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

基本信息

项目摘要

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200万失去肢体的美国人中,包括96,519名退伍军人,60%-90%的人有肢体残疾 截肢时的痛感--称为幻肢痛(PLP)。PLP可以持续数年,并导致 药物依赖、失业和糟糕的生活质量。截肢导致感觉和运动异常 皮质重组,这与PLP有关。更正常的皮质组织的恢复是 与PLP降低相关。目前的治疗方法旨在通过以下方式恢复运动皮质的组织 很少关注感觉处理,这也是有效运动的关键。这些都显示出了成功,但 它们的疗效尚不清楚。我们假设,恢复躯体感觉皮层组织将在 降低PLP。感觉丧失与脑信号中小的或延迟的诱发电位有关 头皮。我们将开发和测试一种新的非侵入性非药物疗法,这种疗法通过培训一名 增加他们的体感诱发电位(SEP)。这种有针对性的神经可塑性方案是 基于操作性条件反射,由我们的研究小组在过去40年中开发,以 神经系统中特定部位的可塑性。我们已经证明,其他人也证实了,这些 靶向神经可塑性方案可促进人和动物脊髓功能的恢复 受伤、中风和其他疾病。SEP也可以受到限制,并影响功能,如中所示 很少有研究。 我们的目标是开发一种通过我们的靶向条件作用方法,在人体内上调SEP的方案 幻肢疼痛,期望它能改善感觉皮质的皮质组织 有助于减轻疼痛,产生更持久的效果。我们将首先优化条件化协议并进行测试 健康退伍军人10例,退伍军人PLP 20例。幻肢的SEP将是 为非痛苦的触觉刺激而激发,具有众所周知的镜像效应-即刺激应用于完好无损的 在镜子中可以看到肢体及其反射,在躯体感觉中唤起电诱发反应 与幻肢对侧的皮质。我们的初步测试是由手臂完好的人和一个 截肢,表明这是可能的。这项研究将评估对退伍军人进行干预的可行性 对于PLP,跨越26个一小时的疗程,超过9周(3次/周)。他们将被随机分配到一个 调理或对照组,每组10人;其中对照组将获得等量的 刺激为条件反射组,但无条件反射。此干预将与我们的 已经开发和使用的成熟的诱发电位操作条件反射系统(EPOCS) 在过去的十年里,我们和其他人成功地进行了类似的条件反射研究。 我们将评估SEP条件反射对功能-疼痛、生活质量、触觉敏锐度、 注意力/认知、生理学-感觉和运动皮质组织、兴奋性和功能性 连通性。我们预计SEP调节将减轻疼痛,并改善感觉-运动皮质 幻肢的组织、兴奋性和感觉运动功能连接。它也可能会改善 触觉敏锐度、生活质量和注意力--评估为探索性结果。这些改进将持续到 至少6个月。与对照组相比,调理组的这些影响会更大。 我们预计,这些初步结果将为后续更大规模的研究提供支持,使我们能够 进一步评价SEP上调术降低PLP、改善皮质功能的疗效 组织,减少药物依赖,提高截肢退伍军人的生活质量。这将会 还推进了影响许多退伍军人的其他中枢神经系统障碍的疼痛研究方法开发(例如, 中风、脊髓损伤、慢性中枢性疼痛、背部疼痛)。

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