Induction of cortical plasticity by biphasic quadro-pulse stimulation

Aims: Long-term potentiation (LTP) and long-term depression (LTD) are forms of cortical plasticity and are considered to be synaptic processes underlying learning and memory. Impairments in developmental disorders (e.g., autism spectrum disorders) have been demonstrated previously. Transcranial magnetic stimulation (TMS) with monophasic quadro-pulse stimulation (QPS) demonstrated to be effective to induce LTD- and LTP-like plasticity in human motor cortex (M1). Here, we aimed to study whether biphasic QPS at different interstimulus and interburst intervals induces plastic changes in human M1.

Methods: We investigated healthy volunteers (n = 10 per protocol) with QPS consisting of repeated bursts of four biphasic TMS pulses (duration: 160µs) separated by interstimulus intervals of 1.5 and 50 milliseconds and interburst intervals of 200 milliseconds, 1 second, and 5 seconds resulting in six different protocols (QPS1.5 – 200, QPS1.5 – 1, QPS1.5 – 5, QPS50 – 200, QPS50 – 1, and QPS50 – 5; 1,440 total stimulus counts per protocol). TMS was applied by a custom-made magnetic stimulator (IMETUM, Munich, Germany). Resting motor threshold (rMT) and motor evoked potential (MEP) amplitudes with stimulus intensities to target amplitudes of 1 and 0.4 mV (SI1mV and SI0.4mV) were measured before (Pre), QPS directly after (Post1), after 15 minutes (Post2), after 30 minutes (Post3), and after 60 minutes (Post4).

Results: We found a significant increase of MEPs after QPS1.5 – 5 at SI0.4mV and a significant decrease after QPS50 – 200, QPS50 – 5, and QPS1.5 – 200 at SI1mV. QPS1.5 – 1 and QPS50 – 1 had no significant effect on MEPs, respectively. Significant changes in rMT, referring to a model of intrinsic plasticity, were observed for QPS50 – 200 but not for QPS50 – 5.

Conclusion: Biphasic QPS demonstrated to induce intensity- and frequency-dependent LTP- or LTD-like effects displayed by an increase or decrease in MEP amplitudes. This form of stimulation might offer new opportunities in investigations of cortical plasticity in humans with and without developmental disorders as well as new therapeutical approaches.