Central thalamic stimulation for traumatic brain injury

中枢丘脑刺激治疗创伤性脑损伤

• 批准号: 9323683
• 负责人: CHRISTOPHER R BUTSON
• 金额: $ 4.18万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9323683
• 关键词: Acute; Advanced Development; Adverse effects; American; Anterior; Arousal; Attention; Behavior; Behavior Control; Behavioral; Bilateral; Brain; Brain Injuries; Cells; Chronic; Clinical; Clinical Research; Clinical Trials; Cognitive; Cognitive deficits; Collaborations; Computer Simulation; 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; Health; Human; Image; Impaired cognition; Impairment; Implant; In Situ; Individual; Lead; Life; Link; Maps; Measurement; Measures; Medial; Mediating; Mental Health; Microelectrodes; Mission; Modeling; Mus; National Institute of Neurological Disorders and Stroke; Neurology; Neurons; Neuropsychology; Neurorehabilitation; 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; Statistical Models; Survivors; System; TBI Patients; Technology; Testing; Thalamic structure; Therapeutic Intervention; Translating; Traumatic Brain Injury; United States Food and Drug Administration; Variant; Work; base; biophysical model; cognitive capacity; cognitive disability; cognitive function; daily functioning; effective therapy; electric field; executive function; flexibility; functional disability; functional improvement; human subject; implantation; improved; memory process; neuroimaging; neurophysiology; neuropsychological; neurosurgery; next generation; nonhuman primate; patient population; pre-clinical; preclinical study; processing speed; response; safety testing; social; targeted delivery; technology development; treatment response; willingness

 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（由适用提供）：每年严重至现代化的创伤性脑损伤（SMTBI）每年都会折磨成千上万的美国人，他们产生缺乏有效治疗的慢性认知障碍。本提案将开发一项关键的首先临床可行性研究，以支持下一代丘脑深脑刺激（CT-DBS）的下一代装置。提议CT-DBS作为SMTBI存活的一种疗法，SMTBI恢复到独立的功能水平，但在其活动中仍然显着限制B慢性认知障碍（在持续的注意力努力，工作记忆，处理速度和疲劳方面持续了困难）。利益相关者，包括确定其认知难度与CT-DBS支持的功能相匹配的患者，已显示出对这种方法的支持，并在提出了这种方法的概念和风险之后愿意考虑参与。 The working hypothesis for the present study is that the pattern of cognitive definitions 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 deathentation 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适当地提供有效的功能改进。初步研究包括在不同，更严重的脑部受伤性脑损伤患者中以及临床前行为，电生理学和计算模型研究中，在完整的非人类隐私（NHP）中支持该假设和方法中的临床前行为，电生理学和计算建模研究。本研究将使用具有灵敏度和记录能力的研究单电极系统的双边放置，以帮助中央丘兰姆的电生理图。我们的支持数据表明，在人和NHP中，单个电极系统都可以实现行为设施。在NHP研究中，我们发现，通过使用能够在中央丘兰姆中特定的纤维道上靶向传递电场的多个电极系统，可以实现更可靠，更健壮的治疗反应。在这里，我们将获取并分析来自人类受试者的神经影像学，计算建模，行为和电生理数据，以提高下一代系统的发展，该系统可能允许在患者中应用CT-DBS的更灵活性和可靠性 脑损伤。这些研究将由一个调查团队进行，旨在开发CT-DBS技术和TBI后认知障碍的治疗。该团队跨越了临床试验，神经病学，神经外科，神经生理学，神经康复，神经心理学，放射学和计算建模方面的专业知识。提出的早期可行性研究是通过对食品药品监督管理局的调查装置豁免的预审审查。