Human Cortical Excitability Increases with Time Awake

http://cercor.oxfordjournals.org/content/early/2012/02/07/cercor.bhs014.abstract?sid=f0bb535d-9375-4b73-adb1-11f76c30564b

Cereb. Cortex first published online February 7, 2012 doi:10.1093/cercor/bhs014

Human Cortical Excitability Increases with Time Awake

Reto Huber1,2, Hanna Mäki3, Mario Rosanova1, Silvia Casarotto1,Paola Canali1, Adenauer G. Casali1, Giulio Tononi4 Marcello Massimini1

+ Author Affiliations

1Department of Clinical Sciences “Luigi Sacco,” Università degli Studi di Milano, 20157 Milan, Italy

2Child Development Center, University Children’s Hospital, 8032 Zurich, Switzerland

3Department of Biomedical Engineering and Computational Science (BECS), Aalto University, 00076 Espoo, Finland

4Department of Psychiatry, University of Wisconsin, Madison, WI 53719, USA

Abstract

Prolonged wakefulness is associated not only with obvious changes in the way we feel and perform but also with well-known clinical effects, such as increased susceptibility to seizures, to hallucinations, and relief of depressive symptoms. These clinical effects suggest that prolonged wakefulness may be associated with significant changes in the state of cortical circuits. While recent animal experiments have reported a progressive increase of cortical excitability with time awake, no conclusive evidence could be gathered in humans. In this study, we combine transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to monitor cortical excitability in healthy individuals as a function of time awake. We observed that the excitability of the human frontal cortex, measured as the immediate (0–20 ms) EEG reaction to TMS, progressively increases with time awake, from morning to evening and after one night of total sleep deprivation, and that it decreases after recovery sleep. By continuously monitoring vigilance, we also found that this modulation in cortical responsiveness is tonic and not attributable to transient fluctuations of the level of arousal. The present results provide noninvasive electrophysiological evidence that wakefulness is associated with a steady increase in the excitability of human cortical circuits that is rebalanced during sleep.