Microstructural and Functional Gradients are Increasingly Dissociated in Transmodal Cortices

Abstract

While the role of cortical microstructure in organising neural function is well established, it remains unclear how structural constraints can give rise to more flexible elements of cognition. While nonhuman primate research has demonstrated a close structure-function correspondence, the relationship between microstructure and function remains poorly understood in humans, in part because of the reliance on post mortem analyses which cannot be directly related to functional data. To overcome this barrier, we developed a novel approach to model the similarity of microstructural profiles sampled in the direction of cortical columns. Our approach was initially formulated based on an ultra-highresolution 3D histological reconstruction of an entire human brain and then translated to myelinsensitive MRI data in a large cohort of healthy adults. This novel method identified a system-level gradient of microstructural differentiation traversing from primary sensory to limbic regions that followed shifts in laminar differentiation and cytoarchitectural complexity. Importantly, while microstructural and functional gradients described a similar hierarchy, they became increasingly dissociated in transmodal default mode and fronto-parietal networks. Meta analytic decoding of these topographic dissociations highlighted involvement in higher-level aspects of cognition such as cognitive control and social cognition. Our findings demonstrate a relative decoupling of macroscale functional from microstructural gradients in transmodal regions, which likely contributes to the flexible role these regions play in human cognition.

Transcriptomic and Cellular Decoding of Regional Brain Vulnerability to Neurodevelopmental Disorders

“…Band thickness was calculated as the Euclidean distance between the respective surfaces. To approximate cellular density, we extended upon recent work on BigBrain microstructure profiles 68 and generated microstructure profiles within supra-and infra-granular bands. Intensity profiles using five equivolumetric surfaces within the predefined surfaces of the BigBrain were then averaged to produce an approximate density value.…”

Myeloarchitecture gradients in the human insula serve as blueprints for its diverse connectivity and function

“…Our final analysis examines whether these unique patterns can account for the range of functions that the insula has been implicated with. To establish correspondence to cognitive taxonomies, we computed spatial associations between the microstructural gradients and local insular activations derived from meta-analytic term maps (24,34,44) (Figure 4A). Changes in term associations along G1 reflected a transition from sensory mechanisms in the posterior insular anchor, and culminated in cognition and emotion-related terms in anterior regions.…”

“…We generated 14 equivolumetric intracortical surfaces (32) that sampled T1w/T2w intensities across cortical depths, yielding distinct intensity profiles reflecting microstructural composition of each vertex contained within the insular boundaries. This number was selected based on the results of stability analyses of the MPC matrix (see below) performed in previous work (24). Vertex-wise microstructural profiles covering the pial to white matter boundary were estimated across these surfaces for both the left and right insula (Figure 1A, S1).…”

“…In particular, contrasts sensitive to intracortical myelin content can quantify myeloarchitecture across the cortical mantle in single individuals and at the population level (20)(21)(22)(23). With the development of multimodal co-registration techniques, microstructurally sensitive MRI data can be complemented with functional imaging methods, particularly resting-state functional MRI, to interrogate the interplay between structure and function in the living brain (24)(25)(26). Recent work has shown that maps of intracortical myeloarchitecture generated from myelin-sensitive contrasts appear to follow changes in task-based functional activation as well as intrinsic functional connectivity across the cortex (25,27,28).…”

“…Recent work has shown that maps of intracortical myeloarchitecture generated from myelin-sensitive contrasts appear to follow changes in task-based functional activation as well as intrinsic functional connectivity across the cortex (25,27,28). Quantitative intracortical in vivo profiling has also been leveraged to establish main axes of change in microstructural differentiation across the cortex in a data-driven manner, and has enriched our understanding of how microstructural composition may constrain the brain's functional organization (24).…”