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(由申请人提供)：严重至中度创伤性脑损伤(SMTBI)每年困扰着数十万美国人，他们患有慢性认知障碍，缺乏有效的治疗。目前的提案将开发一项关键的早期临床可行性研究，以支持提供中央丘脑深部脑刺激(CT-DBS)的下一代设备。CT-DBS被认为是一种治疗SMTBI幸存者的方法，这些幸存者恢复到独立的功能水平，但他们的活动仍然明显受限于慢性认知损害(持续注意力努力、工作记忆、处理速度和疲劳的困难)。利益相关者，包括认为他们的认知困难与CT-DBS建议支持的功能相匹配的患者，在向他们展示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后出现的认知障碍模式起源于SMTBI所产生的神经元连接和细胞丢失的广泛减少，这平均将导致额纹状体系统不成比例的下调和中央丘脑的去传入(这些共同支持SMTBI通常受损的一系列执行认知功能)，并且CT-DBS可以充分激活这些系统，以提供有效的功能改善。初步研究包括CT-DBS在不同的、更严重的脑损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)中的临床前行为、电生理和计算模型研究支持这一假设和方法。本研究将使用具有传感和记录能力的研究性单电极系统的双边放置来辅助中央丘脑的电生理标测。我们的支持数据表明，在人类和NHP中，使用单一电极系统都可以实现行为促进。在NHP研究中，我们发现，通过使用能够通过中央丘脑特定纤维束定向传递电场的多电极系统，可以实现更可靠和更强大的治疗反应。在这里，我们将获得和分析来自人类受试者的神经成像、计算建模、行为和电生理数据，以推动下一代系统的开发，该系统可能会使CT-DBS在患者中的应用更加灵活和可靠 有创伤性脑损伤。这些研究将由一个研究团队进行，该团队与多个长期合作，旨在开发CT-DBS技术和治疗脑外伤后的认知障碍；该团队拥有临床试验、神经学、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。拟议的早期可行性研究已经通过了食品和药物管理局对调查设备豁免的预提交审查。