Human Gamma Oscillations during Slow Wave Sleep Figure 1. Automatic detection of slow waves and gamma events. (A) Examples of scalp (blue line) and intracranial (red line) detected slow waves, inside a 2-seconds window around the central peaks. Scalp slow wave were detected according to defined duration and amplitude criteria (top right). (B) Raw intracranial LFP (gray line) and the corresponding gamma event detected in the filtered LFP (bottom) when the amplitude of the envelope signal was over 3s. Presented times and duration correspond to: toRfirst detection time, tlRlast detection time, tmRmaximal amplitude time, Dtw = tl2toRtotal event duration. doi:10.1371/journal.pone.0033477.g001 the cingulate gyrus and the superior temporal sulcus. For both patterns, the majority of gamma events were constituted by single oscillatory bursts lying in a narrow frequency band (63% and 62% of the cases for Figure 3A and Figure 3B, respectively; see also histograms in Figure S1). For the IN-phase pattern, however, a broad-band extension of activities in the gamma band can be identified as consequence of the overlapping, after averaging, of multiple oscillatory bursts appearing in different frequency bands across the whole gamma range from 30 to 120 Hz (Figure 3A bottom). In contrast, a narrow band extension of gamma activities around 70 Hz were associated with the ANTI-phase pattern (Figure 3B bottom). Additional examples of phasic gamma modulation associated with IN-phase and ANTI-phase patterns are illustrated in Figure 7F. Over all subjects, gamma activities from all investigated electrodes were associated with one of the three patterns by using a measure of similarity between the distributions in time of the detected gamma events (see Material and Methods). From all selected gamma events, 52% of the intracranial contacts (122/233) from 15 of 19 subjects were modulated by the IN-phase pattern (Figure 3C top-left). In contrast, only 9% of the contacts (21/233) from 7 of 19 subjects (5 from the 15 above) were modulated by the ANTI-phase pattern (Figure 3D top-right). The total number of individual slow waves selected from all electrode contacts associated with the IN- phase and ANTI-phase patterns were 20363 and 2078 respec- tively. From these slow waves, gamma oscillations were, in most of the cases, constituted by pure narrow band frequencies for both, IN-phase and ANTI-phase patterns (56% and 60% of the cases respectively). Oscillatory bursts composed of two mixed frequen- cies were seen in 42% and 38% of each case. Concerning the distribution of their frequency, gamma events associated with the IN-phase pattern (Figure 3C top-right) had multiple dominant peaks scattered across the whole gamma range at around 41, 67, 87 and 105 Hz. For the ANTI-phase pattern, in contrast, only two dominant peaks could be seen in the high gamma range around 70 and 97 Hz (Figure 3D top-left). Recorded intracranially, slow waves showed depth-positive or depth-negative components (see Figure 3A and 3B), reflecting respectively inward currents in the superficial layers and outward currents in the deep cortical layers [17]. In order to assess whether IN-phase and ANTI-phase patterns were related to particular depth-components of the slow waves, we examined the value of the central peak of the intracranial slow wave associated to each pattern (Figure 1). In particular, for all slow waves associated with IN-phase and ANTI-phase patterns (from 15/19 and 7/19 subjects respectively, see above) we investigated if there was a systematic reverse of polarity between scalp and intracranial waves. No significant relationship was found between the polarity reversal of the intracranial slow wave and the corresponding phase of appearance of gamma events (Figure 4). We next analyzed the temporal occurrence of IN-phase and ANTI-phase patterns relative to the central peak of the scalp slow wave (time 0 in Figures 3C bottom and 3D bottom). We observed that events associated with the IN-phase pattern preferentially appeared at around 20.5 seconds and 0.28 seconds of the slow wave cycle, and tended to be absent around 20.165 seconds (Figure 3C bottom). In contrast, events associated with the ANTI- phase pattern preferentially occurred at around 20.05 seconds of PLoS ONE | www.plosone.org 3 April 2012 | Volume 7 | Issue 4 | e33477