The Effect of Repetitive Transcranial Magnetic Stimulation on Gamma Oscillatory Activity in Schizophrenia

Background: Gamma (c) oscillations (30-50 Hz) have been shown to be excessive in patients with schizophrenia (SCZ) during working memory (WM). WM is a cognitive process that involves the online maintenance and manipulation of information that is mediated largely by the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive method to stimulate the cortex that has been shown to enhance cognition and c oscillatory activity during WM. Methodology and Principal Findings: We examined the effect of 20 Hz rTMS over the DLPFC on gamma oscillatory activity elicited during the N-back task in 24 patients with SCZ compared to 22 healthy subjects. Prior to rTMS, patients with SCZ elicited excessive gamma oscillatory activity compared to healthy subjects across WM load. Active rTMS resulted in the reduction of frontal gamma oscillatory activity in patients with SCZ, while potentiating activity in healthy subjects in the 3-back, the most difficult condition. Further, these effects on gamma oscillatory activity were found to be specific to the frontal brain region and were absent in the parieto-occipital brain region. Conclusions and Significance: We suggest that this opposing effect of rTMS on gamma oscillatory activity in patients with SCZ versus healthy subjects may be related to homeostatic plasticity leading to differential effects of rTMS on gamma oscillatory activity depending on baseline differences. These findings provide important insights into the neurophysiological mechanisms underlying WM deficits in SCZ and demonstrated that rTMS can modulate gamma oscillatory activity that may be a possible avenue for cognitive potentiation in this disorder.