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

长时程增强(LTP)和长时程抑制(LTD)形式的突触可塑性被认为是学习和记忆的神经生理学联系。这些基本神经生理机制(如LTP和LTD)的损伤被认为在各种疾病(如发育障碍)的发生和表型中起着关键作用。重复性经颅磁刺激(RTMS)是最常用的非侵入性脑刺激方法之一，可用于诱导和研究人类突触的可塑性。它逐渐受到基础神经科学的关注，并被用于治疗各种神经系统疾病，如耐药抑郁症和中风后的康复。在这种情况下，为了减少后遗症的可变性，个体化的刺激可能很重要。这种可变性可能是由所谓的I波的个别振荡触发的。根据它们各自的潜伏期，主要发现了三个峰，称为I1-3波，潜伏期为APP。1.5毫秒。它们似乎有助于并调节人类初级运动皮质(M1)的突触可塑性。I波不仅是与TMS脉冲及时相关的刚性振荡，而且这些下降的抽射的募集模式和潜伏期是个体间潜伏期约1.5ms的差异的基础。在这里，具有单独可调的TMS参数的新技术，如刺激频率、优化的电流和脉冲配置，有可能更好地控制这些影响，并进一步使rTMS在人类中的应用个体化。在初步工作中，我们发现了一种新的、有效的超快速经颅磁刺激方案，即所谓的四脉冲theta Burst刺激(QTBS)，它使研究人员能够瞄准所有三个I波，并在I波周期中以1.5ms的刚性相互刺激间隔诱导突触可塑性。本研究的目的是：(1)通过使用新建立的四脉冲刺激范式(QTBS)研究I波依赖的可塑性，了解早、晚期I波激活对人类M1突触可塑性的作用和相互作用。(2)通过开发一种新的刺激技术，首次推广个体化I波特异型经颅磁刺激覆盖所有三个I波的个体化可调脉冲的研究成果；(3)研究个体化经颅磁刺激对运动学习的影响，最终目的是通过调整刺激模式以适应不同的神经生理条件，在研究和临床实践中提高TMS的治疗效果。这旨在通过开发一种新的、单独可调的磁刺激设备来实现，该设备以所有三个I波的单独潜伏期为目标。

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.