School of Information Engineering, Guangdong Medical University, Dongguan 523808, Guangdong, People's Republic of China. School of Biomedical Sciences & Gerald Choa Neuroscience Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.
Biomed Phys Eng Express. 2020 Mar 2;6(2):027002. doi: 10.1088/2057-1976/ab756e.
Parkinson's disease (PD) is a neurodegenerative disease for which there is no known cure. Deep brain stimulation (DBS) is a surgical treatment effective in reducing motor symptoms for PD patients. Previous work implicates DBS may directly influence motor cortex through stochastic antidromic spikes originating from the site of stimulation. Here we tested the hypothesis that direct randomized cortical stimulation is therapeutically effective in PD animal models.
As a proof-of-principle study, we utilized a multi-channel stimulating system to mimic the effects of stochastic antidromic activation on the motor cortex of rat, by delivering microcurrents randomized temporally and spatially, and assessed the efficacy in ameliorating motor symptoms in a rat PD model.
We found that different combinations of frequency, amplitude and pulse width of randomized electrical currents delivered to the motor cortex exerted different effects on Parkinsonian rats. Among these, some stimulus patterns, defined by specific ranges of pulse width and stimulation frequencies, were able to produce transient beneficial effect on locomotive ability assessed by open-field locomotor activities. These results indicate that, in principle, cortical stimulation could achieve therapeutic outcome in PD.
Direct cortical simulation based on a randomized protocol could be a less invasive approach than standard DBS in treating Parkinsonism. More refined mode of stimulation to achieve long-lasting and more robust effect should be explored.
帕金森病（PD）是一种神经退行性疾病，目前尚无已知的治愈方法。深部脑刺激（DBS）是一种有效的手术治疗方法，可减轻 PD 患者的运动症状。先前的工作表明，DBS 可能通过源自刺激部位的随机逆行尖峰直接影响运动皮层。在这里，我们测试了直接随机皮质刺激在 PD 动物模型中具有治疗效果的假设。
作为一项原理验证研究，我们利用多通道刺激系统通过时空随机传递微电流来模拟随机逆行激活对大鼠运动皮层的影响，并评估其在改善 PD 大鼠运动症状中的疗效。
我们发现，随机电流的频率、幅度和脉冲宽度的不同组合对帕金森大鼠产生不同的影响。其中，一些刺激模式，通过特定的脉冲宽度和刺激频率范围来定义，能够在通过开放场运动活动评估的运动能力方面产生短暂的有益效果。这些结果表明，原则上，皮质刺激可以在 PD 中达到治疗效果。
基于随机方案的直接皮质模拟可能是一种比标准 DBS 治疗帕金森病的侵袭性更小的方法。应该探索更精细的刺激模式以实现更持久和更强大的效果。
