Apparent thinning of visual cortex during childhood is associated with myelination, not pruning

Abstract

Microstructural mechanisms underlying apparent cortical thinning during childhood development are unknown. Using functional, quantitative, and diffusion magnetic resonance imaging in children and adults, we tested if tissue growth (lower T 1 relaxation time and mean diffusivity (MD)) or pruning (higher T 1 and MD) underlies cortical thinning in ventral temporal cortex (VTC). After age 5, T 1 and MD decreased in mid and deep cortex of functionally--defined regions in lateral VTC, and in their adjacent white matter. T 1 and MD decreases were (i) consistent with tissue growth related to myelin proliferation, which we verified with adult postmortem histology and (ii) correlated with apparent cortical thinning. Thus, contrary to prevailing theories, cortical tissue does not thin during childhood, it becomes more myelinated, shifting the gray--white matter boundary deeper into cortex. As tissue growth is prominent in regions with protracted functional development, our data suggest an intriguing hypothesis that functional development and myelination are interlinked.

Charting shared developmental trajectories of cortical thickness and structural connectivity in childhood and adolescence

“…The differential rate of thinning is greatest in association cortex (component 1) compared to primary motor and sensory regions (components 2 and 5), with the exception of the visual cortex (component 4). We anticipate these differences in regional rate of change reflects the differential progress of microstructural processes including synaptic pruning (Huttenlocher, 1979), although recent evidence has suggested that apparent cortical thinning in the visual cortex may be dependent on tissue contrast changes due to intracortial myelination, rather than synaptic remodelling (Natu et al, 2018).…”

Cellular correlates of cortical thinning throughout the lifespan

“…While it represents a robust and stable measure, the interregional thinning profile is unable to provide information neither at an individual level nor across time; hence, a portion of the variability remains unexplored. Relative disparity amongst studies might reside on different characterizations of cortical thinning variability 27 11,26,27,52 . Lack of findings may relate to the nature of the interregional profiles, which represent snapshots in time and, hence, are determined by the differential sum of processes that modulate cortical thickness in each area.…”

“…The human cerebral cortex consists on several types of cells, which can be classified into neuronalmostly pyramidal cells and interneurons -and non-neuronal cells -mostly glial cells, namely microglia, astrocytes and oligodendrocytes [22][23][24] . Histological data suggest that regional variations of cortical thickness may be associated with the number of non-neuronal cells and neuropil volume 25,26 . Yet, this ex vivo approach may be less suited to uncover the microstructural substrate driving age-related changes in cortical thickness in the general population.…”

Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders

“…28,48 This indeterminacy highlights how a number of possibly divergent, heterochronic neurobiological mechanisms may give rise to similar observed patterns of cortical morphology, as highlighted by recent reports of the dependence of MRI-based cortical thickness estimates on intracortical myelin content during development. 53,54 By comparing genes with high expression in regions of accelerated thinning with large databases of gene-disease associations, we found significant enrichment of several cognitive disorder terms. DisGeNET is a discovery platform containing gene-disease associations compiled from multiple sources including GWAS data, animal models and literature searches.…”