A moment of change: shifts in myeloarchitecture characterise adolescent development of cortical gradients

Abstract

The biological processes underpinning adolescent brain maturation remain elusive. Expanding on previous work showing age-related changes in cortical morphology, we studied an accelerated longitudinal cohort of adolescents and young adults (n=223, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelinsensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortical profiles demonstrated two separate processes i) related to overall increases in MT, and ii) showing a flattening of the MT profile related to enhanced signal in mid-to-deeper layers, especially in heteromodal and unimodal association cortices. This development was independent of morphological changes, and enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Covariance analysis between all pairs of intracortical profiles revealed that these intracortical changes contributed to a gradual and dynamic differentiation from higher-order to lower-order systems. Depth-dependent trajectories of intracortical myeloarchitectural development contribute to the maturation of structural hierarchies in the human neocortex, providing a model for adolescent development that bridges microstructural and macroscopic scales of brain organization.Intracortical myelin imposes a spatial structure on cortico-cortical connections, yet little is known about how myeloarchitecture develops throughout youth. We formulated a novel approach to study cortical myeloarchitecture in individual humans and leveraged an accelerated longitudinal design to track agerelated changes from 14-27 years. We discovered two unique processes: one involving increasing mean myelin and another characterised by the preferential accumulation of myelin in mid-to-deeper cortical layers. Both processes contributed to an increasing segregation of lower-order from higher-order systems along the macroscale cortical hierarchy. These findings illustrate how layer specific microstructural changes contribute to the maturation of cortical organization and suggest adolescent fine tuning of hierarchical gradients of cortical networks.

Shaping Brain Structure: Genetic and Phylogenetic Axes of Macro Scale Organization of Cortical Thickness

“…The dorsal-ventral dissociation was only observed in the upper two strata, with ventral regions relating to lower T1wT2 contrast than dorsal regions. Difference in upper and lower strata T1wT2w contrast has been summarized using “skewness”, indicating regions with high difference between upper and lower layers would have a low skewness, whereas regions with a small difference between upper and lower layers having a high skewness 73 . Dorsal regions including the sensory-motor cortex have been reported to have a low skewness, indicating a high difference in myelin between upper and lower layers.…”

Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours

“…average regional MT values are computed for each region across approximately the same number of voxels). The subdivided (308) parcellation was transformed from standard fsaverage space into the native space of each individual using surface-based corregistration to minimise geometric distortions and age-related biases [40,57].…”

“…Given this explanatory power of the latent disinhibition phenotype, coupled with individual differences in myelin-related brain growth during early adulthood [40], understanding the neural mechanisms underpinning this novel latent phenotype is an important next step. Therefore, the primary aim of the current study was to identify relationships between intra-cortical myelination (quantified using MT) and the expression of a latent phenotype of disinhibition [10]; i.e.…”

“…Our premise was that disinhibition arises from alterations in frontal brain architecture, manifesting as increased intra-cortical white matter (MT) and concomitant reductions in cortical thickness. In view of the centrality of certain neurochemical systems in understanding impulsivity and compulsivity [41,42], along with recent methodological developments [40,43], the secondary aim of this study was to inferentially ascertain genes co-localised with disinhibition-related cortical regions, by cross-referencing against a public-domain brain atlas [44]. We hypothesised (i) that disinhibition would be associated with elevated MT (and concomitant reductions in grey matter cortical thickness), in frontal and other cortical regions; and (ii) that genes significantly associated with disinhibitionrelated regions would be identified, which would be inferentially enriched for functional interactions involving receptor signalling pathways implicated in impulsivity/compulsivity.…”

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

“…MPC gradient characterization. Variations in T1w/T2w intensity profiles along the space composed of the first two microstructural gradients were characterized using statistical moment parameterization (36,37,64). We calculated the mean, standard deviation, skewness, and kurtosis of intracortical T1w/T2w profiles of each insular vertex.…”