Inter-channel phase differences during sleep spindles are altered in Veterans with PTSD

Sleep disturbances are common complaints in patients with post-traumatic stress disorder (PTSD). To date, however, objective markers of PTSD during sleep remain elusive. Sleep spindles are distinctive bursts of brain oscillatory activity during non-rapid eye movement (NREM) sleep and have been implicated in sleep protection and sleep-dependent memory processes. In healthy sleep, spindles observed in electroencephalogram (EEG) data are highly synchronized across different regions of the scalp. Here, we aimed to investigate whether the spatiotemporal synchronization patterns between EEG channels during sleep spindles, as quantified by the phase-locking value (PLV) and the mean phase difference (MPD), are altered in PTSD. Using high-density (64-channel) EEG data recorded from 78 combat-exposed Veteran men (31 with PTSD and 47 without PTSD) during two consecutive nights of sleep, we examined group differences in the PLV and MPD for slow (10-13 Hz) and fast (13-16 Hz) spindles separately. To evaluate the reproducibility of our findings, we set apart the first 47 consecutive participants (18 with PTSD) for the initial discovery and reserved the remaining 31 participants (13 with PTSD) for replication analysis. In the discovery analysis, compared to the non-PTSD group, the PTSD group showed smaller MPDs during slow spindles between the frontal and centro-parietal channel pairs on both nights. We obtained reproducible results in the replication analysis in terms of statistical significance and effect size. The PLVs during slow or fast spindles did not significantly differ between groups. The reduced inter-channel phase difference during slow spindles in PTSD may reflect pathological changes in the underlying thalamocortical circuits. This novel finding, if independently validated, may prove useful in developing sleep-focused PTSD diagnostics and interventions.