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ADHD symptoms map onto noise-driven structure–function decoupling between hub and peripheral brain regions

Molecular Psychiatry volume 26, pages 4036–4045 (2021)Cite this article

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Abstract

Adults with childhood-onset attention-deficit hyperactivity disorder (ADHD) show altered whole-brain connectivity. However, the relationship between structural and functional brain abnormalities, the implications for the development of life-long debilitating symptoms, and the underlying mechanisms remain uncharted. We recruited a unique sample of 80 medication-naive adults with a clinical diagnosis of childhood-onset ADHD without psychiatric comorbidities, and 123 age-, sex-, and intelligence-matched healthy controls. Structural and functional connectivity matrices were derived from diffusion spectrum imaging and multi-echo resting-state functional MRI data. Hub, feeder, and local connections were defined using diffusion data. Individual-level measures of structural connectivity and structure–function coupling were used to contrast groups and link behavior to brain abnormalities. Computational modeling was used to test possible neural mechanisms underpinning observed group differences in the structure–function coupling. Structural connectivity did not significantly differ between groups but, relative to controls, ADHD showed a reduction in structure–function coupling in feeder connections linking hubs with peripheral regions. This abnormality involved connections linking fronto-parietal control systems with sensory networks. Crucially, lower structure–function coupling was associated with higher ADHD symptoms. Results from our computational model further suggest that the observed structure–function decoupling in ADHD is driven by heterogeneity in neural noise variability across brain regions. By highlighting a neural cause of a clinically meaningful breakdown in the structure–function relationship, our work provides novel information on the nature of chronic ADHD. The current results encourage future work assessing the genetic and neurobiological underpinnings of neural noise in ADHD, particularly in brain regions encompassed by fronto-parietal systems.

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Acknowledgements

This work was supported by the Ministry of Technology and Science, Taiwan (MOST103-2314-B-002-021-MY3), the National Health Research Institutes, Taiwan (NHRI-EX103-10008PI), Chen-Yung Foundation, and National Taiwan University Hospital (NTUH103-S2458, NTUH104-S2761). LC and JAR are supported by the Australian National Health Medical Research Council (LC, 1099082 and 1138711; JAR, 1145168 and 1144936).

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  1. These authors contributed equally: Luke J. Hearne, Hsiang-Yuan Lin

Authors and Affiliations

  1. Clinical Brain Networks Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    Luke J. Hearne & Luca Cocchi

  2. Department of Psychiatry, National Taiwan University Hospital, and College of Medicine, Taipei, Taiwan

    Hsiang-Yuan Lin & Susan Shur-Fen Gau

  3. Brain Modelling Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    Paula Sanz-Leon & James A. Roberts

  4. Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan

    Wen-Yih Isaac Tseng

  5. Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan

    Wen-Yih Isaac Tseng & Susan Shur-Fen Gau

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Hearne, L.J., Lin, HY., Sanz-Leon, P. et al. ADHD symptoms map onto noise-driven structure–function decoupling between hub and peripheral brain regions. Mol Psychiatry 26, 4036–4045 (2021). https://doi.org/10.1038/s41380-019-0554-6

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