Operant conditioning of spinal reflexes: from basic science to clinical therapy

New 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

H-reflex modulation in the human medial and lateral gastrocnemii during standing and walking

The soleus H-reflex is dynamically modulated during walking. However, modulation of the gastrocnemii H-reflexes has not been studied systematically

Operant down-conditioning of the soleus H-reflex in people after stroke

Through operant conditioning, spinal reflex behaviors can be changed. Previous studies in rats indicate that the sensorimotor cortex and corticospinal tract are essential in inducing and maintaining reflex changes induced through conditioning. In people with incomplete spinal cord injury (SCI), an operant down-conditioning protocol decreased the soleus H-reflex size and improved walking speed and symmetry, suggesting that a partially preserved spinal cord can support conditioning-induced plasticity and benefit from it. This study examined whether down-conditioning can decrease the soleus H-reflex in people with supraspinal injury (i.e., cortical or subcortical stroke). Operant down-conditioning was applied to the soleus H-reflex in a cohort of 12 stroke people with chronic spastic hemiparesis (>12 months from stroke onset of symptoms). Each participant completed 6 baseline and 30 conditioning sessions over 12 weeks. In each baseline session, 225 control H-reflexes were elicited without any feedback on H-reflex size. In each conditioning session, 225 conditioned H-reflexes were elicited while the participant was asked to decrease H-reflex size and was given visual feedback as to whether the resulting H-reflex was smaller than a criterion value. In six of 12 participants, the conditioned H-reflex became significantly smaller by 30% on average, whereas in other 6 participants, it did not. The difference between the subgroups was largely attributable to the difference in across-session control reflex change. Ten-meter walking speed was increased by various extent (+0.04 to +0.35, +0.14 m/s on average) among the six participants whose H-reflex decreased, whereas the change was 0.00 m/s on average for the rest of participants. Although less than what was seen in participants with SCI, the fact that conditioning succeeded in 50% of stroke participants supports the feasibility of reflex down-conditioning in people after stroke. At the same time, the difference in across-session control reflex change and conditioning success rate may reflect a critical role of supraspinal activity in producing long-term plasticity in the spinal cord, as previous animal studies suggested

Maximum Upper Esophageal Sphincter (UES) Admittance: A Non-Specific Marker of UES Dysfunction

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'.© 2015 John Wiley & Sons LtdBackground Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. Methods Sixty-six healthy subjects (n = 50 controls 20–80 years; n = 16 elderly >80 years), 11 patients with CPB (51–83 years) and 16 with MND (58–91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. Key Results In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. Conclusions & Inferences The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction

Impaired bolus clearance in asymptomatic older adults during high resolution impedance manometry

12892This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving. This author accepted manuscript is made available following 12 month embargo from date of publication (26 June 2016) in accordance with the publisher's copyright policy.Background Dysphagia becomes more common in old age. We performed high-resolution impedance manometry (HRIM) in asymptomatic healthy adults (including an older cohort >80 years) to assess HRIM findings in relation to bolus clearance. Methods Esophageal HRIM was performed in a sitting posture in 45 healthy volunteers (n = 30 young control, mean age 37 ± 11 years and n = 15 older subjects aged 85 ± 4 years) using a 3.2-mm solid-state catheter (Solar GI system; MMS, Enschede, The Netherlands) with 25 pressure (1-cm spacing) and 12 impedance segments (2-cm intervals). Five swallows each of 5- and 10-mL liquid and viscous bolus were performed and analyzed using esophageal pressure topography metrics and Chicago classification criteria as well as pressure-flow parameters. Bolus transit was determined using standard impedance criteria. A p-value <0.05 was considered significant. Key Results Impaired bolus clearance occurred more frequently in asymptomatic older subjects compared with young controls (YC) during liquid (40 vs 18%, χ2 = 4.935; p < 0.05) and viscous (60 vs 17%; χ2 = 39.08; p < 0.001) swallowing. Longer peristaltic breaks (p < 0.05) and more rapid peristalsis (L: p < 0.004, V: p = 0.003) occurred in the older cohort, with reduced impedance-based clearance for both bolus consistencies (L: p < 0.05, V: p < 0.001). Decreased peristaltic vigor (distal contractile integral <450 mmHg/s/cm) was associated with reduced liquid clearance in both age groups (p < 0.001) and of viscous swallows in the older group (p < 0.001). Impedance ratio, a marker of bolus retention, was increased in older subjects during liquid (p = 0.002) and viscous (p < 0.001) swallowing. Conclusions & Inferences Impaired liquid and viscous bolus clearance, esophageal pressure topography, and pressure-flow changes were seen in asymptomatic older subjects

Effects of Sensorimotor Rhythm Modulation on the Human Flexor Carpi Radialis H-Reflex

People can learn over training sessions to increase or decrease sensorimotor rhythms (SMRs) in the electroencephalogram (EEG). Activity-dependent brain plasticity is thought to guide spinal plasticity during motor skill learning; thus, SMR training may affect spinal reflexes and thereby influence motor control. To test this hypothesis, we investigated the effects of learned mu (8–13 Hz) SMR modulation on the flexor carpi radialis (FCR) H-reflex in 6 subjects with no known neurological conditions and 2 subjects with chronic incomplete spinal cord injury (SCI). All subjects had learned and practiced over more than 10 &lt; 30-min training sessions to increase (SMR-up trials) and decrease (SMR-down trials) mu-rhythm amplitude over the hand/arm area of left sensorimotor cortex with ≥80% accuracy. Right FCR H-reflexes were elicited at random times during SMR-up and SMR-down trials, and in between trials. SMR modulation affected H-reflex size. In all the neurologically normal subjects, the H-reflex was significantly larger [116% ± 6 (mean ± SE)] during SMR-up trials than between trials, and significantly smaller (92% ± 1) during SMR-down trials than between trials (p &lt; 0.05 for both, paired t-test). One subject with SCI showed similar H-reflex size dependence (high for SMR-up trials, low for SMR-down trials): the other subject with SCI showed no dependence. These results support the hypothesis that SMR modulation has predictable effects on spinal reflex excitability in people who are neurologically normal; they also suggest that it might be used to enhance therapies that seek to improve functional recovery in some individuals with SCI or other CNS disorders