FV 588. Probing Homeostatic and Metaplastic Mechanisms of Synaptic Plasticity in Human Primary Motor Cortex Using High-Frequent Quadri-pulse Theta Burst Stimulation

Background: Synaptic plasticity in forms of long-term potentiation (LTP) and long-term depression (LTD) are considered to be the neurophysiological correlate of learning and memory. Impairments of these mechanisms are discussed as a key mechanism in the pathophysiology of neurodevelopmental disorders. Metaplasticity and homeostatic plasticity are higher forms of synaptic plasticity leading to a balance of inhibitory and facilitatory neuronal influences. Quadri-pulse theta burst stimulation (qTBS) is a newly introduced, high-frequent transcranial magnetic stimulation protocol inducing a long-lasting increase or decrease in synaptic plasticity—referring to the model of LTP and LTD—in human primary motor cortex (M1) that enables the evaluation of metaplastic and homeostatic mechanisms.

Aim: The aim of the study was to investigate metaplastic and homeostatic mechanisms in human M1 using an inhibitory priming qTBS protocol.

Question: To probe homeostatic and metaplastic mechanisms as an important mechanism of successful learning with therapeutic relevance in human M1 using high-frequent qTBS.

Methods: We investigated the priming effects of an inhibitory qTBS protocol with an interstimulus interval (ISI) of 50 milliseconds on a following facilitating qTBS protocol (ISI 5 milliseconds; experiment 1) and a following inhibitory qTBS protocol (ISI 50 milliseconds, experiment 2) in n = 9 healthy volunteers. qTBS consisted of 360 bursts with one burst containing four pulses (pulse duration 160 μs) given continuously over M1 of the contralateral hand (i.e., 1,440 pulses in total) with an ISI of 5 or 50 milliseconds and an interburst interval of 200 milliseconds (qTBS50/200 or qTBS5/200). 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 (post 1), after 15 minutes (post 2), and after 30 minutes (post 3). Following post 3 measurements of the priming protocol, the second stimulation (qTBS5/200 or qTBS50/200) was applied, and the RMT and MEP were measured for 60 minutes (post 4–post 7).

Results: In experiment 1 (qTBS50/200–qTBS5/200), priming with qTBS50/200 led to a decrease of MEP amplitudes (post 1–3), while MEP amplitudes increased following subsequent qTBS5/200 (post 4–7). Mean changes of post 4 to 7 increased significantly as compared with mean changes of post 1 to 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 to 7 increased significantly as compared with mean changes of post 1 to 3.

Conclusion: Our results point toward homeostatic and metaplastic mechanisms of a priming inhibitory qTBS protocol and subsequent inhibitory or facilitatory qTBS. These results indicate that the effects of qTBS, depending on the ISI, reflect LTP- and LTD-like changes in corticospinal excitability in human M1 and that homeostatic and metaplastic mechanisms can be probed. This, in turn, may influence the therapeutic application of noninvasive brain stimulation in the human brain. The very short duration of the protocol of ∼2 minutes may be of particular interest when using this form of stimulation in children.

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