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Novel Neuroimaging Biomarker for Sleep Quality in Insomnia Disorder: A Hypothalamus Resting State Study.

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.

SUBMITTER: Ding S

PROVIDER: S-EPMC7953135 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Insomnia is among the most prevalent of the sleep-related disorders. Insomnia disorder is associated with a brain hyperarousal state manifested by abnormal regional brain activity and resting state functional connectivity. Acupuncture improves sleep quality and modulates the hyperarousal state; however, the underlying neurobiological basis for improved sleep quality is poorly understood. The purpose of this clinical trial is to study the efficacy of acupuncture in the treatment of insomnia disorder. In addition, the neural mechanism by which acupuncture affects insomnia disorder will be explored using resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological parameters. METHODS AND DESIGN:A randomized, patient- and assessor-blinded trial will be conducted. We will randomize (in a 1:1 ratio) 60 eligible patients with insomnia disorder into a real acupuncture group or a sham acupuncture group. Interventions will be administered three times per week over a 4-week period, with an 8-week follow-up period. The healthy control group will consist of 30 age- and sex-matched healthy individuals who sleep well without any treatment intervention. All participants will undergo neuropsychological and rs-fMRI evaluations. The change in Pittsburgh Sleep Quality Index (PSQI) scores is the primary outcome parameter. The secondary outcome parameters include the Hyperarousal scale (HAS), rs-fMRI measurements, the Fatigue scale-14 (FS-14), the Hamilton depression scale (HAMD), the Hamilton anxiety scale (HAMA), a sleep diary, and an actigraph. Assessment of all parameters will be performed at baseline, post-treatment, and during follow-up. Analyses will be implemented based on intention-to-treat. DISCUSSION:The study results will be used to clarify the effectiveness and elucidate the mechanism by which acupuncture improves sleep quality in patients with insomnia disorder. TRIAL REGISTRATION:Chinese Clinical Trials Register, ChiCTR1800015282. Registered on 20 March 2018.

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Novel Neuroimaging Biomarker for Sleep Quality in Insomnia Disorder: A Hypothalamus Resting State Study.

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