Altered hierarchical gradients of intrinsic neural timescales in school-aged youth with autism spectrum disorder

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Abstract

Background : Intrinsic neural timescales (INT) index the temporal persistence of spontaneous neural activity and track the cortex’s hierarchical organization. Although hierarchy-related alterations are reported across neurodevelopmental conditions, evidence in autism spectrum disorder (ASD) school-aged youth remains sparse and is often derived from male-dominated samples. Establishing whether INT varies by diagnosis across hierarchical levels—and whether such variation is sex-dependent—could refine mechanistic accounts of ASD and guide stratified, developmentally informed translation. Materials and methods : Resting-state fMRI from 236 participants (ages 8–18) were preprocessed with fMRIPrep v1.2.5, followed by nuisance-regression denoising. INT were estimated voxel-wise from autocorrelation decay, summarized with the Schaefer-200 parcellation, and annotated using AAL labels. Group effects were evaluated in three analyses: ASD vs. controlled group (CONN) in the full cohort, sex-stratified ASD vs. CONN, and ASD vs. US using a sibling model with a family random effect. All models adjusted for age, motion, and sex where applicable. region of interest (ROI)-wise inference used Type III ANOVA (p$<$0.05) and planned contrasts targeting ASD–CONN differences and sex differences within ASD. Results : Linear mixed-effects analyses revealed a significant diagnosis-by-hierarchical level (HL) interaction: INT–HL slopes were steeper in CONN than ASD. In sex-stratified analyses, males with ASD showed higher INT values than females in exploratory ROI-wise analyses. In within-family contrasts, US showed a steeper INT–HL slope overall,whereas ASD showed higher INT in the lowest 12.5\% of ROIs by HL. In pairwise comparison: 23 ROIs were identified differing between ASD and CONN, concentrated in the Salience/Ventral Attention, Control, and Somatomotor networks; within ASD, male–female contrasts yielded four significant ROIs. Limitations : In ASD-US contrast experiment, power was limited by few ASD–US sibling pairs. In replication, the apparent ASD–CONN sex effect may reflect male–female imbalance. In pairwise comparison, no ROI survived from multiple-comparison correction. Conclusion : ASD shows overall faster cortical activity and altered hierarchical gradients—especially reduced INT values in higher ranked regions. Hierarchy-based metrics from normative ROI rankings capture neurobiological variation and may inform clinical relevance.

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