Work

Structural and functional coupling alterations in autism spectrum disorder with and without comorbid attention deficit hyperactivity disorder

Year: 2026

Type: article

Abstract: Background: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly comorbid. The neural basis of this comorbidity remains unclear. We compared brain structural-functional coupling (SC-FC coupling) across ASD subgroups and typically developing (TD) controls to parse the neurobiological heterogeneity of ASD. Methods: We analyzed T1-weighted and resting-state fMRI data from 331 participants from ABIDE II (130 ASD [39 ASD+ADHD, 91 ASD-only] and 201 TD). For each participant, we extracted multivariate structural features from T1-weighted images to construct an individual structural covariance network. SC-FC coupling for each brain region was quantified by correlating its observed functional connectivity profile with the profile predicted from individual structural features via linear regression. Results: Compared to TD individuals, the ASD group showed altered SC-FC coupling in networks critical for social cognition, emotion, sensory processing, and cognitive control: the default mode network (DMN), limbic system (LimN), somatomotor network (SMN), and frontoparietal network (FPN). Crucially, distinct patterns emerged between ASD subgroups. The ASD-only group had stronger coupling in the left inferior temporal gyrus (ITG.L). The ASD+ADHD group showed increased coupling in specific cerebellar regions: the right cerebellar lobule IX (Cerebellum_9_R) and right cerebellum Crus II (Cerebellum_Crus2_R). Conclusions: Our findings demonstrate both shared and subtype-specific alterations in SC-FC coupling in ASD. Comparing ASD subgroups clarifies that comorbid ADHD is associated with unique neural pathways, particularly involving cerebellar integration for attentional processes. Measuring SC-FC coupling offers a valuable approach for disentangling the heterogeneity in ASD and may aid in developing targeted interventions.

Source: Frontiers in Psychiatry

DOI: 10.3389/fpsyt.2025.1704170

Authors: Xiaolin Zhang, Yan Zhou, Luming Hu, Jingwen Yan, Xuntao Yin