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

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 postulate 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 employ atlas- and voxel-based connectivity approaches to analyze neuroimaging data acquired from two groups of healthy participants. Our findings are consistent across six complementary processing pipelines: 1) SFC and its temporal variance respectively decrease and increase across the unimodal-transmodal and granular-agranular gradients; 2) increased myelination and lower EI-ratio are associated with more rigid SFC and restricted moment-to-moment SFC fluctuations; 3) a gradual shift from EI-ratio to myelination as the principal predictor of SFC occurs when traversing from granular to agranular cortical regions. Collectively, our work delivers a 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.

Pharmaco-resistant temporal lobe epilepsy gradually perturbs the cortex-wide excitation-inhibition balance

“…We calculated the region-wise Hurst exponent value, a metric that is mathematically related to the 1/f exponent of neural signals 21,56 and used as an index of the E/I ratio. As previously described, 5,57 resting-state fMRI time series were modeled as multivariate fractionally integrated processes, and the Hurst exponent was estimated via the univariate maximum likelihood method and discrete wavelet transform. 5 As such, an elevated E/I ratio would manifest in a lower Hurst exponent value.…”

Structure-Function Relationship in Electrical and Hemodynamic Brain Networks: Insights from EEG and fNIRS during Rest and Task States

“…Evidence indicates that the structure-function relationship is not uniform across brain regions, pointing to a more robust coupling in the unimodal cortex, which is sensitive to immediate changes in the sensory environment, and a weaker association in the transmodal cortex, which is sensitive to a prior context [26,27,28,29,30,31]. It has been suggested that this regional heterogeneity may potentially reflect underlying molecular and cytoarchitectural gradients, highlighting a hierarchy of time scales of intrinsic fluctuations across the cortex [2,32,33,34,35,36]. Moreover, it was reported that the structure-function relationship is modality-dependent, suggesting that functional connections estimated from longer time windows overlap significantly with the underlying structural connections.…”