Hierarchical distortions in structure-function coupling linked to multiscale neurobiological characteristics in autism

Autism spectrum disorder is associated with widespread alterations in brain connectivity, but how structural and functional networks are jointly reorganized remains unclear. Here, we show that autism is associated with altered structure-function coupling, particularly in the hierarchical organization of sensory and association systems. Using brain imaging data from 91 individuals with autism and 67 typically developing controls, we model functional connectivity from structural networks using Riemannian optimization and examine communication across multiple steps.

In the resulting simulated networks, hierarchical organization is comparable between groups at lower communication steps but becomes less differentiated in autism as communication extends across multiple steps. These alterations are associated with excitation/inhibition alterations, neurotransmitter distributions, gene expression, and multisensory processing. We also identify atypical connectivity involving the thalamus and putamen.

Importantly, greater hierarchical distortion predicts more severe autistic symptoms, linking macroscale network organization with neurobiology and behavior. These findings highlight hierarchical structure-function coupling as a potential framework for understanding biological and behavioral characteristics in autism. This study was supported by the Institute for Information and Communications Technology Planning and Evaluation (IITP) funded by the Korean Government (MSIT) (No. 2022-0-00448/RS-2022-II220448, Deep Total Recall: Continual Learning for Human-Like Recall of Artificial Neural Networks), National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2025-20253035 and RS-2025-25422106), and a Korea University grant.

Department of Brain and Cognitive Engineering, Korea University, Seoul, Republic of Korea Taeyeon Kim, Jong Young Namgung, Yeongjun Park, Chae Yeon Kim & Bo-yong Park BK21 Four Institute of Precision Public Health, Seoul, Republic of Korea Taeyeon Kim, Yeongjun Park & Chae Yeon Kim Department of Digital Health, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea AI Research Center, Data Science Research Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA Child Mind Institute, Autism Center, New York, NY, USA McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada Bo-yong Park is an Associate Editor for Communications Biology but was not involved in the editorial review or peer review, nor in the decision to publish this article. Bernhardt is co-founder of BrainScores Inc. All other authors declare no competing interests.

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If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Kim, T., Namgung, J.Y., Park, Y. et al.