sample tasks in groups of schizophrenic patients (DSM-II1-R) and healthy controls. While demands on working memory enhanced PINY amplitude primarily in schizophrenic patients, PINV amplitude increased with ambiguity of the matching in controls and schizophrenics alike. Differential effects of ambiguity and performance requirements (Go-NoGo) on PINY amplitude and its scalp distribution suggest that performance uncertainty contributes to PINV generation and that the threshold for performance uncertainty is reduced in schizophrenics. Topographical analyses suggest that the PINY is generated symmetrically in the frontal lobes in schizophrenics, while it shows a right frontal dominance in controls. Research was supported by the Deutsche Forschungsgemeinschaft (Ro 805).
and normal controls over the posterior sagittal midline of the head, with first episode affective patients intermediate. First episode schizophrenics displayed smaller amplitudes than both first episode affective psychotics and normal controls over left temporal lobe, but groups showed no differences over right temporal lobe. Left-sided P300 abnormality in first episode schizophrenia relative to first episode affective psychosis and controls suggests P300 asymmetry is specific to schizophrenic psychosis and is present at initial psychopathology, and implicates left temporal lobe cortical dysfunction at the onset of schizophrenia. More specifically, the left temporal P300 reduction may reflect reduced cortical gray matter volume of left posterior STG at initial schizophrenic psychosis.
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TEMPORAL P300 ASYMMETRY IN SCHIZOPHRENIA VS. MANIC PSYCHOSIS AND CONTROLS Dean F. Salisbury, Iris A. Fischer, Martha E. Shenton, Andrea R. Sherwood, Paola Mazzoni, Robert W. McCarley
Harvard Medical School/McLean Hospital. 115 Mill Street, Belmont. MA 02178
~7! TEMPORAL P300 ASYMMETRY IN FIRST EPISODE SCHIZOPHRENIA Dean F. Salisbury, Andrea R. Sherwood, Martha E. Shenton, Iris A. Fischer, Deborah A. YurgelunTodd, Mauricio Tohen, Robert W. McCarley
Harvard Medical School/McLean Hospital. 115 Mill Street. Belmont. MA 02178 Schizophrenia is associated with central midline reductions and topographic asymmetry of P300, with reduced left temporal voltage. This P300 asymmetry is, in tum, linked to cortical gray matter volume asymmetry in posterior superior temporal gyrus. It is unknown whether P300 asymmetry is specific to schizophrenia, and whether central and lateral P300 abnormalities are due to chronic morbidity, neuroleptic medication, and/or hospitalization, or are present at illness onset. To examine these questions, P300 was recorded in first episode schizophrenia (n=14, 10 M, 4 F, mean age 31.1 (9.I)yrs, right-handed), first episode affective psychosis (n ... 14, 12 M, 2 F, mean age 24.9 (6.6)yrs, right-handed), and controls (n= 14, 12 M, 2 F, mean age 25.9 (8.4)yrs, right-handed). Peak amplitude of P300 and integrated voltage over 300 to 400 ms were significantly different between first episode schizophrenics
Data from our laboratory and others have demonstrated a reduction of P300 over left temporal lobe in schizophrenia, producing a topographic asymmetry. This asymmetry is, in turn, linked to MR-demonstrated cortical gray matter volume reduction of left posterior superior temporal gyrus, a putative P300 generator site, and positive symptomatology. This triad of inter-correlated measures is thought to reflect a core element of schizophrenic pathology. P300 was measured in a new sample of schizophrenics (n ...29, mean age (sd) - 36.1 (6.7) yrs, male, right-handed), a contrast group of psychotic manics (n ... 16, mean age (sd)-30.1 (6.7) yrs, male, right-handed), and controls (n=24, mean age (sd)-3S.6 (7.7) yrs, male, righthanded) to determine if P300 asymmetry was present in a nonchronically institutionalized schizophrenic sample, and not in psychosis of affective etiology. Schizophrenics and affective psychotics did not differ significantly in BPRS, GAS. or medications. Both patient samples showed significantly smaller midline peak Cz amplitude than controls (Sz: 9.9IlV; Aff: 9.1; Con: 16.3). In contrast, analysis of left (T3) and right (T4) temporal voltages revealed significant differences in P300 lateralization between schizophrenics and the other groups. Schizophrenics were significantly asymmetrical, with left deficit (T3: 4.3IlV; T4: 5.0), relative to controls (T3: 6.7 /-IV; T4: 6.3, Group x Side interaction p-O.022), and manic psychotics (T3: S.4IlV; T4: 4.9, p-O.06). These preliminary data suggest that left temporal P300 reduction is present in schizophrenia. but not in affective psychosis, and may represent a biobehavioral probe of underlying schizophrenic neuropathology.
In the neuropsychological approach to psychopathology event-related brain potentials (ERPs) are examined to uncover electrocortical correlates of cognitive or behavioral characteristics in schizophrenic patients. While smaller amplitudes of several ERP-components have been repeatedly reported for schizophrenic patients versus control groups, a larger slow surface-negative potential following the completion of a forewarned (motor or cognitive) response, called postimperative negative variation (PINY), has been reliably found in schizophrenic patients by several authors, but only rarely in healthy subjects. In a series of studies we examined contributions to the PINY by varying task-related features in visual and auditory delayed-matching-to-sample tasks in groups of schizophrenic patients (DSM-II1-R) and healthy controls. While demands on working memory enhanced PINY amplitude primarily in schizophrenic patients, PINV amplitude increased with ambiguity of the matching in controls and schizophrenics alike. Differential effects of ambiguity and performance requirements (Go-NoGo) on PINY amplitude and its scalp distribution suggest that performance uncertainty contributes to PINV generation and that the threshold for performance uncertainty is reduced in schizophrenics. Topographical analyses suggest that the PINY is generated symmetrically in the frontal lobes in schizophrenics, while it shows a right frontal dominance in controls. Research was supported by the Deutsche Forschungsgemeinschaft (Ro 805).
and normal controls over the posterior sagittal midline of the head, with first episode affective patients intermediate. First episode schizophrenics displayed smaller amplitudes than both first episode affective psychotics and normal controls over left temporal lobe, but groups showed no differences over right temporal lobe. Left-sided P300 abnormality in first episode schizophrenia relative to first episode affective psychosis and controls suggests P300 asymmetry is specific to schizophrenic psychosis and is present at initial psychopathology, and implicates left temporal lobe cortical dysfunction at the onset of schizophrenia. More specifically, the left temporal P300 reduction may reflect reduced cortical gray matter volume of left posterior STG at initial schizophrenic psychosis.
'7~
TEMPORAL P300 ASYMMETRY IN SCHIZOPHRENIA VS. MANIC PSYCHOSIS AND CONTROLS Dean F. Salisbury, Iris A. Fischer, Martha E. Shenton, Andrea R. Sherwood, Paola Mazzoni, Robert W. McCarley
Harvard Medical School/McLean Hospital. 115 Mill Street, Belmont. MA 02178
~7! TEMPORAL P300 ASYMMETRY IN FIRST EPISODE SCHIZOPHRENIA Dean F. Salisbury, Andrea R. Sherwood, Martha E. Shenton, Iris A. Fischer, Deborah A. YurgelunTodd, Mauricio Tohen, Robert W. McCarley
Harvard Medical School/McLean Hospital. 115 Mill Street. Belmont. MA 02178 Schizophrenia is associated with central midline reductions and topographic asymmetry of P300, with reduced left temporal voltage. This P300 asymmetry is, in tum, linked to cortical gray matter volume asymmetry in posterior superior temporal gyrus. It is unknown whether P300 asymmetry is specific to schizophrenia, and whether central and lateral P300 abnormalities are due to chronic morbidity, neuroleptic medication, and/or hospitalization, or are present at illness onset. To examine these questions, P300 was recorded in first episode schizophrenia (n=14, 10 M, 4 F, mean age 31.1 (9.I)yrs, right-handed), first episode affective psychosis (n ... 14, 12 M, 2 F, mean age 24.9 (6.6)yrs, right-handed), and controls (n= 14, 12 M, 2 F, mean age 25.9 (8.4)yrs, right-handed). Peak amplitude of P300 and integrated voltage over 300 to 400 ms were significantly different between first episode schizophrenics
Data from our laboratory and others have demonstrated a reduction of P300 over left temporal lobe in schizophrenia, producing a topographic asymmetry. This asymmetry is, in turn, linked to MR-demonstrated cortical gray matter volume reduction of left posterior superior temporal gyrus, a putative P300 generator site, and positive symptomatology. This triad of inter-correlated measures is thought to reflect a core element of schizophrenic pathology. P300 was measured in a new sample of schizophrenics (n ...29, mean age (sd) - 36.1 (6.7) yrs, male, right-handed), a contrast group of psychotic manics (n ... 16, mean age (sd)-30.1 (6.7) yrs, male, right-handed), and controls (n=24, mean age (sd)-3S.6 (7.7) yrs, male, righthanded) to determine if P300 asymmetry was present in a nonchronically institutionalized schizophrenic sample, and not in psychosis of affective etiology. Schizophrenics and affective psychotics did not differ significantly in BPRS, GAS. or medications. Both patient samples showed significantly smaller midline peak Cz amplitude than controls (Sz: 9.9IlV; Aff: 9.1; Con: 16.3). In contrast, analysis of left (T3) and right (T4) temporal voltages revealed significant differences in P300 lateralization between schizophrenics and the other groups. Schizophrenics were significantly asymmetrical, with left deficit (T3: 4.3IlV; T4: 5.0), relative to controls (T3: 6.7 /-IV; T4: 6.3, Group x Side interaction p-O.022), and manic psychotics (T3: S.4IlV; T4: 4.9, p-O.06). These preliminary data suggest that left temporal P300 reduction is present in schizophrenia. but not in affective psychosis, and may represent a biobehavioral probe of underlying schizophrenic neuropathology.