Does TMS help to Better Understand Schizophrenia and Mechanisms of Neuroleptic Treatment?

Transcranial magnetic stimulation (TMS) provides an intriguing in vivo method to investigate motor cortex excitability in men. This offers new insights into the neurophysiological effects of neuroleptic drug treatment. We studied several TMS paradigms in first-episode schizophrenic patients before treatment initiation and under steady-state conditions with different neuroleptic drugs. The patient group demonstrated a significantly lower resting motor threshold as compared with healthy controls, whereas TMS paradigms of cortical silent period, intracortical inhibition and intracortical facilitation failed to show significant differences between patients and controls. This pattern of TMS parameters is similar to that obtained in healthy volunteers investigated under increasing doses of ketamine, a central-acting drug, known to produce psychosis-like effects. In agreement with recent results of functional imaging, our neurophysiological findings suggest that drug-induced and naturally occurring psychosis may share a common pathway, which may base on dysfunctional glutamatergic mechanisms. Neuroleptic treatment was reflected by an increase of cortical silent period and motor thresholds, pointing to a treatment induced improvement of inhibitory functions. These findings demonstrate the potential of TMS to detect excitability changes associated with schizophrenia and with neuroleptic treatment. This method could be further developed as a diagnostic tool or for endophenotypization.