Beyond Aging, Sex and Insomnia Disorder Shape NREM Brain Oscillations

Abstract Objectives Chronic 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. Methods After 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. Results Age, 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. Conclusions The 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 Significance Insomnia 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.