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Dissociation of ERP topographies for verbal and nonverbal auditory oddball tasks: Findings for schizophrenic patients and healthy controls
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response to the second of a pair of closely spaced clicks is reduced (gated) compared to the first. Previous work in the anesthetized rat has shown that disruption of cholinergic input by fimbria-fornix disconnection blocked auditory gating in the hippocampus. The aim of the current study was to assess the effect of selective cholinergic denervation of the hippocampus, or entire brain, on gating in unanesthetized rats . 192 IgGsaporin (saporin), an antibody to the rat low affinity nerve growth factor receptor conjugated to a ribosome-inactivating protein, is a potent and selective toxin for central cholinergic neurons. Adult male Sprague Dawley rats received 0.466 Jlg of saporin injected into the medial septal area or 4.0 Jlg injected into the lateral ventricle. Recorded waveform variables at the surface and hippocampus (condition amplitude, test amplitude, and test/condition amplitude ratios) were examined prior to and following saporin administration. Surprisingly, although cholinergic depletion was essentially complete, saporin did not alter auditory gating. These data suggest another aspect of fimbria-fornix lesions is responsible for altering auditory gating.
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SENSORY GATING DEFICIT IN SCHIZOPHRENIA: RELATION TO CATHECHOLAMINE METABOLITES Dae-Yeob Kang, John Poole, Keith McCallin, George Fein, Sophia Vinogradov
116C PsychiatryService. Department of Veterans Affairs. 4150 ClementSt. San Francisco. CA 94121 A sizable portion ofschizophrenic patients show an abnormal PSO auditory event-related potential conditioning-testing (C-T) response to paired stimuli. This abnormality is taken as evidence of impaired sensory gating in schizophrenia. There have been several reports that the sensory gating deficit is correlated with plasma 3-methoxy-4-hydroxyphenylglycol (pMHPG) in mania, but not in schizophrenia. Animal models suggest a link between cathecholaminergic neurotransmission and sensory gating in humans; however, the precise identity of the neuronal circuit involved in generation of the PSO is unknown. In this study, we examined the relationship between cathecholaminergic metabolism and the PSO C-T measure in schizophrenia. Twentytwo chronically ill schizophrenic patients (13 males, 9 females) were examined for the PSO auditory-evoked response to paired stimuli. The gating of the PSO wave was measured as the ratio of the amplitude of the second testing response to the amplitude of the first conditioning response (C-T ratio). In order to determine levels of plasma homovanillic acid (pHVA) and pMHPG, blood samples were taken by venipuncture, and analysed by high performance liquid chromatography (HPLC). There was significant positive correlation between CoT ratio and pMHPG (Spearman's r=0.37, P .. 0.046), but no significant correlation between CoT ratio and pHVA. These data differ from previous findings in schizophrenia, and suggest that adrenergic neuronal mechanisms may play at least a modulatory role of sensory gating in schizophrenia.
~v7 DISSOCIATION OF ERP TOPOGRAPHIES FOR VERBAL AND NONVERBAL AUDITORY ODDBALL TASKS: FINDINGS FOR SCHIZOPHRENIC PATIENTS AND HEALTHY CONTROLS Jurgen Kayser, Gerard Bruder, Craig Tenke, Jennifer Watson, Dolores Malaspina, Xavier Amador, and Jack Gorman
New York State Psychiatric Institute, 722 West168thStreet. New York, NY 10032 Prior studies have found a relationship between anomalous asymmetries of the P3 event-related brain potential (ERP) and structural left temporal lobe abnormalities. However, other researchers have not found abnormal P3 asymmetries in schizophrenia during 'oddbal1' tasks with tones. To further test the hypothesis of a left temporal lobe dysfunction in schizophrenia, two different oddbal1 tasks using binaural1y presented verbal (conson ant-vowel syl1able)and nonverbal (complex tone) stimuli (20% targets, 80% non-targets) were employed. Twentynine right-h anded pat ients from the Schizophrenia Research Unit with a DSM-IV consensus diagno sis of schizophrenia (n=22) or schizoaffective (n=7) and 23 matched healthy control subjects responded manually to targets. Response hand was counterbalanced across subjects. ERPs elicited by the stimuli were recorded from 30 scalp placements . Overall, the amplitude of early negative ERP components (N I, N2) and N2-P3 were markedly reduced in patients (each p
~t AUTOMATED ANALYSIS OF EEG SLEEP DEFICITS IN SCHIZOPHRENIA Matcheri S. Keshavan, Debra Montrose, Jean Miewald, Charles F. Reynolds III
Western PsychiatricInstituteand Clinic. pittsburghPA 15213 A reduction in slow wave sleep (SWS), or delta sleep is seen in schizophrenia. Its pathophysiological significance, however, rema ins unclear. Studies in cats suggest that the SWS in the 1-2 Hz range probably reflects thalamocortical activity in contrast to the < I Hz activity which might represent an intra
response to the second of a pair of closely spaced clicks is reduced (gated) compared to the first. Previous work in the anesthetized rat has shown that disruption of cholinergic input by fimbria-fornix disconnection blocked auditory gating in the hippocampus. The aim of the current study was to assess the effect of selective cholinergic denervation of the hippocampus, or entire brain, on gating in unanesthetized rats . 192 IgGsaporin (saporin), an antibody to the rat low affinity nerve growth factor receptor conjugated to a ribosome-inactivating protein, is a potent and selective toxin for central cholinergic neurons. Adult male Sprague Dawley rats received 0.466 Jlg of saporin injected into the medial septal area or 4.0 Jlg injected into the lateral ventricle. Recorded waveform variables at the surface and hippocampus (condition amplitude, test amplitude, and test/condition amplitude ratios) were examined prior to and following saporin administration. Surprisingly, although cholinergic depletion was essentially complete, saporin did not alter auditory gating. These data suggest another aspect of fimbria-fornix lesions is responsible for altering auditory gating.
(,(, (,
SENSORY GATING DEFICIT IN SCHIZOPHRENIA: RELATION TO CATHECHOLAMINE METABOLITES Dae-Yeob Kang, John Poole, Keith McCallin, George Fein, Sophia Vinogradov
116C PsychiatryService. Department of Veterans Affairs. 4150 ClementSt. San Francisco. CA 94121 A sizable portion ofschizophrenic patients show an abnormal PSO auditory event-related potential conditioning-testing (C-T) response to paired stimuli. This abnormality is taken as evidence of impaired sensory gating in schizophrenia. There have been several reports that the sensory gating deficit is correlated with plasma 3-methoxy-4-hydroxyphenylglycol (pMHPG) in mania, but not in schizophrenia. Animal models suggest a link between cathecholaminergic neurotransmission and sensory gating in humans; however, the precise identity of the neuronal circuit involved in generation of the PSO is unknown. In this study, we examined the relationship between cathecholaminergic metabolism and the PSO C-T measure in schizophrenia. Twentytwo chronically ill schizophrenic patients (13 males, 9 females) were examined for the PSO auditory-evoked response to paired stimuli. The gating of the PSO wave was measured as the ratio of the amplitude of the second testing response to the amplitude of the first conditioning response (C-T ratio). In order to determine levels of plasma homovanillic acid (pHVA) and pMHPG, blood samples were taken by venipuncture, and analysed by high performance liquid chromatography (HPLC). There was significant positive correlation between CoT ratio and pMHPG (Spearman's r=0.37, P .. 0.046), but no significant correlation between CoT ratio and pHVA. These data differ from previous findings in schizophrenia, and suggest that adrenergic neuronal mechanisms may play at least a modulatory role of sensory gating in schizophrenia.
~v7 DISSOCIATION OF ERP TOPOGRAPHIES FOR VERBAL AND NONVERBAL AUDITORY ODDBALL TASKS: FINDINGS FOR SCHIZOPHRENIC PATIENTS AND HEALTHY CONTROLS Jurgen Kayser, Gerard Bruder, Craig Tenke, Jennifer Watson, Dolores Malaspina, Xavier Amador, and Jack Gorman
New York State Psychiatric Institute, 722 West168thStreet. New York, NY 10032 Prior studies have found a relationship between anomalous asymmetries of the P3 event-related brain potential (ERP) and structural left temporal lobe abnormalities. However, other researchers have not found abnormal P3 asymmetries in schizophrenia during 'oddbal1' tasks with tones. To further test the hypothesis of a left temporal lobe dysfunction in schizophrenia, two different oddbal1 tasks using binaural1y presented verbal (conson ant-vowel syl1able)and nonverbal (complex tone) stimuli (20% targets, 80% non-targets) were employed. Twentynine right-h anded pat ients from the Schizophrenia Research Unit with a DSM-IV consensus diagno sis of schizophrenia (n=22) or schizoaffective (n=7) and 23 matched healthy control subjects responded manually to targets. Response hand was counterbalanced across subjects. ERPs elicited by the stimuli were recorded from 30 scalp placements . Overall, the amplitude of early negative ERP components (N I, N2) and N2-P3 were markedly reduced in patients (each p
~t AUTOMATED ANALYSIS OF EEG SLEEP DEFICITS IN SCHIZOPHRENIA Matcheri S. Keshavan, Debra Montrose, Jean Miewald, Charles F. Reynolds III
Western PsychiatricInstituteand Clinic. pittsburghPA 15213 A reduction in slow wave sleep (SWS), or delta sleep is seen in schizophrenia. Its pathophysiological significance, however, rema ins unclear. Studies in cats suggest that the SWS in the 1-2 Hz range probably reflects thalamocortical activity in contrast to the < I Hz activity which might represent an intra