Data_Sheet_2_Effect of Pulse Duration and Direction on Plasticity Induced by 5 Hz Repetitive Transcranial Magnetic Stimulation in Correlation With Neuronal Depolarization.PDF

Introduction: High frequency repetitive transcranial magnetic stimulation applied to the motor cortex causes an increase in the amplitude of motor evoked potentials (MEPs) that persists after stimulation. Here, we focus on the aftereffects generated by high frequency controllable pulse TMS (cTMS) with different directions, intensities, and pulse durations. Objectives: To investigate the influence of pulse duration, direction, and amplitude in correlation to induced depolarization on the excitatory plastic aftereffects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) using bidirectional cTMS pulses. Methods: We stimulated the hand motor cortex with 5 Hz rTMS applying 1,200 bidirectional pulses with the main component durations of 80, 100, and 120 μs using a controllable pulse stimulator TMS (cTMS). Fourteen healthy subjects were investigated in nine sessions with 80% resting motor threshold (RMT) for posterior-anterior (PA) and 80 and 90% RMT anterior-posterior (AP) induced current direction. We used a model approximating neuronal membranes as a linear first order low-pass filter to estimate the strength–duration time constant and to simulate the membrane polarization produced by each waveform. Results: PA and AP 5 Hz rTMS at 80% RMT produced no significant excitation. An exploratory analysis indicated that 90% RMT AP stimulation with 100 and 120 μs pulses but not 80 μs pulses led to significant excitation. We found a positive correlation between the plastic outcome of each session and the simulated peak neural membrane depolarization for time constants >100 μs. This correlation was strongest for neural elements that are depolarized by the main phase of the AP pulse, suggesting the effects were dependent on pulse direction. Conclusions: Among the tested conditions, only 5 Hz rTMS with higher intensity and wider pulses appeared to produce excitatory aftereffects. This correlated with the greater depolarization of neural elements with time constants slower than the directly activated neural elements responsible for producing the motor output (e.g., somatic or dendritic membrane). Significance: Higher intensities and wider pulses seem to be more efficient in inducing excitation. If confirmed, this observation could lead to better results in future clinical studies performed with wider pulses.引言：施加于运动皮层的高频重复经颅磁刺激（repetitive transcranial magnetic stimulation, rTMS）可使运动诱发电位（motor evoked potentials, MEPs）的振幅升高，且该效应在刺激结束后仍可持续存在。本研究聚焦于采用不同方向、强度与脉冲时长的可控脉冲经颅磁刺激（controllable pulse TMS, cTMS）所产生的刺激后效应。 研究目的：采用双向可控脉冲经颅磁刺激（bidirectional cTMS），探究脉冲时长、方向及与诱导去极化相关的振幅，对5 Hz重复经颅磁刺激（rTMS）的兴奋性可塑性刺激后效应的影响。 研究方法：本研究借助可控脉冲经颅磁刺激（cTMS）仪，以5 Hz频率对受试者手部运动皮层施加刺激，共给予1200次双向脉冲，其主成分时长分别为80、100与120 μs。共纳入14名健康受试者，完成9次实验，刺激强度分别为后前位（posterior-anterior, PA）方向的80%静息运动阈值（resting motor threshold, RMT），以及前后位（anterior-posterior, AP）方向的80%与90% RMT。本研究采用将神经元膜近似为线性一阶低通滤波器的模型，以估算强度-时长时间常数，并模拟每种波形所诱导的膜电位去极化水平。 研究结果：以80% RMT强度施加PA与AP方向的5 Hz rTMS，未产生显著的兴奋效应。探索性分析显示，采用90% RMT强度、100 μs与120 μs脉冲的AP方向刺激，可引发显著兴奋效应，而80 μs脉冲则无此效果。我们发现，当时间常数大于100 μs时，各实验的可塑性结局与模拟得到的神经元膜峰值去极化水平呈正相关。该相关性在以AP脉冲主相位去极化的神经元结构中最为显著，提示刺激效应依赖于脉冲方向。 研究结论：在本研究测试的所有条件中，仅采用更高强度与更宽脉冲时长的5 Hz rTMS，可产生兴奋性刺激后效应。该结果与时间常数慢于直接激活运动输出的神经元结构（如胞体或树突膜）的神经元更大程度的去极化水平相关。 研究意义：更高的刺激强度与更宽的脉冲时长似乎更易诱导兴奋效应。若该结论得以验证，可为未来采用更宽脉冲的临床研究带来更佳的实验结果。