Differences at an overall α level <0.05 were considered significant. Results are reported as mean ± SD. Results The application of TMS at supramotor threshold intensities reliably induces an initial excitatory response followed by a period of silence in the recorded muscle activity lasting up to 250 msec (Fuhr et al. 1991; Valls-Solé et al. 1992). We established a stimulation intensity for each participant that reliably achieved silent periods following stimulation of greater than 100 msec. Sham TMS was applied

using Inhibitors,research,lifescience,medical the same TMS intensity so that the auditory effect of stimulation remained consistent across experimental conditions. Examples of responses to TMS and sham TMS are presented in Figure 1B. It is clear from Figure 1B that sham TMS did not elicit

the same excitatory or inhibitory response in the target muscle as real TMS. Although the data shown are taken from one participant, Inhibitors,research,lifescience,medical the same pattern of EMG response to TMS and sham stimuli was observed for every participant. Real or sham TMS was followed Inhibitors,research,lifescience,medical in each trial 50 msec later by a wrist flexion perturbation that elicited a stretch reflex. Examples of the resultant EMG responses are shown in Figure 2 for a single participant. Changes in the amplitude of the elicited reflexes across the eight experimental conditions (two mechanical environments × two TMS positions × two TMS conditions) are addressed below according to Inhibitors,research,lifescience,medical hypothesis. Figure 2 Responses of the ECR muscle in one individual to wrist flexion perturbations with and without preceding cortical stimulation. The traces shown are Galunisertib averaged across 20 trials in each condition. While real TMS applied to the left (ipsilateral) primary motor … Hypothesis 1: that the amplitude of the LLSR elicited during interactions with a compliant manipulandum would be larger than those elicited during interactions

with a stiff manipulandum. When wrist perturbations were applied following sham stimulation the amplitude of the resulting LLSR was significantly greater when Inhibitors,research,lifescience,medical participants were interacting with a compliant manipulandum (0.1 ± 0.09 mV) than when the manipulandum was stiff (0.073 ± 0.075 mV, P = 0.003). This confirms our hypothesis and replicates the Carnitine palmitoyltransferase II results of previous studies of stretch reflex modulation under similar task conditions. Hypothesis 2: that inhibiting the contralateral (right) primary motor cortex would reduce the amplitude of the LLSR. Consistent with our hypothesis, the application of supramotor threshold TMS to the primary motor cortex contralateral to the target ECR muscle 50 msec prior to wrist perturbations resulted in a period of corticospinal inhibition (Fig. 1B) and reduced the amplitude of the LLSR within the period of induced inhibition (Fig. 2A and C). Reductions in the amplitude of the LLSR were observed in both stiff (sham: 0.059 ± 0.063 mV, TMS: 0.04 ± 0.062 mV; P = 0.