Cerebellar Deep Brain Stimulation

小脑深部脑刺激

基本信息

批准号：
10096950
负责人：
Roy Vincent Sillitoe
金额：
$ 40.11万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10096950
关键词：
Address Affect Anatomy Animal Behavior Animal Model Ataxia Behavior Biological Biological Markers Brain Brain Diseases Brain region Cell Nucleus Cerebellar Diseases Cerebellar Nuclei Cerebellum Cerebral Palsy Chronic Code Custom Deep Brain Stimulation Defect Dentate nucleus Development Disease Disease Outcome Disease model Drug resistance Dystonia Eating Disorders Electrophysiology (science)Epilepsy Feedback Fiber Foundations Frequencies Functional disorder Genetic Genetic Models Gilles de la Tourette syndrome Globus Pallidus Goals Healthcare Learning Link Location Locomotion Measures Mental disorders Methods Molecular Motor Movement Mus Muscle Musculoskeletal Equilibrium Neurons Neurophysiology - biologic function Obsessive-Compulsive Disorder Output Pain Parkinson Disease Patients Pattern Pharmaceutical Preparations Population Predisposition Proxy Purkinje Cells Quality of life Recovery of Function Research Resolution Rest Role Schizophrenia Signal Transduction Site Spinal Cord Structure Structure of subthalamic nucleus Symptoms Synapses System Testing Thalamic structure Therapeutic Traditional Medicine Tremor Work base behavioral outcome behavioral response brain repair burden of illness cognitive function design effective intervention effective therapy experimental study human disease human model improved in vivo insight motor behavior motor deficit motor disorder mouse genetics mouse model nervous system disorder neural circuit neuronal patterning neuropsychiatric disorder neurotransmission optogenetics relating to nervous system spasticity stroke therapy

项目摘要

PROJECT SUMMARY/ABSTRACT Neurological and neuropsychiatric diseases are a growing concern worldwide as the consequences are often lethal, or at best they leave patients incapacitated. Unfortunately, most patients with these diseases do not respond to the current medications, and in the few cases that do work, they too can eventually develop drug resistance. Deep brain stimulation (DBS), a neurosurgical approach, has become an effective treatment when traditional medicines are not an option. However, even DBS has its limitations, as a large number of people do not respond to the treatment. Research using humans and animal models suggests that the current brain locations into which DBS is directed are not always adequate. As a first step towards identifying better targets for brain repair, we designed a genetic toolkit in mice that provides a versatile method for generating mouse models for severe motor disease. The toolkit is based on controlling the function of neural circuits in a brain region called the cerebellum, a structure involved in motor and cognitive function and a susceptibility site in a growing list of brain diseases. In Aim1, we will use a combination of these genetic models, high-resolution anatomy and in vivo electrophysiology conducted in behaving mice to define neural signatures for different motor diseases. In Aim2, we will use these neural signatures as biomarkers to test the feasibility of providing targeted close-loop cerebellar DBS to eliminate motor deficits with fast moment-to-moment precision. The ultimate goal of this work is to reverse the behavioral outcomes of disease by correcting brain function and restoring mobility. The availability of additional treatment options for incurable neurological and neuropsychiatric diseases will provide alternate healthcare considerations for reducing the impact of disease and improving the quality of life of affected patients.

项目摘要/摘要神经和神经精神疾病在全球范围内越来越关注，因为后果通常是致命的，或者充其量会使患者无能为力。不幸的是，大多数患者疾病对当前药物没有反应，在少数情况下，它们也可以最终发展耐药性。深脑刺激（DBS）是一种神经外科方法，具有当不选择传统药物时，成为一种有效的治疗方法。但是，即使是DB也有它的局限性，因为许多人对治疗没有反应。研究人类的研究动物模型表明，目前DBS的当前大脑位置不是总是足够的。作为确定更好的大脑维修目标的第一步，我们设计了一个小鼠的遗传工具包，该工具包提供了一种用于生成严重电机鼠标模型的多功能方法疾病。该工具包基于控制神经回路的功能，称为小脑，一种参与运动和认知功能的结构，以及在不断增长的脑疾病清单。在AIM1中，我们将使用这些遗传模型的组合，高分辨率在行为小鼠中进行的解剖学和体内电生理学，以定义神经特征不同的运动疾病。在AIM2中，我们将使用这些神经签名作为生物标志物来测试提供有针对性的近环小脑DB的可行性，以快速消除运动缺陷时刻的精度。这项工作的最终目标是扭转通过纠正大脑功能并恢复活动能力来疾病。额外治疗的可用性无法治愈的神经系统和神经精神疾病的选择将提供替代的医疗保健减少疾病影响并改善受影响患者的生活质量的考虑因素。