4.7 Article

Personalized Intrinsic Network Topography Mapping and Functional Connectivity Deficits in Autism Spectrum Disorder

Journal

BIOLOGICAL PSYCHIATRY
Volume 84, Issue 4, Pages 278-286

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2018.02.1174

Keywords

Autism spectrum disorder; Child development; Connectome; Functional magnetic resonance imaging; Individuality; Resting state

Funding

  1. Canadian Institute for Health Research
  2. Ontario Mental Health Foundation
  3. Centre for Addiction and Mental Health Foundation
  4. Ontario Ministry of Research and Innovation
  5. Canadian Foundation for Innovation
  6. National Institute of Mental Health [K23MH087770, R03MH096321, BRAINS-RO1MH094639-01]
  7. National Institutes of Health [K23MH087770, DC011095, MH084164, K01MH092288, HD55748, KO1MH081191, MH67924, K08MH092697, P50MH60450, R01NS34783, R01MH080826, T32DC008553, R01HD065282, R01MH081218, R21MH084126-NYU, MH066496]
  8. Autism Speaks
  9. National Institute of Neurological Disorders and Stroke [R01NS048527]
  10. Eunice Kennedy Shriver National Institute of Child Health and Human Development
  11. Simons Foundation
  12. Belgian Interuniversity Attraction Poles Grant [P6/29]
  13. Ben B. and Iris M. Margolis Foundation
  14. European Commission (Marie Curie Excellence Grant) [MEXT-CT-2005-023253]
  15. Flanders Fund for Scientific Research [1841313N, G.0354.06, G.0758.10]
  16. Hartford Hospital
  17. John Merck Scholars Fund
  18. Kyulan Family Foundation
  19. Michigan Institute for Clinical and Health Research (MICHR Predoctoral Fellowship) [UL1RR024986]
  20. National Children's Hospital
  21. National Initiative for Brain and Cognition National Cancer Institute Human Cancer Models Initiative [056-13-014, 056-13-017]
  22. Netherlands Organisation for Scientific Research [051.07.003, 452-04-305, 400-08-089]
  23. Netherlands Brain Foundation [KS 2010(1)-29]
  24. National Research Service Award Predoctoral Fellowship [F31DC010143]
  25. Research Council of the University of Leuven
  26. Stanford Institute for Neuro-Innovations and Translational Neurosciences
  27. Leon Levy Foundation
  28. Meath Foundation
  29. Adelaide and Meath Hospital
  30. Stavros Niarchos Foundation
  31. UCLA Autism Center of Excellence
  32. University of Utah Multidisciplinary Research Seed Grant (University of Utah School of Medicine)
  33. National Institutes of Mental Health [K08MH092697, R01MH080826, R01MH080243]
  34. The National Institues of Health [R21MH079871, U19HD035482, R00MH091238, R01MH086654, R01MH096773, R01MH081023, 1R01HD06528001, K01MH071284, R01MH080721]

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BACKGROUND: Recent advances in techniques using functional magnetic resonance imaging data demonstrate individually specific variation in brain architecture in healthy individuals. To our knowledge, the effects of individually specific variation in complex brain disorders have not been previously reported. METHODS: We developed a novel approach (Personalized Intrinsic Network Topography, PINT) for localizing individually specific resting-state networks using conventional resting-state functional magnetic resonance imaging scans. Using cross-sectional data from participants with autism spectrum disorder (ASD; n = 393) and typically developing (TD) control participants (n = 496) across 15 sites, we tested: 1) effect of diagnosis and age on the variability of intrinsic network locations and 2) whether prior findings of functional connectivity differences in persons with ASD compared with TD persons remain after PINT application. RESULTS: We found greater variability in the spatial locations of resting-state networks within individuals with ASD compared with those in TD individuals. For TD persons, variability decreased from childhood into adulthood and increased in late life, following a U-shaped pattern that was not present in those with ASD. Comparison of intrinsic connectivity between groups revealed that the application of PINT decreased the number of hypoconnected regions in ASD. CONCLUSIONS: Our results provide a new framework for measuring altered brain functioning in neurodevelopmental disorders that may have implications for tracking developmental course, phenotypic heterogeneity, and ultimately treatment response. We underscore the importance of accounting for individual variation in the study of complex brain disorders.

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