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bioRxiv · 10.1101/2025.10.10.681732

Shared and distinct neural signatures of inhibitory control deficits in attention-deficit/hyperactivity disorder and autism

Roussat, M.·Gao, Z.·Cai, W.·Vaidya, C.·Supekar, K.
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Abstract

BackgroundAttention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share deficits in inhibitory control, yet direct comparisons of their neurobiological underpinnings remain sparse and are often confounded by comorbidity. We examined shared and distinct abnormalities in brain activation and circuit connectivity associated with inhibitory control in non-comorbid ADHD and ASD. MethodsBrain activity and hyperdirect pathway connectivity during inhibitory control were examined in children with non-comorbid ADHD (age: 11.1{+/-}0.24y) and children with non-comorbid ASD (age: 11.1{+/-}0.39y), compared with typically developing (TD) children (age: 10.9{+/-}0.09y), and benchmarked against healthy adults (age: 24.1{+/-}1.26y), using fMRI stop-signal task data. ResultsBoth ADHD and ASD groups showed reduced activation in salience and frontoparietal network regions alongside increased activation in default mode network (DMN) regions, consistent with triple-network dysfunction. These activation deficits were more pronounced in ASD, whose activation profile also diverged most from adults. At the circuit level, only ASD showed abnormal hyperdirect connectivity, involving insula-STN and preSMA-STN pathways and further reflected in a composite insula/IFG-STN connectivity measure, indicating broader cortical-STN disruption. Importantly, across all children, reduced salience/frontoparietal relative to DMN engagement correlated with greater parent-reported inhibitory control deficits, and in ASD, individual differences in insula/IFG-STN connectivity showed the same association, highlighting the behavioral relevance of both network- and circuit-level abnormalities. ConclusionsADHD and ASD share network-level but differ in circuit-level abnormalities underlying inhibitory control deficits. Together, these insights advance the neurobiology of inhibitory control in ADHD and ASD and provide potential targets for neuroscience-informed interventions addressing both shared and disorder-specific mechanisms.

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Roussat, M., Gao, Z., Cai, W., Vaidya, C., Supekar, K.. 2025-10-12. Shared and distinct neural signatures of inhibitory control deficits in attention-deficit/hyperactivity disorder and autism. https://doi.org/10.1101/2025.10.10.681732

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