Proprioceptive training for patients with degenerative cerebellar ataxia.

小脑退行性共济失调是一种缓慢进行性疾病，可导致运动障碍的增加。发展一种健全的、以研究为基础的行为疗法似乎是最有希望改善共济失调的途径，直到将来药物或基因治疗可能成为可能。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患者的运动表现，但缺乏专门的训练计划，这需要考虑到小脑的生理学和病理生理学知识。例如，尽管小脑接受大量本体感觉事件，但现有的物理治疗方法并未强调小脑共济失调中本体感觉功能的改善。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，该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粹的本体感觉训练（即没有视觉反馈）来改善，并且利用完整的外显记忆机制可以进一步改善运动功能。具体来说，我们提出本体感觉训练可以提高本体感觉的敏感性和/或被动和主动运动感觉的敏锐度。在退行性共济失调患者中，我们将检验本体感觉训练比传统的内隐视觉运动学习产生更好的运动表现结果的假设。此外，我们验证了外显、策略学习机制与内隐运动学习相结合的假设，在小脑退行性共济失调患者中，内隐运动学习比单独内隐运动学习效果更好。为了实现这一目标，将提供有关关节位置误差和改善运动性能所需调整的明确口头信息。神经成像将用于提供有关这种训练的神经关联的信息。我们验证了本体感觉训练导致小脑皮层灰质密度增加，小脑上小脑脚分数各向异性（FA）增加，小脑静息状态网络活动增加的假设。此外，我们测试了外显策略学习导致额叶皮层（背外侧前额叶皮层、吻侧辅助运动区、前扣带皮层）灰质密度增加和内囊前肢投射纤维FA增加。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共同执行：人类小脑损伤研究（Timmann-Braun）、临床运动科学（Konczak）和脑成像（van 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).