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Myelination and excitation-inhibition balance synergistically shape structure-function coupling across the human cortex

View ORCID ProfilePanagiotis Fotiadis, View ORCID ProfileMatthew Cieslak, View ORCID ProfileXiaosong He, View ORCID ProfileLorenzo Caciagli, Mathieu Ouellet, Theodore D. Satterthwaite, Russell T. Shinohara, View ORCID ProfileDani S. Bassett
doi: https://doi.org/10.1101/2022.10.20.512802
Panagiotis Fotiadis
1Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
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  • For correspondence: panosf@pennmedicine.upenn.edu dsb@seas.upenn.edu
Matthew Cieslak
3Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Xiaosong He
4Department of Psychology, University of Science and Technology of China, Hefei, Anhui, 230026, China
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Lorenzo Caciagli
2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
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Mathieu Ouellet
2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
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Theodore D. Satterthwaite
3Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Russell T. Shinohara
5Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA 19104, USA
6Center for Biomedical Image Computing & Analytics, University of Pennsylvania, Philadelphia, PA 19104, USA
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Dani S. Bassett
2Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
3Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
7Department of Electrical & Systems Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA
8Department of Physics & Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA
9Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
3Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
11Santa Fe Institute, Santa Fe, NM 87501, USA
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  • For correspondence: panosf@pennmedicine.upenn.edu dsb@seas.upenn.edu
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ABSTRACT

Recent work has demonstrated that the relationship between structural and functional connectivity varies regionally across the human brain, with reduced coupling emerging along the sensory-association cortical hierarchy. The biological underpinnings driving this expression, however, remain largely unknown. Here, we postulated that intracortical myelination and excitation-inhibition (EI) balance mediate the heterogeneous expression of structure-function coupling (SFC) and its temporal variance across the cortical hierarchy. We employed atlas-and voxel-based connectivity approaches to analyze neuroimaging data acquired from two groups of healthy participants. Our findings were consistent across processing pipelines: 1) increased myelination and lower EI-ratio associated with more rigid SFC and restricted moment-to-moment SFC fluctuations; 2) a gradual shift from EI-ratio to myelination as the principal predictor of SFC occurred when traversing from granular to agranular cortical regions. Collectively, our work delivers a novel framework to conceptualize structure-function relationships in the human brain, paving the way for an improved understanding of how demyelination and/or EI-imbalances induce reorganization in brain disorders.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted October 21, 2022.
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Myelination and excitation-inhibition balance synergistically shape structure-function coupling across the human cortex
Panagiotis Fotiadis, Matthew Cieslak, Xiaosong He, Lorenzo Caciagli, Mathieu Ouellet, Theodore D. Satterthwaite, Russell T. Shinohara, Dani S. Bassett
bioRxiv 2022.10.20.512802; doi: https://doi.org/10.1101/2022.10.20.512802
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Myelination and excitation-inhibition balance synergistically shape structure-function coupling across the human cortex
Panagiotis Fotiadis, Matthew Cieslak, Xiaosong He, Lorenzo Caciagli, Mathieu Ouellet, Theodore D. Satterthwaite, Russell T. Shinohara, Dani S. Bassett
bioRxiv 2022.10.20.512802; doi: https://doi.org/10.1101/2022.10.20.512802

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