Human Gamma Oscillations during Slow Wave Sleep Mario Valderrama1,4, Benoıˆt Cre´ pon1,3, Vicente Botella-Soler2, Jacques Martinerie1, Dominique Hasboun1,3, Catalina Alvarado-Rojas1, Michel Baulac1,3, Claude Adam1,3, Vincent Navarro1,3, Michel Le Van Quyen1* 1 Centre de Recherche de l’Institut du Cerveau et de la Moelle e´pinie`re (CRICM), Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) UMRS 975, Centre National de la Recherche Scientifique (CNRS) - UMR 7225, Universite´ Pierre et Marie Curie (UPMC), Hoˆ pital de la Pitie´-Salpeˆtrie`re, Paris, France, 2 Departament de F´ısica Teo` rica and Instituto de F´ısica Corpuscular (IFIC), Universitat de Vale`ncia - Consejo Superior de Investigaciones Cient´ıficas (CSIC), Vale`ncia, Spain, 3 Epilepsy Unit, Assistance publique - Hoˆ pitaux de Paris (AP-HP), Groupe Hospitalier Pitie´-Salpeˆtrie`re, Paris, France, 4 Departamento de Ingenier´ıa Ele´ctrica y Electro´ nica, Universidad de Los Andes, Bogota´, Colombia Abstract Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30–50 Hz) and high (60–120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves (‘‘IN-phase’’ pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave (‘‘ANTI-phase’’ pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks. Citation: Valderrama M, Cre´pon B, Botella-Soler V, Martinerie J, Hasboun D, et al. (2012) Human Gamma Oscillations during Slow Wave Sleep. PLoS ONE 7(4): e33477. doi:10.1371/journal.pone.0033477 Editor: Olaf Sporns, Indiana University, United States of America Received July 15, 2011; Accepted February 15, 2012; Published April 4, 2012 Copyright: 2012 Valderrama et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was partially supported by the European Union-FP7 Project EPILEPSIAE (Evolving Platform for Improving Living Expectation of Subjects Suffering from IctAl Events, Grant No 211713). Mario Valderrama thanks the University of Los Andes and the Administrative Department for Science, Technology and Innovation (COLCIENCIAS), Colombia, for financial support. Vicente Botella-Soler thanks Generalitat Valenciana for financial support. Vincent Navarro was supported by Contrat d’Interface INSERM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: quyen@t-online.de Introduction When sleep reaches its deepest levels during slow wave sleep (SWS), the electroencephalogram (EEG) is dominated by globally coherent slow wave activity in the low frequency range (0.5– 3.5 Hz) [1,2]. Local field potentials (LFPs) studies in animals, moreover, have demonstrated that the power time course of these slow oscillations shows correlations to other frequency bands. According to Steriade and coworkers [3], the slow oscillations have the ability to trigger and group faster cortical oscillations like spindles (12–15 Hz) and high-frequency activities in the beta (from 15 to 25 Hz) or gamma range (from 30 to 120 Hz). Evidence for this coupling between slow waves and gamma oscillations comes from in vivo LFP recordings of the rodent and feline cortex [3–7] and it can be reproduced in vitro in acute brain slices [8,9]. These experiments demonstrated that gamma oscillations occur prefer- entially over the active component of the slow wave (‘UP’ state) characterized by rhythmic cycles of synaptically mediated depolarization and disappear during the hyperpolarizing phase (‘DOWN’ state). A recent study with microelectrode LFPs in the human cortex has confirmed that gamma oscillations are strongly expressed during SWS and are reliably associated with a marked increase in local cellular discharges, suggesting that they were associated with cortical UP states [10,11]. Nevertheless, although activities in the gamma-range have been observed at the scalp level during a variety of cognitive tasks [12], no evidences of a phasic expression of gamma activities during SWS in human macroscopic EEG recordings were reported so far. For example, Fell and colleagues [13] used the scalp EEG data during sleep and showed that sigma activity (12–16 Hz) is modulated by slow EEG oscillations. In another study, Molle and collaborators [14] found that grouping of spindles and beta oscillations are coincident with slow waves in human SWS. However, both studies didn’t find a significant phasic modulation of the gamma activities (.30 Hz) by the slow waves. It was suggested that the resistive properties of the skull, muscle artifacts and the relative distance of scalp electrodes from deeper generators may make it difficult to observe an intracortical modulation of gamma activity during sleep. These drawbacks can nevertheless be overcome with the use of intracranial recordings which furthermore allow the analysis of PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e33477