The regional variation of laminar thickness in the human isocortex is related to cortical hierarchy and interregional connectivity

Abstract

The human isocortex consists of tangentially organized layers with unique cytoarchitectural properties. These layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support function through enabling targeted corticocortical connections. Here, leveraging maps of the 6 cortical layers based on 3D human brain histology, we aimed to quantitatively characterize the systematic covariation of laminar structure in the cortex and its functional consequences. After correcting for the effect of cortical curvature, we identified a spatial pattern of changes in laminar thickness covariance from lateral frontal to posterior occipital regions, which differentiated the dominance of infra- versus supragranular layer thickness. Corresponding to the laminar regularities of cortical connections along cortical hierarchy, the infragranular-dominant pattern of laminar thickness was associated with higher hierarchical positions of regions, mapped based on resting-state effective connectivity in humans and tract-tracing of structural connections in macaques. Moreover, we show that regions with similar laminar thickness patterns have a higher likelihood of structural connections and strength of functional connections. In sum, here, we characterize the organization of laminar thickness in the human isocortex and its association with cortico-cortical connectivity, illustrating how laminar organization may provide a foundational principle of cortical function.

Cytoarchitectonic gradients of laminar degeneration in behavioral variant frontotemporal dementia

“…27,29,31,37,77,78 In addition to the structural organization of cortical gradients, a growing literature suggests that they are evolutionary conserved across mammals 27,28,43,68,69,86 and correspond to gradients of gene expression, 38,87,88 distributions of neurotransmitters, 89 patterns of circuit connectivity, 42,90,91 and hierarchies of functional and cognitive networks. 92–97 Therefore, measuring deviations to an otherwise healthy cortical gradient in neurodegenerative disorders can potentially inform why, and to what degree, pathologic changes have occurred where they were measured. Consistent with previous studies of healthy human cortex, 29,43 we confirmed the reliable sampling of cytoarchitectonic types along the cortical gradient by demonstrating that the predominance of supragranular layer SMI32-ir pyramidal neurons increases along the cortical gradient of our healthy control cohort ( Fig.…”

Hyperphosphorylated tau in Alzheimer's disease disseminates along pathways predicted by the Structural Model for Cortico‐cortical Connections

“…For obvious reasons, tract‐tracing techniques are not applicable to the human brain; thus, contemporary researchers have turned to “trace” human brain pathways using in vivo image techniques. Such studies in the human cerebral cortex have showed that patterns of laminar thickness (estimated by MRi) and structural connections (as seen by tractography) are related (e.g., Saberi et al., 2023), but image techniques do not have enough resolution to trace pathways to the level of synapses (Grisot et al., 2021), nor to their origin or termination layers. Therefore, synaptic tract‐tracing studies in nonhuman primates provide indispensable information for inferring synaptic pathways in the human brain.…”

Microstructural asymmetry in the human cortex

“…First, we studied the BigBrain, which is an ultra high-resolution whole-brain post-mortem histological atlas of a 65-year-old man. It allowed the quantification of asymmetry in cortical cytoarchitecture at the level of individual layers (Amunts et al, 2013; Saberi et al, 2023; Wagstyl et al, 2018, 2020). Second, we studied in vivo microstructural asymmetry to evaluate inter-individual variation.…”