Parkinson's disease (PD) is a common degenerative neurological disorder, characterized by static tremor, bradykinesia, myotonia and postural abnormalities. Dopaminergic drugs are the main drugs in the treatment of PD, but long-term use will lead to drug efficacy loss, and even cause some adverse reactions such as dyskinesia and "on-off" phenomenon. Neuromodulation is a kind of biomedical engineering technology that can stimulate or inhibit the activity of brain neurons and regulate the changes of neuroplasticity by means of electric energy, magnetic field, ultrasound and other methods, so as to achieve treatment and improvement of diseases. In the non-drug treatment of PD, neuromodulation, as a new therapeutic means, has shown good efficacy, and has the advantages of small adverse reactions and easy tolerance. Based on this, this article reviews the research progress of several common neuromodulation in PD, including deep brain stimulation, transcranial magnetic stimulation, transcranial direct current stimulation and transcranial focused ultrasound.
Keywords：neuromodulation
;
Parkinson's disease (PD)
;
deep brain stimulation (DBS)
;
transcranial magnetic stimulation (TMS)
;
transcranial direct current stimulation (tDCS)
;
transcranial focused ultrasound (tFUS)
HU Canfang, ZHONG Chuanyu, CAO Li. Research progress of neuromodulation in the treatment of Parkinson's disease. Journal of Shanghai Jiao Tong University (Medical Science)[J], 2024, 44(2): 258-263 doi:10.3969/j.issn.1674-8115.2024.02.012
神经调控技术是一类通过电能、磁场、超声等物理方式来兴奋或抑制大脑神经元活动、调节神经可塑性变化，从而达到治疗、改善疾病的生物医学工程技术［4］；该技术已广泛应用于PD、癫痫、肌张力障碍、震颤、抑郁等神经精神疾病。目前，神经调控技术被分为侵入性和非侵入性两大类，前者以脑深部电刺激（deep brain stimulation，DBS）为典型代表，后者包括经颅磁刺激（transcranial magnetic stimulation，TMS）、经颅直流电刺激（transcranial direct current stimulation，tDCS）和经颅聚焦超声（transcranial focused ultrasound，tFUS）等；且不同的调控技术所作用的脑功能区域和核团有所区别，即DBS和tFUS主要作用于脑深部核团，而TMS和tDCS主要作用于大脑皮层。本文针对DBS、TMS、tDCS和tFUS这4种神经调控技术在PD治疗中的应用研究进展进行介绍。
TMS由BARKER等［24］于1985年创立，是一种基于法拉第电磁感应科学原理，利用电流通过线圈在颅内聚焦产生感应磁场，引发神经元动作电位，从而影响大脑皮层兴奋性的神经调控技术［25］。根据刺激模式的不同，TMS可分为单脉冲刺激、双脉冲刺激和重复经颅磁刺激（repetitive transcranial magnetic stimulation，rTMS）。其中，rTMS的临床应用最广泛，起初主要用于神经精神疾病，如抑郁症、脑卒中。1994年，PASCUAL-LEONE等［26］首次将rTMS应用于PD治疗，结果显示，与正常对照组相比，rTMS治疗可显著改善PD患者的运动症状；且其作用机制被认为可能是，rTMS通过刺激大脑皮层来促进神经营养因子的生成、增加单胺类神经递质的释放，从而调节直接通路和间接通路的兴奋性［27］。近年来，国内外已开展了多项采用rTMS治疗PD患者运动及非运动症状的临床研究［28-30］，且该刺激已成为治疗PD的一种重要的非药物手段。
2021年，王丽娟等［31］发布了《中国帕金森病重复经颅磁刺激治疗指南》，对PD不同症状的治疗靶点及刺激频率的选择进行了明确规定。该指南推荐：①高频rTMS刺激初级运动皮层（primary motor cortex，M1）区可改善PD患者的运动迟缓症状，但对其震颤症状的改善不明显；刺激M1区和辅助运动区（supple-mentary motor area，SMA）对PD冻结步态短期可能有效；刺激左侧背外侧前额叶（dorsolateral prefrontal cortex，DLPFC）或双侧M1区可改善PD患者的抑郁症状，而刺激双侧DLPFC可改善患者的焦虑症状。②低频rTMS刺激SMA可改善PD患者的姿势步态障碍，与是否使用抗PD药物无关。此外该指南还提及，目前针对高频rTMS治疗PD患者认知障碍的相关研究结果并不一致，如高频（25 Hz）rTMS刺激右侧DLPFC可能改善PD患者的执行功能［32］、刺激额下回可能有助于改善其额叶认知功能［33］；高频（5 Hz）rTMS刺激右顶叶皮层可能有助于提高其学习能力［34］；高频rTMS还可改善PD患者的睡眠质量［35］。
HU Canfang was responsible for literature search and thesis writing. ZHONG Chuanyu participated in article revision. CAO Li was responsible for guiding article writing and participated in paper revision. All the authors have read the last version of paper and consented for submission.
利益冲突声明
所有作者声明不存在利益冲突。
COMPETING INTERESTS
All authors disclose no relevant conflict of interests.
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... 神经调控技术是一类通过电能、磁场、超声等物理方式来兴奋或抑制大脑神经元活动、调节神经可塑性变化，从而达到治疗、改善疾病的生物医学工程技术［4］；该技术已广泛应用于PD、癫痫、肌张力障碍、震颤、抑郁等神经精神疾病.目前，神经调控技术被分为侵入性和非侵入性两大类，前者以脑深部电刺激（deep brain stimulation，DBS）为典型代表，后者包括经颅磁刺激（transcranial magnetic stimulation，TMS）、经颅直流电刺激（transcranial direct current stimulation，tDCS）和经颅聚焦超声（transcranial focused ultrasound，tFUS）等；且不同的调控技术所作用的脑功能区域和核团有所区别，即DBS和tFUS主要作用于脑深部核团，而TMS和tDCS主要作用于大脑皮层.本文针对DBS、TMS、tDCS和tFUS这4种神经调控技术在PD治疗中的应用研究进展进行介绍. ...
