People with incomplete spinal cord injury (SCI) often have substantial disabilities, even after completing conventional therapy. Common motor abnormalities after SCI include spasticity and weak voluntary muscle control. Altered spinal reflex pathways contribute to these problems. In this population, exaggerated stretch reflex and abnormal reflex modification of the ankle extensors are frequently observed. Normally, spinal reflexes are modulated from standing to walking, and during walking reflexes are further modulated between different phases of the gait cycle. However, in individuals after SCI, modulation of the soleus H-reflex during walking is often absent or greatly diminished (i.e., the reflex amplitude remains high even in the early stance or swing phase, where the H-reflex is normally very small or absent). Spinal reflexes can be changed through operant conditioning. Previous work in rats and monkeys shows that successful operant conditioning of a spinal reflex changes not only the reflex pathway that is conditioned but also the activity of other spinal and supraspinal pathways. Therefore, it may be possible to guide central nervous system plasticity associated with learning to change the activity of a spinal reflex pathway such that movement disabilities can be ameliorated. The goal of this project is to investigate the impact of changing a spinal reflex on impaired locomotion after chronic incomplete SCI in people. In humans, reflex conditioning with a far smaller number of trials per day than those used in rats can produce a comparable amount of reflex change. Recent work in rats shows that soleus H-reflex operant conditioning changes soleus behavior during locomotion, and indicates that appropriate conditioning can improve locomotion after incomplete SCI. Based on these findings, this project will test two hypotheses. The first hypothesis is that, in subjects with spastic hyperreflexia due to chronic incomplete SCI, decreasing the soleus H-reflex by operant down-conditioning can improve locomotion. The second hypothesis is that, locomotion can be further improved by applying down-conditioning procedures during appropriate phases of locomotion, when the H-reflex should normally be absent. These hypotheses will be tested by applying down-conditioning of the soleus H-reflex in spastic subjects with incomplete SCI. The impact of conditioning on the locomotor EMG activity, reflex modulation during gait, gait kinematics, and walking speed will be assessed, before and after conditioning. We will also assess the persistence of these effects. We expect to find that successful H-reflex down-conditioning can improve locomotion recovery after incomplete SCI and that this improvement will persist. Successful completion of this project will facilitate development of spinal reflex operant conditioning as a new, therapeutic approach to improving motor function recovery for individuals after SCI. This new method should complement existing methods and augment restoration of useful function.

Public Health Relevance

With recent advances in acute care after spinal cord injury (SCI); which has resulted in more cases of incomplete SCI; and development of regeneration therapies; rehabilitation for functional recovery is becoming increasingly important for re-establishing an active; productive; fulfilling life in these individuals. In order to maximize functional recovery after SCI; it is extremely important to continue developing new therapeutic approaches beyond conventional rehabilitation techniques. The goal of this project is to investigate the therapeutic effects of changing a spinal reflex on impaired locomotion after chronic incomplete SCI. Successful completion of this project will open up a new therapeutic approach for treating individuals after SCI.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Musculoskeletal Rehabilitation Sciences Study Section (MRS)
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Jakeman, Lyn B
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Medical University of South Carolina
United States
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Thompson, Aiko K; Favale, Briana M; Velez, Jacqueline et al. (2018) Operant Up-Conditioning of the Tibialis Anterior Motor-Evoked Potential in Multiple Sclerosis: Feasibility Case Studies. Neural Plast 2018:4725393
Thompson, Aiko K; Wolpaw, Jonathan R (2015) Targeted neuroplasticity for rehabilitation. Prog Brain Res 218:157-72
Thompson, Aiko K; Wolpaw, Jonathan R (2015) Restoring walking after spinal cord injury: operant conditioning of spinal reflexes can help. Neuroscientist 21:203-15
Thompson, Aiko K; Wolpaw, Jonathan R (2014) The simplest motor skill: mechanisms and applications of reflex operant conditioning. Exerc Sport Sci Rev 42:82-90
Makihara, Yukiko; Segal, Richard L; Wolpaw, Jonathan R et al. (2014) Operant conditioning of the soleus H-reflex does not induce long-term changes in the gastrocnemius H-reflexes and does not disturb normal locomotion in humans. J Neurophysiol 112:1439-46
Thompson, Aiko K; Pomerantz, Ferne R; Wolpaw, Jonathan R (2013) Operant conditioning of a spinal reflex can improve locomotion after spinal cord injury in humans. J Neurosci 33:2365-75
Thompson, Aiko K; Chen, Xiang Yang; Wolpaw, Jonathan R (2013) Soleus H-reflex operant conditioning changes the H-reflex recruitment curve. Muscle Nerve 47:539-44
Makihara, Yukiko; Segal, Richard L; Wolpaw, Jonathan R et al. (2012) H-reflex modulation in the human medial and lateral gastrocnemii during standing and walking. Muscle Nerve 45:116-25
Thompson, Aiko K (2012) Interlimb coordination during locomotion: finding available neural pathways and using them for gait recovery. Clin Neurophysiol 123:635-7