The purpose of the proposed research is to examine the effects of temporal variability on the sensory gating deficit observed in schizophrenia. Schizophrenics show impaired sensory gating as measured by the response of the early P50 component of the event-related potential (ERP) in a dual- clock, conditioning-testing procedure. In the healthy nervous system, the ERP response to the second or testing click (S) is typically gated or inhibited, compared with the response to the first or conditioning click (S1). Schizophrenics do not inhibit (or gate) responses to the second stimulus. These findings support hypotheses of neuronal hyperexcitability possibly related to a defect in inhibitory neuronal pathways, and are consistent with clinical observations of defective attention in schizophrenia. Preliminary studies conducted in our laboratory have confirmed the gating abnormality in schizophrenics, but indicate that it may be due primarily to temporal variability detected in their single-trial evoked potentials. This increased variability contributes to a diminished P50 amplitude in schizophrenics, particularly at S1, and appears to account for the increased S2/S1 gating ratios in schizophrenics. In the proposed research, 50 schizophrenics (25 undifferentiated, 25 paranoid) will be tested using the dual-click conditioning-testing procedure in order to: (1) replicate the finding that, compared to normal controls, the P50 responses of schizophrenics in the conditioning-testing paradigm show a defect in sensory gating; (2) determine the extent to which the differences between schizophrenics and normals on P50 amplitude and the P50 gating ratio are reduced or eliminated when temporal variability is controlled using latency correction of the ERP (i.e., when the potentials are aligned using the peak latency of each single trial); (3) determine the contribution of intrasubject temporal variability in single trials to the P50 gating ratio; and (4) determine the contribution of temporal variability in the early P50 peak to variability in the later N100 and P180 peaks of the ERP. These studies will provide information regarding the mechanisms underlying the observed sensory gating deficits in schizophrenia.
| Patterson, J V; Jin, Y; Gierczak, M et al. (2000) Effects of temporal variability on p50 and the gating ratio in schizophrenia: a frequency domain adaptive filter single-trial analysis. Arch Gen Psychiatry 57:57-64 |
