Inducing Homeostatic-Like Plasticity in Human Motor Cortex Through Converging Corticocortical Inputs

Abstract

Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1_HAND) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression (LTD)–like or long-term potentiation (LTP)–like plasticity in left M1_HAND through different afferents. We hypothesized that the left M1_HAND would integrate LTP- and LTD-like plasticity in a homeostatic fashion. In ten healthy volunteers, low-intensity repetitive transcranial magnetic stimulation (rTMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1_HAND via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve and left M1_HAND to induce spike-time–dependent plasticity in sensory-to-motor inputs to left M1_HAND. We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PAS_N20+2ms) or an LTD-like decrease (PAS_N20−5ms) in corticospinal excitability. The amplitude of motor-evoked potentials was recorded from intrinsic hand muscles to assess stimulation-induced changes in corticospinal excitability. Premotor-to-motor preconditioning triggered a homeostatic response to subsequent sensory-to-motor PAS. After facilitatory 5 Hz rTMS, “facilitatory” PAS_N20+2ms suppressed corticospinal excitability. Likewise, “inhibitory” PAS_N20−5ms facilitated corticospinal excitability after “inhibitory” 1 Hz rTMS. There was a negative linear relationship between the excitability changes induced by PMD rTMS and those elicited by subsequent PAS. Excitability changes were not paralleled by changes in performance during a finger-tapping task. These results provide evidence for a homeostatic response pattern in the human M1_HAND that integrates acute plastic changes evoked through different “input channels.”