Potentiation of Gamma Oscillatory Activity through Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex

Neuronal oscillations in the gamma (gamma) frequency range (30-50 Hz) have been associated with cognition. Working memory (WM), a cognitive task involving the on-line maintenance and manipulation of information, elicits increases in gamma oscillations with greater cognitive demand, particularly in the dorsolateral prefrontal cortex (DLPFC). The generation and modulation of gamma oscillations have been attributed to inhibitory interneuron networks that use gamma-aminobutyric acid (GABA) as their principal neurotransmitter. Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive method to stimulate the cortex that has been shown to modify cognition and GABA inhibitory mechanisms, particularly with higher frequencies (ie, 10-20 Hz). We measured the effect of high-frequency rTMS applied to the DLPFC on gamma-oscillations elicited during the N-back WM task in healthy individuals. Active rTMS significantly increased gamma-oscillations generated during the N-back conditions with the greatest cognitive demand. Further, no significant changes were found in other frequency ranges, suggesting that rTMS selectively modulates gamma-oscillations in the frontal brain regions. These findings provide important insights into the neurophysiological mechanisms that underlie higher-order cognitive processes, and suggest that rTMS may be used as a cognitive enhancing strategy in neuropsychiatric disorders that suffer from cognitive deficits. Neuropsychopharmacology (2009) 34, 2359-2367; doi: 10.1038/npp.2009.79; published online 15 July 2009