Optimal inter-stimulus interval for paired associative stimulation with mechanical stimulation

In this paper, inter-stimulus interval (ISI) of paired associative stimulation (PAS) with mechanical stimulation was analyzed. PAS is a prominent therapeutic intervention for individuals after stroke and helps to improve limb function by strengthening excitatory synapses and inducing neural plasticity. This intervention involves repeated application of transcranial magnetic stimulation (TMS) followed by peripheral stimulation. When responses to both stimulations are overlapped in the brain at the same time, this successful PAS is expected to induce long term potentiation (LTP) which leads to a neural plasticity phenomenon. Therefore ISI between these two stimulations is very crucial in this treatment. Instead of electrical stimulation in general PAS, mechanical stimulation was used in this study due to some promising aspects of mechanical stimulation. Long latency stretch response (LLSR) was observed in electromyography (EMG) during the PAS with mechanical stimulation, since LLSR reflects successful overlapping of two stimulations. Each subject had specific range of ISIs, or a time window, that leads to successful overlapping of paired stimulations. These time window lengths varied between 5ms and 105 ms, and within this range it can be guaranteed to obtain LLSR in EMG at least 40% among the all PAS trials. In addition, normally distributed responses within time window suggests that the optimal ISI which results in the highest number of LLSRs is the average of the time window. This result suggests that PAS with mechanical stimulation could lead to a rehabilitation effect by regaining motor functionality when the two stimulations are paired with the optimal ISI and it could provide a significant advancement in neuromodulation.