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。

• 批准号: 10015410
• 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
• 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/10015410
• 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; Equilibrium; Fall prevention; Freedom; Functional disorder; Gait; Goals; Health; Human; Image; Impairment; Individual; Lateral; Lead; 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; Pharmacotherapy; Physiological; Physiological Processes; Physiology; Play; Process; Psychophysics; Research; Research Personnel; Role; Signal Transduction; Structure of subthalamic nucleus; System; Techniques; Testing; Thalamic structure; 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; side effect; therapeutically effective; tractography; way finding; white matter

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.

帕金森病 (PD) 是一种常见的神经退行性疾病，影响人类运动。 这只是一种运动疾病，它还会导致对自我编码至关重要的多感觉处理受损。 最终，这会导致空间导航异常、行走时横向漂移。 约 70% 的患者接受常规药物治疗或深部脑部治疗（转向）、姿势不稳定和跌倒。 DBS 刺激（DBS）对于治疗这些使人衰弱的症状有不同的效果，可以改善平衡。 有些患者会出现功能障碍，而有些患者则不会影响平衡甚至使平衡变得更糟。 治疗需要正确理解 PD 导航障碍的机制，并了解如何 DBS 调节平衡功能 我们研究计划的一个独特愿景是： 1) 揭示 DBS 如何调节多感觉集成系统过程的生理基础 控制对自身运动的感知，这对于 PD 中的空间导航、步态和平衡至关重要 2) 能够。 持续治疗导航障碍，例如接受丘脑底核 (STN) DBS 的 PD 患者的遮盖 同时保留其治疗震颤和增加肌张力以及减少药物治疗的其他益处 为了实现这一目标，当前的优点审查应用程序重点关注前庭。 系统 – 感知自身线性运动的关键系统，即前庭航向感知 – 这项任务必须准确，以便正确控制平衡、导航和避免跌倒。 值得指出的是，STN DBS 对前庭方向知觉和遮蔽的影响取决于 STN 内活性电极接触的具体位置和小脑丘脑通路的调节 已知携带前庭信号并且位于 STN 的物理附近以便检验该假设。 我们将客观地衡量一个人感知线性运动方向的能力（即前庭航向感知）， 行走时的横向漂移（即遮盖）在 PD 中很常见，然后我们将比较这些目标 测量三种独立条件 - 背侧 STN DBS、腹侧 STN DBS 和 DBS 关闭 The Aim 1。 将检查 STN 内组织激活体积的位置对前庭变化的影响 我们将整理人类帕金森病患者的方向知觉和遮盖力的物理位置。 当发现前庭方向知觉和遮蔽发生变化时，所有患者都会激活。 位置，生成概率刺激图集，将提供有关 STN 区域的见解，这些区域可以 影响 PD 中的平衡功能。目标 2 将检查轴突通路的募集指标。 由 STN DBS 调节，与 PD 中前庭方向知觉和遮蔽的变化相关 它将直接检查已知传播的小脑丘脑通路的参与作用。 总而言之，通过采取自上而下的方法和在 STN 附近。 利用多学科研究团队研究人类 PD 患者的 STN DBS、神经影像学、 和计算模型；我们将揭示 STN DBS 调节前庭的机制 最后，我们将应用这种机制理解来设计一致且有效的。 利用 DBS 预防 PD 跌倒的治疗策略。