Enhanced brain structure-function tethering in transmodal cortex revealed by high-frequency eigenmodes

Abstract The brain’s structural connectome supports signal propagation between neuronal elements, shaping diverse coactivation patterns that can be captured as functional connectivity. While the link between structure and function remains an ongoing challenge, the prevailing hypothesis is that the structure-function relationship may itself be gradually decoupled along a macroscale functional gradient spanning unimodal to transmodal regions. However, this hypothesis is strongly constrained by the underlying models which may neglect requisite signaling mechanisms. Here, we transform the structural connectome into a set of orthogonal eigenmodes governing frequency-specific diffusion patterns and show that regional structure-function relationships vary markedly under different signaling mechanisms. Specifically, low-frequency eigenmodes, which are considered sufficient to capture the essence of the functional network, contribute little to functional connectivity reconstruction in transmodal regions, resulting in structurefunction decoupling along the unimodal-transmodal gradient. In contrast, high-frequency eigenmodes, which are usually on the periphery of attention due to their association with noisy and random dynamical patterns, contribute significantly to functional connectivity prediction in transmodal regions, inducing gradually convergent structure-function relationships from unimodal to transmodal regions. Although the information in high-frequency eigenmodes is weak and scattered, it effectively enhances the structure-function correspondence by 35% in unimodal regions and 56% in transmodal regions. Altogether, our findings suggest that the structure-function divergence in transmodal areas may not be an intrinsic property of brain organization, but can be narrowed through multiplexed and regionally specialized signaling mechanisms.