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  Atypical integration of sensory-to-transmodal functional systems mediates symptom severity in autism

Park, S., Haak, K. V., Cho, H. B., Valk, S. L., Bethlehem, R. A. I., Milham, M. P., et al. (2021). Atypical integration of sensory-to-transmodal functional systems mediates symptom severity in autism. Frontiers in Psychiatry, 12: 699813. doi:10.3389/fpsyt.2021.699813.

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Park, Shinwon1, 2, Author
Haak, Koen V.3, Author
Cho, Han Byul1, 2, Author
Valk, Sofie L.4, 5, Author              
Bethlehem, Richard A. I.6, 7, Author
Milham, Michael P.8, 9, Author
Bernhardt, Boris C.10, Author
Di Martino, Adriana11, Author
Hong, Seok-Jun1, 2, 8, Author
1Center for Neuroscience Imaging Research, Sungkyunkwan University, Seoul, Republic of Korea, ou_persistent22              
2Department of Biomedical Engineering, Sungkyunkwan University, Seoul, Republic of Korea, ou_persistent22              
3Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, the Netherlands, ou_persistent22              
4Otto Hahn Group Cognitive Neurogenetics, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_3222264              
5Institute of Neuroscience and Medicine, Research Center Jülich, Germany, ou_persistent22              
6Autism Research Centre, University of Cambridge, United Kingdom, ou_persistent22              
7Brain Mapping Unit, Department of Psychiatry, University of Cambridge, United Kingdom, ou_persistent22              
8Center for the Developing Brain, Child Mind Institute, New York, NY, USA, ou_persistent22              
9Center for Biomedical Imaging and Neuromodulation (C-BIN), Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA, ou_persistent22              
10McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montréal, QC, Canada, ou_persistent22              
11Autism Center, Child Mind Institute, New York, NY, USA, ou_persistent22              


Free keywords: Autism spectrum disoder; Connectopic mapping; Cortical hierarchy; High-order system; Low-level sensory; Subcortico-cortical connectivity
 Abstract: A notable characteristic of autism spectrum disorder (ASD) is co-occurring deficits in low-level sensory processing and high-order social interaction. While there is evidence indicating detrimental cascading effects of sensory anomalies on the high-order cognitive functions in ASD, the exact pathological mechanism underlying their atypical functional interaction across the cortical hierarchy has not been systematically investigated. To address this gap, here we assessed the functional organisation of sensory and motor areas in ASD, and their relationship with subcortical and high-order trandmodal systems. In a resting-state fMRI data of 107 ASD and 113 neurotypical individuals, we applied advanced connectopic mapping to probe functional organization of primary sensory/motor areas, together with targeted seed-based intrinsic functional connectivity (iFC) analyses. In ASD, the connectopic mapping revealed topological anomalies (i.e., excessively more segregated iFC) in the motor and visual areas, the former of which patterns showed association with the symptom severity of restricted and repetitive behaviors. Moreover, the seed-based analysis found diverging patterns of ASD-related connectopathies: decreased iFCs within the sensory/motor areas but increased iFCs between sensory and subcortical structures. While decreased iFCs were also found within the higher-order functional systems, the overall proportion of this anomaly tends to increase along the level of cortical hierarchy, suggesting more dysconnectivity in the higher-order functional networks. Finally, we demonstrated that the association between low-level sensory/motor iFCs and clinical symptoms in ASD was mediated by the high-order transmodal systems, suggesting pathogenic functional interactions along the cortical hierarchy. Findings were largely replicated in the independent dataset. These results highlight that atypical integration of sensory-to-high-order systems contributes to the complex ASD symptomatology.


Language(s): eng - English
 Dates: 2021-04-242021-07-162021-08-20
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3389/fpsyt.2021.699813
Other: eCollection 2021
PMID: 34489757
PMC: PMC8417581
 Degree: -



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Project name : -
Grant ID : 28436
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Funding organization : Brain & Behavior Research Foundation
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Grant ID : IBS-R15-D1
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Funding organization : Institute for Basic Science
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Grant ID : NWO-Veni 016.171.068
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Funding organization : Dutch Research Council
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Grant ID : NSERC Discovery-1304413
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Funding organization : National Science and Engineering Research Council of Canada
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Grant ID : CIHR FDN-154298, PJT-174995
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Funding organization : Canadian Institutes of Health Research
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Grant ID : NI17-039
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Funding organization : SickKids Foundation
Project name : -
Grant ID : R21MH107045, R01MH115363, R01MH105506, U01MH099059, R01MH081218, R01MH083246, R21MH084126 and K23MH087770
Funding program : -
Funding organization : National Institute of Mental Health

Source 1

Title: Frontiers in Psychiatry
  Abbreviation : Front Psychiatry
Source Genre: Journal
Publ. Info: Lausanne, Switzerland : Frontiers Research Foundation
Pages: - Volume / Issue: 12 Sequence Number: 699813 Start / End Page: - Identifier: ISSN: 1664-0640
CoNE: https://pure.mpg.de/cone/journals/resource/16640640