Integrating multimodal and multiscale connectivity blueprints of the human cerebral cortex in health and disease

Author:

Hansen Justine Y.ORCID,Shafiei Golia,Voigt Katharina,Liang Emma X.,Cox Sylvia M. L.,Leyton Marco,Jamadar Sharna D.,Misic Bratislav

Abstract

The brain is composed of disparate neural populations that communicate and interact with one another. Although fiber bundles, similarities in molecular architecture, and synchronized neural activity all reflect how brain regions potentially interact with one another, a comprehensive study of how all these interregional relationships jointly reflect brain structure and function remains missing. Here, we systematically integrate 7 multimodal, multiscale types of interregional similarity (“connectivity modes”) derived from gene expression, neurotransmitter receptor density, cellular morphology, glucose metabolism, haemodynamic activity, and electrophysiology in humans. We first show that for all connectivity modes, feature similarity decreases with distance and increases when regions are structurally connected. Next, we show that connectivity modes exhibit unique and diverse connection patterns, hub profiles, spatial gradients, and modular organization. Throughout, we observe a consistent primacy of molecular connectivity modes—namely correlated gene expression and receptor similarity—that map onto multiple phenomena, including the rich club and patterns of abnormal cortical thickness across 13 neurological, psychiatric, and neurodevelopmental disorders. Finally, to construct a single multimodal wiring map of the human cortex, we fuse all 7 connectivity modes and show that the fused network maps onto major organizational features of the cortex including structural connectivity, intrinsic functional networks, and cytoarchitectonic classes. Altogether, this work contributes to the integrative study of interregional relationships in the human cerebral cortex.

Funder

Natural Sciences and Engineering Research Council of Canada

Canadian Institutes of Health Research

Brain Canada Foundation Future Leaders Fund

Canada Research Chairs

Michael J. Fox Foundation for Parkinson's Research

Healthy Brains for Healthy Lives Initiative

Helmholtz International Research School for Teratronics, Karlsruher Institut für Technologie

The Neuro Irv and Helga Cooper Foundation

National Health and Medical Research Council of Australia

Publisher

Public Library of Science (PLoS)

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience

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