Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, London, United Kingdom.
PLoS Comput Biol. 2022 Mar 4;18(3):e1009887. doi: 10.1371/journal.pcbi.1009887. eCollection 2022 Mar.
Synchronization of neural oscillations is thought to facilitate communication in the brain. Neurodegenerative pathologies such as Parkinson's disease (PD) can result in synaptic reorganization of the motor circuit, leading to altered neuronal dynamics and impaired neural communication. Treatments for PD aim to restore network function via pharmacological means such as dopamine replacement, or by suppressing pathological oscillations with deep brain stimulation. We tested the hypothesis that brain stimulation can operate beyond a simple "reversible lesion" effect to augment network communication. Specifically, we examined the modulation of beta band (14-30 Hz) activity, a known biomarker of motor deficits and potential control signal for stimulation in Parkinson's. To do this we setup a neural mass model of population activity within the cortico-basal ganglia-thalamic (CBGT) circuit with parameters that were constrained to yield spectral features comparable to those in experimental Parkinsonism. We modulated the connectivity of two major pathways known to be disrupted in PD and constructed statistical summaries of the spectra and functional connectivity of the resulting spontaneous activity. These were then used to assess the network-wide outcomes of closed-loop stimulation delivered to motor cortex and phase locked to subthalamic beta activity. Our results demonstrate that the spatial pattern of beta synchrony is dependent upon the strength of inputs to the STN. Precisely timed stimulation has the capacity to recover network states, with stimulation phase inducing activity with distinct spectral and spatial properties. These results provide a theoretical basis for the design of the next-generation brain stimulators that aim to restore neural communication in disease.
神经振荡的同步被认为有助于大脑中的信息交流。神经退行性疾病，如帕金森病（PD），可能导致运动回路的突触重组，导致神经元动力学的改变和神经通讯的受损。PD 的治疗方法旨在通过药理学手段（如多巴胺替代）或通过深部脑刺激抑制病理性振荡来恢复网络功能。我们测试了这样一个假设，即大脑刺激可以超越简单的“可逆性损伤”效应来增强网络通讯。具体来说，我们检查了 beta 波段（14-30 Hz）活动的调制，beta 波段活动是运动缺陷的已知生物标志物，也是 PD 刺激的潜在控制信号。为此，我们建立了一个皮质基底节丘脑（CBGT）回路中的群体活动的神经质量模型，其参数被约束为产生与实验性帕金森病中相似的光谱特征。我们调制了已知在 PD 中被破坏的两个主要途径的连接，并对自发活动的光谱和功能连接进行了统计总结。然后，我们使用这些来评估闭环刺激对运动皮层的影响，以及与丘脑底核（STN）beta 活动同步的刺激。我们的结果表明，beta 同步的空间模式取决于 STN 的输入强度。精确定时的刺激有恢复网络状态的能力，刺激相位诱导具有独特光谱和空间特性的活动。这些结果为新一代旨在恢复疾病中神经通讯的脑刺激器的设计提供了理论基础。
