P55. Probing homeostatic and metaplastic mechanisms of quadri-pulse theta burst stimulation using an inhibitory priming protocol

Question Changes in synaptic and neuronal efficacy such as long-term potentiation (LTP) and long-term depression (LTD) are thought to reflect synaptic processes underlying learning and memory. Homeostatic plasticity is considered to stabilize neural activity within a physiologically reasonable and dynamic range. Quadri-pulse-thetaburst stimulation (qTBS) is a recently introduced patterned transcranial magnetic stimulation (TMS) protocol that induced lasting increase or decrease in neuronal excitability of human primary motor cortex (M1) probably corresponding to the model of LTP- and LTD-like plasticity. Here, we aimed to probe homeostatic and metaplastic interactions of an inhibitory priming qTBS protocol on subsequent facilitating and inhibitory qTBS. Methods We investigated the priming mechanisms of inhibitory qTBS on subsequent facilitating qTBS (experiment 1) in 8 healthy volunteers and on subsequent inhibitory qTBS (experiment 2) in 9 healthy volunteers. Inhibitory qTBS consisted of 360 bursts given continuously to M1 (i.e. 1440 full-sine pulses) with bursts of four biphasic TMS pulses (duration 160 μ s) separated by inter-stimulus intervals (ISI) of 50 ms (20 Hz) and inter-burst intervals of 200 ms (5 Hz) (qTBS50/200). Facilitatory qTBS consisted of the same burst pattern but with ISI of 5 ms (200 Hz) (qTBS5/200). TMS was applied by a custom-made magnet stimulator (MSB, Munich). Resting motor threshold (RMT) and motor evoked potential (MEP) amplitudes with stimulus intensities to target amplitudes of 1 mV were measured before priming qTBS50/200 (pre), directly after priming qTBS50/200 (post1), after 15 min (post2) and after 30 min (post3). Following post 3 measurements, the second stimulation (qTBS5/200 or qTBS50/200) was applied and the RMT and MEP were measured for 60 min (post4–post7). Results In experiment 1 (qTBS50/200–qTBS5/200), priming with qTBS50/200 led to a decrease of MEP amplitudes (post1–3), while MEP amplitudes increased following subsequent qTBS5/200 (post 4–7). Mean changes of post 4–7 increased significantly as compared to mean changes of post 1–3. In experiment 2 (qTBS50/200–qTBS50/200), MEP amplitudes decreased following the priming protocol (post 1–3) and returned to baseline with a slight increase on post 6 after the subsequent qTBS50/200 protocol. Mean changes of post 4–7 increased significantly as compared to mean changes of post 1–3. Conclusion Our preliminary results may point towards homeostatic mechanisms of facilitatory qTBS5/200 following priming with qTBS50/200. In contrast, subsequent qTBS50/200 led to a de-depression like effect of MEP amplitudes suggesting metaplastic effects of two inhibitory qTBS protocols applied over M1. Our findings may support the assumption that changes in cortico-spinal excitability following qTBS represent LTP- and LTD-like changes in synaptic transmission and corroborate metaplastic de-depression effects of high-frequency patterned rTMS protocols in human M1.