Cortical inhibition in the pathophysiology of schizophrenia

Cortical Inhibition in the Pathophysiology of Schizophrenia


Principal Investigators: Professor Paul Fitzgerald, Adjunct Associate Professor Brendan Murphy

Project description

Cortical Inhibition (CI) is the neurophysiological process by which inhibitory brain cells (interneurons) selectively reduce the activity of other (largely excitatory) cells in the cortex of the brain. It has a variety of important functional roles including the prevention of seizures, the control of neuronal firing, the regulation of synchronous activation of excitatory neurons, and the regulation of neuronal plasticity. In recent years it has been proposed that dysfunctional or reduced CI could be the mechanism through which symptoms of schizophrenia occur. Patients with schizophrenia demonstrate reductions in both synchronous neuronal activity and cortical plasticity, while a range of studies demonstrate direct evidence for reduced CI.

Transcranial magnetic stimulation (TMS) is a unique experimental modality with which to assess CI in healthy and diseased states. The research team has used TMS to demonstrate CI deficits associated with the motor cortex in patients with schizophrenia. The team has subsequently developed a new technique, linking TMS to electroencephalography (EEG), which allows recording of CI from other cortical regions such as the dorsolateral prefrontal cortex (DLPFC), which are likely to be more relevant in understanding the pathogenesis of schizophrenia.

The current study will assess whether patients with schizophrenia display deficits of CI in the DLPFC. Data will be collected for first onset and chronic patients to explore whether deficits are related to illness stage. Clear demonstration of reduced CI will enhance current understanding of the causes of schizophrenia and the development of new therapeutic approaches.

Project status

A NHMRC grant application is currently under review for this project.