Hortobágyi T, Richardson SP, Lomarev M, Shamim E, Meunier S, Russman H, Dang N, Hallett M. Chronic low-frequency rTMS of primary motor cortex diminishes exercise training-induced gains in maximal voluntary force in humans. J Appl Physiol 106: 403-411, 2009. First published November 13, 2008 doi:10.1152/japplphysiol.90701.2008Although there is consensus that the central nervous system mediates the increases in maximal voluntary force (maximal voluntary contraction, MVC) produced by resistance exercise, the involvement of the primary motor cortex (M1) in these processes remains controversial. We hypothesized that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of M1 during resistance training would diminish strength gains. Forty subjects were divided equally into five groups. Subjects voluntarily (Vol) abducted the first dorsal interosseus (FDI) (5 bouts ϫ 10 repetitions, 10 sessions, 4 wk) at 70 -80% MVC. Another group also exercised but in the 1-min-long interbout rest intervals they received rTMS [VolϩrTMS, 1 Hz, FDI motor area, 300 pulses/ session, 120% of the resting motor threshold (rMT)]. The third group also exercised and received sham rTMS (VolϩSham). The fourth group received only rTMS (rTMS_only). The 37.5% and 33.3% gains in MVC in Vol and VolϩSham groups, respectively, were greater (P ϭ 0.001) than the 18.9% gain in VolϩrTMS, 1.9% in rTMS_only, and 2.6% in unexercised control subjects who received no stimulation. Acutely, within sessions 5 and 10, single-pulse TMS revealed that motor-evoked potential size and recruitment curve slopes were reduced in VolϩrTMS and rTMS_only groups and accumulated to chronic reductions by session 10. There were no changes in rMT, maximum compound action potential amplitude (M max), and peripherally evoked twitch forces in the trained FDI and the untrained abductor digiti minimi. Although contributions from spinal sources cannot be excluded, the data suggest that M1 may play a role in mediating neural adaptations to strength training. muscle; transcranial magnetic stimulation; cortical excitability IT IS WELL ESTABLISHED that neural mechanisms mediate the initial gains in maximal voluntary strength in response to chronic resistance exercise (9,16,19,20,39). However, there is disagreement concerning the magnitude and nature of involvement of specific structures of the central nervous system in neuronal adaptations to chronic exercise. A handful of studies used transcranial magnetic stimulation (TMS) to determine whether the primary motor cortex (M1) contributes to neuronal adaptations to resistance training-induced increases in voluntary force (9,25,30). Carroll et al. (9) found that resistance training did not modify the size of the TMSproduced motor-evoked potentials (MEPs) at rest, but the force of the first dorsal interosseus muscle (FDI) at which maximum MEP amplitude occurred significantly shifted from ϳ50% maximal voluntary force (maximal voluntary contraction, MVC) before training to ϳ35% MVC after training. Coupled with data produced by transcranial ele...