Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Neurophysiology, Medical Faculty, Ruhr-University Bochum, Bochum, Germany.
Clin Neurophysiol. 2022 Aug;140:59-97. doi: 10.1016/j.clinph.2022.04.022. Epub 2022 May 18.
Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.
经颅（电）磁刺激（TMS）是目前非侵入性地诱导人脑神经活动的首选方法。单个经颅刺激会在大脑中产生时变电场，可能会在皮质神经元中引发动作电位。局部诱导电场与受刺激神经元之间的空间关系决定了轴突去极化。诱导电场受组织隔室的导电性影响，在目标皮质回的浅层和下方的白质中最强。TMS 可能靶向兴奋性和抑制性神经元的轴突。个别轴突对 TMS 产生动作电位的倾向取决于它们的几何形状、髓鞘化以及与施加的电场的空间关系和神经元的生理状态。后者由其跨突触树突和体细胞输入、内在膜电位和放电率决定。建模工作表明，TMS 的主要目标是皮质回冠顶和唇区的轴突末梢。诱导电场还可能兴奋皮质回下方近皮质白质中髓鞘化轴突的弯曲。神经元兴奋沿刺激轴突进行 ortho- 和 antidromically 传播，并导致目标区域内局部皮质内微循环中连接的神经元群体的二次兴奋。兴奋的轴突和跨突触传播也沿着皮质-皮质和皮质-下皮质连接发生，影响靶向网络中的神经元活动。局部和远程神经兴奋都严重依赖于受刺激目标区域和网络的功能状态。TMS 还会引起外周神经系统的大量直接共刺激。外周共兴奋在听觉和躯体感觉网络中向中枢传播，但也会在其他参与多感觉整合、定向或唤醒的网络中产生大脑反应。对 TMS 反应的复杂性需要对其生理和行为后果进行谨慎解释，并且对 TMS 的机械基础有更深入的了解对于将其作为科学和治疗工具推进至关重要。
