EFFECTS OF DISEASE AND PALLIDAL DEEP BRAIN STIMULATION ON ANKLE MUSCLE CONTROL IN PARKINSON'S DISEASE

疾病和苍白球深部脑刺激对帕金森病患者踝关节肌肉控制的影响

• 批准号: 10749673
• 负责人: Emily Elizabeth Lecy
• 金额: $ 4.6万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749673
• 关键词: Acute; Affect; Ankle; Axon; Basal Ganglia; Behavioral; Bradykinesia; Brain Stem; Computer Models; Data Collection; Deep Brain Stimulation; Disease; Efferent Pathways; Extensor; Flexor; Force of Gravity; Future; Gait; Gait abnormality; Gastrocnemius Muscle; Generations; Globus Pallidus; Half-Life; Human; Individual; Intervention; Leg; Length; Levodopa; Lower Extremity; Measures; Mediating; Methods; Modeling; Motor; Motor Cortex; Motor Evoked Potentials; Movement; Muscle; Muscle function; Neural Pathways; Neurodegenerative Disorders; Neurons; North America; Outcome; Parkinson Disease; Participant; Pathway interactions; Patients; Performance; Persons; Phase; Physiologic pulse; Play; Posture; Prevalence; Process; Property; Quality of life; Reaction Time; Research; Resistance; Role; Scientist; Soleus Muscle; Structure of subthalamic nucleus; Testing; Therapeutic Effect; Torque; Training; Transcranial magnetic stimulation; Upper Extremity; Walking; aging population; comparison control; dopamine replacement therapy; experimental study; falls; improved; insight; multimodality; neurophysiology; posture instability; response; skills; therapy development; tibialis anterior muscle

Project Abstract Postural instability and gait deficits are common causes of falls, decreased mobility, and increased morbidity in people with Parkinson's disease (PD). These axial motor signs are often resistant to current treatments, including dopamine replacement therapy (levodopa) and deep brain stimulation (DBS). Currently, the mechanisms contributing to the impaired control of the lower limbs are poorly understood. Extensor muscles of the lower limbs are critical for maintaining vertical support against gravity and generating power during gait. In people with PD, impairment in extensor muscle strength is greater than the flexors. Levodopa and subthalamic DBS (STN DBS) improve strength in both the flexors and extensors but have less of an effect in the extensors. Similarly, levodopa and STN DBS do not significantly improve plantar flexor torque generation during gait. Currently, the mechanisms contributing to greater defici ts in extensor compared to flexor muscle function in PD are unknown, but likely reflect differences in corticospinal, basal ganglia and brainstem contributions to the control of these muscles. This project aims to understand how flexors (tibialis anterior) and extensors (gastrocnemius, soleus) of the ankle contribute to leg rigidity and bradykinesia and gait in people with PD. Aim 1a will use transcranial magnetic stimulation of the leg region of the motor cortex to examine the excitability of corticomotoneuronal and intracortical pathways controlling the ankle flexors and extensors in PD, and controls. Aim 1b will examine the relationships between intracortical and corticomotoneuronal responses and quantitative measures of ankle bradykinesia and rigidity, and gait. Aim 2 will evaluate the response dynamics (60 minute wash-out, 60 minute wash-in) of globus pallidus DBS (GP DBS) on ankle rigidity, bradykinesia, and gait in PD to test the hypothesis that the acute and steady-state effects of GP DBS are different between the ankle flexors and extensors. Response dynamics across these behavioral measures will be examined in relation to the activation of neural pathways in and around the globus pallidus (estimated via patient-specific computational modeling of DBS) to determine which pathways are associated with which motor outcomes. The results of this project will provide an increased understanding of how PD and targeted TMS and GP DBS interventions impact the function of the ankle dorsi and plantar flexors. This knowledge will be important for the development and testing of novel interventions to treat postural and gait disorders and improve quality of life in people with PD.

项目摘要 姿势不稳定和步态缺陷是跌倒，流动性降低和增加的常见原因 帕金森氏病（PD）患者的发病率。这些轴向电机标志通常对电流有抵抗力 治疗，包括多巴胺替代疗法（左旋多巴）和深脑刺激（DBS）。 当前，对下肢控制受损受损的机制知之甚少。 下肢的伸肌肌肉对于维持重力和重力的垂直支撑至关重要 在步态过程中产生力量。在患有PD的人中，伸肌强度的损害大于 屈肌。左旋多巴和丘脑下DBS（STN DBS）提高了屈肌和延伸器的强度 但是在伸肌中的影响较小。同样，左旋多巴和STN DBS并不能显着改善 步态过程中的足底屈肌扭矩产生。当前，导致更大缺陷的机制 与PD中的屈肌肌肉功能相比，伸肌尚不清楚，但可能反映了 皮质脊髓，基底神经节和脑干对控制这些肌肉的控制。这个项目的目标 了解脚踝的屈肌（胫骨前）和伸肌（胃gas）如何贡献 PD患者的腿部刚性和胸肌和步态。 AIM 1A将使用经颅磁 刺激运动皮层的腿部区域，以检查皮质瘤的兴奋性和 在PD中控制踝关节屈肌和伸肌的皮质内途径以及对照。 AIM 1B将检查 心脏内和皮质瘤性神经元反应与定量度量之间的关系 脚踝的肌肌症和刚性以及步态。 AIM 2将评估响应动力学（60分钟洗涤， 在脚踝刚度，胸肌和步态下，在PD上进行60分钟洗涤）的Globus Pallidus DBS（GP DBS）（GP DBS） 脚踝屈肌之间GP DBS的急性和稳态效应不同的假设 和伸肌。这些行为措施的响应动态将与 Globus pallidus内外神经途径的激活（通过患者特异性估计 DBS的计算模型）以确定哪些途径与哪些运动结果相关联。 该项目的结果将对PD和靶向TM和GP的方式有更多的了解 DBS干预会影响踝背屈肌和足底屈肌的功能。这些知识将是 对于开发和测试新干预措施以治疗姿势和步态障碍以及 改善PD患者的生活质量。