Impact of sleep on the A$_{1}$ adenosine receptor, neuronal activity, and structural connectivity of the human brain : a multi-modal neuroimaging approach

Regular sleep is an essential function to maintain our physical and mental health. Without sufficient sleep, the people have higher risks for the abnormalities of brain and behavior. Using multi-modal neuroimaging techniques (e.g. Resting-state (rs-)fMRI, Diffusion tensor imaging, and Positron emission tomography techniques), previous studies showed that some brain regions play key roles in sleep-wake regulation, such as thalamus, prefrontal cortex, and visual cortices. Nevertheless, we are still lacking systematical investigations about how the sleep-wake dysregulation affects brain structural and functional architectures, as well as A1 adenosine receptor (A1AR) availability in healthy population. First, we calculated some local parameters, including Regional homogeneity, Amplitude of low-frequency fluctuations, and Degree centrality, which characterize the temporal and spatial features of spontaneous neuronal activity during rs-fMRI scans. Then, we performed whole brain voxel-wise comparisons of above properties between 52 hours of sleep deprivation (SD52) and 14 hours of recovery sleep (RS14), as well as the associations with corresponding A1AR availability and neuropsychological tests. Notably, the significant negative correlations between local rs-fMRI metrics and A1AR availability after acute sleep loss were mainly observed in left superior/middle temporal gyrus and left postcentral gyrus. Secondly, in two sleep-deprived conditions (SD52 vs. RS14; two rested wakefulness vs. 28 hours of sleep deprivation), we separately applied graph theoretical approach to examine their altered topological properties of brain functional networks. Our findings revealed that acute sleep loss enhanced the small-world properties. Further network-based statistic approach identified one decreased functional connectivity component involving cerebellar-cortical and subcortical-cortical subnetworks, whereas one increased component containing cortical regions. Thirdly, we used sliding-window correlation analysis to capture the temporal features of spontaneous brain activity in terms of short frames of time courses during rs-fMRI scans. We then explored the between-group differences of dynamic functional connectivity properties in two above sleep-deprived conditions. We demonstrated that the prolonged wakefulness remarkably reduced the occurrences of a globally hypo-connected state reflecting self-focused processing, but increased amounts of a functional connectivity pattern signifying light sleep/drowsiness. Moreover, sleep-loss induced changes of dynamic connectivity states were associated with increased sleepiness and impaired cognitive performances. In the last part of this project, based on the 1000BRAINS database, we compared the significant differences of white matter microstructures between poor sleepers and good sleepers, as well as the mediation effects with life stress or depressive symptomatology. Our results showed that the white matter integrity of pontine crossing tract and bilateral inferior cerebellar peduncle were significantly higher in the males than females. Additionally, the diffusion metrics of corpus callosum partially mediate the associations of poor sleep quality/high stress with high scores of depressive symptomatology. In summary, our multi-modal neuroimaging studies provide that high homeostatic sleep pressure produces reliable functional alterations across different spatial scales in human brain, which are related with the A1AR availability and neuropsychological performances. Meanwhile, the white matter microstructure of corpus callosum is critical to mediate the relationships among sleep quality, current stress, and depressive symptomatology in a large cohort of aging population