UC Berkeley Press Release

TMS-Induced Cortical Potentiation during Wakefulness Locally Increases Slow Wave Activity during Sleep

Reto Huber, # Steve K. Esser, # Fabio Ferrarelli, Marcello Massimini, Michael J. Peterson, and Giulio Tononi *

Department of Psychiatry, University of Wisconsin , Madison, Madison , Wisconsin , United States of America

Mick Rugg, Academic Editor

University of California , Irvine , United States of America

# Contributed equally.

* To whom correspondence should be addressed. E-mail: gtononi@wisc.edu

Conceived and designed the experiments: RH GT SE. Performed the experiments: RH SE FF MM MP. Analyzed the data: RH SE. Contributed reagents/materials/analysis tools: RH SE FF MM. Wrote the paper: RH GT.

Received January 11, 2007; Accepted February 13, 2007.

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Sleep 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 Findings

To 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.


These results provide direct evidence for a link between plastic changes and the local regulation of sleep need.

Figure 1

Figure 1

Responses to TMS before and after 5 Hz conditioning. Total activation produced by TMS as measured by the global mean field power (GMFP) derived from all 60 electrodes. The GMFP was increased between 10 and 130 ms post stimulus (gray area) following rTMS (more ...)

Table 1

Table 1

Sleep architecture for the first NREM sleep episode.

Figure 2

Figure 2

Changes in local SWA homeostasis during sleep after 5-Hz rTMS conditioning. A. Topographic distribution of SWA after 5-Hz conditioning (top) and the sham control (bottom) condition. Average EEG power density at 1–4.5 Hz (n  =  10 (more ...)

Figure 4

Figure 4

The increase in TMS-evoked responses predicts the local increase of SWA. Topographic depiction of positive correlations between SWA change and the change in global mean field power in the late component of the TMS-evoked response after 5-Hz rTMS conditioning. (more ...)


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