Borgetto, F. | Search bioRxiv

bioRxiv2026

Beyond Aging, Sex and Insomnia Disorder Shape NREM Brain Oscillations

ObjectivesChronic insomnia (INS) is particularly prevalent in older adults and females. Sex-and age-related differences in neurophysiological markers of sleep quality (sleep spindles and slow-wave activity [SWA]) may underlie differential vulnerability to INS. This study investigated the effects of sex and insomnia on spindle and SWA beyond aging, to better understand the mechanistic differences contributing to the higher prevalence of INS in females. MethodsAfter a habituation night, one night of sleep assessed with polysomnography was analyzed in 222 adults (aged 18-82) including 119 INS (71% female) and 103 healthy sleepers (HS; 61% female). Spindle density, slow oscillation (SO) density, relative sigma power and SWA were derived during NREM sleep. Age, group, sex, and group-by-sex interactions were examined, with age as a covariate. ResultsAge, insomnia, and sex each contributed uniquely to NREM oscillatory activity. INS primarily reduced spindle and SO density, while sex accounted for differences in SWA. While SWA was higher in females overall, sex differences were not significant within the INS or HS groups. Female INS reported highest rates of insomnia severity as well as lower sigma power than males in the INS group. Spindle and SO density deficits were also present in female INS relative to female HS, as well as male INS relative to male HS. ConclusionsThe combination of reduced sigma power in females with insomnia relative to their male counterparts, as well as less spindle and SO density compared to female healthy sleepers may contribute to greater insomnia severity in females. Statement of SignificanceInsomnia is a growing public health concern that is more commonly reported in females, yet the neural mechanisms underlying this sex difference remain poorly understood. Our findings suggest that specific markers of sleep quality are disproportionately disrupted in females with insomnia, potentially contributing to greater vulnerability and symptom severity. These results provide new insight into how sex influences the neurophysiology of insomnia disorder and identify oscillatory markers that could serve as targets for personalized interventions. Future research should investigate whether these alterations represent persistent dysfunction or reversible changes, which could advance understanding of the biological basis of insomnia and inform strategies to improve sleep health in at-risk populations.

neuroscience↗

bioRxiv2025

Sleep deprivation constrains dynamic configurations of integrated and segregated brain states impacting cognitive performance

The breakdown of cognitive control following sleep deprivation is widely recognised, but the physiological mechanisms and brain signatures that produce this vulnerability have not been resolved. Effective cognition relies on large-scale brain networks flexibly reconfiguring between states of integration and segregation. Here we combined functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and electrocardiography (ECG) collected during cognitive tasks under rested wakefulness, after sleep deprivation, and following a recovery nap to test the hypothesis that sleep deprivation constrains this dynamical repertoire and disrupts its physiological regulation. Using time-resolved functional connectivity and graph theory, we show that sleep deprivation increases the distribution of connections across networks, while reducing the temporal variability of between-network connectivity. Furthermore, dynamic fluctuations between integrated and segregated modes of network topology were dampened, with brain regions spending more time in intermediate configurations and showing greater instability of mode transitions. These alterations were tightly linked to behavioural impairment: participants who exhibited greater contraction toward intermediate topologies also showed poorer task accuracy and slower responses. Under well-rested conditions, thalamic activity peaked prior to transitions into integrated states and was suppressed during transitions into segregated states, consistent with a coordinating role in cortical dynamics. Sleep deprivation weakened and delayed this thalamic coupling. Finally, global and regional fMRI fluctuations were elevated after sleep loss, becoming decoupled from cardiac physiology while more strongly coupled to EEG delta power, further linking reduced arousal to constrained network flexibility. Together, these findings show that sleep deprivation narrows the brains dynamical repertoire, due to disrupted thalamic regulation and changes to the physiological integration with cortical networks.

neuroscience↗