Abstract

BackgroundGamma (γ) 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 γ oscillatory activity during WM.Methodology and Principal FindingsWe examined the effect of 20 Hz rTMS over the DLPFC on γ 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 γ oscillatory activity compared to healthy subjects across WM load. Active rTMS resulted in the reduction of frontal γ oscillatory activity in patients with SCZ, while potentiating activity in healthy subjects in the 3-back, the most difficult condition. Further, these effects on γ oscillatory activity were found to be specific to the frontal brain region and were absent in the parieto-occipital brain region.Conclusions and SignificanceWe suggest that this opposing effect of rTMS on γ oscillatory activity in patients with SCZ versus healthy subjects may be related to homeostatic plasticity leading to differential effects of rTMS on γ 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 γ oscillatory activity that may be a possible avenue for cognitive potentiation in this disorder.

Highlights

  • Gamma (c) oscillations (30–50 Hz) are associated with working memory (WM)

  • We suggest that this opposing effect of Repetitive transcranial magnetic stimulation (rTMS) on c oscillatory activity in patients with SCZ versus healthy subjects may be related to homeostatic plasticity leading to differential effects of rTMS on c 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 c oscillatory activity that may be a possible avenue for cognitive potentiation in this disorder

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Summary

Introduction

WM involves the maintenance and manipulation of information [1] and has been shown to increase c oscillations with increases in WM load in healthy subjects [2], in the dorsolateral prefrontal cortex (DLPFC; [3]). Schizophrenia (SCZ) patients have marked deficits in WM [4] that has been attributed to altered c oscillatory activity. We demonstrated that SCZ patients compared to healthy subjects elicit excessive c oscillatory activity while performing the N-back task at all WM loads that was accompanied by impaired performance [5]. Gamma (c) oscillations (30–50 Hz) have been shown to be excessive in patients with schizophrenia (SCZ) during working memory (WM). 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

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