Cerebellar Deep Brain Stimulation

小脑深部脑刺激

基本信息

批准号：
10683752
负责人：
Roy Vincent Sillitoe
金额：
$ 40.13万
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/10683752
关键词：
Address Affect Anatomy Animal Behavior Animal Model Ataxia Behavior Biological Biological Markers Brain Brain Diseases Brain region Cell Nucleus Cerebellar Cortex Cerebellar Diseases Cerebellar Nuclei Cerebellum Cerebral Palsy Chronic Code Deep Brain Stimulation Defect Dentate nucleus Development Disease Disease Outcome Disease model Drug resistance Dystonia Eating Disorders Electrophysiology (science)Epilepsy Equilibrium 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 Neurons Neurophysiology - biologic function Obsessive-Compulsive Disorder Output Pain Parkinson Disease Patients Pattern Persons Pharmaceutical Preparations Population Posture 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 behavioral outcome behavioral response brain repair burden of illness cognitive function design drug resistance development effective intervention effective therapy experimental study feasibility testing human disease human model improved in vivo insight motor behavior motor deficit motor disorder mouse genetics mouse model nervous system disorder neural neural circuit neuronal patterning neuropsychiatric disorder neurosurgery neurotransmission optogenetics 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.

项目概要/摘要神经系统和神经精神疾病在全世界范围内日益受到关注，因为其后果通常是致命的，或者充其量会使患者丧失行为能力。不幸的是，大多数患有这些疾病的患者疾病对当前的药物没有反应，在少数有效的情况下，它们也可以最终产生耐药性。深部脑刺激（DBS）是一种神经外科方法，当无法选择传统药物时，成为一种有效的治疗方法。然而，即使是星展银行（DBS）它的局限性，因为很多人对治疗没有反应。利用人类进行研究动物模型表明，目前 DBS 所针对的大脑位置并不总是足够的。作为确定更好的大脑修复目标的第一步，我们设计了一个小鼠遗传工具包提供了一种生成严重运动小鼠模型的通用方法疾病。该工具包基于控制大脑区域中神经回路的功能，该区域称为小脑是一种参与运动和认知功能的结构，也是生长发育中的易感部位脑部疾病清单。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解剖学和体内电生理学，以确定神经特征不同的运动疾病。在 Aim2 中，我们将使用这些神经特征作为生物标记来测试提供有针对性的闭环小脑 DBS 以快速消除运动缺陷的可行性每时每刻的精确度。这项工作的最终目标是扭转行为结果通过纠正大脑功能和恢复活动能力来治疗疾病。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医疗保健减少疾病影响和改善受影响患者的生活质量的考虑因素。