Evidence for Impaired Cortical Inhibition in Schizophrenia Using Transcranial Magnetic Stimulation

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Abstract
SEVERAL LINES of evidence suggest that schizophrenia is a disorder associated with deficits in cortical inhibition (CI). These deficits have been demonstrated in cognitive, motor, neurophysiologic, and neuropathologic studies. First, cognitive studies suggest that patients with schizophrenia have impaired sensorimotor gating, inferred from their performance in prepulse inhibition tasks. Swerdlow and Koob1 posit that such impairment is due to excess activation of subcortical dopamine that leads to decreased activation of cortical inhibitory projections. Second, Walker et al2 posit that the motor abnormalities in schizophrenia, ranging from generalized incoordination to agitation and catatonia, are a corollary to disinhibition of cortical inhibitory neurotransmission. Third, neurophysiologic studies by Freedman et al3-6 demonstrate that patients with schizophrenia have impaired inhibition of event-related potential responses to paired auditory stimuli. Fourth, neuropathologic studies have shown that patients with schizophrenia have morphologic changes in cortical γ-aminobutyric acid (GABA) inhibitory interneurons,7 which may in turn be linked to findings of reduced gray matter volume in these patients.8 Collectively, these results suggest that CI is dysfunctional in schizophrenia.