1063 Hyper-Synchronization of Slow Waves During NREM Sleep in Major Depressive Disorder

Abstract Introduction Major depressive disorder (MDD) has been posited to be characterized by a state of hyper-synchronization or "network rigidity" during wakefulness. During sleep, cortical synchronization is the hallmark of slow-wave activity, and while multiple studies have shown that MDD is characterized by reduced slow-wave activity during sleep, little is known about the spatio-temporal synchronization of sleep slow-waves in healthy individuals and those with MDD. In particular, it remains unclear whether the hyper-synchronized state observed during wakefulness in MDD persists into sleep. Therefore, the objective of this study was to assess whether sleep slow-waves showed altered synchronization patterns in individuals with MDD. Methods To characterize macro-scale intra- and inter-hemispheric connectivity, EEG (F3/4, C3/4, O1/2) was recorded in individuals with MDD(N=30) and healthy (N=17) subjects during a baseline night of sleep. For each pair of electrodes, we estimated phase-lagged synchronization in the Delta band (0.4-3.9Hz) during the first NREM period using the Weighted Phase Lag Index (wPLI). The wPLI proxies brain connectivity by capturing the lagged coupling of EEG signals while mitigating artifacts associated with volume conduction. We computed the average wPLI value, or node strength, of each electrode. We performed cluster-based permutation testing to determine if there were significant differences in node strength between those with MDD and healthy controls. This approach corrects for the multiple comparisons problem by clustering spatially adjacent electrodes that exhibit significant effects (cluster-forming threshold p < 0.05). Results Our analysis revealed a significant cluster of electrodes (O1/2) exhibiting higher node strength in depressed individuals relative to controls (p-value = 0.0293), indicating hyper-synchronization of delta-band activity during NREM sleep. Conclusion These results indicate that the “network rigidity” characteristic of MDD during wakefulness persists into NREM sleep, particularly in occipital regions of the brain. This suggests that MDD may involve not only alterations in slow-wave activity, but also alterations in the spatio-temporal synchronization of sleep slow-waves. Although the functional consequences of this hyper-synchronization remain unclear, future work should examine possible implications for the restorative function of slow-wave activity in MDD. Support (if any)