PALLIDAL PHYSIOLOGY IN HUMAN AND PRIMATE DYSTONIA

描述（改编自申请人的摘要）：肌张力障碍是一种运动， 一种定义为持续肌肉收缩综合征的疾病， 扭曲和重复的动作，以及不正常的姿势。其病理生理 是很难理解的。最近，人们试图了解运动 在涉及皮层的环路改变方面的疾病， 基底神经节和丘脑。苍白球在神经系统疾病中占有重要地位， 因为它是基底神经节的主要输出结构。 另一种运动障碍，帕金森氏病，已被发现与 苍白球活动过度和异常这一发现导致 改善帕金森病的手术治疗， 失活 与PD相反，对肌张力障碍的更好理解受到以下因素的阻碍： 缺乏关于这种情况下基底神经节生理学的数据， 缺乏良好表征的肌张力障碍动物模型。这两个问题都是 在这个提案中。外部和内部的单个单元记录 苍白球是常规进行手术导航过程中， 损伤或电极植入苍白球。自发和 将分析在这种手术期间记录的运动相关放电。 类似的记录将在局灶性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运动员的重复动作产生的 任务毁损苍白球对运动功能的影响 将分析灵长类动物局灶性肌张力障碍。 实验将测试以下假设：1。人类的肌张力障碍 与苍白球异常神经元放电有关。2.）的情况。类似 苍白球放电的异常存在于肌张力障碍的灵长类动物模型中。 3.）第三章灵长类动物模型中苍白球的失活改善了运动功能 在肌张力障碍的手的性能，并防止诱导肌张力障碍， 正常的灵长类动物这些实验将证实或反驳现有的理论， 肌张力障碍的病理生理机制，并提供理论支持， 通过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.