Abstract

BackgroundSleep slow wave activity (SWA) is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning.Methodology/Principal FindingsTo test this hypothesis directly, we used transcranial magnetic stimulation (TMS) in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1±17.4%, p<0.01, n = 10). Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep.Conclusions/SignificanceThese results provide direct evidence for a link between plastic changes and the local regulation of sleep need.

Highlights

  • During non rapid eye movement (NREM) sleep the EEG is dominated by slow waves of high amplitude, which are generated by millions of neurons switching from a depolarized up-state to a hyperpolarized down-state [1,2]

  • The results show that repetitive TMS (rTMS) but not sham stimulation produces a local potentiation of cortical responses, and that this potentiation is followed as predicted by a local increase in sleep slow wave activity (SWA), in line with the hypothesis that sleep regulation is linked to synaptic plasticity

  • We found no significant correlation between the time interval from the end of the rTMS conditioning to sleep onset and the local increase of SWA at the beginning of sleep (r = 0.2, p = 0.5)

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Summary

Introduction

During non rapid eye movement (NREM) sleep the EEG is dominated by slow waves of high amplitude, which are generated by millions of neurons switching from a depolarized up-state to a hyperpolarized down-state [1,2]. Sleep SWA was locally decreased over right sensorimotor cortex if a subject’s left arm had been immobilized during the day, leading to a deterioration in motor performance and to a decrease in somatosensory and motor evoked potentials [8]. These experiments suggest that sleep SWA is affected by plastic changes in local cortical circuits and, that SWA should increase with synaptic potentiation and decrease with synaptic depression [9]. These results provide direct evidence for a link between plastic changes and the local regulation of sleep need

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