Essential tremor is a neurological syndrome of heterogeneous pathology and aetiology that is characterized by tremor primarily in the upper extremities. This tremor is commonly hypothesized to be driven by a single or multiple neural oscillator(s) within the cerebello-thalamo-cortical pathway. Several studies have found an association of blood-oxygen level-dependent (BOLD) signal in the cerebello-thalamo-cortical pathway with essential tremor, but there is behavioural evidence that also points to the possibility that the severity of tremor could be influenced by visual feedback. Here, we directly manipulated visual feedback during a functional MRI grip force task in patients with essential tremor and control participants, and hypothesized that an increase in visual feedback would exacerbate tremor in the 4–12 Hz range in essential tremor patients. Further, we hypothesized that this exacerbation of tremor would be associated with dysfunctional changes in BOLD signal and entropy within, and beyond, the cerebello-thalamo-cortical pathway. We found that increases in visual feedback increased tremor in the 4–12 Hz range in essential tremor patients, and this increase in tremor was associated with abnormal changes in BOLD amplitude and entropy in regions within the cerebello-thalamo-motor cortical pathway, and extended to visual and parietal areas. To determine if the tremor severity was associated with single or multiple brain region(s), we conducted a birectional stepwise multiple regression analysis, and found that a widespread functional network extending beyond the cerebello-thalamo-motor cortical pathway was associated with changes in tremor severity measured during the imaging protocol. Further, this same network was associated with clinical tremor severity measured with the Fahn, Tolosa, Marin Tremor Rating Scale, suggesting this network is clinically relevant. Since increased visual feedback also reduced force error, this network was evaluated in relation to force error but the model was not significant, indicating it is associated with force tremor but not force error. This study therefore provides new evidence that a widespread functional network is associated with the severity of tremor in patients with essential tremor measured simultaneously at the hand during functional imaging, and is also associated with the clinical severity of tremor. These findings support the idea that the severity of tremor is exacerbated by increased visual feedback, suggesting that designers of new computing technologies should consider using lower visual feedback levels to reduce tremor in essential tremor.

中文翻译：

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广泛的视觉敏感功能网络与原发性震颤中的症状有关

原发性震颤是一种病理学和病因学不同的神经系统综合症，其特征是主要在上肢发生震颤。通常认为该震颤是由小脑-丘脑-皮质途径内的单个或多个神经振荡器驱动的。几项研究发现小脑-丘脑-皮质途径中血氧水平依赖性（BOLD）信号与原发性震颤有关，但是有行为证据也表明，视力会影响震颤的严重性回馈。在这里，我们在患有功能性震颤和对照的患者进行功能性MRI抓紧力任务期间直接操纵了视觉反馈，并假设视觉反馈的增加会在本质性震颤患者的4–12 Hz范围内加剧震颤。此外，我们假设震颤的加剧与小脑-丘脑-皮质途径内外的BOLD信号和熵功能异常有关。我们发现，视觉反馈的增加在原发性震颤患者中在4-12 Hz范围内增加了震颤，而这种震颤的增加与小脑-丘脑-运动皮质通路内区域的BOLD振幅和熵的异常变化有关，并延长了到视觉和顶叶区域。为了确定震颤的严重程度是否与单个或多个大脑区域相关，我们进行了双向正向逐步多元回归分析，发现超出小脑-丘脑-运动皮质通路的广泛功能网络与震颤的变化有关在成像方案中测量的严重程度 此外，该网络与使用Fahn，Tolosa，Marin震颤评估量表测量的临床震颤严重程度相关，这表明该网络具有临床意义。由于增加的视觉反馈也减少了力误差，因此对该网络进行了力误差评估，但该模型并不重要，表明该模型与力震颤有关，但与力误差无关。因此，这项研究提供了新的证据，即广泛的功能网络与功能性影像同时在手部进行测量的原发性震颤患者的震颤严重程度有关，并且还与震颤的临床严重程度有关。这些发现支持了这样的想法，即视力反馈的增加会加剧震颤的严重性，