Distinct neural generators of sensory gating in schizophrenia

Abstract

Although malfunctioning of inhibitory processes is proposed as a pathophysiological mechanism in schizophrenia and has been studied extensively with the P50 gating paradigm, the brain regions involved in generating and suppressing the P50 remain unclear. The current investigation used EEG source analysis and the standard S1-S2 paradigm to clarify the neural structures associated with P50 gating in 16 schizophrenia patients and 14 healthy subjects. Based on prior research, the superior temporal gyrus, hippocampus, dorsolateral prefrontal cortex, thalamus, and their dipole moments were evaluated. In modeling the P50, a neural network involving all four brain regions provided the best goodness-of-fit across both groups. In healthy subjects, the P50 ratio score correlated positively with the hippocampal dipole moment ratio, whereas a significant association with the DLPFC dipole moment ratio was observed in schizophrenia patients. In each instance, the neural structure was found to account for unique variance in explaining the P50 ratio, along with some suggestion of DLPFC involvement in healthy subjects.

Figure 1

Grand average event-related potential waveforms at the Cz recording site. Waveforms are unfiltered, and the N40 and P50 components are indicated with arrowheads.

Figure 2

Mean P50 suppression ratios and P50 amplitudes to paired stimuli for healthy comparison subjects and schizophrenia patients.

Figure 3

Mean dipole moments to paired stimuli for the hippocampus, thalamus, dorsolateral prefrontal cortex, and superior temporal gyrus for healthy comparison subjects and schizophrenia patients. Note: μAmm, micro Ampere per millimeter; HC, Hippocampus; TH, Thalamus; DLPFC, Dorsolateral prefrontal cortex; STG, Superior temporal gyrus

Figure 4

Associations between the P50 suppression ratio and the hippocampal dipole moment ratio for healthy comparison subjects and schizophrenia patients.