Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala–cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala–ACC connectivity.

Sleep plays a paramount role in human health, yet billions of people worldwide grapple with inadequate sleep or sleep disorders. Among these, insomnia emerges as the most prevalent sleep disorder and ranks as the second most common neuropsychiatric disorder [ 1, 2]. Approximately 10% of adults contend with an insomnia disorder, while an additional 20% experience intermittent insomnia symptoms. Often assuming a chronic trajectory, insomnia exhibits a 40% persistence rate over a 5-year span [ 3]. Chronic insomnia disorder (CID), ubiquitous in the general population and frequently encountered in clinical settings, poses substantial threats to individual academic attainment, quality of life, safety, as well as mental and physical well-being [ 4–7]. CID also imposes a noteworthy economic impacts, manifested in both direct treatment expenses and indirect costs arising from increased work absenteeism and diminished productivity [ 3].

The glymphatic system (GS) plays a key role in maintaining brain homeostasis by clearing metabolic waste during sleep, with the coupling between global blood-oxygen-level-dependent (gBOLD) and cerebrospinal fluid (CSF) signals serving as a potential marker for glymphatic clearance function. However, the test-retest reliability and spatial heterogeneity of gBOLD-CSF coupling after different sleep conditions remain unclear. In this study, we assessed the test-retest reliability of gBOLD-CSF coupling following either normal sleep or total sleep deprivation (TSD) in 64 healthy adults under controlled laboratory conditions. The reliability was high after normal sleep (ICC = 0.763) but decreased following TSD (ICC = 0.581). Moreover, spatial heterogeneity was evident in participants with normal sleep, with lower-order networks (visual, somatomotor, and attention) showing higher ICC values compared to higher-order networks (default-mode, limbic, and frontoparietal). This spatial variation was less distinct in the TSD group. These results demonstrate the robustness of the gBOLD-CSF coupling method and emphasize the significance of considering sleep history in glymphatic function research.

Resting-state functional magnetic resonance imaging (fMRI) with graph theoretical modeling has been increasingly applied for assessing whole brain network topological organization, yet its reproducibility remains controversial. In this study, we acquired three repeated resting-state fMRI scans from 16 healthy controls during a strictly controlled in-laboratory study and examined the test-retest reliability of seven global and three nodal brain network metrics using different data processing and modeling strategies. Among the global network metrics, the characteristic path length exhibited the highest reliability, whereas the network small-worldness performed the poorest. Nodal efficiency was the most reliable nodal metric, whereas betweenness centrality showed the lowest reliability. Weighted global network metrics provided better reliability than binary metrics, and reliability from the AAL90 atlas outweighed those from the Power264 parcellation. Although global signal regression had no consistent effects on the reliability of global network metrics, it slightly impaired the reliability of nodal metrics. These findings provide important implications for the future utility of graph theoretical modeling in brain network analyses.

While the significance of obtaining restful sleep at night and maintaining daytime alertness is well recognized for human performance and overall well-being, substantial variations exist in the development of sleepiness during diurnal waking periods. Despite the established roles of the hypothalamus and striatum in sleep-wake regulation, the specific contributions of this neural circuit in regulating individual sleep homeostasis remain elusive. This study utilized resting-state functional magnetic resonance imaging (fMRI) and mathematical modeling to investigate the role of hypothalamus-striatum connectivity in subjective sleepiness variation in a cohort of 71 healthy adults under strictly controlled in-laboratory conditions. Mathematical modeling results revealed remarkable individual differences in subjective sleepiness accumulation patterns measured by the Karolinska Sleepiness Scale (KSS). Brain imaging data demonstrated that morning hypothalamic connectivity to the dorsal striatum significantly predicts the individual accumulation of subjective sleepiness from morning to evening, while no such correlation was observed for the hypothalamus-ventral striatum connectivity. These findings underscore the distinct roles of hypothalamic connectivity to the dorsal and ventral striatum in individual sleep homeostasis, suggesting that hypothalamus-dorsal striatum circuit may be a promising target for interventions mitigating excessive sleepiness and promoting alertness.