Neurophysiologic Correlates of Aging-Related Muscle Weakness

38 Muscle weakness associated with aging implicates central neural degeneration. However, role of 39 the primary motor cortex (M1) is poorly understood despite evidence that gains in strength in younger 40 adults are associated with its adaptations. We investigated whether weakness of biceps brachii in aging 41 analogously relates to processes in M1. We enrolled 20 young (22.6±0.87 years) and 28 old (74.79±1.37 42 years) right-handed participants. Using Transcranial Magnetic Stimulation, representation of biceps in 43 M1 was identified. We examined the effect of age and gender on strength of left elbow flexion, 44 voluntary activation of biceps, corticospinal excitability and output, and short-interval intra-cortical and 45 inter-hemispheric inhibition. Inter-hemispheric inhibition was significantly exaggerated in the old (p = 46 0.047), while strength tended to be lower (p= 0.075). Overall, females were weaker (p<0.001). Processes 47 of M1 related to strength or voluntary activation of biceps, but only in older adults. Corticospinal 48 excitability was lower in weaker individuals (r= 0.38), and corticospinal output, intra-cortical inhibition 49 and inter-hemispheric inhibition were reduced too in individuals who poorly activated biceps (r=0.43, 50 0.54 and 0.38). Lower intra-cortical inhibition may reflect compensation for reduced corticospinal 51 excitability, allowing weaker older adults to spread activity in M1 to recruit synergists and attempt to 52 sustain motor output. Exaggerated inter-hemispheric inhibition, however, conflicts with previous 53 evidence, potentially related to greater callosal damage in our older sample, our choice of proximal 54 versus distal muscle and differing influence of measurement of inhibition in restversus active-states of 55 muscle. Overall, age-specific relation of M1 to strength and muscle activation emphasizes that its 56 adaptations only emerge when necessitated, as in a weakening neuromuscular system in aging. 57