Corticospinal tract excitability can be altered by age, physical activity (PA), and possibly sex, but whether these effects differ between upper and lower limb muscles is unknown. We determined the influence of age, PA, and sex on corticospinal excitability of an upper limb and a lower limb muscle during submaximal contractions by comparing stimulus-response curves of motor evoked potentials (MEPs). Transcranial magnetic stimulation (TMS) was used to evoke stimulus-response curves in active muscles by incrementally increasing the stimulator intensity from below the active motor threshold (AMT) until a plateau in MEP amplitudes was achieved. Stimulus-response curves were analyzed from the first dorsal interosseous (FDI) of 30 young (23.9 ± 3.8 yr) and 33 older (72.6 ± 5.6 yr) men and women and the vastus lateralis (VL) of 13 young (23.2 ± 2.2 yr) and 25 older (72.7 ± 5.5 yr) men and women. Corticospinal excitability was determined by fitting the curves with a four-parameter sigmoidal curve and calculating the maximal slope (slopemax). PA was assessed with triaxial accelerometry, and participants were dichotomized into high-PA (\u3e10,000 steps/day, n = 15) or low-PA (n = 43) groups. Young adults had larger FDI MEP amplitudes (% maximum amplitude of compound muscle action potential) at higher TMS intensities (120–150% AMT) and greater slopemax than older adults (P \u3c 0.05), with no differences between high- and low-PA groups (P \u3e 0.05). VL MEP amplitudes and slopemax, however, were lower in the high-PA than low-PA participants, with no age or sex differences. These data suggest that aging and PA, but not sex, differentially influence the excitability of the corticospinal tracts projecting to muscles of the upper compared with the lower limb
