Regional and network patterns of sleep-depth-associated brain diffusion changes: an EEG-informed multishell diffusion MRI study.

Sleep is thought to modulate brain fluid transport; however, whether these physiological processes are reflected in regional diffusion magnetic resonance imaging (MRI) parameters and their interregional organization during sleep remains unclear. We performed simultaneous electroencephalography (EEG) and repeated multishell diffusion MRI during zolpidem-facilitated sleep in 12 healthy adults. Analyses included nine participants who maintained sleep throughout all diffusion acquisitions. Scan-wise sleep depth was quantified using the odds ratio product (ORP), which showed excellent agreement with EEG-defined arousal states and an expected inverse association with relative delta power. The diffusion tensor and kurtosis metrics were quantified within the JHU ICBM-DTI-81 white-matter and the Automated Anatomical Labeling atlas, v. 2 (AAL2) gray-matter regions. We examined regional sleep-depth associations and interregional correlation networks. Exploratory analyses showed that deeper sleep was associated with lower white-matter anisotropy, reflected in reduced fractional anisotropy and kurtosis fractional anisotropy within major projection and association pathways. In the gray matter, associations with sleep depth were more pronounced, with lower axial, mean, and radial diffusivities, whereas the corresponding kurtosis metrics showed associations in the opposite direction that reached nominal significance. These associations were primarily localized to the frontocentral sensorimotor and medial frontal-cingulate regions. Correlation network analysis identified seven interregional correlations that were sensitive to sleep depth after controlling for global covariance. Four were located within the middle cerebral artery territory, two within the posterior circulation cerebellar and vermian regions, and one sensorimotor correlation spanned the anterior and middle cerebral artery territories. These findings demonstrate region-specific and coordinated diffusion changes during human sleep and establish an exploratory network-based framework for investigating diffusion patterns relevant to glymphatic physiology.