Divergent disruption of brain networks following total and chronic sleep loss: a longitudinal fMRI study

Abstract Study Objectives Sleep loss significantly disrupts cognitive and emotional functioning, yet the neural consequences of different types of sleep deprivation remain unclear. Methods In a within-subject resting-state functional magnetic resonance imaging study, we examined how acute total sleep deprivation (TSD) and chronic sleep restriction (CSR) alter intrinsic functional brain organization in 28 healthy adults scanned under three conditions: rested wakefulness (RW), after one night of TSD, and after five nights of CSR. To quantify network-level disruption, we applied graph-theoretical analyses, including a novel within-subject adaptation of the Hub Disruption Index and Covariate-Constrained Manifold Learning (CCML), an unsupervised embedding technique sensitive to subject-level covariates. Moreover, we assessed subjective sleep quality, sleepiness, and circadian traits. Results Both TSD and CSR were associated with a consistent reorganization of graph topology relative to RW. Furthermore, direct comparisons revealed that TSD and CSR affect different brain hubs. Regional changes in degree, closeness, and clustering coefficients were most prominent in subsystems of the default mode network, frontoparietal network, and cerebellum. These differences were also captured in CCML embeddings, supporting the hypothesis that acute and chronic sleep deprivation exert divergent effects on brain connectivity. Findings were robust across graph thresholds, brain atlases, and nodal metrics. Moreover, these results were further supported by subjective measures—sleepiness was associated with reduced network integration in RW, and circadian phenotype emerged as a key determinant of individual sensitivity to sleep loss. Conclusions Our results show that TSD and CSR induce divergent alterations in brain functional organization, offering new insights into their neural impact.