Combined brain and peripheral nerve stimulation to enhance beneficial effects of

结合大脑和周围神经刺激，增强有益效果

• 批准号: 8495273
• 负责人: ADRIANA B CONFORTO
• 金额: $ 7.96万
• 依托单位: FUNDACAO FACULDADE DE MEDICINA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8495273
• 关键词: Activities of Daily Living; Address; Adult; Affect; Animals; Applications Grants; Area; Biomedical Engineering; Brain; Brazil; Cerebrovascular Disorders; Chronic Phase; Clinic; Clinical; Collaborations; Country; Coupled; Crossover Design; Data; Devices; Electric Stimulation; Equipment; Funding; Grant; Hand; Hand functions; Healthcare; Hospitals; Human; Income; Independent Living; Institution; Intervention; Investigation; Laboratories; Link; Motor; Movement; Muscle; National Institute of Neurological Disorders and Stroke; Neurologic; Neurons; Operative Surgical Procedures; Outcome; Pain; Painless; Paralysed; Patients; Performance; Peripheral; Peripheral Nerve Stimulation; Peripheral Nerves; Physiology; Placebo Effect; Placebos; Protocols documentation; Quality of life; Rehabilitation therapy; Research; Research Infrastructure; Research Personnel; Sensory; Staging; Stroke; Techniques; Testing; Therapeutic; Time; Training; Translational Research; United States National Institutes of Health; Universities; Upper Extremity; Work; design; disability; evidence base; experience; global health; improved; innovation; motor function improvement; motor impairment; multidisciplinary; neuroregulation; neurosurgery; novel; novel strategies; professor; restoration; somatosensory; stroke rehabilitation; tool; training aid

DESCRIPTION (provided by applicant): Worldwide, every other second someone suffers a stroke, the #1 cause of disability in western countries. The catastrophic burden of stroke and the scarcity of evidence-based rehabilitation interventions to decrease disability from stroke represent a major challenge to global health care. There is a gap between studies in animals demonstrating "rewiring" of neuronal circuits and availability of neurorehabilitative strategies to restore independent living in the clinical domain. Basic infrastructure to implement research in stroke rehabilitation has been developed at the Neurostimulation Laboratory at Hospital das Clmnicas/ Sao Paulo University/ Fundagao Faculdade de Medicina, Brazil, in great part due to a previous successful R21 grant funded by NIH. A strong partnership was developed between the Neurostimulation Laboratory and the Human Cortical Physiology and Stroke Rehabilitation Section at NINDS. In the R21 grant, peripheral sensory stimulation (PSS) was applied to enhance effects of training in patients in with stroke. In PSS, electrical currents are delivered to peripheral nerves, in the absence of pain. Increase in sensory input by PSS enhances excitability of brain motor areas and can improve hand motor performance, as demonstrated by results from our R-21 grant and from other studies. Another painless emerging technique to enhance motor function is transcranial direct current stimulation (tDCS) that enhances brain excitability non-invasively. Most neuromodulation research to improve motor function in stroke has focused on patients with mild hand motor impairment. This grant proposal will build on results of the R-21, by using a novel approach to treat patients with moderate to severe hand weakness in the chronic phase after stroke, to whom there are virtually no universally accepted options to decrease hand disability. In these patients, electrical currents delivered to muscles in the form of functional electrical stimulation (FES) can assist movement performance and motor training. We will combine FES, PSS and tDCS in an innovative strategy. The first aim of this grant is to compare effects of a single session of FES in close association with either tDCS alone, PSS alone, tDCS + PNS or sham tDCS + sham PSS, on motor impairment of patients with moderate to severe upper limb weakness in the chronic phase after stroke. The second aim is to compare the effects of several sessions of the most powerful neuromodulation intervention according to results of Aim 1, and effects of placebo (sham PSS/tDCS) combined with FES + task-specific training, on the ability to perform activities of daily living. In Aim 2, the interventions will be administered over six weeks to two groups of adult stroke patients with moderate to severe hand weakness. The proposed paradigm represents a step forward to break barriers in translational research by means of a multidisciplinary link. The P.I., Dr. Conforto, chief of the Neurostimulatation Laboratory in Brazil, the middle-income country (MIC) institution, will collaborate with researchers from high-income country (HIC) institutions: Dr. Leonardo Cohen, an eminent researcher that leads the Human Cortical Physiology and Stroke Rehabilitation Section at Intramural NINDS; Dr. P. Hunter Peckham, a distinguished researcher and pioneer on FES, who is Professor of Biomedical Engineering at the Case Western Reserve University; Dr. Andre Machado, Director of the Center for Neurological Restoration and Assistant Professor of Surgery in the Neurosurgery Department at the Cleveland Clinic, who has extensive experience in neuromodulation protocols. The collaboration between MIC and HIC institutions will set the stage for advancing research on non-invasive cortical neuromodulation and biomedical engineering, needed to ripen strategies for stroke rehabilitation. Equipment and facilities are available at the MIC institution that will provide full support to this proposal.

描述(申请人提供)：在世界范围内，每隔一秒钟就有人中风，这是西方国家导致残疾的头号原因。中风造成的灾难性负担以及减少中风致残的循证康复干预措施的匮乏，是全球卫生保健面临的重大挑战。在动物身上的研究证明了神经元回路的“重新连接”，与恢复临床领域独立生活的神经康复策略之间存在差距。实施中风康复研究的基本基础设施已经在巴西克拉姆尼卡斯医院/圣保罗大学/美第奇那基金会的神经刺激实验室建立，这在很大程度上要归功于之前由NIH资助的成功的R21赠款。神经刺激实验室和NINDS的人类皮质生理学和中风康复科之间建立了牢固的伙伴关系。在R21拨款中，应用外周感觉刺激(PSS)来提高中风患者的训练效果。在PSS中，电流在没有疼痛的情况下被传递到周围神经。PSS增加感觉输入增强了大脑运动区的兴奋性，并可以改善手运动能力，正如我们的R-21拨款和其他研究的结果所证明的那样。另一种无痛的增强运动功能的新兴技术是经颅直流电刺激(Tdcs)，它非侵入性地增强大脑的兴奋性。大多数改善中风患者运动功能的神经调节研究都集中在轻度手运动障碍的患者身上。这项赠款建议将以R-21的结果为基础，通过使用一种新的方法来治疗中风后慢性期中到重度手无力的患者，对这些患者来说，几乎没有普遍接受的减少手残疾的选择。在这些患者中，以功能性电刺激(FES)的形式传递到肌肉的电流可以帮助运动能力和运动训练。我们将把FES、PSS和TDC结合在一个创新的战略中。这项赠款的第一个目的是比较单一的FES治疗与单独的TDC、单独的PSS、TDC+PNS或Sham TDCs+Sham PSS密切相关的治疗对中风后慢性期中到重度上肢无力患者的运动障碍的影响。第二个目的是根据目标1的结果比较几次最强大的神经调节干预的效果，以及安慰剂(假PSS/tDCS)结合FES+任务特定训练对日常生活活动能力的影响。在目标2中，干预措施将在六周内对两组手部中度到重度无力的成年中风患者进行治疗。所提出的范式代表着通过多学科联系在翻译研究中打破障碍的一步。这位P.I.，中等收入国家(MIC)机构巴西神经刺激实验室的负责人Conforto博士将与来自高收入国家(HIC)机构的研究人员进行合作，这些研究人员包括：著名研究员Leonardo Cohen博士，NINDS人体皮质生理学和中风康复科负责人；FES的杰出研究员和先驱、凯斯西储大学生物医学工程教授P.Hunter Peckham博士；神经学恢复中心主任兼克利夫兰诊所神经外科外科助理教授Andre Machado博士，他在神经调制协议方面拥有丰富的经验。MIC和HIC机构之间的合作将为推进非侵入性皮质神经调节和生物医学工程的研究奠定基础，这是成熟中风康复策略所必需的。MIC机构提供了设备和设施，将为这项提议提供全面支持。