Grouping of spindle activity during slow oscillations in human non-rapid eye movement sleep

Abstract

Based on findings primarily in cats, the grouping of spindle activity and fast brain oscillations by slow oscillations during slow-wave sleep (SWS) has been proposed to represent an essential feature in the processing of memories during sleep. We examined whether a comparable grouping of spindle and fast activity coinciding with slow oscillations can be found in human SWS. For negative and positive half-waves of slow oscillations (dominant frequency, 0.7-0.8 Hz) identified during SWS in humans (n = 13), wave-triggered averages of root mean square (rms) activity in the theta (4-8 Hz), alpha (8-12 Hz), spindle (12-15 Hz), and beta (15-25 Hz) range were formed. Slow positive half-waves were linked to a pronounced and microV (23.4%; p < 0.001, with reference to baseline) at the midline central electrode (Cz). In contrast, spindle activity was suppressed during slow negative half-waves, on average by -0.65 +/- 0.06 microV at Cz (-22%; p < 0.001). An increase in spindle activity 400-500 msec after negative half-waves was more than twofold the increase during slow positive half-waves (p < 0.001). A similar although less pronounced dynamic was observed for beta activity, but not for alpha and theta frequencies. Discrete spindles identified during stages 2 and 3 of non-rapid eye movement (REM) sleep coincided with a discrete slow positive half-wave-like potential preceded by a pronounced negative half-wave (p < 0.01). These results provide the first evidence in humans of grouping of spindle and beta activity during slow oscillations. They support the concept that phases of cortical depolarization during slow oscillations, reflected by surface-positive (depth-negative) field potentials, drive the thalamocortical spindle activity. The drive is particularly strong during cortical depolarization, expressed as surface-positive field potentials.

Fig. 1.

Selection of slow-oscillation half-waves. From top to bottom, Sleep hypnogram for the first cycle from an individual night (W, wake;R, REM sleep; S1–S4, non-REM sleep stages 1–4). Dots underneath indicate time points of the largest slow-positive and negative-oscillation half-waves chosen for analysis (see Materials and Methods for details). DC-recorded (0–30 Hz) original EEG signal, slow-oscillation signal (bandpass, 0.16–4 Hz), spindle activity (12–15 Hz), and spindle rms signal are shown. Parallel vertical bars indicate a critical 20 sec time interval used for the analyses as depicted in Figure3A.

Fig. 2.

Averaged spectral power density for the slow oscillation frequency band (0.16–4 Hz) at Fz (solid line) and Cz (dashed line). Note the peak power density at 0.7–0.8 Hz.

Fig. 3.

Steps of analysis illustrated for two 20 sec epochs of recordings for an individual subject (same as in Fig. 1).A, Analysis of slow oscillation-dependent changes in spindle activity. From top to bottom, DC-recorded (0–30 Hz) original EEG signal, slow oscillatory signal (0.16–4 Hz) with detected slow positive and negative half-waves indicated by a thick solid line, and spindle rms signal. For one positive and one negative half-wave each, the peak time used for time-locked averaging and the ±1 sec averaging interval are indicated by a dotted line and two solid vertical lines, respectively. B, Analysis of spindle-dependent changes in the DC potential, exemplified on discrete spindles that occurred during the first period of sleep stage 2 shown in Figure 1. From top to bottom, DC-recorded (0–30 Hz) original EEG during non-REM sleep stage 2, spindle activity filtered at 12–15 Hz, and spindle rms signal with identified spindle periods indicated by a thick solid line. Only the largest spindles were selected for analysis by a thresholding procedure applied to the spindle rms signal. For one spindle, the center time used for time-locked averaging and the ±1 sec averaging interval are indicated by a dotted line andtwo solid vertical lines, respectively.

Fig. 4.

A, top, Superimposed slow negative (left) and positive (right) half-waves. A, bottom, Corresponding spindle band signals (black line, right axis) and mean spindle rms activity (white dashed line, left axis) in a single subject at Cz. B, Grand means (across 13 subjects) of results from wave-triggered analysis of slow negative (left) and positive (right) half-waves. The mean ± SEM slow-oscillation signal (top) and spindle rms signal (bottom) at Cz are shown.Dashed lines indicate mean values at Fz (without SEM).C, Grand means of beta rms signal. Note that the temporal dynamics of beta activity were similar to spindle activity, in particular at Cz. Vertical dotted lines indicate the half-wave peak time used for time-locked averaging.

Fig. 5.

Grand means (across 13 subjects) of sleep-spindle-dependent changes in the DC potential. The mean ± SEM spindle rms signal (top) and DC potential (bottom) at Fz, both averaged time-locked to the spindle center, are shown. Dashed lines indicate respective mean values from Cz (without SEM). The vertical dotted lineindicates the spindle center time used for time-locked averaging.

Fig. 6.

Mean ± SEM cross-correlation function between slow-oscillation signal and spindle rms signal across 13 subjects at Fz (top) and Cz (bottom).Dashed horizontal lines indicate a p< 0.005 level of significance. The vertical dotted lineindicates the time lag of 0 sec.