Pathophysiology of dystonia

肌张力障碍的病理生理学

• 批准号: 7780516
• 负责人: JAY L. ALBERTS
• 金额: $ 21.64万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7780516
• 关键词: Address; Adult; Affect; Basal Ganglia; Biomechanics; Body part; Brain; Cell Count; Cells; Cervical; Cervical Dystonia; Characteristics; Child; Chronic; Clinical; Collection; Data; Deep Brain Stimulation; Development; Disease; Dyskinetic syndrome; Dystonia; Exhibits; Frequencies; Functional disorder; Future; Generations; Globus Pallidus; Impairment; Incidence; Involuntary Movements; Isometric Exercise; Kinetics; Lead; Limb structure; Location; Maps; Measures; Microelectrodes; Motor; Movement; Movement Disorders; Muscle; Muscle Contraction; Nature; Neck; Neurons; Operating Rooms; Operative Surgical Procedures; Patients; Pattern; Performance; Phase; Physiological; Posture; Primary Dystonias; Process; Production; Property; Relative (related person); Rest; Severities; Spasmodic torticollis; Symptoms; Time; improved; insight; motor control; motor impairment; neuromuscular activity; neurophysiology; receptive field; relating to nervous system; response; segregation; somatosensory

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.

该项目的总体目的是阐明Globus Pallidus（GPI）内部段的神经元活性与主要概括（PGD）患者（PGD）患者的发育，表型分布和严重程度的发育，表型分布和严重程度之间的关系。 。将解决三个基本问题：1）PGD和CD患者基底神经节神经元的生理特征是什么？ 2）这些生理特征（例如平均排放率，体感应响应特性，或在低振荡频率下具有破裂或功率的细胞数量）与肌张力障碍严重程度的临床测量（Burke Fahn Marsden Marsden Marsdonia rystonia rystonia rystonia runtstonia rytstonia rystonia ryts量表CD的多伦多西部痉挛性核核糖评级量表）？ 3）GPI中神经元的相对比例和分布有差异，这些神经元在PGD患者和CD患者之间证明了这些肌张力特征？作为深脑刺激手术的一部分，在GPI的微电极映射期间，将在手术室同时收集神经和力控制数据。作为这项为期两年项目的一部分，将从18名（9个PGD和9 CD）肌张力障碍患者中收集神经元，EMG和力控制数据。具体目的1和2的重点是确定GPI内神经元活性（即平均排放率，模式，振荡活性和体感响应特性）之间的关系以及PGD和CD的严重程度。目标1和2的最后阶段是比较PGD和CD患者GPI内的神经活动。这种比较将使我们能够确定PGD和CD患者在神经活动中是否有共同改变，或者每种类型的肌张力障碍都有其独特的病理生理学。在特定的目标3中，患者将在记录GPI内神经活动期间执行武力跟踪运动任务。运动性能将通过生物力学测量方法进行客观量化。神经和运动数据的同时收集是独一无二的，将阐明PGD和CD患者GPI内的神经元活性及其在控制肌肉力的控制方面的特定障碍，尤其是力量的缩放和聚焦。确定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隔离，并了解每种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缓解肌张力障碍症状。