A Temporally Asymmetric Hebbian Rule Governing Plasticity in the Human Motor Cortex

TLDR

Synaptic plasticity depends on the temporal order of pre‑ and postsynaptic activity, and paired associative stimulation can increase human motor cortical excitability. The study paired median‑nerve stimulation with TMS over the abductor pollicis brevis representation, measured corticomotor excitability before and after, and used F‑wave and brain‑stem stimulation to localize plastic changes to the motor cortex. Decreasing the interstimulus interval to 10 ms during PAS produced a 90‑minute depression of motor‑evoked potentials that was blocked by NMDA or L‑type calcium‑channel antagonists, indicating that strict temporal Hebbian rules drive long‑term depression‑like plasticity in human motor cortex.

Abstract

Synaptic plasticity is conspicuously dependent on the temporal order of the pre- and postsynaptic activity. Human motor cortical excitability can be increased by a paired associative stimulation (PAS) protocol. Here we show that it can also be decreased by minimally changing the interval between the two associative stimuli. Corticomotor excitability of the abductor pollicis brevis (APB) representation was tested before and after repetitively pairing of single right median nerve simulation with single pulse transcranial magnetic stimulation (TMS) delivered over the optimal site for activation of the contralateral APB. Following PAS, depression of TMS-evoked motor-evoked potentials (MEPs) was induced only when the median nerve stimulation preceded the TMS pulse by 10 ms, while enhancement of cortical excitability was induced using an interstimulus interval of 25 ms, suggesting an important role of the sequence of cortical events triggered by the two stimulation modalities. Experiments using F-wave studies and electrical brain stem stimulation indicated that the site of the plastic changes underlying the decrease of MEP amplitudes following PAS (10 ms) was within the motor cortex. MEP amplitudes remained depressed for approximately 90 min. The decrease of MEP amplitudes was blocked when PAS(10 ms) was performed under the influence of dextromethorphan, an N-methyl-d-aspartate-receptor antagonist, or nimodipine, an L-type voltage-gated calcium-channel antagonist. The physiological profile of the depression of human motor cortical excitability following PAS(10 ms) suggests long-term depression of synaptic efficacy to be involved. Together with earlier findings, this study suggests that strict temporal Hebbian rules govern the induction of long-term potentiation/long-term depression-like phenomena in vivo in the human primary motor cortex.