Motor Circuit Abnormalities in First-episode Schizophrenia Assessed with Transcranial Magnetic Stimulation

Abstract

Abnormalities in corticosubcortical circuits in schizophrenia have been described by previous neuroimaging and electrophysiological studies. Previous studies assessing excitability of the motoneural system by measuring cortical silent period (CSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) with transcranial magnetic stimulation (TMS) revealed conflicting results. We assessed resting motor threshold (RMT), SICI (interstimulus interval 3 milliseconds), ICF (interstimulus interval 7 milliseconds) and the duration of the contralateral CSP in the left and right first dorsal interosseus muscles (FDI) in 29 first-episode schizophrenia patients (FE-SZ) with limited exposure to antipsychotic treatment compared to 44 healthy control subjects (HC). CSP was measured during isometric contraction using stimulation intensities of 120, 140, 160 and 180% of RMT. Patients with FE-SZ demonstrated significant prolongation of CSP using stimulation intensities of 120% RMT (p=0.027), 140% RMT (p=0.015) and 160% RMT (p =0.010) of left motor cortex (right FDI) compared to HC. In addition, reduced SICI after stimulation of the right motor cortex was observed in FE-SZ (58.9% in FE-SZ vs. 31.4% in HC; p=0.050). RMT was similar in patients and controls. The reduced SICI in first-episode patients points towards a GABA(A)ergic deficit in schizophrenia. The prolonged CSP may reflect compensatory increased GABA(B)ergic transmission induced by hyperactivity of the dopaminergic system, although effects of antipsychotic medication could not be excluded.