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The Journal of Neuroscience, July 30, 2008, 28(31):7911-7918; doi:10.1523/JNEUROSCI.1636-08.2008

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Behavioral/Systems/Cognitive
Measures of Cortical Plasticity after Transcranial Paired Associative Stimulation Predict Changes in Electroencephalogram Slow-Wave Activity during Subsequent Sleep

Reto Huber,^1,2 Sara Määttä,¹ Steve K. Esser,¹ Simone Sarasso,¹ Fabio Ferrarelli,¹ Adam Watson,¹ Florinda Ferreri,³ Michael J. Peterson,¹ and Giulio Tononi¹

¹Department of Psychiatry, University of Wisconsin–Madison, Madison, Wisconsin 53719, ²University Children's Hospital Zurich, CH-8032 Zurich, Switzerland, and ³Department of Neurology, University Campus Biomedico, I-00155 Rome, Italy

Correspondence should be addressed to Giulio Tononi, Department of Psychiatry, University of Wisconsin–Madison, 6001 Research Park Boulevard, Madison, WI 53719-1176. Email: gtononi{at}wisc.edu

Sleep slow-wave activity (SWA) is thought to reflect sleep need, increasing in proportion to the previous time awake and decreasing during sleep, although the underlying mechanisms are unclear. Recent studies have shown that procedures presumably leading to local plastic changes in the cerebral cortex can lead to local changes in SWA during subsequent sleep. To further investigate the connection between cortical plasticity and sleep SWA, in this study we used a paired associative stimulation (PAS) protocol, in which median nerve stimuli were followed at different intervals (25 or 10 ms) by transcranial magnetic stimulation (TMS) pulses to the contralateral cortical hand area. As expected, such a protocol led to a sustained increase (long-term potentiation-like) or decrease (long-term depression-like) of cortical excitability as measured by motor evoked potentials. By using a TMS-compatible high-density electroencephalographic (EEG) system, we also found that, in individual subjects, TMS-evoked cortical responses over sensorimotor cortex changed with different interstimulus intervals. Moreover, during subsequent sleep, SWA increased locally in subjects whose TMS-evoked cortical responses had increased after PAS, and decreased in subjects whose cortical responses had decreased. Changes in TMS-evoked cortical EEG response and change in sleep SWA were localized to similar cortical regions and were positively correlated. Together, these results suggest that changes in cortical excitability in opposite directions lead to corresponding changes in local sleep regulation, as reflected by SWA, providing evidence for a tight relationship between cortical plasticity and sleep intensity.

Key words: sleep homeostasis; synaptic plasticity; high-density EEG; transcranial magnetic stimulation; slow oscillations; cortical excitability

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Received Nov. 5, 2007; revised June 11, 2008; accepted June 12, 2008.

Correspondence should be addressed to Giulio Tononi, Department of Psychiatry, University of Wisconsin–Madison, 6001 Research Park Boulevard, Madison, WI 53719-1176. Email: gtononi{at}wisc.edu

This article has been cited by other articles:

				D. Bushey, G. Tononi, and C. Cirelli The Drosophila Fragile X Mental Retardation Gene Regulates Sleep Need J. Neurosci., February 18, 2009; 29(7): 1948 - 1961. [Abstract] [Full Text] [PDF]

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