Divergent dFC stability of DMN and SMN in narcolepsy

Narcolepsy type 1 (NT1) is characterized by profound sleep-wake state instability, pointing to a fundamental dysregulation of large-scale brain network dynamics. To elucidate this, we assessed whole-brain dynamic functional connectivity (dFC) stability using resting-state fMRI in 27 patients with NT1 and 25 matched healthy controls. Our analysis revealed a pattern of opposing alterations: patients exhibited significantly increased dFC stability within the bilateral somatomotor network (SMN), concurrent with decreased stability in the medial prefrontal default mode network (Default_PFCm). These opposing alterations were clinically relevant, as increased SMN stability correlated with poorer objective sleep efficiency, and decreased Default_PFCm stability was similarly associated with lower objective sleep efficiency. Here, we identify for the first time this coexisting neural signature of SMN hyper-stability and Default_PFCm instability in NT1. By simultaneously destabilizing higher-order cognitive networks and disinhibiting primary sensorimotor processing, orexin deficiency may contribute to a synergistic dysregulation that blurs sleep-wake boundaries. The divergence in dynamic network stability provides a novel systems-level framework for understanding state instability in NT1.