CENTRAL THALAMIC DEEP BRAIN STIMULATION MODELS

丘脑中央深部脑刺激模型

• 批准号: 7770323
• 负责人: CHRISTOPHER R BUTSON
• 金额: $ 69.19万
• 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/7770323
• 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; Intellectual Property; Interdisciplinary Study; Iron; Knee; Knowledge; Laboratories; Lead; Left; Life; 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 Ethics Committees; 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）：拟议的研究的目的是开发两种互补的动物模型，以推动中央丘脑中部（CT）的深层脑刺激（DB），作为治疗因创伤性脑损伤（TBI）而导致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制定一项多学科研究计划，以提高丘脑中央脑刺激（CT/DBS）的功效。 该研究团队将与威尔·康奈尔医疗公司（Weill Cornell Medical）的研究人员一起与威斯康星州洛克菲勒大学和医学院的研究人员合作。 尼古拉斯·席夫（Weill-Cornell）博士（Weill-Cornell）是CT/DBS和人脑损伤研究领域的主要神经科学家/神经科学家，将充当P.I. R01与专家系统神经生理学家Keith Purpura（Weill-Cornell）一起进行的，以完整的警报和行为猴子进行一系列实验研究。 与猴子的工作将检查电刺激不同模式对丘脑中央丘脑神经元的影响。 这些神经元将控制唤醒的脑干与大脑皮层联系在一起，并在整合皮质，纹状体和丘脑中起着至关重要的作用。 连续刺激和在特定时间应用的短暂脉冲的行为效应将在执行两个基本认知任务的过程中评估。 还将检查猴子额叶和之后刺激期间的神经活动。 唐纳德·普法夫（Donald Pfaff）博士（洛克菲勒（Rockefeller））是行为细胞基础的世界知名专家，将适应他为小鼠开发的一组审查的唤醒分析，以研究CT/DBS的研究。 他的实验室的初步结果表明，小鼠中的CT/DB可以促进诱发脑外伤后的行为表现。 克里斯托弗·巴森（Christopher Butson）博士（威斯康星州医学院）是脑电刺激的生物工程师兼计算建模专家，将开发在Weill-Cornell和Rockefeller的动物实验中激活的组织体积的详细模型。 他还将监督对概率地图集的开发和分析，以识别CT/DBS最佳应用的地点。 该地图集将有助于建造人类地图集，该地图集可用于治疗非进行脑损伤。 因此，这项工作的远距离目标是优化采用中央丘脑电刺激的神经调节策略，以治疗TBI后的认知障碍。 公共卫生相关性：严重的脑损伤后，每年有多达100,000名美国人患有毁灭性的残疾，获得了认知障碍。 此处提出的研究将有助于促进必要的知识，以进一步发展和进一步的电脑刺激应用，旨在改善患有这些终生挑战的患者的生活。