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.

帕金森病是一种常见的影响人体运动的神经退行性疾病。PD不是