CENTRAL THALAMIC DEEP BRAIN STIMULATION MODELS

丘脑中央深部脑刺激模型

• 批准号: 8509796
• 负责人: CHRISTOPHER R BUTSON
• 金额: $ 58.35万
• 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 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509796
• 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(申请人提供)：拟议研究的目标是发展两种互补的动物模型，以推进中央丘脑(CT)的脑深部刺激(DBS)，作为治疗创伤性脑损伤(TBI)引起的获得性认知障碍的治疗策略。每年大约有4000名美国人遭受创伤性脑损伤(TBI)，每年有多达10万人患有长期认知障碍。我们将形成一个多学科的研究计划，利用系统、神经科学和生物工程方法来提高中央丘脑刺激(CT/DBS)的疗效。研究小组将由Weill-Cornell Medical的研究人员领导，并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(Weill-Cornell饰)，CT/DBS和人脑损伤研究领域的领先神经学家/神经学家，将与专家系统神经生理学家Keith PurPura博士(Weill-Cornell饰)一起担任R01的私人侦探，在保持警觉的猴子行为中进行一系列实验研究。这项以猴子为对象的研究将检验不同模式的电刺激对丘脑吻部中央神经元的影响。这些神经元将控制觉醒的脑干中心与大脑皮层联系起来，在整合皮质、纹状体和丘脑方面发挥着至关重要的作用。持续刺激和在特定时间施加短暂脉冲的行为效果将在两个基本认知任务的执行过程中进行评估。还将检查猴子在刺激过程中和刺激后额叶的神经活动。世界著名的行为细胞基础专家Donald Pfaff(洛克菲勒)博士将把他为小鼠开发的一套经过审查的唤醒分析方法应用于CT/DBS研究。他的实验室的初步结果表明，CT/DBS在小鼠中可以促进诱导创伤性脑损伤后的行为表现。生物工程师克里斯托弗·巴特森博士(威斯康星医学院)是脑电刺激计算建模方面的专家，他将在威尔-康奈尔和洛克菲勒的动物实验中开发激活组织体积的详细模型。他还将监督编制和分析概率图集，以确定最佳应用CT/DBS的地点。这份图集将有助于构建一份可用于治疗非进行性脑损伤的人类图集。因此，这项工作的长期目标是优化神经调节策略，使用中央丘脑的电刺激来治疗脑外伤后的认知障碍。 公共卫生相关性：严重脑损伤后的获得性认知障碍每年导致多达10万美国人患有毁灭性的残疾。这里提出的研究将有助于增进必要的知识，以促进和进一步开发旨在改善患有这些终生挑战的患者的生活的脑电刺激的新应用。

项目成果

Temporally-patterned deep brain stimulation in a mouse model of multiple traumatic brain injury.

多发性脑外伤小鼠模型中的时间模式深部脑刺激。

• DOI: 10.1016/j.bbr.2014.07.026
• 发表时间: 2014
• 期刊: Behavioural brain research
• 影响因子: 2.7
• 作者: Tabansky,Inna;Quinkert,AmyWells;Rahman,Nadera;Muller,SalomonZev;Lofgren,Jesper;Rudling,Johan;Goodman,Alyssa;Wang,Yingping;Pfaff,DonaldW
• 通讯作者: Pfaff,DonaldW