Subthalamic deep brain stimulation to modulate vestibular heading perception in Parkinson’s disease.

丘脑深部脑刺激可调节帕金森病的前庭方向知觉。

基本信息

批准号：
10579821
负责人：
Aasef G Shaikh
金额：
--
依托单位：
LOUIS STOKES CLEVELAND VA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10579821
关键词：
Address Affect Anatomy Area Atlases Axon Basal Ganglia Cell Nucleus Cerebellum Clinical Computer Models Data Deep Brain Stimulation Disabled Persons Discrimination Distal Dorsal Electrodes Electronics Equilibrium Fall prevention Freedom Functional disorder Gait Goals Health Human Image Impairment Individual Lateral Location Maintenance Maps Measures Morbidity - disease rate Motion Motion Perception Movement Muscle Hypertonia Neural Pathways Neurodegenerative Disorders Neurologic Neurology Operative Surgical Procedures Outcome Parkinson Disease Pathway interactions Patients Pattern Perception Personal Satisfaction Persons Pharmacotherapy Physiological Physiological Processes Physiology Process Psychophysics Research Research Personnel Role Signal Transduction Structure of subthalamic nucleus System Techniques Testing Tissues Tremor Veterans Vision Visuospatial Walking Work design disabling symptom equilibration disorder experimental study falls functional independence hexapod improved insight military veteran motor disorder multidisciplinary multisensory neuroimaging posture instability preservation programs recruit sensory integration side effect therapeutically effective tractography transmission process way finding white matter

项目摘要

Parkinson’s Disease (PD) is a common neurodegenerative disorder affecting human movements. PD is not just a motor disease. It also results in impaired multi-sensory processing that is critical for encoding self- orientation and self-motion. Ultimately, this leads to abnormal spatial navigation, lateral drifts while walking (veering), postural instability and falls in about 70% of patients. Conventional pharmacotherapy or deep brain stimulation (DBS) for PD are variably effective in treating these debilitating symptoms. DBS improves balance dysfunction in some patients, while in some it does not affect balance or even makes it worse. Defining consistent therapy requires a proper understanding of the mechanisms of navigational impairments in PD, and to know how DBS modulates the balance function. A singular vision of our research program is: 1) To reveal the physiological underpinnings of how DBS modulates the process by which multisensory integrated systems govern perception of one’s own motion critical for spatial navigation, gait and balance in PD. 2) To be able to consistently treat navigational impairments such as veering in PD patients with subthalamic nucleus (STN) DBS while preserving its other benefits of treating tremor and increased muscle tone, and reducing pharmacotherapy burden with bothersome side effects. With this goal the current Merit Review application focuses on the vestibular system – the critical system for the perception of one’s own linear motion, i.e. vestibular heading perception – the task that is has to be accurate for the proper control of balance, navigation, and averting falls. We hypothesize that effects of STN DBS on vestibular heading perception and veering are dependent upon the specific location of the active electrode contact within the STN and modulation of the cerebello-thalamic pathway that is known to carry the vestibular signal and is in physical vicinity of the STN. In order to test this hypothesis we will objectively measure one’s ability to perceive direction of linear motion (i.e., vestibular heading perception), lateral drifts while walking (i.e., veering) that is common in PD, and then we will compare these objective measures among three independent conditions – dorsal STN DBS, ventral STN DBS, and DBS off. The Aim 1 will examine the effects of the location of volume of tissue activation within the STN on the change in vestibular heading perception and veering in human PD patients. We will collate physical location of the volume of tissue activation from all patients when the change in vestibular heading perception and veering was found. These locations, generating the probabilistic stimulation atlas, will provide insights about areas of STN that could influence balance function in PD. The Aim 2 will examine the recruitment metrics of the axonal pathways modulated by the STN DBS that correlates with change in vestibular heading perception and veering in PD patients. It will directly examine the role of involvement of cerebello-thalamic pathway that is known to transmit vestibular perception information and is in vicinity of the STN. In summary, by taking a top-down approach and leveraging a multidisciplinary team of investigators studying human PD patients with STN DBS, neuroimaging, and computational modeling; we will unravel mechanisms through which STN DBS modulates the vestibular heading perception in PD. Finally we will apply this mechanistic understanding to design consistent and effective therapeutic strategies utilizing DBS to prevent falls in PD.

帕金森氏病（PD）是影响人类运动的常见神经退行性疾病。 PD不是只是汽车疾病。这也导致多感官处理受损，这对于编码自我至关重要方向和自我运动。最终，这导致空间航行异常，行走时进行横向钻（弯曲），姿势不稳定，大约70％的患者落下。常规药物疗法或深脑 PD的刺激（DBS）在治疗这些使人衰弱的症状方面非常有效。 DBS改善平衡在某些患者中功能障碍，虽然在某些患者中不会影响平衡甚至会使情况恶化。定义一致治疗需要正确了解PD导航损伤机制，并知道如何 DBS调节平衡功能。我们研究计划的单一愿景是：1）揭示 DBS如何调节多感觉集成系统的过程的生理基础控制着对PD的空间导航，步态和平衡至关重要的人的感知。 2）能够一贯治疗导航障碍，例如在丘脑下核（STN）DBS患者中转向同时保留其治疗树和增加肌肉张力的其他好处，并减少药物治疗负担都有两种副作用。有了这个目标，当前的功绩审查申请将重点放在前庭系统 - 感知自己的线性运动的关键系统，即前庭标题感知 - 必须准确地控制平衡，导航和避免避免的任务。我们假设STN DB对前庭标题感知和转向的影响取决于活动电极接触的特定位置和小脑 - 丘脑途径的调节众所周知，它具有前庭信号，并且位于STN的物理附近。为了检验这一假设我们将客观地衡量一个人感知线性运动方向的能力（即前庭标题感知），在PD中常见的步行时（即弯曲）时的横向钻头，然后我们将比较这些目标在三个独立条件下进行的措施 - 背面DBS，腹侧STN DBS和DBS OFF。目标1 将检查STN内组织激活体积的位置对前庭变化的影响人类PD患者的标题感知和转向。我们将协作组织体积的物理位置当发现前庭标题感知和转向的变化时，所有患者的激活。这些产生概率刺激地图集的位置将提供有关STN区域的见解 PD的影响平衡功能。目标2将检查轴突途径的募集指标由STN DBS调节，与前庭标题感知变化和PD转向相关患者。它将直接检查已知可以传播的小脑 - 丘脑途径的参与的作用前庭感知信息，位于STN附近。总而言之，采用自上而下的方法和利用研究人类PD患者的研究人员的多学科团队，神经影像学，和计算建模；我们将解开STN DBS调节前庭的机制 PD的标题感知。最后，我们将采用这种机械理解来设计一致有效的使用DBS的治疗策略来防止PD跌落。