Maturation and degeneration of the human brainstem across the adult lifespan

Abstract

Brainstem tissue microstructural properties change across the adult lifespan. However, studies elucidating the biological processes that govern brainstem maturation and degeneration in-vivo are lacking. In the present work, conducted on a large cohort of 140 cognitively unimpaired subjects spanning a wide age range of 21 to 94 years, we implemented a multi-parameter approach to characterize the sex-and age differences. In addition, we examined regional correlations between myelin water fraction (MWF), a direct measure of myelin content, and diffusion tensor imaging indices, and transverse and longitudinal relaxation rates to evaluate whether these metrics provide information complementary to MWF. We observed region-dependent differences in myelin content and axonal density with age and found that both exhibit an inverted U-shape association with age in several brainstem substructures. We emphasize that the microstructural differences captured by our distinct MRI metrics, along with their weak associations with MWF, strongly indicate the potential of using these outcome measures in a multi-parametric approach. Furthermore, our results support the gain-predictsloss hypothesis of tissue maturation and degeneration in the brainstem. Indeed, our results indicate that myelination follows a temporally symmetric time course across the adult life span, while axons appear to degenerate significantly more rapidly than they mature. AGINGTable 2. The slopes and standard error (SE) of the maturation and degeneration phases of the standardized MWF, R1, R2, and DTI indices for six brainstem substructures. Maturation and degeneration slopes ± SE Slope of maturation Slope of degeneration p-value Slope of maturation Slope of degeneration p-value MWF Cerebral peduncle

Sexual Dimorphism in VEMP peak to trough Latency

“…They also found a laterality difference, with male rats having more neurons in the left than the right MVN, and female rats having more neurons in the right than the left MVN. In the brainstem generally, as in the cerebrum, the indication is that women have higher myelin content than men (Arshad et al, 2016;Bouhrara et al, 2020;Bouhrara et al, 2021). This is consistent with an interpretation in which proliferation of neuroglia and myelin proteins are regulated differently in women compared to men (Cerghet et al, 2006;Greer et al, 2004).…”

“…Several studies have found that cerebellar vermis is larger in men than women (Raz et al, 1992(Raz et al, , 1998(Raz et al, , 2001Tiemeier et al, 2010), although sometimes the opposite has been found (Luft et al, 1999) and some studies have found no group difference (Rhyu et al, 1999;Bernard et al, 2015;Metwally et al, 2021). Vestibular nuclei span the pons and medulla, which have been investigated in humans using diffusion tensor imaging (Bouhrara et al, 2021). Sex differences were found in the pons but not the medulla, via measures of fractional anisotropy, mean diffusivity and radial diffusivity.…”

In vivo marker of brainstem myelin is associated to quantitative sleep parameters in healthy young men

“…In the central nervous system, myelin is present not only in white matter, but also in varying amounts in many grey matter areas where it is present around neurites near the neuron cell body 14 , 15 . Most brainstem nuclei constitute densely myelinated regions which undergo progressive myelination until early adulthood 16 . How this progressive change is reflected in sleep has not been investigated.…”

Comparing neuromotor functions in 45- and 65-year-old adults with 18-year-old adolescents

“…The changes in CAMs in the ~45- and ~ 65-year-olds in comparison to the norm population align with studies on changes in white matter in the brain over the lifespan ( Cincotta and Ziemann, 2008 ; Bartzokis et al, 2010 ; Bender et al, 2016 ; Slater et al, 2019 ; Bethlehem et al, 2022 ). We know that myelin content and axonal density decrease in the course of aging, leading to lower conduction velocities and less protection of the nerve fibers in older adults ( Slater et al, 2019 ; Bouhrara et al, 2021 ). These changes in the structure of myelin are reflected in functional changes, as was shown by Gooijers and Swinnen (2014) .…”