Supplementary Figure 6: Spindle-ripple coupling as a function of associated SOs.

a. Peri-event time histogram (PETH) showing the probability of SO occurrence (SO down-state) relative to spindle centers (t = 0 s, dashed vertical line). Dark gray area shows time interval used to determine whether a given spindle is located in the up-state of an SO (i.e., a SO down-state is temporally preceding a spindle at −1 to −0.2 s). Note that while there is a clear peak of SO occurrences in the temporal vicinity of spindles (with the asymmetry pointing to a predominant SO -> spindle sequence), many spindles occurred independently of SOs. The subsequent analyses separated spindle-ripple coupling into spindles immediately preceded by SO down-states (left column, average number of events across participants = 124, range = 30–315) and spindles not immediately preceded by SO down-states (right column, average number of events across participants = 697, range = 154–1467). b. Event-locked analysis. (i) (top) Grand average unfiltered iEEG trace across participants (mean ± s.e.m.), aligned to the maximum of the spindle trough. Insets show the bandpass filtered trace from 0.5–1.25 Hz (SO range) and from 12–16 Hz (spindle range) to better illustrate the relation of the spindle to the SO down-state. Note the pronounced SO emerging in spindle-locked raw traces on the left. (middle) Average of spindle-trough-locked TFR (% change from pre-event baseline). (bottom) Statistically significant change from pre-event baseline (P < .05, corrected, with the initial cluster threshold also set to P <.05 to accommodate smaller trial numbers). Inset shows unit circle of preferred phases of the spindle-ripple modulation for each participant. Both V tests (testing for preferred phase at 180°) are significant: spindles immediately preceded by SO down-states: V = 4.36, P =.037, spindles not immediately preceded by SO down-states: V = 5.75, P =.010. (ii) Direct comparison of spindle-trough-locked TFRs (immediately preceded by SO down-states vs. not immediately preceded by SO down-states), revealing only a relative power decrease at SO down-states, but no differential spindle-ripple modulation. (iii) Example data from one participant (same as in main Fig. 2,3,4), showing the nesting of ripples in spindle troughs for both event types. c. Comodulogram analysis. PAC was calculated for data segments around spindles (–2.5 s to +2.5 s relative to the maximum spindle trough). Maps show cluster-corrected comparisons against phase-scrambled surrogate data (all P <.05). Direct comparison of MI averaged from 12–16 Hz phase-providing frequency and 80–100 Hz amplitude-providing frequency revealed no difference between spindles immediately preceded by SO down-states vs. spindles not immediately preceded by SO down-states (using surrogate corrected MI or non-surrogate-corrected MI, both t(11) < 0.71, P >.49).