Triggering sleep slow waves by transcranial magnetic stimulation

doi:10.1073/pnas.0702495104

Triggering sleep slow waves by transcranial magnetic stimulation

*Department of Psychiatry, University of Wisconsin, 6001 Research Park Boulevard, Madison, WI 53719; and
^†Department of Clinical Sciences, University of Milan, Via G.B. Grassi 74, 20157 Milan, Italy

Communicated by Rodolfo R. Llinas, New York University Medical School, New York, NY, March 16, 2007 (received for review November 26, 2006)

Abstract

During much of sleep, cortical neurons undergo near-synchronous slow oscillation cycles in membrane potential, which give rise to the largest spontaneous waves observed in the normal electroencephalogram (EEG). Slow oscillations underlie characteristic features of the sleep EEG, such as slow waves and spindles. Here we show that, in sleeping subjects, slow waves and spindles can be triggered noninvasively and reliably by transcranial magnetic stimulation (TMS). With appropriate stimulation parameters, each TMS pulse at <1 Hz evokes an individual, high-amplitude slow wave that originates under the coil and spreads over the cortex. TMS triggering of slow waves reveals intrinsic bistability in thalamocortical networks during non-rapid eye movement sleep. Moreover, evoked slow waves lead to a deepening of sleep and to an increase in EEG slow-wave activity (0.5–4.5 Hz), which is thought to play a role in brain restoration and memory consolidation.

Footnotes

^‡To whom correspondence should be addressed. E-mail: gtononi{at}wisc.edu
Author contributions: M. Massimini and G.T. designed research; M. Massimini, F.F., S.K.E., B.A.R., R.H., M. Murphy, and M.J.P. performed research; M. Massimini and F.F. analyzed data; and M. Massimini and G.T. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0702495104/DC1.
Abbreviations:

TMS,

transcranial magnetic stimulation;

NREM,

non-rapid eye movement;

EEG,

electroencephalogram;

SWA,

slow-wave activity;

SO,

slow oscillation.