Institute of Systems Motor Science, Center of Brain, Behavior and Metabolism, Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
Department of Neurology, University Hospital Schleswig Holstein, Lübeck, Germany.
Sci Rep. 2022 Aug 22;12(1):14279. doi: 10.1038/s41598-022-17545-w.
Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such as timing, action preparation and feedback processing, have not been investigated so far. In an active time estimation task with trial-by-trial feedback, participants indicated a target interval (1200 ms) by a motor response. We compared 12 patients tested (in fixed order) under their current levodopa medication ("ON") and after levodopa withdrawal ("OFF") to matched healthy controls (HC), measured twice to control for repetition effects. We assessed time estimation accuracy, trial-to-trial adjustment, as well as task- and feedback-related pupil-linked arousal responses. Patients showed comparable time estimation accuracy ON medication as HC but reduced performance OFF medication. Task-related pupil responses showed the reverse pattern. Trial-to-trial adjustments of response times were reduced in DRD, particularly OFF medication. Our results indicate differential alterations of time estimation accuracy and task-related arousal dynamics in DRD patients as a function of dopaminergic medication state. A medication-independent alteration of task repetition effects in DRD cannot be ruled out with certainty but is discussed as less likely.
多巴反应性肌张力障碍（DRD）是由于 GTP-环水解酶-1（GCH1）缺乏导致多巴胺生物合成受损引起的，导致出现肌张力障碍和帕金森症的组合症状。然而，到目前为止，还没有研究过 GCH1 突变和左旋多巴治疗对简单运动以外的运动控制的影响，如定时、动作准备和反馈处理。在一项具有逐次反馈的主动时间估计任务中，参与者通过运动反应来指示目标间隔（1200 毫秒）。我们将 12 名患者（按固定顺序）在服用当前左旋多巴药物（“ON”）和停药后（“OFF”）与匹配的健康对照组（HC）进行比较，为了控制重复效应，我们进行了两次测量。我们评估了时间估计的准确性、逐次调整以及与任务和反馈相关的瞳孔链接唤醒反应。患者在服用药物时的时间估计准确性与 HC 相当，但停药后则降低。任务相关的瞳孔反应则呈现相反的模式。DRD 患者的反应时间逐次调整减少，尤其是停药后。我们的结果表明，DRD 患者的时间估计准确性和与任务相关的唤醒动力学存在差异，这取决于多巴胺能药物状态。不能肯定地排除 DRD 中存在与药物无关的任务重复效应改变，但认为不太可能。
