Inducing homeostatic-like plasticity in human motor cortex through converging

24 Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand 25 area of the human primary motor cortex (M1HAND) that controls stimulation induced changes in 26 corticospinal excitability. Here we combined two interventional protocols which induce long27 term depression (LTD)-like or long-term potentiation (LTP)-like plasticity in left M1HAND 28 through different afferents. We hypothesized that the left M1HAND would integrate LTPand 29 LTD-like plasticity in a homeostatic fashion. In ten healthy volunteers, low-intensity repetitive 30 transcranial magnetic stimulation (rTMS) of left dorsal premotor cortex (PMD) was first applied 31 to produce an LTP-like increase (5Hz rTMS) or LTD-like decrease (1Hz rTMS) in corticospinal 32 excitability in left M1HAND via premotor-to-motor inputs. Following PMD rTMS, paired33 associative stimulation (PAS) was applied to the right median nerve and left M1HAND to induce 34 spike-time dependent plasticity (STDP) in sensory-to-motor inputs to left M1HAND. We adjusted 35 the interstimulus interval to the N20-latency of the median nerve somatosensory-evoked cortical 36 potential to produce an LTP-like increase (PASN20+2ms) or an LTD-like decrease (PASN20-5ms) in 37 corticospinal excitability. The amplitude of motor-evoked potentials (MEPs) was recorded from 38 intrinsic hand muscles to assess stimulation-induced changes in corticospinal excitability. 39 Premotor-to-motor preconditioning triggered a homeostatic response to subsequent sensory-to40 motor PAS. After facilitatory 5Hz rTMS, “facilitatory” PASN20+2ms suppressed corticospinal 41 excitability. Likewise, “inhibitory” PASN20-5ms facilitated corticospinal excitability after 42 “inhibitory” 1Hz rTMS. There was a negative linear relationship between the excitability changes 43 induced by PMD rTMS and those elicited by subsequent PAS. Excitability changes were not 44 paralleled by changes in performance during a finger tapping task. These results provide evidence 45 for a homeostatic response pattern in the human M1HAND that integrates acute plastic changes 46 evoked through different “input channels”. 47 Homeostatic plasticity in motor cortex 3