02092nas a2200217 4500008004100000022001400041245009800055210006900153260001200222300001100234490000700245520143300252653001301685653001501698653002301713653002701736653002001763100002201783700002101805856004801826 2015 eng d a1089-409800aRestoring walking after spinal cord injury: operant conditioning of spinal reflexes can help.0 aRestoring walking after spinal cord injury operant conditioning c04/2015 a203-150 v213 a
People with incomplete spinal cord injury (SCI) frequently suffer motor disabilities due to spasticity and poor muscle control, even after conventional therapy. Abnormal spinal reflex activity often contributes to these problems. Operant conditioning of spinal reflexes, which can target plasticity to specific reflex pathways, can enhance recovery. In rats in which a right lateral column lesion had weakened right stance and produced an asymmetrical gait, up-conditioning of the right soleus H-reflex, which increased muscle spindle afferent excitation of soleus, strengthened right stance and eliminated the asymmetry. In people with hyperreflexia due to incomplete SCI, down-conditioning of the soleus H-reflex improved walking speed and symmetry. Furthermore, modulation of electromyographic activity during walking improved bilaterally, indicating that a protocol that targets plasticity to a specific pathway can trigger widespread plasticity that improves recovery far beyond that attributable to the change in the targeted pathway. These improvements were apparent to people in their daily lives. They reported walking faster and farther, and noted less spasticity and better balance. Operant conditioning protocols could be developed to modify other spinal reflexes or corticospinal connections; and could be combined with other therapies to enhance recovery in people with SCI or other neuromuscular disorders.
10aLearning10aLocomotion10aspinal cord injury10aspinal cord plasticity10aspinal reflexes1 aThompson, Aiko, K1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/2463695402145nas a2200217 4500008004100000022001400041245008500055210006900140260001200209300000700221490000600228520150000234653001301734653002401747653001501771653002301786653002701809100002201836700002101858856004801879 2014 eng d a1662-514500aOperant conditioning of spinal reflexes: from basic science to clinical therapy.0 aOperant conditioning of spinal reflexes from basic science to cl c03/2014 a250 v83 aNew appreciation of the adaptive capabilities of the nervous system, recent recognition that most spinal cord injuries are incomplete, and progress in enabling regeneration are generating growing interest in novel rehabilitation therapies. Here we review the 35-year evolution of one promising new approach, operant conditioning of spinal reflexes. This work began in the late 1970's as basic science; its purpose was to develop and exploit a uniquely accessible model for studying the acquisition and maintenance of a simple behavior in the mammalian central nervous system (CNS). The model was developed first in monkeys and then in rats, mice, and humans. Studies with it showed that the ostensibly simple behavior (i.e., a larger or smaller reflex) rests on a complex hierarchy of brain and spinal cord plasticity; and current investigations are delineating this plasticity and its interactions with the plasticity that supports other behaviors. In the last decade, the possible therapeutic uses of reflex conditioning have come under study, first in rats and then in humans. The initial results are very exciting, and they are spurring further studies. At the same time, the original basic science purpose and the new clinical purpose are enabling and illuminating each other in unexpected ways. The long course and current state of this work illustrate the practical importance of basic research and the valuable synergy that can develop between basic science questions and clinical needs.10aH-Reflex10alearning and memory10aLocomotion10aspinal cord injury10aspinal cord plasticity1 aThompson, Aiko, K1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/2467244102425nas a2200289 4500008004100000022001400041245008700055210006900142260001200211300001200223490000800235520161100243653002601854653001301880653001501893653001101908653001801919653001901937653002301956653002701979100001302006700001302019700001302032700002102045700002102066856004802087 2014 eng d a1522-159800aPersistent beneficial impact of H-reflex conditioning in spinal cord-injured rats.0 aPersistent beneficial impact of Hreflex conditioning in spinal c c11/2014 a2374-810 v1123 aOperant conditioning of a spinal cord reflex can improve locomotion in rats and humans with incomplete spinal cord injury. This study examined the persistence of its beneficial effects. In rats in which a right lateral column contusion injury had produced asymmetric locomotion, up-conditioning of the right soleus H-reflex eliminated the asymmetry while down-conditioning had no effect. After the 50-day conditioning period ended, the H-reflex was monitored for 100 [±9 (SD)] (range 79-108) more days and locomotion was then reevaluated. After conditioning ended in up-conditioned rats, the H-reflex continued to increase, and locomotion continued to improve. In down-conditioned rats, the H-reflex decrease gradually disappeared after conditioning ended, and locomotion at the end of data collection remained as impaired as it had been before and immediately after down-conditioning. The persistence (and further progression) of H-reflex increase but not H-reflex decrease in these spinal cord-injured rats is consistent with the fact that up-conditioning improved their locomotion while down-conditioning did not. That is, even after up-conditioning ended, the up-conditioned H-reflex pathway remained adaptive because it improved locomotion. The persistence and further enhancement of the locomotor improvement indicates that spinal reflex conditioning protocols might supplement current therapies and enhance neurorehabilitation. They may be especially useful when significant spinal cord regeneration becomes possible and precise methods for retraining the regenerated spinal cord are needed.
10aH-reflex conditioning10aLearning10aLocomotion10aMemory10aMotor control10aRehabilitation10aspinal cord injury10aspinal cord plasticity1 aChen, Yi1 aChen, Lu1 aWang, Yu1 aWolpaw, Jonathan1 aChen, Xiang Yang uhttp://www.ncbi.nlm.nih.gov/pubmed/2514354201903nas a2200301 4500008004100000022001400041245010700055210006900162260001200231300001800243490000700261520101900268653002601287653001301313653001501326653001101341653001801352653001901370653002301389653002701412100001301439700002101452700002101473700001301494700002501507700002101532856004801553 2006 eng d a1529-240100aOperant conditioning of H-reflex can correct a locomotor abnormality after spinal cord injury in rats.0 aOperant conditioning of Hreflex can correct a locomotor abnormal c11/2006 a12537–125430 v263 aThis study asked whether operant conditioning of the H-reflex can modify locomotion in spinal cord-injured rats. Midthoracic transection of the right lateral column of the spinal cord produced a persistent asymmetry in the muscle activity underlying treadmill locomotion. The rats were then either exposed or not exposed to an H-reflex up-conditioning protocol that greatly increased right soleus motoneuron response to primary afferent input, and locomotion was reevaluated. H-reflex up-conditioning increased the right soleus burst and corrected the locomotor asymmetry. In contrast, the locomotor asymmetry persisted in the control rats. These results suggest that appropriately selected reflex conditioning protocols might improve function in people with partial spinal cord injuries. Such protocols might be especially useful when significant regeneration becomes possible and precise methods for reeducating the regenerated spinal cord neurons and synapses are needed for restoring effective function.
10aH-reflex conditioning10aLearning10aLocomotion10aMemory10aMotor control10aRehabilitation10aspinal cord injury10aspinal cord plasticity1 aChen, Yi1 aChen, Xiang Yang1 aJakeman, Lyn, B.1 aChen, Lu1 aStokes, Bradford, T.1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/1713541502708nas a2200289 4500008004100000022001400041245010300055210006900158260001200227300001600239490000700255520184500262653002602107653001302133653001502146653002502161653001802186653001902204653002702223100001302250700002102263700002102284700001902305700002502324700002102349856004802370 2005 eng d a1529-240100aThe interaction of a new motor skill and an old one: H-reflex conditioning and locomotion in rats.0 ainteraction of a new motor skill and an old one Hreflex conditio c07/2005 a6898–69060 v253 aNew and old motor skills can interfere with each other or interact in other ways. Because each skill entails a distributed pattern of activity-dependent plasticity, investigation of their interactions is facilitated by simple models. In a well characterized model of simple learning, rats and monkeys gradually change the size of the H-reflex, the electrical analog of the spinal stretch reflex. This study evaluates in normal rats the interactions of this new skill of H-reflex conditioning with the old well established skill of overground locomotion. In rats in which the soleus H-reflex elicited in the conditioning protocol (i.e., the conditioning H-reflex) had been decreased by down-conditioning, the H-reflexes elicited during the stance and swing phases of locomotion (i.e., the locomotor H-reflexes) were also smaller. Similarly, in rats in which the conditioning H-reflex had been increased by up-conditioning, the locomotor H-reflexes were also larger. Soleus H-reflex conditioning did not affect the duration, length, or right/left symmetry of the step cycle. However, the conditioned change in the stance H-reflex was positively correlated with change in the amplitude of the soleus locomotor burst, and the correlation was consistent with current estimates of the contribution of primary afferent input to the burst. Although H-reflex conditioning and locomotion did not interfere with each other, H-reflex conditioning did affect how locomotion was produced: it changed soleus burst amplitude and may have induced compensatory changes in the activity of other muscles. These results illustrate and clarify the subtlety and complexity of skill interactions. They also suggest that H-reflex conditioning might be used to improve the abnormal locomotion produced by spinal cord injury or other disorders of supraspinal control.10aH-reflex conditioning10aLearning10aLocomotion10amemory consolidation10aMotor control10aRehabilitation10aspinal cord plasticity1 aChen, Yi1 aChen, Xiang Yang1 aJakeman, Lyn, B.1 aSchalk, Gerwin1 aStokes, Bradford, T.1 aWolpaw, Jonathan uhttp://www.ncbi.nlm.nih.gov/pubmed/16033899