帕金森病中一致的活力网络：脑刺激效应的潜在靶点。

文献信息

中文摘要

引言： 在具有重复试验的运动任务中，帕金森病（PD）患者的运动活力在试验间存在显著差异。一个关键问题是，神经变异性反映的是行为变异性，还是在神经信号转化为运动时出现了额外的变异性。我们旨在识别一个与活力相关的神经网络，为脑刺激提供候选靶点。
方法： 我们分析了18名PD患者的单试次fMRI数据，这些患者在OFF和ON用药状态下执行过度学习的爆发性握力任务，同时接受不同刺激波形的阈下前庭电刺激（GVS）。单试次fMRI反应使用GLMsingle估计，并输入一个约束优化框架，以识别一个具有任务激活、编码行为、试次间变异性低且空间连贯的网络。
结果： 分析识别出一个分布式的活力网络，其活动仍与行为活力相关，但变异性低于行为本身。该网络包括运动、纹状体、小脑、丘脑、顶叶、颞-边缘和眶额区域，并与标准任务激活图重叠有限。与更快反应相关的GVS波形伴随着活力网络活动的相应变化，但更广泛的任务激活网络未出现这种变化。多巴胺能药物也与活力网络内更强的局部功能连接相关。
讨论： 这些发现提示，PD中的运动变异性可能部分源于一个相对稳定的中枢活力相关指令向下游转化为运动时。因此，所识别的网络可能为旨在提高PD患者运动活力的神经调控方法提供潜在靶点。仍需独立验证和未来的因果测试。

英文摘要

INTRODUCTION: In motor tasks with repetitive trials, motor vigor varies substantially from trial to trial in people with Parkinson's disease (PD). A key question is whether neural variability reflects behavioral variability or whether additional variability emerges as the neural signal is translated into movement. We aimed to identify a vigor-related neural network that could provide a candidate target for brain stimulation.
METHODS: We analyzed individual-trial fMRI data from 18 participants with PD who performed an overlearned ballistic hand-squeeze task in OFF- and ON-medication sessions while receiving subthreshold galvanic vestibular stimulation (GVS) with different stimulus waveforms. Single-trial fMRI responses were estimated using GLMsingle and entered into a constrained optimisation framework designed to identify a network that was task-active, encoded behavior, showed low trial-to-trial variability, and was spatially coherent.
RESULTS: The analysis identified a distributed vigor network whose activity remained related to behavioral vigor while showing lower variability than behavior itself. The network included motor, striatal, cerebellar, thalamic, parietal, temporal-limbic, and orbitofrontal regions and showed limited overlap with the standard task-activation map. GVS waveforms associated with faster responses were accompanied by corresponding changes in vigor-network activity, but not in the broader task-activation network. Dopaminergic medication was also associated with stronger local functional connectivity within the vigor network.
DISCUSSION: These findings suggest that movement variability in PD may arise partly when a relatively stable central vigor-related command is translated downstream into movement. The identified network may therefore provide a potential target for neuromodulation approaches aimed at increasing motor vigor in people with PD. Independent validation and future causal testing are needed.