Abnormal sleep oscillations in relation to disturbed sleep in adolescents with autism and their siblings

Sleep disturbances, primarily insomnia (difficulty initiating or maintaining sleep), are reported in up to 80 percent of children with autism spectrum disorder (ASD). Although they exacerbate symptoms and impair daytime functioning, mechanistic biomarker-driven interventions are lacking. Understanding the neural basis of poor sleep is a critical step towards effective treatment and is the primary goal of this proposal.

Using home sleep EEG recordings and clinical data from the Simons Sleep Project (ASD n=102; siblings n=98; ages 10 to 17), this program will test whether alterations in non-rapid eye movement (NREM) sleep oscillations underlie insomnia in ASD. Sleep spindles, brief thalamocortical oscillations, play a critical role in sleep onset and maintenance, are reduced in ASD, and correlate with sleep quality. Spindles are temporally organized by infraslow oscillations (ISOs), generated in the locus coeruleus, which divide NREM sleep into phases of increased vigilance, with few sleep-promoting spindles, and offline phases, rich in spindles that promote memory consolidation.

Aim 1 of this proposal will test the hypothesis that the spindle reduction in ASD is related to an imbalanced ISO, marked by increased time in the vigilance phase, resulting in fewer spindles and more fragmented sleep. Aim 2 will test whether NREM sleep oscillations aggregate within families, distinguish affected from unaffected siblings, and correlate with dimensional measures of autism-related traits. If these oscillations are shown to be familial, diagnosis linked, related to autism phenotypes, and predictive of sleep disturbance, they will provide mechanistically grounded biomarkers. Such biomarkers can increase the power of clinical trials by allowing the selection of individuals most likely to benefit from a particular intervention and by serving as surrogate markers of treatment response. This project will advance our understanding of pathophysiology and inform the development of interventions to restore sleep oscillations, increase sleep continuity and improve quality of life in adolescents with ASD and their families.