Abstract
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.
Highlights
As the most common sleep disorder, insomnia disorder (ID) is characterized by difficulties in falling asleep, maintaining sleep, or non-restorative sleep (Riemann et al, 2015)
There were no significant differences in age or gender between ID patients and healthy controls (HC)
Impaired sleep quality measured by Pittsburgh sleep quality index (PSQI) scores was found in ID patients (13.62 ± 3.56) compared with HCs (4.29 ± 2.05)
Summary
As the most common sleep disorder, insomnia disorder (ID) is characterized by difficulties in falling asleep, maintaining sleep, or non-restorative sleep (Riemann et al, 2015). In order to develop more effective treatment, it is necessary to discover novel neuroimaging biomarkers for sleep quality in IDs. The pathophysiology of ID had been investigated by examining both peripheral and central nervous measurements from the perspective of the hyperarousal model (Riemann et al, 2010, 2015). The hypothalamus has a central role in sleep-wake regulation by communicating with different brain regions (Saper et al, 2005). In the neuroimage studies of ID, patients show a slightly decreased relative metabolism of the hypothalamus from waking to non-rapid eye movement (NREM) sleep states compared with healthy controls (HC) (Nofzinger et al, 2004).
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