Operant conditioning of sensory evoked potentials to reduce phantom limb pain

感觉诱发电位的操作性条件反射可减少幻肢痛

• 批准号: 10703170
• 负责人: Jodi ANN Brangaccio
• 金额: --
• 依托单位: STRATTON VETERANS ADMIN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703170
• 关键词: Affect; American; Amputation; Analgesics; Animals; Area; Attention; Back Pain; Blinded; Brain; Central Nervous System Diseases; Chronic; Clonus; Cognition; Complement; Contralateral; Control Groups; Data; Deep Brain Stimulation; Dependence; Development; Dimensions; Discrimination; Disease; Drug Addiction; Electroencephalography; Equipment and supply inventories; Esthesia; Evoked Potentials; Extensor; Feedback; Foot-drop; Future; H-Reflex; Home; Human; Impairment; Intervention; Job loss; Leg; Limb structure; Locomotion; Measures; Motor Cortex; Motor Evoked Potentials; Movement; Nervous System; Neuronal Plasticity; Nonpharmacologic Therapy; Operant Conditioning; Outcome; Pain; Pain Research; Painless; Peripheral; Persons; Phantom Limb; Phantom Limb Pain; Pharmaceutical Preparations; Physiology; Protocols documentation; Psychological reinforcement; Quality of life; Randomized; Recovery of Function; Research; Scalp structure; Sensory; Sensory Physiology; Signal Transduction; Site; Soleus Muscle; Somatosensory Cortex; Somatosensory Evoked Potentials; Spinal cord injury; Stimulus; Stroke; System; Tactile; Telemedicine; Testing; Training; Transcranial magnetic stimulation; Treatment Efficacy; Veterans; Walking; West Haven-Yale Multidimensional Pain Inventory; Work; arm; arm function; brain machine interface; central pain; chronic painful condition; conditioning; expectation; follow-up; grasp; hand dysfunction; improved; innovation; interest; limb amputation; limb loss; method development; novel; novel therapeutics; pain reduction; pain sensation; response; restoration; sensory cortex; social; somatosensory; success; tactile stimulation; visual feedback

Abstract/ project summary Among the two million Americans who have lost a limb, including 96,519 Veterans, 60-90% have a sensation of pain in the amputated limb– called phantom limb pain (PLP). PLP can last for years and lead to drug dependence, job loss, and poor quality of life. Limb amputation leads to abnormal sensory and motor cortex reorganization, which is associated with PLP. Restoration of more normal cortical organization is associated with reduced PLP. Current therapies have aimed to restore organization in the motor cortex with little focus on sensory processing, which is also crucial in effective movement. These have shown success, but their efficacy remains unclear. We hypothesize that restoring somatosensory cortex organization will be vital in reducing PLP. Sensory loss correlates with a small or delayed evoked potential in brain signals recorded from the scalp. We will develop and test a novel noninvasive non-pharmacological therapy which works by training a person to increase their somatosensory evoked potentials (SEPs). This targeted neuroplasticity protocol is based on operant conditioning, and was developed by our research group, over the past 40 years, to target plasticity to specific sites in the nervous system. We have shown, and others have confirmed, that these targeted neuroplasticity protocols can enhance recovery of function in people and animals with spinal cord injury, stroke, and other disorders. SEPs can also be conditioned, and affect function, as has been shown in few studies. We aim to develop a protocol for up-conditioning SEPs, with our targeted conditioning approach, in people with phantom limb pain, with the expectation that it will improve the cortical organization of the sensory cortex and help reduce the pain, with longer lasting effects. We will first optimize the conditioning protocol and test it in 10 healthy Veterans, and then apply it in 20 Veterans with PLP. The SEPs for the phantom limb will be elicited for non-painful tactile stimuli, with the well-known mirror effect–i.e. the stimuli is applied to the intact limb and its reflection is viewed in the mirror, evoking an electrical evoked response in the somatosensory cortex contralateral to the phantom limb. Our preliminary tests in person with intact arms and a person with amputated arm, shows that this is possible. The study will assess the feasibility of the intervention in Veterans with PLP, across 26 one-hr sessions, over 9-weeks (3 sess/week). They will be randomly assigned to a Conditioning or a Control group, 10 people per group; where Control group will receive equal amount of stimulation as the conditioning group, but no conditioning feedback. This intervention will be performed with our well established Evoked Potential Operant Conditioning System (EPOCS), that has been developed and used successfully, by us and others, over the past decade, for similar conditioning studies. We will assess the impact of SEP conditioning on function–pain, quality of life, tactile acuity, attention/cognition, and physiology–sensory and motor cortical organization, excitability and functional connectivity. We expect that SEP conditioning will reduce pain, and improve the sensory-motor cortical organization, excitability and sensorimotor functional connectivity for the phantom limb. It may also improve tactile acuity, QoL and attention –assessed as exploratory outcomes. These improvements will persist for at least 6 months. These effects will be larger for the Conditioning group, relative to the Control group. We expect that these initial results will provide support for subsequent larger studies that enable us to further assess the therapeutic efficacy of SEP up-conditioning for reducing PLP, improving cortical organization, reducing medication dependence, and enhancing QoL in Veterans with amputations. This would also advance method development for pain research for other CNS disorders that affect many Veterans (e.g., stroke, spinal cord injury, chronic central pain, back pain).

摘要/项目摘要 在失去肢体的200万美国人中，包括96,519名退伍军人，有60-90％的美国人有一个 截肢肢体中疼痛的感觉称为幻影肢体疼痛（PLP）。 PLP可以持续多年，并导致 药物依赖，失业和生活质量差。肢体截肢导致异常感觉和运动 皮质重组，与PLP相关。恢复更普通的皮质组织是 与PLP减少有关。当前的疗法旨在通过使用 几乎没有关注感官处理，这对于有效运动也至关重要。这些表现出成功，但是 他们的效率尚不清楚。我们假设恢复体感皮质组织对 减少PLP。感官丧失与从记录的大脑信号中的较小或延迟的诱发潜力相关 头皮。我们将开发和测试一种新型的非侵入性非药物疗法，该疗法通过训练 增加其体感诱发潜力（SEP）的人。该针对的神经可塑性方案是 基于运营条件，并由我们的研究小组在过去40年中开发 神经系统中特定部位的可塑性。我们已经表明，其他人已经证实了这些 有针对性的神经可塑性方案可以增强脊髓人和动物的功能恢复 受伤，中风和其他疾病。 SEP也可以调节并影响功能，如所示 很少的研究。 我们旨在通过我们的目标调节方法制定一种用于上限SEP的协议 幻影肢体疼痛，期望它将改善感觉皮质的皮质组织 并有助于减轻疼痛，持久影响更长。我们将首先优化调理协议并进行测试 在10位健康的退伍军人中，然后将其涂在20名带有PLP的退伍军人中。幻影肢的sep将是 引起了非吸引人的触觉刺激，具有众所周知的镜像效果 - i.e。刺激应用于完整 肢体及其反射在镜子中观看，唤起体感中的电诱发响应 皮质与幻影肢体对侧。我们的初步测试亲自进行了完整的武器和一个人 截肢手臂，表明这是可能的。该研究将评估退伍军人干预的可行性 与PLP一起进行26个小时的课程，超过9周（每周3次）。他们将被随机分配给 条件或对照组，每组10人；对照组将获得相等数量的地方 刺激为调节组，但没有调节反馈。这种干预将与我们一起进行 已开发和使用的良好诱发的潜在操作调节系统（EPOC） 在过去的十年中，我们和其他人成功地完成了类似的条件研究。 我们将评估SEP调节对功能，生活质量，触觉敏锐度的影响， 注意/认知，生理学 - 感官和运动皮质组织，令人兴奋和功能 连接性。我们预计SEP调节会减轻疼痛，并改善感觉运动皮质 幻影肢体的组织，激动和感觉运动功能连接。它也可能有所改善 触觉敏锐度，质量和注意力 - 评估为探索性结果。这些改进将持续到AT 至少6个月。相对于对照组，这些效果对于调节组将更大。 我们希望这些初始结果将为随后的大型研究提供支持，使我们能够 进一步评估SEP上调节的治疗效率，以减少PLP，改善皮质 组织，减少用药依赖性，并在截肢的退伍军人中增强QoL。这会 还可以推进针对影响许多退伍军人的其他中枢神经系统疾病的疼痛研究的方法开发（例如 中风，脊髓损伤，慢性中心疼痛，背痛）。