Induction of Synaptic Plasticity in the Human Brain by individualized biphasic repetitive I-wave Transcranial Magnetic Stimulation

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Synaptic plasticity in forms of long-term potentiation (LTP) and long term depression (LTD) is considered to be the neurophysiological correlate of learning and memory. Impairments of these basal neurophysiological mechanisms (i.e. LTP and LTD) are thought to play a pivotal role in the development and phenotype of various medical conditions (e.g. developmental disorder). Repetitive transcranial magnetic stimulation (rTMS) – e.g. theta-burst stimulation (TBS) or quadri-pulse stimulation – is one of the most popular methods for non-invasive brain stimulation that can be used to induce and to investigate synaptic plasticity in humans. It becomes gradually more noticed in basic neuroscience as well as in the treatment of various neurological diseases such as drug resistant depression and rehabilitation after stroke. To reduce variability of after effects in this context, an individualized stimulation may be important. This variability may be triggered by individual oscillations so called I-waves. According to their individual latency, mainly three peaks have been discovered, termed I1-3 waves with a latency of app. 1.5 ms. They seem to contribute to and to modulate synaptic plasticity in human primary motor cortex (M1). I-waves are not only rigid oscillations with timely relation to TMS pulses but the recruitment pattern and latency of these descending volleys underlies inter-individual variability in latencies of around 1.5 ms. Here, new techniques with individual adjustable TMS parameters such as stimulation frequency, optimized current flow and pulse configuration have the potential to better control these effects and to further individualize rTMS application in humans. In a preliminary work, we discovered a new and effective ultra-fast transcranial magnetic stimulation protocol, so called quadri pulse theta burst stimulation (qTBS) that enables the investigator to target all three I-waves and that demonstrated to induce synaptic plasticity at I-wave periodicity with rigid interstimulus intervals of 1.5 ms. The aim of the proposal is to (1) Understand the role and interaction of early and late I-wave activation on synaptic plasticity in human M1 by means of investigation on I-wave dependent metaplasticity using a newly established quadri-pulse stimulation paradigm (qTBS), (2) To extend findings on individualized I-wave specific transcranial magnetic stimulation covering – for the first time – all three I-waves with individual adjustable pulses by developing a new stimulation technique with a new device and to (3) Investigate the influence of individualized TMS on motor learning with the ultimate aim of enhancing therapeutical effects of TMS in research and clinical practice by adapting the stimulation pattern to individual neurophysiological conditions. This is intended to be realized by the development of a new, and individual adjustable magnetic stimulation device that target all three I-waves at their individual latencies.