权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Central thalamic stimulation for traumatic brain injury

中枢丘脑刺激治疗创伤性脑损伤

基本信息

批准号：
10246247
负责人：
CHRISTOPHER R BUTSON
金额：
$ 127.1万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10246247
关键词：
Acute Advanced Development Adverse effects American Anatomy Anterior Arousal Attention Behavior Behavior Control Behavioral Behavioral Model Bilateral Brain Brain Injuries Cells Chronic Clinical Clinical Research Clinical Trials Cognitive Cognitive deficits Collaborations Computer Models Data Databases Deafferentation procedure Deep Brain Stimulation Deterioration Development Device Designs Devices Diffusion Magnetic Resonance Imaging Dorsal Down-Regulation Electrodes Electrophysiology (science)Elements Family Fatigue Feasibility Studies Fiber Funding Glasgow Outcome Scale Goals Human Impaired cognition Impairment Implant Individual Investigation Lead Link Measurement Measures Medial Mediating Mental Health Microelectrodes Mission Modeling Mus National Institute of Neurological Disorders and Stroke Neurology Neurons Neuropsychology Outcome Outcome Measure Pathology Patients Pattern Performance Physiological Population Positioning Attribute Primates Prosencephalon Psychometrics Public Health Quality of life Radiology Specialty Recovery Regulation Research Resolution Resources Risk Safety Severities Short-Term Memory Sleep Societies Standardization Statistical Models Study models Survivors System TBI Patients Technology Testing Thalamic structure Therapeutic Intervention Translating Traumatic Brain Injury United States Food and Drug Administration Variant base biophysical model clinical development cognitive capacity cognitive disability cognitive function daily functioning effective therapy electric field executive function flexibility functional disability functional improvement human data human imaging human subject imaging study implantation improved in situ imaging neuroimaging neurological rehabilitation neurophysiology neurosurgery next generation nonhuman primate patient population pre-clinical preclinical study processing speed public health relevance response safety testing social engagement sustained attention targeted delivery technology development therapeutically effective treatment response willingness

项目摘要

DESCRIPTION (provided by applicant): Severe to moderate traumatic brain injury (smTBI) annually afflicts many hundreds of thousands of Americans producing chronic cognitive disabilities that lack effective treatments. The present proposal will develop a critical first-in-an early clinical feasibility study to support a next generation device to provide central thalamic deep brain stimulation (CT-DBS). CT-DBS is proposed as a therapy for the survivors of smTBI who recover to independent functional levels but remain significantly limited in their activities b chronic cognitive impairment (difficulties with sustained attentional effort, working memory, processing speed and fatigue). Stakeholders, including patients identifying their cognitive difficulties as matched to the functions proposed to be supported by CT-DBS, have shown support for this approach and willingness to consider participation after having the concepts and risks of this approach presented to them. The working hypothesis for the present study is that the pattern of cognitive deficits seen after smTBI takes origin in a broad reduction of neuronal connections and cell loss produced by smTBI that will on average produce disproportionate down-regulation of frontostriatal systems and deafferentation of the central thalamus (which collectively support the range of executive cognitive functions typically impaired in smTBI), and that CT-DBS can activate these systems sufficiently to provide effective functional improvements. Preliminary studies including evidence of CT-DBS facilitation of cognitive function in a different, more severely brain-injured population of patients with traumatic brain injuries as well as pre-clinical behavioral, electrophysiological, and computational modeling studies in intact non-human primates (NHP) support the hypothesis and the approach. The present study will use bilateral placement of a research single- electrode system with sensing and recording capabilities to aid the electrophysiological mapping of the central thalamus. Our supporting data demonstrate that behavioral facilitation can be achieved with a single electrode system in both the human and NHP. In NHP studies we have found that a more reliable and robust therapeutic response can be achieved through the use of a multiple electrode system capable of targeted delivery of electric fields across a specific fiber tract in the central thalams. Here we will obtain and analyze neuroimaging, computational modeling, behavioral, and electrophysiological data from human subjects to advance the development of a next-generation system that may allow more flexibility and reliability of for the application of CT-DBS in patients with traumatic brain injuries. These studies will be carried out by an investigative team with multiple, long-standing collaborations aimed at the development of CT-DBS technologies and treatment of cognitive impairment following TBI; the team spans expertise in clinical trials, neurology, neurosurgery, neurophysiology, neurorehabilitation, neuropsychology, radiology, and computational modeling. The early feasibility study proposed has been through a presubmission review for an Investigational Device Exemption with the Food and Drug Administration.

描述（由申请人提供）：每年有数十万美国人遭受重度至中度创伤性脑损伤（smTBI）的折磨，产生慢性认知障碍，且缺乏有效的治疗方法。目前的提案将开发一项关键的早期临床可行性研究，以支持下一代提供中枢丘脑深部脑刺激（CT-DBS）的设备。 CT-DBS 被提议作为 smTBI 幸存者的一种治疗方法，这些幸存者恢复到独立功能水平，但由于慢性认知障碍（持续注意力、工作记忆、处理速度和疲劳方面的困难），其活动仍然受到明显限制。利益相关者，包括那些认为自己的认知困难与 CT-DBS 支持的功能相匹配的患者，在向他们介绍了这种方法的概念和风险后，表示支持这种方法并愿意考虑参与。本研究的工作假设是，smTBI 后出现的认知缺陷模式源于 smTBI 产生的神经元连接广泛减少和细胞丢失，这平均会导致额纹状体系统不成比例的下调和中央丘脑的传入阻滞（共同支持 smTBI 中通常受损的执行认知功能范围），并且 CT-DBS 可以充分激活这些系统以提供有效的功能改进。初步研究包括 CT-DBS 在不同的、更严重的脑外伤患者群体中促进认知功能的证据，以及在完整的非人类灵长类动物 (NHP) 中进行的临床前行为、电生理学和计算模型研究，支持了这一假设和方法。本研究将使用具有传感和记录功能的研究单电极系统的双边放置来帮助中央丘脑的电生理图绘制。我们的支持数据表明，使用单个电极系统可以在人类和 NHP 中实现行为促进。在 NHP 研究中，我们发现通过使用能够在丘脑中央特定纤维束上定向输送电场的多电极系统，可以实现更可靠、更稳健的治疗反应。在这里，我们将获取并分析来自人类受试者的神经影像、计算模型、行为和电生理学数据，以推进下一代系统的开发，该系统可能为患者的 CT-DBS 应用提供更大的灵活性和可靠性患有脑外伤。这些研究将由一个长期合作的调查小组进行，旨在开发 CT-DBS 技术和治疗 TBI 后的认知障碍；该团队涵盖临床试验、神经病学、神经外科、神经生理学、神经康复、神经心理学、放射学和计算模型方面的专业知识。拟议的早期可行性研究已通过美国食品和药物管理局研究设备豁免的提交前审查。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies.

DOI：
10.1038/s41582-020-00428-x
发表时间：
2021-03
期刊：
Nature reviews. Neurology
影响因子：
0
作者：
Edlow BL;Claassen J;Schiff ND;Greer DM
通讯作者：
Greer DM

Improved Vim targeting for focused ultrasound ablation treatment of essential tremor: A probabilistic and patient-specific approach.

DOI：
10.1002/hbm.25157
发表时间：
2020-12
期刊：
Human brain mapping
影响因子：
4.8
作者：
Su JH;Choi EY;Tourdias T;Saranathan M;Halpern CH;Henderson JM;Pauly KB;Ghanouni P;Rutt BK
通讯作者：
Rutt BK

Targeting Neuronal Fiber Tracts for Deep Brain Stimulation Therapy Using Interactive, Patient-Specific Models.

使用交互式、患者特异性模型针对神经元纤维束进行深部脑刺激治疗。