Neurophysiological correlates of aging-related muscle weakness

Abstract

Muscle weakness associated with aging implicates central neural degeneration. However, role of the primary motor cortex (M1) is poorly understood, despite evidence that gains in strength in younger adults are associated with its adaptations. We investigated whether weakness of biceps brachii in aging analogously relates to processes in M1. We enrolled 20 young (22.6 Ϯ 0.87 yr) and 28 old (74.79 Ϯ 1.37 yr) right-handed participants. Using transcranial magnetic stimulation, representation of biceps in M1 was identified. We examined the effect of age and sex on strength of left elbow flexion, voluntary activation of biceps, corticospinal excitability and output, and short-interval intracortical and interhemispheric inhibition. Interhemispheric inhibition was significantly exaggerated in the old (P ϭ 0.047), while strength tended to be lower (P ϭ 0.075). Overall, women were weaker (P Ͻ 0.001). Processes of M1 related to strength or voluntary activation of biceps, but only in older adults. Corticospinal excitability was lower in weaker individuals (r ϭ 0.38), and corticospinal output, intracortical inhibition and interhemispheric inhibition were reduced too in individuals who poorly activated biceps (r ϭ 0.43, 0.54 and 0.38). Lower intracortical inhibition may reflect compensation for reduced corticospinal excitability, allowing weaker older adults to spread activity in M1 to recruit synergists and attempt to sustain motor output. Exaggerated interhemispheric inhibition, however, conflicts with previous evidence, potentially related to greater callosal damage in our older sample, our choice of proximal vs. distal muscle and differing influence of measurement of inhibition in rest vs. active states of muscle. Overall, age-specific relation of M1 to strength and muscle activation emphasizes that its adaptations only emerge when necessitated, as in a weakening neuromuscular system in aging.

Reproducibility of transcranial magnetic stimulation metrics in the study of proximal upper limb muscles

“…Biceps brachii, being a proximal large muscle, is especially important in founding subsequent recovery of the hand in neurologic populations (Kumar et al, 1989). However, based on present findings and previous evidence from our work and of others (Plow et al, 2013; Plow et al, 2014; van Kuijk et al, 2009; Brasil-Neto et al, 1992), it becomes clear that the variable nature of its MEPs renders test-retest measurements of its TMS metrics weakly reproducible. Nevertheless, choosing metrics that define its excitability and output in terms of intensity of TMS device (RMTs or supra-maximal MEP intensities) and/or spatial spread of excitability (COGs and hotspots) would serve as robust markers to longitudinally track recovery and prognosticate upper extremity function across populations, such as stroke, and spinal cord injury.…”

“…We delivered paired pulses at intervals of 1 through 5 ms (Perez et al, 2004). However, we only report ICI at 2 ms because most of our subjects exhibited peak inhibition at this interval as also noted in our previous report (Plow et al, 2013). …”

“…Our emphasis is novel because proximal muscles are typically less studied than distal owing to the challenge in assaying with TMS. For instance, fewer cortico-motor-neuronal projections that are spread over a relatively wider area (Brasil-Neto et al, 1992), we have recently reported, render their MEPs small and extremely variable (Plow et al, 2013, 2014). Along similar lines, examining reliability of all major metrics is important, because in the study of distal muscles, a divergence is identified, where certain measures are more reliable than others (Malcolm et al, 2006).…”

“…The criterion ranges of supra-maximal MEPs were set lower than that which is generally adopted for study of distal hand muscles (~1 mV) because it is difficult to evoke larger MEPs from biceps brachii (Chen et al, 1998; Harris-Love et al, 2007; Plow et al, 2014). A wider range was chosen because MEPs elicited in biceps brachii are more variable (Brasil-Neto et al, 1992; Plow et al, 2013,) than those in distal muscles (van Kuijk et al, 2009). …”

The Effects of Dietary Omega-3s on Muscle Composition and Quality in Older Adults

“…This finding differs to in intact humans where the deterioration in muscle function occurs at ~2–3-fold greater rate than the loss of muscle mass (declines of ~2–3% vs. ~0.5–1.0% per year, respectively) [29, 30]. The reduction in muscle quality (i.e., strength per unit of muscle mass) with aging has been postulated to be occur due to changes in the muscle architecture [31], an increase in intermuscular fat infiltration [32–34], greater muscle fibrosis [35, 36], and reduced neuromuscular activation [37, 38]. …”