Abstract
BackgroundIdentification of ASD biomarkers is a key priority for understanding etiology, facilitating early diagnosis, monitoring developmental trajectories, and targeting treatment efforts. Efforts have included exploration of resting state encephalography (EEG), which has a variety of relevant neurodevelopmental correlates and can be collected with minimal burden. However, EEG biomarkers may not be equally valid across the autism spectrum, as ASD is strikingly heterogeneous and individual differences may moderate EEG-behavior associations. Biological sex is a particularly important potential moderator, as females with ASD appear to differ from males with ASD in important ways that may influence biomarker accuracy.MethodsWe examined effects of biological sex, age, and ASD diagnosis on resting state EEG among a large, sex-balanced sample of youth with (N = 142, 43% female) and without (N = 138, 49% female) ASD collected across four research sites. Absolute power was extracted across five frequency bands and nine brain regions, and effects of sex, age, and diagnosis were analyzed using mixed-effects linear regression models. Exploratory partial correlations were computed to examine EEG-behavior associations in ASD, with emphasis on possible sex differences in associations.ResultsDecreased EEG power across multiple frequencies was associated with female sex and older age. Youth with ASD displayed decreased alpha power relative to peers without ASD, suggesting increased neural activation during rest. Associations between EEG and behavior varied by sex. Whereas power across various frequencies correlated with social skills, nonverbal IQ, and repetitive behavior for males with ASD, no such associations were observed for females with ASD.ConclusionsResearch using EEG as a possible ASD biomarker must consider individual differences among participants, as these features influence baseline EEG measures and moderate associations between EEG and important behavioral outcomes. Failure to consider factors such as biological sex in such research risks defining biomarkers that misrepresent females with ASD, hindering understanding of the neurobiology, development, and intervention response of this important population.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and repetitive behaviors [1], and by extreme heterogeneity in symptom severity, cognitive functioning, comorbid conditions, and medical involvement
Delta slow waves are related to eventrelated detection of attention, salience, and motivation (e.g., [11]), with differences in delta power observed in neurodevelopmental concerns such as ADHD [12], dyslexia [13], and preterm birth [14]
Recruitment Data collection sites included Boston Children’s Hospital (BCH), Seattle Children’s Research Institute (SCRI), the University of California Los Angeles (UCLA), and Yale University, with the data coordinating center located at the University of Southern California (USC)
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by social communication impairments and repetitive behaviors [1], and by extreme heterogeneity in symptom severity, cognitive functioning, comorbid conditions, and medical involvement. The field of ASD research has sought to identify biomarkers with specificity for ASD, with multiple goals of characterizing brain systems associated with its etiology, contributing to diagnostic clarification, delineating subgroups within the larger ASD population, and monitoring change due to intervention and developmental processes [2,3,4,5] Within these efforts, electroencephalography (EEG) carries tremendous promise, as it is well tolerated by children with ASD [6], appropriate across a range of verbal and attentional skills, and suitable for multisite assessment [5]. Biological sex is a important potential moderator, as females with ASD appear to differ from males with ASD in important ways that may influence biomarker accuracy
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