A new temporal window for inducing depressant associative plasticity in human primary motor cortex

Objective: Spike-timing dependent plasticity (STDP) usually refers to synaptic plasticity induced by nearsynchronous activation of neuronal input and neuronal firing. However, some models of STDP predict effects that deviate from this tight temporal synchrony. We aimed to characterise the induction of STDP using paired associative stimulation (PAS) when the pre-synaptic input arrives in primary motor cortex (M1) at (i) intermediate intervals (50-80 ms; PAS(50),..PAS(80)) before the post-synaptic neuron is activated and (ii) long intervals (100-450 ms; PAS(-100),..PAS(-450)) after the post-synaptic neuron is activated. PAS at near-synchronicity (PAS(25)) was applied for comparison. Methods: To characterise the physiological effects of the different PAS protocols, we examined short- and long-interval intra-cortical inhibition; intra-cortical facilitation and short- and long-latency afferent inhibition, in addition to recording MEPs in 45 healthy individuals. Results: MEP amplitude was reduced at PAS intervals between -250 and -450 ms, increased with PAS(25), and unaltered at the remaining intervals. There was no change in intra-cortical inhibitory or facilitatory circuits following any PAS protocol. Conclusions: These findings provide evidence of a previously unreported temporal window in which PAS induces a depression of corticospinal excitability in human M1. Significance: Establishing new temporal rules for STDP broadens its applicability for therapeutic usage in future