| Summary: | Despite striking progress in the understanding of the neurobiology of insomnia disorder (ID), about 40% of ID patients do not reach sustained remission with the primary treatments. It is necessary to reveal novel neuroimaging biomarkers for sleep quality in ID. The hypothalamus has a central role in sleep-wake regulation by communicating with different brain regions. However, the functional implications of hypothalamus circuitry with other brain areas remains largely unknown in ID. It may be speculated that dysfunctional circuitry in the hypothalamus is involved in the pathogenesis of ID. Thus, we investigated the different network organizations of the bilateral hypothalamus during the resting-state between 26 ID patients and 28 healthy controls (HC). Correlation analysis has been carried out to link the neuroimaging findings and Pittsburgh sleep quality index (PSQI) scores. Group comparisons reveal that the resting-state functional connectivity (RSFC) between the left hypothalamic region and a few other brain regions, including the medial prefrontal cortex (mPFC) and pallidum, are significantly higher in ID compared with HC. The right inferior temporal cortex showed reduced RSFC with the left hypothalamus. No significantly different RSFC between ID and HC was detected for the right hypothalamus. Positive correlations with PSQI scores were observed for RSFC strength between the left hypothalamus and bilateral mPFC (left: r = 0.2985, p = 0.0393; right: r = 0.3723, p = 0.0056). Similarly, the RSFC strength between the right hypothalamus and bilateral mPFC (left: r = 0.3980, p = 0.0029; right: r = 0.2972, p = 0.0291) also showed significant positive correlations with PSQI scores. In conclusion, we reveal a novel neuroimaging biomarker for sleep quality, i.e., the RSFC strength of the hypothalamus-mPFC pathway. Consistent with the hyperarousal model of ID, our results shed new insights into the implications of the hyper-connection within hypothalamus circuits in the pathology of the ID.
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