Abnormal functional connectivity in the habenula is associated with subjective hyperarousal state in chronic insomnia disorder

Abstract

Background: The hyperarousal process model plays a central role in the physiology of chronic insomnia disorder (CID). Recent evidence has demonstrated that the habenula is involved in the arousal and sleep–wake cycle. However, whether the intrinsic habenular functional network contributes to the underlying mechanism of CID and its relationship to the arousal state in CID remains unclear. Methods: This single-centered study included 34 patients with subjective CID and 22 matched good sleep control (GSC), and underwent a series of neuropsychological tests and resting-state functional magnetic resonance imaging scans. The habenular functional network was assessed using seed-based functional connectivity (FC) analysis. The subjective arousal state was evaluated with the hyperarousal scale (HAS). Alterations in the habenular FC network and their clinical significance in patients with CID were explored. Results: Compared with the GSC group, the CID group showed decreased habenular FC in the left caudate nucleus and right inferior parietal lobule and increased FC in the right habenula, bilateral calcarine cortex, and posterior cingulate cortex. The decreased FC between the left habenula and caudate nucleus was associated with an increased arousal state in the CID group. Conclusion: The present results provide evidence for a dysfunctional habenular network in patients with CID. These findings extend our understanding of the neuropathological mechanisms underlying the hyperarousal model in chronic insomnia.