Operant conditioning of sensory evoked potentials to reduce phantom limb pain

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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).