Effects of total sleep deprivation and light therapy on resting-state activity and neurovascular coupling in bipolar depression

Introduction Bipolar depression (BD) is associated with altered intrinsic brain activity, and possibly impaired neurovascular coupling (NVC). Although rapid-acting chronotherapies are effective in BD, their neurophysiological mechanisms remain unclear. Methods In this longitudinal resting-state fMRI study, we examined fractional amplitude of low-frequency fluctuations (fALFF), indexing spontaneous neural activity, and hemodynamic response function (HRF) parameters, used as proxies of NVC, in 50 BD inpatients undergoing three cycles of combined total sleep deprivation and light therapy (TSD + LT), and in 30 healthy controls (HCs). Patients were scanned before (day 0) and after treatment (day 7), and depressive symptoms were evaluated with the Beck Depression Inventory Short Form. Results At baseline, BD patients showed reduced fALFF in frontal, temporal, insular–opercular, and cerebellar regions relative to HCs. After TSD + LT, fALFF increased in widespread occipito-temporal, frontal, and cerebellar clusters in BD patients. HRF analyses showed no baseline between-group differences, but revealed a significant post-treatment increase in HRF response height across occipital, temporal, frontal, and cerebellar regions. Remission after TSD + LT was associated with fALFF changes, whereas larger HRF response height increases were observed in patients who did not require antidepressant treatment switch or augmentation during hospitalization. Conclusion TSD + LT was associated with modulation of both intrinsic neural activity and resting-state hemodynamic responses, with fALFF and HRF reflecting partly distinct aspects of short-term clinical outcome.