Contralateral Negative Bold Responses in the Motor Network during Subthreshold High-Frequency Interleaved Tms-Fmri over the Human Primary Motor Cortex

Objective: Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that stimulates a localized brain region underneath a coil. Recently, the application of repetitive Transcranial Magnetic Stimulation (rTMS) to the primary motor cortex (M1) has been used to promote functional recovery in stroke patients with hemiparesis. High-frequency rTMS (5 Hz or greater) was applied over the affected hemisphere to reactivate hypoactive regions. Because of recent advances in MRI technology and, in particular, the gradient coils, high-frequency whole brain rTMS-fMRI is possible. The use of interleaved rTMS-fMRI during stimulation at a frequency of 5 Hz aids in understanding how the brain is modulated during stimulation. Method: We measured BOLD signal changes in whole brain during interleaved rTMS-fMRI (5Hz) using 3T MRI. Image processing and statistical analyses were carried out using the Statistical Parametric Mapping (SPM8) software. Results: Distinct BOLD signal changes extending to the remote motor network during 5 Hz-rTMS over the M1 were successfully demonstrated using interleaved rTMS-fMRI. Negative BOLD responses were observed in the contralateral M1, the dorsal premotor cortex (PMd), and the bilateral supplementary motor cortex (SMA), even though no significant BOLD signal changes were observed in the stimulated M1. The negative BOLD responses gradually became marked during (3 mins 57 sec). Therefore, long-lasting plastic changes may occur within 4 mins. Negative BOLD responses in remote regions away from the directly stimulated M1 suggest that subthreshold high frequency rTMS over the motor cortex induced neuromodulation via neuronal networks. Conclusion: The remarkable negative BOLD responses in the contralateral M1 induced by high-frequency rTMS may be useful for identifying a treatment strategy involving M1 stimulation.

目的：经颅磁刺激（TMS）是一种非侵入性技术，可刺激线圈下方的局部脑区。最近，重复经颅磁刺激（rTMS）应用于初级运动皮层（M1）已被用于促进偏瘫脑卒中患者的功能恢复。高频rTMS（5Hz或更高频率）应用于患侧半球以重新激活活动减弱的区域。由于磁共振成像（MRI）技术的最新进展，特别是梯度线圈的发展，高频全脑rTMS - 功能性磁共振成像（fMRI）成为可能。在5Hz频率刺激期间使用交错式rTMS - fMRI有助于了解刺激过程中大脑是如何被调节的。 方法：我们使用3T MRI测量交错式rTMS - fMRI（5Hz）过程中全脑的血氧水平依赖（BOLD）信号变化。使用统计参数映射（SPM8）软件进行图像处理和统计分析。 结果：通过交错式rTMS - fMRI成功展示了在M1上方进行5Hz - rTMS时延伸至远程运动网络的明显BOLD信号变化。在对侧M1、背侧前运动皮层（PMd）和双侧辅助运动皮层（SMA）观察到负性BOLD反应，尽管在受刺激的M1中未观察到显著的BOLD信号变化。在（3分57秒）期间负性BOLD反应逐渐变得明显。因此，在4分钟内可能会发生持久的可塑性变化。远离直接受刺激的M1的远程区域的负性BOLD反应表明，运动皮层上的阈下高频rTMS通过神经网络诱导了神经调节。 结论：高频rTMS在对侧M1中引起的显著负性BOLD反应可能有助于确定涉及M1刺激的治疗策略。