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 姿势不稳和步态缺陷是跌倒、活动能力下降和步态增加的常见原因。 帕金森病 (PD) 患者的发病率。这些轴向电机标志通常耐电流 治疗，包括多巴胺替代疗法（左旋多巴）和深部脑刺激（DBS）。 目前，人们对导致下肢控制受损的机制知之甚少。 下肢的伸肌对于维持垂直支撑以抵抗重力和 步态期间发电。 PD 患者的伸肌力量受损程度大于 屈肌。左旋多巴和底丘脑 DBS (STN DBS) 可提高屈肌和伸肌的力量 但对伸肌的影响较小。同样，左旋多巴和 STN DBS 也没有显着改善 步态期间跖屈肌扭矩的产生。目前，造成更大赤字的机制 PD 中伸肌与屈肌功能的比较尚不清楚，但可能反映了 皮质脊髓、基底神经节和脑干对这些肌肉的控制做出了贡献。该项目旨在 了解踝关节的屈肌（胫骨前肌）和伸肌（腓肠肌、比目鱼肌）如何发挥作用 帕金森病患者的腿部僵硬、运动迟缓和步态。目标 1a 将使用经颅磁 刺激运动皮质的腿部区域以检查皮质运动神经元和皮质运动神经元的兴奋性 PD 中控制踝关节屈肌和伸肌的皮质内通路以及对照。目标 1b 将检查 皮质内和皮质运动神经元反应之间的关系以及定量测量 踝关节运动迟缓和僵硬，以及步态。目标 2 将评估响应动态（60 分钟清除， 60 分钟冲洗）苍白球 DBS (GP DBS) 对 PD 中踝关节僵硬、运动迟缓和步态的影响 GP DBS 对踝屈肌的急性和稳态效应不同的假设 和伸肌。这些行为措施的反应动态将根据 苍白球内部和周围神经通路的激活（通过患者特异性估计） DBS 的计算模型）以确定哪些路径与哪些运动结果相关。 该项目的结果将加深人们对 PD、靶向 TMS 和 GP 的理解 DBS 干预会影响踝背肌和跖屈肌的功能。这些知识将会 对于开发和测试治疗姿势和步态障碍的新干预措施非常重要 改善帕金森病患者的生活质量。