Cortical and spinal contributions to remote interlimb facilitation in humans

Voluntary contraction in one limb can facilitate motor output in a distant limb, a phenomenon commonly referred to as the remote effect. However, the neural mechanisms underlying this remote interlimb facilitation remain unclear. This study investigated cortical and spinal contributions to the remote effect in able-bodied participants. Transcranial magnetic stimulation (TMS) was applied over the hand area of the primary motor cortex using posterior-anterior (PA) and anterior-posterior (AP) current directions, which are sensitive to different cortical inputs. Cortical excitability was assessed using single- and paired-pulse paradigms to measure short-interval intracortical inhibition (SICI), short-interval intracortical facilitation (SICF), and short-latency afferent inhibition (SAI). Spinal motoneuron excitability was assessed from F-waves elicited by peripheral nerve stimulation. During voluntary lower-limb contractions, single-pulse TMS elicited larger motor evoked potentials in hand muscles across current directions, indicating a broad increase in net corticospinal output. However, only AP-sensitive paired-pulse measures showed reduced SICI and enhanced SICF during contraction, whereas PA-sensitive SICI and SICF were not significantly altered, suggesting that cortical modulation during the remote effect is expressed more clearly in AP-sensitive measures. SAI with PA stimulation was less consistently expressed during contraction, suggesting that afferent-related inhibitory modulation may also be influenced during the remote effect. In parallel, F-wave amplitude and persistence increased, consistent with enhanced spinal motoneuron excitability. Together, these results provide converging evidence that the remote effect in humans involves broad corticospinal and spinal facilitation, accompanied by current direction-dependent modulation of cortical excitability measures. KEY POINTS SUMMARYO_LIVoluntary contraction in one limb can facilitate motor output in a distant limb, but the mechanisms underlying this remote interlimb facilitation remain unclear. C_LIO_LIWe tested whether remote lower-limb contraction modulates corticospinal output, intracortical excitability, and spinal motoneuron excitability in a resting hand muscle. C_LIO_LISingle-pulse transcranial magnetic stimulation showed that motor evoked potentials in the hand were facilitated during remote lower-limb contraction across multiple current directions, indicating a broad increase in net corticospinal output. C_LIO_LIPaired-pulse measures were modulated preferentially with anterior-posterior stimulation, with reduced short-interval intracortical inhibition and increased short-interval intracortical facilitation, suggesting current direction-dependent modulation of cortical excitability measures. C_LIO_LIF-wave amplitude and persistence were also enhanced during remote lower-limb contraction, indicating increased spinal motoneuron excitability. These findings provide converging evidence that the remote effect involves both cortical and spinal contributions. C_LI