Lifespan trajectory of myelin integrity and maximum motor speed

Abstract

Objective: Myelination of the human brain results in roughly quadratic trajectories of myelin content and integrity, reaching a maximum in mid-life and then declining in older age. This trajectory is most evident in vulnerable later myelinating association regions such as frontal lobes and may be the biological substrate for similar trajectories of cognitive processing speed. Speed of movement, such as maximal finger tapping speed (FTS), requires high-frequency action potential (AP) bursts and is associated with myelin integrity. We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity.

Methods: A sensitive in vivo MRI biomarker of myelin integrity (calculated transverse relaxation rates (R(2))) of frontal lobe white matter (FLwm) was measured in a sample of very healthy males (N=72) between 23 and 80 years of age. To assess specificity, R(2) of a contrasting early-myelinating region (splenium of the corpus callosum) was also measured.

Results: FLwm R(2) and FTS measures were significantly correlated (r=.45, p<.0001) with no association noted in the early-myelinating region (splenium). Both FLwm R(2) and FTS had significantly quadratic lifespan trajectories that were virtually indistinguishable and both reached a peak at 39 years of age and declined with an accelerating trajectory thereafter.

Conclusions: The results suggest that in this very healthy male sample, maximum motor speed requiring high-frequency AP burst may depend on brain myelin integrity. To the extent that the FLwm changes assessed by R(2) contribute to an age-related reduction in AP burst frequency, it is possible that other brain functions dependent on AP bursts may also be affected. Non-invasive measures of myelin integrity together with testing of basic measures of processing speed may aid in developing and targeting anti-aging treatments to mitigate age-related functional declines.

Fig. 1

White matter regions of interest (ROIs).

Fig. 2

(A-D) Age trajectories for finger tapping speed (FTS) and white matter transverse relaxation rate (R₂) in frontal lobe (FLwm) and Splenium (Swm). Figures depict the relationships of finger tapping speed (FTS) performance (A), transverse relaxation rate in the frontal lobe white matter (FLwm R₂) (B), and transverse relaxation rate in splenium of corpus callosum comparison region (Swm R₂) (C) with age. (D) Depicts the trajectories of FTS, FLwm R₂ and Swm R₂ across the age range of 23-80 based on mixed effects regression models.

Fig. 3

Correlations between finger tapping speed (FTS) and white matter transverse relaxation rate (R₂) in frontal lobe (FLwm) and splenium (Swm) regions.