Pathophysiology of dystonia

本项目的总体目标是阐明原发性全身性（PGD）和颈性肌张力障碍（CD）患者苍白球（GPi）内段神经元活动与肌张力障碍运动的发生、表型分布和严重程度之间的关系。本文将探讨三个基本问题：1）PGD和CD患者基底节神经元的生理特征是什么？2)这些生理特征（例如，平均放电率、体感反应特性或在低振荡频率下爆发或功率的细胞数量）与肌张力障碍严重程度的临床指标（PGD的Burke Fahn Marsden肌张力障碍评定量表和CD的多伦多西部痉挛性斜颈评定量表）之间是否存在关系？和3）在表现出这些张力障碍特征的GPi中神经元的相对比例和分布在PGD患者和CD患者之间是否存在差异？作为深部脑刺激手术的一部分，在GPi的微电极标测期间，将在手术室中同时收集神经和力控制数据。作为这项为期两年的项目的一部分，将从18名（9名PGD和9名CD）肌张力障碍患者中收集神经元、EMG和力控制数据。具体目标1和2分别侧重于确定GPi内神经元活动（即平均放电率、模式、振荡活动和体感反应特性）与PGD和CD严重程度之间的关系。目标1和2的最后阶段将是比较PGD和CD患者的GPi内的神经活动。这种比较将使我们能够确定PGD和CD患者是否有共同的神经活动改变，或者每种类型的肌张力障碍是否有其独特的病理生理学。在特定目标3中，患者将在记录GPi内的神经活动期间执行力跟踪运动任务。运动性能将使用生物力学测量进行客观量化。神经和运动数据的同时收集是独特的，将澄清PGD和CD患者的GPi内的神经元活动与其在肌肉力量控制中的特定损伤之间的关系，特别是力量的缩放和聚焦。识别与肌张力障碍相关的特定生理特征，确定PGD和CD中受影响神经元的空间分离，并了解每个神经元的特定运动障碍，将完善当前的手术策略，并可能导致新的手术方法来缓解肌张力障碍症状。

The overall aim of this project is to clarify the relationship between neuronal activity in the internal segment of the globus pallidus (GPi) and the development, phenotypic distribution and severity of dystonic movements in patients with primary generalized (PGD) and cervical dystonia (CD). Three fundamental questions will be addressed: 1) What are the physiological characteristics of neurons in the basal ganglia in patients with PGD and CD? 2) Is there a relationship between those physiological characteristics ( e.g. mean discharge rate, somatosensory response properties, or the number of cells with bursting or power at low oscillatory frequencies) and clinical measures of dystonia severity (Burke Fahn Marsden Dystonia Rating Scale for PGD and Toronto Western Spasmodic Torticollis Rating Scale for CD)? and 3) Is there a difference in the relative proportion and distribution of neurons in the GPi that demonstrate these dystonic characteristics between patients with PGD and those with CD? Neural and force control data will be gathered simultaneously in the operating room during microelectrode mapping of the GPi as part of deep brain stimulation surgery. As part of this two-year project, neuronal, EMG and force control data will be collected from 18 (9 PGD and 9 CD) dystonia patients. Specific Aims 1 and 2 are focused on determining the relationship between neuronal activity (i.e. mean discharge rate, pattern, oscillatory activity and somatosensory response properties) within the GPi and the severity of PGD and CD, respectively. The final phase of Aims 1 and 2 will be to compare the neural activity within the GPi in patients with PGD and CD. This comparison will allow us to determine if PGD and CD patients have common alterations in neural activity or if each type of dystonia has its own unique' pathophysiology. In Specific Aim 3, patients will perform a force-tracking motor task during the recording of neural activity within GPi. Motor performance will be objectively quantified using biomechanical measures. The simultaneous collection of neural and motor data is unique and will clarify the relationship between neuronal activity within the GPi of PGD and CD patients and their specific impairments in the control of muscle forces, in particular the scaling and focusing of force. Identifying specific physiological characteristics associated with dystonia, determining the spatial segregation of affected neurons in PGD and CD and understanding the specific motor impairments of each will refine current surgical strategies and may lead to new surgical approaches to relieve dystonic symptoms.