Essential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituation to the stimulation. Several non-invasive neuromodulation techniques targeting other parts of the central nervous system, including cerebellar, motor cortex, or peripheral nerves, have also been developed for treating ET, but the clinical outcomes remain inconsistent. Existing studies suggest that pathology in ET may emerge from multiple cortical and subcortical areas, but its exact mechanisms remain unclear. By simultaneously capturing neural activities from motor cortices and thalami, and hand tremor signals recorded via accelerometers in fifteen human subjects who have undergone lead implantations for DBS, we systematically characterized the efferent and afferent cortico-thalamic tremor networks. Through the comparisons of these network characteristics and tremor amplitude between DBS OFF and ON conditions, we further investigated the associations between different tremor network characteristics and the magnitude of DBS effect. Our findings implicate the thalamus, specifically the contralateral hemisphere, as the primary generator of tremor in ET, with a significant contribution of the ipsilateral hemisphere as well. Although there is no direct correlation between the cortico-tremor connectivity and tremor power or reduced tremor by DBS, the strength of connectivity from the motor cortex to the thalamus and vice versa at tremor frequency predicts baseline tremor power and effect of DBS. Interestingly, there is no correlation between these two connectivity pathways themselves, suggesting that, independent of the subcortical pathway, the motor cortex appears to play a relatively distinct role, possibly mediated through an afferent/feedback loop in the propagation of tremor. DBS has a greater clinical effect in those with stronger cortico-thalamo-tremor connectivity involving the contralateral thalamus, which is also associated with bigger and more stable tremor measured with an accelerometer. Interestingly, stronger cross-hemisphere coupling between left and right thalami is associated with more unstable tremor. Together this study provides important insights into a better understanding of the cortico-thalamic tremor generating network and its implication for the development of patient-specific therapeutic approaches for ET.

中文翻译：

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特发性震颤中皮质丘脑震颤回路及其与脑深部刺激作用的关系


特发性震颤 （ET） 是成人最常见的运动障碍之一。丘脑腹侧中间核 （VIM） 和/或丘脑后底区 （PSA） 的深部脑刺激 （DBS） 已被证明可为 ET 患者提供显着的震颤抑制，但患者间差异和对刺激的习惯性显着。几种针对中枢神经系统其他部分（包括小脑、运动皮层或周围神经）的非侵入性神经调控技术也被开发用于治疗 ET，但临床结果仍不一致。现有研究表明，ET 的病理可能来自多个皮质和皮质下区域，但其确切机制尚不清楚。通过同时捕获来自运动皮层和丘脑的神经活动，以及通过加速度计记录的 15 名接受 DBS 铅植入术的人类受试者的手震颤信号，我们系统地表征了传出和传入皮质丘脑震颤网络。通过比较这些网络特征和 DBS OFF 和 ON 条件下的震荡幅度，我们进一步研究了不同震颤网络特征与 DBS 效应幅度之间的关联。我们的研究结果表明，丘脑，特别是对侧半球，是 ET 中震颤的主要来源，同侧半球也有显着贡献。尽管皮质-震颤连接与 DBS 的震颤功率或震颤减轻之间没有直接相关性，但在震颤频率下，从运动皮层到丘脑的连接强度（反之亦然）可预测基线震颤强度和 DBS 的效果。 有趣的是，这两个连接通路本身之间没有相关性，这表明，独立于皮层下通路，运动皮层似乎发挥着相对不同的作用，可能是通过震颤传播中的传入/反馈回路介导的。DBS 对涉及对侧丘脑的皮质-丘脑-震颤连接更强的患者具有更大的临床效果，这也与使用加速度计测量的更大、更稳定的震颤有关。有趣的是，左右丘脑之间较强的跨半球耦合与更不稳定的震颤有关。总之，这项研究为更好地了解皮质-丘脑震颤产生网络及其对开发 ET 患者特异性治疗方法的影响提供了重要见解。