A biophysical network model reveals the link between deficient inhibitory cognitive control and major neurotransmitter and neural connectivity hypotheses in schizophrenia

TL;DR

This study uses a biophysical network model to link dopamine and NMDA receptor hypoactivity, as well as disrupted prefrontal connectivity, to inhibitory cognitive deficits in schizophrenia, validated by antisaccade task data.

Contribution

The paper introduces a biophysical network model that integrates neurotransmitter activity and connectivity patterns to explain cognitive deficits in schizophrenia.

Findings

Model accurately predicts dopamine hypoactivity in schizophrenia

Reproduces NMDA receptor hypo-function effects

Replicates prefrontal connectivity disruptions

Abstract

We address a biophysical network dynamical model to study how the modulation of dopamine (DA) activity and related N-methyl-d-aspartate (NMDA) glutamate receptor activity as well as the emerging Pre-Frontal Cortex (PFC) functional connectivity network (FCN) affect inhibitory cognitive function in schizophrenia in an antisaccade task. The values of the model parameters and the topology of the PFC-FCN were estimated by minimizing the differences between simulations and the observed distributions of reaction times (RT) during the performance of the antisaccade task in 30 patients with schizophrenia and 30 healthy controls. We show that the proposed model approximates remarkably well the predicted prefrontal cortical DA hypo-activity and the related NMDA receptor hypo-function as well as the FCN dysconnection pattern that are considered as the major etio-pathological hypotheses to explain cognitive deficits in schizophrenia.