Figure 10.

Cortical ripples occur during sleep spindles on the down-to-upstate transition. A, Example cortical ripple occurring during a spindle on a down-to-upstate transition during NREM. B, Times of downstate peaks plotted relative to local cortical ripple centers at t = 0 across significant channels (N = 258/273, Patients S1-S17) during NREM. Downstate maxima occurred on average 450 ms before the cortical ripple center. Dashed red lines indicate 99% CI of the null distribution (200 shuffles/channel). C, Same as in B, but with spindle onsets (N = 80/273). Spindles began on average 225 ms before the cortical ripple center, indicating that ripples occurred during spindles (yellow shaded area represents average spindle interval of 634 ms). D, Same as in B, but with upstate peaks (N = 260/273). Upstate maxima occurred on average 100 ms after the cortical ripple center. E, Percent of channels with significant peri-ripple modulations of sleep waves detected on the same channels within ±1000 ms (e.g., US | R represents upstate peaks relative to cortical ripples at t = 0; one-sided randomization test, 200 shuffles, 50 ms nonoverlapping bins, 2 consecutive bins with post-FDR p < 0.05 required for significance). DS and US were significantly associated with ripples in ∼95% of channels, sleep spindles less frequently. F, Percent of channels with significant modulations that had significant sidedness preference around t = 0 (post-FDR p < 0.05, one-sided binomial test, −1000 to −1 ms vs 1-1000 ms, expected = 0.5). G, Percent of channels with significant sidedness preference that had cortical ripples leading the other sleep waves (according to counts in −1000 to −1 ms vs 1-1000 ms). Downstate peaks and spindle onsets typically preceded ripples, and upstate peaks followed. H, Probabilities of ripple centers preceding upstates, following downstates, occurring during spindles in isolation or during spindles following downstates (DS-SS), or during spindles preceding upstates (SS-US). The time window used following a downstate or preceding an upstate was 634 ms, which was the average spindle duration. The probability of a ripple occurring was greatest during spindles preceding upstates (post-FDR p < 0.0001, two-sided paired t test, channel-wise). Table 4 contains results from E-G in tabular format. DS, Downstate; SS, sleep spindle; US, upstate.