Functional interaction pattern from solely circadian rhythm disturbance to circadian rhythm sleep disorder

The coupling between sleep-awake and dark-light cycles has played an important role in understanding external and internal biological clocks. However, how functional patterns of brain regions involved in these two coupled cycles deteriorate from circadian rhythm disturbance to circadian rhythm sleep disorder remains largely unexplored in neuroimaging research. In this study, we built a whole-brain computational framework based on the well-established Hopf model and collected multimodal brain imaging data from 77 participants. We investigated how the activation of the anterior cingulate cortex (ACC) and the functional connectivity between the hypothalamus (HT) and basal forebrain (BF) vary across three groups: healthy controls (HC), subjects with isolated circadian rhythm disturbance (SCO), and subjects with circadian rhythm sleep disorders (SCW). We also studied how variations in the oscillatory patterns of the hypothalamus may contribute to these observed functional differences. We found that altering the bifurcation parameter of the hypothalamus node within the Hopf model, fitted to the functional connectivity of SCO, could reproduce the empirical patterns observed in HC and SCW. In addition to revealing progressive impairments in ACC activation and HT–BF functional connectivity, we further validated the model by demonstrating that the temporal dynamics of HT and BF precede those of ACC, and that these dynamics become increasingly disrupted from SCO to SCW. These findings enhance the mechanistic understanding of circadian rhythm disturbance and circadian rhythm sleep disorder, and elucidate the pathological progression in fMRI patterns from isolated circadian disruption to full circadian rhythm sleep disorder.