The Functional Consequences of Cortical Circuit Abnormalities on Gamma Oscillations in Schizophrenia: Insights from Computational Modeling

Abstract

Schizophrenia is characterized by cortical circuit abnormalities, which might be reflected in γ-frequency (30–100 Hz) oscillations in the electroencephalogram. Here we used a computational model of cortical circuitry to examine the effects that neural circuit abnormalities might have on γ generation and network excitability. The model network consisted of 1000 leaky integrate-and-fire neurons with realistic connectivity patterns and proportions of neuron types [pyramidal cells (PCs), regular-spiking inhibitory interneurons, and fast-spiking interneurons (FSIs)]. The network produced a γ oscillation when driven by noise input. We simulated reductions in: (1) recurrent excitatory inputs to PCs; (2) both excitatory and inhibitory inputs to PCs; (3) all possible connections between cells; (4) reduced inhibitory output from FSIs; and (5) reduced NMDA input to FSIs. Reducing all types of synaptic connectivity sharply reduced γ power and phase synchrony. Network excitability was reduced when recurrent excitatory connections were deleted, but the network showed disinhibition effects when inhibitory connections were deleted. Reducing FSI output impaired γ generation to a lesser degree than reducing synaptic connectivity, and increased network excitability. Reducing FSI NMDA input also increased network excitability, but increased γ power. The results of this study suggest that a multimodal approach, combining non-invasive neurophysiological and structural measures, might be able to distinguish between different neural circuit abnormalities in schizophrenia patients. Computational modeling may help to bridge the gaps between post-mortem studies, animal models, and experimental data in humans, and facilitate the development of new therapies for schizophrenia and neuropsychiatric disorders in general.