CENTRAL THALAMIC DEEP BRAIN STIMULATION MODELS

丘脑中央深部脑刺激模型

• 批准号: 8112006
• 负责人: CHRISTOPHER R BUTSON
• 金额: $ 62.63万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8112006
• 关键词: A Mouse; Acute; Affect; American; Animal Experiments; Animal Model; Animals; Anterior; Arousal; Atlases; Award; Behavior; Behavioral; Bilateral; Biological Assay; Biomedical Engineering; Brain; Brain Injuries; Brain Stem; Categories; Cerebral cortex; Chronic; Clinic; Clinical Research; Clinical Trials; Cognition; Cognition Disorders; Cognitive; Collaborations; Computer Simulation; Corpus striatum structure; Craniocerebral Trauma; Data; Databases; Deep Brain Stimulation; Development; Disease model; Drops; Drowsiness; Effectiveness; Electric Stimulation; Electrical Stimulation of the Brain; Electrodes; Electroencephalography; Evaluation; Event; Experimental Models; Expert Systems; Face; Frequencies; Goals; Grant; Histology; Human; Impaired cognition; Implant; Injury; Institutional Review Boards; Intellectual Property; Interdisciplinary Study; Iron; Knee; Knowledge; Laboratories; Lead; Left; Linear Models; Link; Location; Macaca mulatta; Medical; Methods; Minimally Conscious States; Modeling; Monkeys; Mus; National Institute of Neurological Disorders and Stroke; Nature; Neurologist; Neurons; Neurosciences; Outcome; Pathway interactions; Patients; Pattern; Performance; Persons; Physiologic pulse; Play; Population; Prefrontal Cortex; Primates; Prosencephalon; Public Health; Purpura; Research; Research Personnel; Research Support; Retinal Cone; Rodent; Role; Selection Criteria; Series; Short-Term Memory; Site; Speed; Stroke; Structure; System; Taxes; Thalamic structure; Therapeutic; Time; Tissues; Training; Trauma; Traumatic Brain Injury; United States National Institutes of Health; Universities; Visual; Visual attention; Wisconsin; Work; awake; base; cognitive function; design; disability; effective therapy; frontal lobe; human subject; improved; inattention; injured; medical schools; mouse model; neurophysiology; neuroregulation; nonhuman primate; novel; patient population; programs; public health relevance; relating to nervous system; research study; response; software development; treatment strategy

DESCRIPTION (provided by applicant): The goal of the proposed studies is to develop two complementary animal models to advance deep brain stimulation (DBS) of the central thalamus (CT) as a therapeutic strategy for the treatment of acquired cognitive disabilities resulting from traumatic brain injury (TBI). Each day of the year approximately 4,000 Americans suffer a traumatic brain injury (TBI), leaving as many as 100,000 persons/year with long-term cognitive disabilities. We will form a multidisciplinary research program utilizing systems neuroscience and bioengineering methods to improve the efficacy of central thalamic brain stimulation (CT/DBS). The research team will be lead by investigators at Weill- Cornell Medical in partnership with researchers at The Rockefeller University and Medical College of Wisconsin. Dr. Nicholas Schiff (Weill-Cornell), a leading neurologist/neuroscientist in the fields of CT/DBS and human brain injury studies, will act as P.I. of the R01 along with Dr. Keith Purpura (Weill-Cornell), an expert systems neurophysiologist, to carry out a series of experimental studies in intact alert, behaving monkeys. The work with monkeys will examine the influence of different patterns of electrical stimulation on rostral central thalamic neurons. These neurons link the brain stem centers that control arousal with the cerebral cortex, and play a crucial role in integrating cortex, striatum and thalamus. Behavioral effects of continuous stimulation and of brief pulses applied at specific times will be evaluated during the performance of two elementary cognitive tasks. Neural activity in the monkey's frontal lobe during and following stimulation will also be examined. Dr. Donald Pfaff (Rockefeller), a world- renowned expert on the cellular basis of behavior, will adapt a vetted set of arousal assays he developed for the mouse to studies of CT/DBS. Preliminary results in his laboratory have shown that CT/DBS in the mouse can facilitate behavioral performance following induced traumatic brain injury. Dr. Christopher Butson (Medical College of Wisconsin), a bioengineer and expert in computational modeling of brain electrical stimulation will develop detailed models of the volume of tissue activated in the animal experiments at Weill-Cornell and Rockefeller. He will also supervise the development and analysis of a probabilistic atlas to identify the sites of optimal application of CT/DBS. This atlas will assist in the construction of a human atlas that could be used in the treatment of non-progressive brain injuries. Thus, the long-range goal of this work is to optimize neuromodulation strategies employing electrical stimulation of the central thalamus to treat cognitive impairment following TBI. PUBLIC HEALTH RELEVANCE: Acquired cognitive impairment following severe brain injury leave as many as 100,000 Americans each year with devastating disabilities. The studies proposed here will help to advance the necessary knowledge to advance and further develop a novel application of electrical brain stimulation aimed at improving the lives of patients suffering with these lifelong challenges.

描述（由申请人提供）：拟议研究的目标是开发两种互补的动物模型，以推进中央丘脑（CT）的深部脑刺激（DBS），作为治疗由创伤性脑损伤（TBI）引起的获得性认知障碍的治疗策略。 一年中每天约有 4,000 名美国人遭受创伤性脑损伤 (TBI)，每年有多达 100,000 人患有长期认知障碍。 我们将利用系统神经科学和生物工程方法形成一个多学科研究计划，以提高中枢丘脑刺激（CT/DBS）的功效。 该研究小组将由威尔康奈尔医学中心的研究人员领导，与洛克菲勒大学和威斯康星医学院的研究人员合作。 Nicholas Schiff 博士（威尔康奈尔大学）是 CT/DBS 和人脑损伤研究领域的领先神经学家/神经科学家，他将担任该项目的 P.I。 R01 与系统神经生理学家 Keith Purpura 博士（威尔-康奈尔大学）一起，在保持警觉、行为正常的猴子身上进行了一系列实验研究。 对猴子的研究将检查不同模式的电刺激对丘脑喙中央神经元的影响。 这些神经元将控制觉醒的脑干中心与大脑皮层连接起来，在整合皮层、纹状体和丘脑方面发挥着至关重要的作用。 在执行两项基本认知任务期间，将评估连续刺激和在特定时间施加的短暂脉冲的行为效果。 还将检查刺激期间和之后猴子额叶的神经活动。 Donald Pfaff 博士（洛克菲勒）是世界著名的细胞行为基础专家，他将采用他为小鼠开发的一套经过审查的唤醒测定法来研究 CT/DBS。 他的实验室的初步结果表明，CT/DBS 可以促进小鼠在诱发脑外伤后的行为表现。 Christopher Butson 博士（威斯康星医学院）是一位生物工程师和脑电刺激计算模型专家，他将开发威尔康奈尔大学和洛克菲勒大学动物实验中激活的组织体积的详细模型。 他还将监督概率图谱的开发和分析，以确定 CT/DBS 的最佳应用场所。 该图谱将有助于构建可用于治疗非进行性脑损伤的人体图谱。 因此，这项工作的长期目标是优化利用中央丘脑电刺激的神经调节策略来治疗 TBI 后的认知障碍。 公共卫生相关性：严重脑损伤后获得性认知障碍每年导致多达 100,000 名美国人遭受严重残疾。 这里提出的研究将有助于增进必要的知识，以推进和进一步开发脑电刺激的新颖应用，旨在改善遭受这些终生挑战的患者的生活。