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

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 fMRI 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 the 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 distinct alterations in brain functional organization, offering new insights into their neural impact. Graphical abstract Statement of significance Sleep deprivation is a growing public health concern, yet it remains unclear whether total and chronic sleep loss affect the brain in the same way. In this study, participants underwent one sleepless night and five consecutive days of reduced sleep (as in working week). We found that these two forms of sleep loss disrupt brain networks in fundamentally different ways. This distinction closes a critical gap in understanding how the brain responds to the total and chronic sleep loss. Recognizing that not all sleep deprivation is alike has important implications for managing fatigue in occupational, educational, and clinical contexts. Our findings highlight the need for personalized strategies to protect brain health and performance under conditions of sleep disruption.