Essential tremor (ET), a movement disorder characterized by involuntary oscillations of the limbs during movement, remains to date not well understood. It has been recently suggested that the tremor originates from impaired delay compensation, affecting movement representation and online control. Here we tested this hypothesis directly with 24 ET patients (14 female; 10 male) and 28 neurologically intact (NI) human volunteers (17 female; 11 male) in an upper limb postural perturbation task. After maintaining their hand in a visual target, participants experienced perturbations of unpredictable direction and magnitude and were instructed to counter the perturbation and steer their hand back to the starting position. In comparison with NI volunteers, ET patients’ early muscular responses (short and long-latency responses, 20–50 and 50–100 ms, respectively) were preserved or even slightly increased. However, they exhibited perturbation-dependent deficits when stopping and stabilizing their hand in the final target supporting the hypothesis that the tremor was generated by the feedback controller. We show in a computational model that errors in delay compensation accumulating over time produced the same small increase in initial feedback response followed by oscillations that scaled with the perturbation magnitude as observed in ET population. Our experimental results therefore validate the computational hypothesis that inaccurate delay compensation in long-latency pathways could be the origin of the tremor.

特发性震颤 (ET) 是一种运动障碍，其特征是运动过程中肢体不自主摆动，迄今为止仍不清楚。最近有人提出，震颤源于延迟补偿受损，影响了运动表现和在线控制。在这里，我们在上肢姿势扰动任务中直接对 24 名 ET 患者（14 名女性；10 名男性）和 28 名神经完整 (NI) 人类志愿者（17 名女性；11 名男性）测试了这一假设。将手保持在视觉目标上后，参与者经历了不可预测的方向和幅度的扰动，并被指示对抗扰动并将他们的手引导回起始位置。与 NI 志愿者相比，ET 患者的早期肌肉反应（短潜伏期反应和长潜伏期反应，分别为 20-50 毫秒和 50-100 毫秒）得以保留，甚至略有增加。然而，当他们将手停止并稳定在最终目标上时，他们表现出与扰动相关的缺陷，这支持了颤抖是由反馈控制器产生的假设。我们在计算模型中表明，随着时间的推移累积的延迟补偿误差会导致初始反馈响应同样小幅增加，随后会出现与 ET 群体中观察到的扰动幅度成比例的振荡。因此，我们的实验结果验证了计算假设，即长潜伏期路径中不准确的延迟补偿可能是震颤的根源。