Waves of Maturation and Senescence in Micro-structural MRI Markers of Human Cortical Myelination over the Lifespan.

Ameera X Patel,Aaron F Alexander-Bloch,Kirstie Whitaker,Anders M Fjell,Donatas Sederevičius,Håkon Grydeland,Kristine B Walhovd,Edward T Bullmore,Rafael Romero-Garcia,Atle Bjørnerud,Christian K Tamnes,Petra E Vértes,Lars T Westlye,Simon R White,František Váša

doi:10.1093/cercor/bhy330

Abstract

Seminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8–85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of seven cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30-s but there was a second wave reaching stability in the 50-s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60-s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.

Highlights

The cortex contains myelinated axons (Gennari 1782) critical for efficient neuronal communication (Zalc and Colman 2000)
Using a microstructural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle
The average T1w/T2w ratio map across all participants shows that highly myelinated primary motor and sensory areas have higher T1w/T2w values compared with association areas (Fig. 1A)

Summary

Introduction

The cortex contains myelinated axons (Gennari 1782) critical for efficient neuronal communication (Zalc and Colman 2000). More than a century ago, Paul Flechsig (1847–1929) noted that cortical myelination did not occur simultaneously in all regions, but rather in a succession of waves peaking at different ages (Flechsig 1901). Motor and sensory cortical regions myelinated earlier than association cortical regions. Yakovlev and Lecours (1967) extended this notion of waves of myelinogenesis, and noted how intracortical fibers of the association cortex appeared to have a long myelination cycle, demonstrating an immature “greyish pallor” beyond the third decade of life. Studies in rodents have shown myelin-forming oligodendrocyte cells are produced in waves (Kessaris et al 2006). Primate histology studies have reported cortical myelin degeneration, and aberrant remyelination (Peters 2009)

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