PALLIDAL PHYSIOLOGY IN HUMAN AND PRIMATE DYSTONIA

描述(改编自申请者摘要)：肌张力障碍是一种运动 疾病定义为持续肌肉收缩的综合征，导致 扭曲和重复的动作，以及不正常的姿势。其病理生理学 人们对此知之甚少。最近，人们试图理解运动 在涉及大脑皮层的环路改变方面的紊乱， 基底节和丘脑。苍白球在 这一环路既是基底节的主要输出结构。 另一种运动障碍，帕金森氏症，已被发现与 伴随着过度和异常的苍白球活动。这一发现导致了 改善帕金森氏病的苍白球外科治疗 失活。 与帕金森病不同，对肌张力障碍的更好理解受到了 在这种情况下缺乏关于基底神经节生理学的数据， 缺乏一种具有良好特征的肌张力障碍动物模型。这两个问题都是 在本提案中提到的。单个单元-在外部和内部记录 苍白球是外科手术导航过程中的常规操作 损毁或电极植入苍白球。自发的和 将对此类手术期间记录的与运动相关的放电进行分析。 类似的记录将在局灶性手臂肌张力障碍的灵长类动物模型中获得， 其中肌张力障碍是由熟练的马达的重复执行而产生的 任务。苍白球毁损术对运动功能的影响 将对灵长类局灶性肌张力障碍进行分析。 这些实验将检验以下假设：1)人类的肌张力障碍是 与苍白球异常神经元放电有关。2.)类似 在一种肌张力障碍的灵长类动物模型中，苍白球放电出现异常。 3.)灵长类动物模型中苍白球的失活可改善运动 在肌张力障碍的手中的表现，并防止诱发肌张力障碍 正常的灵长类动物。这些实验将证实或驳斥现有的理论 为肌张力障碍的病理生理学研究提供理论支持。 苍白球手术治疗肌张力障碍。

DESCRIPTION (Adapted From The Applicant's Abstract): Dystonia is a movement disorder defined as a syndrome of sustained muscle contractions, causing twisting and repetitive movements, and abnormal postures. Its pathophysiology is poorly understood. Recently, attempts have been made to understand movement disorders in terms of alterations in a loop circuit involving, the cortex, basal ganglia and thalamus. The globus pallidus occupies a critical position in this circuit since it is the major output structure of the basal ganglia. Another movement disorder, Parkinson's disease, has been found to be associated with excessive and abnormally patterned pallidal activity. This finding has led to improved surgical treatments for Parkinson's disease by pallidal inactivation. In contrast to PD, a better understanding of dystonia has been hampered by a lack of data on the physiology of the basal ganglia in this condition, and by the lack of a well-characterized animal model of dystonia. Both problerns are addressed in this proposal. Single unit-recording in the external and internal pallidum is routinely performed for surgical navigation during the course of lesioning or electrode implantation into the globus pallidus. Spontaneous and movement-related discharges recorded during such surgeries will be analyzed. Similar recordings will be obtained in a primate model of focal arm dystonia, in which dystonia is generated by repetitive performance of a skilled motor task. The effect on motor performance of lesioning the globus pallidus in primate focal dystonia will be analyzed. The experiments will test the following hypotheses: 1.) Dystonia in humans is associated with abnormal neuronal discharge in the g1obus pallidus. 2.) Similar abnormalities of pallidal discharge are present in a primate model of dystonia. 3.) Inactivation of the globus pallidus in the primate model improves motor performance in the dystonic hand and prevents the induction of dystonia in normal primates. These experiments will confirm or refute existing theories of the pathophysiology of dystonia as well as provide theoretical support for the treatment of dystonia by pallidal surgery.