Studies on mechanisms underlying lasting effects of repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS)

我们将rTMS应用于三个临床试验。对于帕金森病，rTMS对临床体征和症状的影响并不比真实的假刺激更有益（参考文献2）。这项研究证明了假刺激的方法对我们得到的结论是至关重要的。与假刺激相比，1 Hz rTMS在原发性运动皮层上显著减少了压力性失禁或急迫性失禁患者的失禁发作和排尿频率（参考文献1）。它应该有临床用途。与假刺激相比，运动皮层上的1 Hz rTMS明显减少了对侧前臂皮下注射红帽皂苷引起的疼痛（参考文献7）。这可能适用于顽固性疼痛的治疗。rTMS期间的PET研究表明，对与直接刺激区域相连的远端区域的影响也可以解释rTMS引起的一些效应，以及对线圈下方区域的直接影响（文献3）。除了对人类的研究，我们还对猴子进行了一些实验。我们制作了一种特殊的猴子刺激线圈（参考文献6），它能够在猴子大脑中唤起比其他动物实验中使用的线圈更多的局部涡流。在猴子中，经过运动皮层的高频rTMS诱导腹侧纹状体释放内源性多巴胺（参考文献8）。这种释放可以部分解释临床有益效果。脑深部电刺激（DBS）治疗帕金森病患者，我们比较了DBS开启和关闭状态下的EDO-PET结果。这些研究表明，在受刺激的运动皮层同侧的运动前区和前扣带区，在ON状态下的葡萄糖代谢高于OFF状态。这可能在一定程度上解释了DBS对运动的作用机制

rTMSWe applied rTMS to three clinical trials. For Parikison disease, rTMS had no more beneficial effects on clinical signs and symptoms than realistic sham stimulation (ref 2). This study proved that the method of sham stimulation is very critical to what conclusion we get. 1 Hz rTMS over the primary motor cortex significantly more decreased incontinence episodes and urination frequency as compared with sham stimulation in patients with stress incontinence or urge incontinence (ref 1). It should have clinical usefulness. I Hz rTMS over the motor cortex significantly more reduced pain elicited by a subcutaneous cap saicin injection to the contralateral forearm area than sham stimulation (ref 7). This may be applicable to intractable pain treatment. PET studies during rTMS suggested that effects on distant area connecting with the directly stimulated area may also explain some effects evoked by rTMS as well as the direct effects on the area just under the coil (ref 3).In addition to studies on humans, we performed a few experiments on monkeys. We made a special coil for monkey stimulation (ref 6), which is able to evoke more localized eddy currents in monkey brain than other coils used in animal experiments. In monkeys, high frequency rTMS over the motor cortex induced endogenous dopamine release at the ventral striatum (ref 8). This release may partly explain clinical beneficial effects.DBSIn patients with Parkinson disease treated with deep brain stimulation (DBS), we compared EDO-PET results between DBS on and off states. These studies revealed that glucose metabolism was higher at premotor and anterior cingulated areas ipsilateral to the stimulated motor cortex in ON condition than OFF condition. This may partly explain the mechanism for DBS on movement