Non-Invasive Brain Stimulation Combined with Exercise: Synergistic Neuroplasticity in Parkinson’s disease: A comprehensive Review

Motor and non-motor deficits resulting from dopaminergic neuron loss are hallmarks of Parkinson's disease (PD), a progressive neurodegenerative illness. Non-pharmacological therapies that encourage neuroplasticity are becoming more popular since, despite their ability to alleviate symptoms, pharmaceutical treatments are unable to stop the progression of the disease. Among these, non-invasive brain stimulation (NIBS) and exercise have shown promise. Exercise, especially aerobic, resistance, and task-specific training, improves motor and cognitive abilities by increasing cerebral perfusion, synaptic plasticity, and brain-derived neurotrophic factor (BDNF) levels. Similarly, long-term potentiation (LTP)-related mechanisms can be facilitated and cortical excitability modulated by NIBS techniques such as recurrent transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). Although their effects are minimal when taken separately, new research indicates that NIBS and exercise may work in concert to improve neuroplastic responses during recovery. The data currently available on the neurobiological processes and therapeutic effects of combined NIBS-exercise therapies in Parkinson's disease is summarized in this review. Along with results from clinical trials showing improved gait, balance, motor performance, and executive function, it talks about their common routes, which include increased BDNF signaling, cortico-striatal connection, and dopaminergic modulation. The necessity of individualized treatment approaches is emphasized by addressing methodological limitations, such as protocol variability and patient responsiveness. Overall, by utilizing synergistic plasticity mechanisms, NIBS and exercise together offer a viable non-invasive method to enhance neurorehabilitation in Parkinson's disease. To comprehend long-term consequences and enhance methods, more research is required.

因多巴胺能神经元丢失引发的运动与非运动功能缺损，是帕金森病（Parkinson's Disease, PD）——一种进行性神经退行性疾病——的标志性特征。尽管药物治疗可缓解症状，但无法阻断疾病进展，因此旨在促进神经可塑性的非药物疗法正日益受到重视。其中，无创脑刺激（non-invasive brain stimulation, NIBS）与运动干预展现出可观的应用潜力。运动干预，尤其是有氧运动、抗阻训练及任务特异性训练，可通过提升脑灌注、增强突触可塑性以及提高脑源性神经营养因子（brain-derived neurotrophic factor, BDNF）水平，改善运动与认知能力。类似地，重复经颅磁刺激（repetitive transcranial magnetic stimulation, rTMS）、经颅直流电刺激（transcranial direct current stimulation, tDCS）等无创脑刺激技术，可调控皮层兴奋性并促进长时程增强（long-term potentiation, LTP）相关机制的激活。尽管单独使用时效果有限，但最新研究显示，无创脑刺激与运动干预可协同发挥作用，增强康复过程中的神经可塑性反应。本综述总结了当前关于帕金森病患者接受无创脑刺激联合运动疗法的神经生物学机制与治疗效果的现有研究数据。除了阐述二者的共同作用通路——包括增强脑源性神经营养因子信号传导、改善皮层-纹状体连接以及调节多巴胺能功能——之外，本文还介绍了相关临床试验中该联合疗法在改善步态、平衡能力、运动功能与执行功能方面的研究结果。针对干预方案异质性、患者响应性差异等方法学局限展开的讨论，也凸显了个体化治疗方案的必要性。总体而言，通过利用协同性可塑性机制，无创脑刺激联合运动干预为帕金森病患者的神经康复提供了一种可行的非侵入性手段。未来仍需开展更多研究以明确其长期疗效并优化干预方案。