Proprioceptive training for patients with degenerative cerebellar ataxia.

小脑退行性共济失调是一种缓慢进展的疾病，它导致运动障碍的增加。发展一个健全的，以研究为基础的行为疗法似乎是最有前途的途径，以改善共济失调，直到药理学或基因治疗可能成为在未来可用。虽然有第一个证据表明，物理治疗可以改善退行性共济失调的运动表现，但缺乏具体的训练计划，其中考虑到小脑的生理学和病理生理学知识。例如，尽管小脑接受大量的本体感受传入，但现有的物理治疗没有强调小脑共济失调的本体感受功能的改善。同样，训练与基本完整的外显记忆机制之间的联系也没有得到系统的研究。因此，本项目的主要目标是提供一个原理证明，即退行性共济失调患者的运动功能可以通过纯本体感受训练的方案（即，没有视觉反馈），并且利用完整的外显记忆机制导致运动功能的进一步改善。具体而言，我们建议，本体感受训练导致改善的本体感受灵敏度和/或被动和主动运动感的敏锐度。我们将检验这样一个假设，即在退行性共济失调患者中，本体感觉训练比传统的内隐视觉学习产生更好的运动表现结果。此外，我们测试的假设，耦合外显，策略学习机制与内隐运动学习产生更好的结果比内隐运动学习单独在小脑退行性共济失调患者。为了实现这一目标，将提供有关关节位置错误和改善运动表现所需的调整的明确的口头信息。神经成像将用于提供有关此类训练的神经相关信息。我们测试的假设，本体感觉训练导致小脑皮质的灰质密度增加，增加分数各向异性（FA）的上级小脑脚，并增加小脑静息状态网络的活动。此外，我们测试，外显策略学习导致额叶皮层（背外侧前额叶皮层，吻侧补充运动区，前扣带皮层）的灰质密度增加和增加FA的内囊前肢的投射纤维。此外，我们预测外显策略学习与基底神经节灰质密度增加有关，并导致额-基底神经节网络活动增加。该项目由三个在运动障碍研究方面具有互补专业知识的小组联合进行：人类小脑病变研究（Timmann-Braun），临床运动科学（Konczak）和脑成像（货车Eimeren，Granert）。

Cerebellar degenerative ataxias are slowly progressive disorders, which lead to increasing motor impairments. The development of a sound, research-based behavioral therapy seems to be the most promising avenue to improve ataxia until pharmacological or genetic treatments may become available in the future. Although there is first evidence that physiotherapy improves motor performance in degenerative ataxias, there is lack of specific training programs, which take knowledge about the physiology and pathophysiology of the cerebellum in account. For example, despite the fact that the cerebellum receives massive proprioceptive afferents, no existing physical therapy stresses the improvement of proprioceptive function in cerebellar ataxia. Likewise, the linking of training with largely intact explicit memory mechanisms has not been researched systematically. It is thus the main goal of this project to provide a proof of principle that motor function of patients with a degenerative ataxias can improve through a regime of pure proprioceptive training (i.e., without visual feedback), and that exploitation of intact explicit memory mechanisms leads to further improvement of motor function. Specifically, we propose that proprioceptive training leads to improved proprioceptive sensitivity and/or acuity of passive and active motion sense. We will test the hypothesis that proprioceptive training yields better motor performance outcomes than conventional implicit visuomotor learning in patients with degenerative ataxia. In addition, we test the hypothesis that coupling explicit, strategic learning mechanisms with implicit motor learning yields better outcomes than implicit motor learning alone in patients with cerebellar degenerative ataxia. To operationalize this aim, explicit verbal information about joint position errors and the required adjustments to improve motor performance will be provided.Neuroimaging will be used to provide information on the neural correlate of such training. We test the hypothesis that proprioceptive training leads to increased gray matter density of the cerebellar cortex, increased fractional anisotropy (FA) of superior cerebellar peduncles, and increased activity of the cerebellar resting state network. Furthermore, we test that explicit strategic learning leads to increased gray matter density of the frontal cortex (dorsolateral prefrontal cortex, rostral supplementary motor area, anterior cingulate cortex) and increased FA of projection fibers of the anterior limb of the internal capsule. In addition, we predict that explicit strategic learning is related to increased gray matter density of basal ganglia and leads to increased activity in fronto-basal-ganglia networks. The project is performed jointly between three groups with complementary expertise in the study of motor disorders: human cerebellar lesion studies (Timmann-Braun), clinical movement science (Konczak) and brain imaging (van Eimeren, Granert).