Variability of corticospinal and spinal reflex excitability for the ankle dorsiflexor tibialis anterior across repeated measurements in people with and without incomplete spinal cord injury.

To adequately evaluate the corticospinal and spinal plasticity in health and disease, it is essential to understand whether and to what extent the corticospinal and spinal responses fluctuate systematically across multiple measurements. Thus, in this study, we examined the session-to-session variability of corticospinal excitability for the ankle dorsiflexor tibialis anterior (TA) in people with and without incomplete spinal cord injury (SCI). In neurologically normal participants, the following measures were obtained across 4 days at the same time of day (N = 13) or 4 sessions over a 12-h period (N = 9, at 8:00, 12:00, 16:00, and 20:00): maximum voluntary contraction (MVC), maximum M-wave and H-reflex (Mmax and Hmax), motor evoked potential (MEP) amplitude, and silent period (SP) after MEP. In participants with chronic incomplete SCI (N = 17), the same measures were obtained across 4 days. We found no clear diurnal variation in the spinal and corticospinal excitability of the TA in individuals with no known neurological conditions, and no systematic changes in any experimental measures of spinal and corticospinal excitability across four measurement days in individuals with or without SCI. Overall, mean deviations across four sessions remained in a range of 5-13% for all measures in participants with or without SCI. The study shows the limited extent of non-systematic session-to-session variability in the TA corticospinal excitability in individuals with and without chronic incomplete SCI, supporting the utility of corticospinal and spinal excitability measures in mechanistic investigation of neuromodulation interventions. The information provided through this study may serve as the reference in evaluating corticospinal plasticity across multiple experimental sessions.

Enhancing neurorehabilitation by targeting beneficial plasticity.

Neurorehabilitation is now one of the most exciting areas in neuroscience. Recognition that the central nervous system (CNS) remains plastic through life, new understanding of skilled behaviors (skills), and novel methods for engaging and guiding beneficial plasticity combine to provide unprecedented opportunities for restoring skills impaired by CNS injury or disease. The substrate of a skill is a distributed network of neurons and synapses that changes continually through life to ensure that skill performance remains satisfactory as new skills are acquired, and as growth, aging, and other life events occur. This substrate can extend from cortex to spinal cord. It has recently been given the name "heksor." In this new context, the primary goal of rehabilitation is to enable damaged heksors to repair themselves so that their skills are once again performed well. Skill-specific practice, the mainstay of standard therapy, often fails to optimally engage the many sites and kinds of plasticity available in the damaged CNS. New noninvasive technology-based interventions can target beneficial plasticity to critical sites in damaged heksors; these interventions may thereby enable much wider beneficial plasticity that enhances skill recovery. Targeted-plasticity interventions include operant conditioning of a spinal reflex or corticospinal motor evoked potential (MEP), paired-pulse facilitation of corticospinal connections, and brain-computer interface (BCI)-based training of electroencephalographic (EEG) sensorimotor rhythms. Initial studies in people with spinal cord injury, stroke, or multiple sclerosis show that these interventions can enhance skill recovery beyond that achieved by skill-specific practice alone. After treatment ends, the repaired heksors maintain the benefits.

Methods for automated delineation and assessment of EMG responses evoked by peripheral nerve stimulation in diagnostic and closed-loop therapeutic applications.

Objective.Surface electromyography measurements of the Hoffmann (H-) reflex are essential in a wide range of neuroscientific and clinical applications. One promising emerging therapeutic application is H-reflex operant conditioning, whereby a person is trained to modulate the H-reflex, with generalized beneficial effects on sensorimotor function in chronic neuromuscular disorders. Both traditional diagnostic and novel realtime therapeutic applications rely on accurate definitions of the H-reflex and M-wave temporal bounds, which currently depend on expert case-by-case judgment. The current study automates such judgments.Approach.Our novel wavelet-based algorithm automatically determines temporal extent and amplitude of the human soleus H-reflex and M-wave. In each of 20 participants, the algorithm was trained on data from a preliminary 3 or 4 min recruitment-curve measurement. Output was evaluated on parametric fits to subsequent sessions' recruitment curves (92 curves across all participants) and on the conditioning protocol's subsequent baseline trials (∼1200 per participant) performed nearHmax. Results were compared against the original temporal bounds estimated at the time, and against retrospective estimates made by an expert 6 years later.Main results.Automatic bounds agreed well with manual estimates: 95% lay within ±2.5 ms. The resulting H-reflex magnitude estimates showed excellent agreement (97.5% average across participants) between automatic and retrospective bounds regarding which trials would be considered successful for operant conditioning. Recruitment-curve parameters also agreed well between automatic and manual methods: 95% of the automatic estimates of the current required to elicitHmaxfell within±1.4%of the retrospective estimate; for the 'threshold' current that produced an M-wave 10% of maximum, this value was±3.5%.Significance.Such dependable automation of M-wave and H-reflex definition should make both established and emerging H-reflex protocols considerably less vulnerable to inter-personnel variability and human error, increasing translational potential.

Effects of active and sham tDCS on the soleus H-reflex during standing.

Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (Hmax) and M-wave (Mmax) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways.

Altered cutaneous reflexes to non-noxious stimuli in the triceps surae of people with chronic incomplete spinal cord injury.

Following spinal cord injury (SCI) task-dependent modulation of spinal reflexes are often impaired. To gain insight into the state of the spinal interneuronal pathways following injury, we studied the amplitude modulation of triceps surae cutaneous reflexes to non-noxious stimuli during standing and early-to-mid stance phase of walking in participants with and without chronic incomplete SCI. Reflex eliciting nerve stimulation was delivered to the superficial peroneal, sural, and distal tibial nerves about the ankle. Reflexes were analyzed in the short (SLR, 50-80 ms post stimulation onset) and the medium (MLR, 80-120 ms) latency response windows. Further, the relation between cutaneous and H-reflexes was also examined during standing. In participants without injuries the soleus SLR was modulated task-dependently with nerve specificity, and the soleus and medial gastrocnemius MLRs were modulated task-dependently. In contrast, participants with SCI, no task-dependent or nerve-specific modulation of triceps cutaneous reflexes was observed. The triceps surae cutaneous and H-reflexes were not correlated in either group (r = 0.01-0.37). The presence of cutaneous reflexes but the absence of significant amplitude modulation may suggest impaired function of spinal interneuronal pathways in this population. The lack of correlation between the cutaneous and H-reflexes may suggest that interneurons that are involved in H-reflex modulation and cutaneous reflex modulation do not receive common input, or the impact of the common input is outweighed by other input. Present findings highlight the importance of examining multiple spinal reflexes to better understanding spinal interneuronal pathways that affect motor control in people after SCI.

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.

The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders.

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle responses in people with neuromuscular disorders, which in turn can improve sensorimotor function when applied appropriately. EPOCS monitors the state of specific target muscles-e.g., from surface electromyography (EMG) while standing, or from gait cycle measurements while walking on a treadmill-and automatically triggers calibrated stimulation when pre-defined conditions are met. It provides two forms of feedback that enable a person to learn to modulate the targeted pathway's excitability. First, it continuously monitors ongoing EMG activity in the target muscle, guiding the person to produce a consistent level of activity suitable for conditioning. Second, it provides immediate feedback of the response size following each stimulation and indicates whether it has reached the target value. To illustrate its use, this article describes a protocol through which a person can learn to decrease the size of the Hoffmann reflex-the electrically-elicited analog of the spinal stretch reflex-in the soleus muscle. Down-conditioning this pathway's excitability can improve walking in people with spastic gait due to incomplete spinal cord injury. The article demonstrates how to set up the equipment; how to place stimulating and recording electrodes; and how to use the free software to optimize electrode placement, measure the recruitment curve of direct motor and reflex responses, measure the response without operant conditioning, condition the reflex, and analyze the resulting data. It illustrates how the reflex changes over multiple sessions and how walking improves. It also discusses how the system can be applied to other kinds of evoked responses and to other kinds of stimulation, e.g., motor evoked potentials to transcranial magnetic stimulation; how it can address various clinical problems; and how it can support research studies of sensorimotor function in health and disease.

Soleus H-reflex modulation during a double-legged drop landing task.

Muscle spindle afferent feedback is modulated during different phases of locomotor tasks in a way that facilitates task goals. However, only a few studies have studied H-reflex modulation during landing. This study aimed to characterize soleus (SOL) H-reflex modulation during the flight and early landing period of drop landings. Since landing presumably involves a massive increase in spindle afferent firing due to rapid SOL muscle stretching, we hypothesized H-reflex size would decrease near landing reflecting neural modulation to prevent excessive motoneuron excitation. The soleus H-reflex was recorded during drop landings from a 30 cm height in nine healthy adults. Electromyography (SOL, tibialis anterior (TA), medial gastrocnemius, and vastus lateralis), ankle and knee joint motion and ground reaction force were recorded during landings. Tibial nerve stimulation was timed to elicit H-reflexes during the flight and early ground contact period (five 30 ms Bins from 90 ms before to 60 ms after landing). The H-reflexes recorded after landing (0-30 and 30-60 ms) were significantly smaller (21-36% less) than that recorded during the flight periods (90-0 ms before ground contact; P ≤ 0.004). The decrease in H-reflex size not occurring until after ground contact indicates a time-critical modulation of reflex gain during the last 30 ms of flight (i.e., time of tibial nerve stimulation). H-reflex size reduction after ground contact supports a probable neural strategy to prevent excessive reflex-mediated muscle activation and thereby facilitates appropriate musculotendon and joint stiffness.

H-reflex conditioning during locomotion in people with spinal cord injury.

KEY POINTS: In people or animals with incomplete spinal cord injury (SCI), changing a spinal reflex through an operant conditioning protocol can improve locomotion. All previous studies conditioned the reflex during steady-state maintenance of a specific posture. By contrast, the present study down-conditioned the reflex during the swing-phase of locomotion in people with hyperreflexia as a result of chronic incomplete SCI. The aim was to modify the functioning of the reflex in a specific phase of a dynamic movement. This novel swing-phase conditioning protocol decreased the reflex much faster and farther than did the steady-state protocol in people or animals with or without SCI, and it also improved locomotion. The reflex decrease persisted for at least 6 months after conditioning ended. The results suggest that conditioning reflex function in a specific phase of a dynamic movement offers a new approach to enhancing and/or accelerating recovery after SCI or in other disorders. ABSTRACT: In animals and people with incomplete spinal cord injury, appropriate operant conditioning of a spinal reflex can improve impaired locomotion. In all previous conditioning studies, the reflex was conditioned during steady-state maintenance of a stable posture; this steady-state protocol aimed to change the excitability of the targeted reflex pathway; reflex size gradually changed over 8-10 weeks. The present study introduces a new protocol, comprising a dynamic protocol that aims to change the functioning of the reflex pathway during a specific phase of a complex movement. Specifically, we down-conditioned the soleus H-reflex during the swing-phase of locomotion in people with hyperreflexia as a result of chronic incomplete SCI. The swing-phase H-reflex, which is absent or very small in neurologically normal individuals, is abnormally large in this patient population. The results were clear. With swing-phase down-conditioning, the H-reflex decreased much faster and farther than did the H-reflex in all previous animal or human studies with the steady-state protocol, and the decrease persisted for at least 6 months after conditioning ended. The H-reflex decrease was accompanied by improvements in walking speed and in the modulation of locomotor electromyograph activity in proximal and distal muscles of both legs. These results provide new insight into the factors controlling spinal reflex conditioning; they suggest that the conditioning protocols targeting reflex function in a specific movement phase provide a promising new opportunity to enhance functional recovery after SCI or in other disorders.

Can Operant Conditioning of EMG-Evoked Responses Help to Target Corticospinal Plasticity for Improving Motor Function in People With Multiple Sclerosis?

Corticospinal pathway and its function are essential in motor control and motor rehabilitation. Multiple sclerosis (MS) causes damage to the brain and descending connections, and often diminishes corticospinal function. In people with MS, neural plasticity is available, although it does not necessarily remain stable over the course of disease progress. Thus, inducing plasticity to the corticospinal pathway so as to improve its function may lead to motor control improvements, which impact one's mobility, health, and wellness. In order to harness plasticity in people with MS, over the past two decades, non-invasive brain stimulation techniques have been examined for addressing common symptoms, such as cognitive deficits, fatigue, and spasticity. While these methods appear promising, when it comes to motor rehabilitation, just inducing plasticity or having a capacity for it does not guarantee generation of better motor functions. Targeting plasticity to a key pathway, such as the corticospinal pathway, could change what limits one's motor control and improve function. One of such neural training methods is operant conditioning of the motor-evoked potential that aims to train the behavior of the corticospinal-motoneuron pathway. Through up-conditioning training, the person learns to produce the rewarded neuronal behavior/state of increased corticospinal excitability, and through iterative training, the rewarded behavior/state becomes one's habitual, daily motor behavior. This minireview introduces operant conditioning approach for people with MS. Guiding beneficial CNS plasticity on top of continuous disease progress may help to prolong the duration of maintained motor function and quality of life in people living with MS.

Effect of Ankle Angles on the Soleus H-Reflex Excitability During Standing.

This study investigated effects of ankle joint angle on the Hoffman's reflex (H-reflex) excitability during loaded (weight borne with both legs) and unloaded (full body weight borne with the contralateral leg) standing in people without neurological injuries. Soleus H-reflex/M-wave recruitment curves were examined during upright standing on three different slopes that imposed plantar flexion (-15°), dorsiflexion (+15°), and neutral (0°) angles at the ankle, with the test leg loaded and unloaded. With the leg loaded and unloaded, maximum H-reflex/maximum M-wave ratio of -15° was significantly larger than those of 0° and +15° conditions. The maximum H-reflex/maximum M-wave ratios were 51%, 43%, and 41% with loaded and 56%, 46%, and 44% with unloaded for -15°, 0°, and +15° slope conditions, respectively. Thus, limb loading/unloading had limited impact on the extent of influence that ankle angles exert on the H-reflex excitability. This suggests that task-dependent central nervous system control of reflex excitability may regulate the influence of sensory input on the spinal reflex during standing.

Modulation of soleus stretch reflexes during walking in people with chronic incomplete spinal cord injury.

In people with spasticity due to chronic incomplete spinal cord injury (SCI), it has been presumed that the abnormal stretch reflex activity impairs gait. However, locomotor stretch reflexes across all phases of walking have not been investigated in people with SCI. Thus, to understand modulation of stretch reflex excitability during spastic gait, we investigated soleus stretch reflexes across the entire gait cycle in nine neurologically normal participants and nine participants with spasticity due to chronic incomplete SCI (2.5-11 year post-injury). While the participant walked on the treadmill at his/her preferred speed, unexpected ankle dorsiflexion perturbations (6° at 250°/s) were imposed every 4-6 steps. The soleus H-reflex was also examined. In participants without SCI, spinal short-latency "M1", spinal medium latency "M2", and long-latency "M3" were clearly modulated throughout the step cycle; the responses were largest in the mid-stance and almost completely suppressed during the stance-swing transition and swing phases. In participants with SCI, M1 and M2 were abnormally large in the mid-late-swing phase, while M3 modulation was similar to that in participants without SCI. The H-reflex was also large in the mid-late-swing phase. Elicitation of H-reflex and stretch reflexes in the late swing often triggered clonus and affected the soleus activity in the following stance. In individuals without SCI, moderate positive correlation was found between H-reflex and stretch reflex sizes across the step cycle, whereas in participants with SCI, such correlation was weak to non-existing, suggesting that H-reflex investigation would not substitute for stretch reflex investigation in individuals after SCI.

Operant conditioning of the motor-evoked potential and locomotion in people with and without chronic incomplete spinal cord injury.

Foot drop is very common among people with chronic incomplete spinal cord injury (SCI) and likely stems from SCI that disturbs the corticospinal activation of the ankle dorsiflexor tibialis anterior (TA). Thus, if one can recover or increase the corticospinal excitability reduced by SCI, motor function recovery may be facilitated. Here, we hypothesized that in people suffering from weak dorsiflexion due to chronic incomplete SCI, increasing the TA motor-evoked potential (MEP) through operant up-conditioning can improve dorsiflexion during locomotion, while in people without any injuries, it would have little impact on already normal locomotion. Before and after 24 MEP conditioning or control sessions, locomotor electromyography (EMG) and kinematics were measured. This study reports the results of these locomotor assessments. In participants without SCI, locomotor EMG activity, soleus Hoffmann reflex modulation, and joint kinematics did not change, indicating that MEP up-conditioning or repeated single-pulse transcranial magnetic stimulation (i.e., control protocol) does not influence normal locomotion. In participants with SCI, MEP up-conditioning increased TA activity during the swing-to-swing stance transition phases and ankle joint motion during locomotion in the conditioned leg and increased walking speed consistently. In addition, the swing-phase TA activity and ankle joint motion also improved in the contralateral leg. The results are consistent with our hypothesis. Together with the previous operant conditioning studies in humans and rats, the present study suggests that operant conditioning can be a useful therapeutic tool for enhancing motor function recovery in people with SCI and other central nervous system disorders. NEW & NOTEWORTHY This study examined the functional impact of operant conditioning of motor-evoked potential (MEP) to transcranial magnetic stimulation that aimed to increase corticospinal excitability for the ankle dorsiflexor tibialis anterior (TA). In people with chronic incomplete spinal cord injury (SCI), MEP up-conditioning increased TA activity and improved dorsiflexion during locomotion, while in people without injuries, it had little impact on already normal locomotion. MEP conditioning may potentially be used to enhance motor function recovery after SCI.

Operant conditioning of the tibialis anterior motor evoked potential in people with and without chronic incomplete spinal cord injury.

The activity of corticospinal pathways is important in movement control, and its plasticity is essential for motor skill learning and re-learning after central nervous system (CNS) injuries. Therefore, enhancing the corticospinal function may improve motor function recovery after CNS injuries. Operant conditioning of stimulus-induced muscle responses (e.g., reflexes) is known to induce the targeted plasticity in a targeted pathway. Thus, an operant conditioning protocol to target the corticospinal pathways may be able to enhance the corticospinal function. To test this possibility, we investigated whether operant conditioning of the tibialis anterior (TA) motor evoked potential (MEP) to transcranial magnetic stimulation can enhance corticospinal excitability in people with and without chronic incomplete spinal cord injury (SCI). The protocol consisted of 6 baseline and 24 up-conditioning/control sessions over 10 wk. In all sessions, TA MEPs were elicited at 10% above active MEP threshold while the sitting participant provided a fixed preset level of TA background electromyographic activity. During baseline sessions, MEPs were simply measured. During conditioning trials of the conditioning sessions, the participant was encouraged to increase MEP and was given immediate feedback indicating whether MEP size was above a criterion. In 5/8 participants without SCI and 9/10 with SCI, over 24 up-conditioning sessions, MEP size increased significantly to ~150% of the baseline value, whereas the silent period (SP) duration decreased by ~20%. In a control group of participants without SCI, neither MEP nor SP changed. These results indicate that MEP up-conditioning can facilitate corticospinal excitation, which is essential for enhancing motor function recovery after SCI. NEW & NOTEWORTHY We investigated whether operant conditioning of the motor evoked potential (MEP) to transcranial magnetic stimulation can systematically increase corticospinal excitability for the ankle dorsiflexor tibialis anterior (TA) in people with and without chronic incomplete spinal cord injury. We found that up-conditioning can increase the TA MEP while reducing the accompanying silent period (SP) duration. These findings suggest that MEP up-conditioning produces the facilitation of corticospinal excitation as targeted, whereas it suppresses inhibitory mechanisms reflected in SP.

Operant Up-Conditioning of the Tibialis Anterior Motor-Evoked Potential in Multiple Sclerosis: Feasibility Case Studies.

Damage to the corticospinal pathway often results in weak dorsiflexion of the ankle, thereby limiting the mobility of people with multiple sclerosis (MS). Thus, strengthening corticospinal connectivity may improve locomotion. Here, we investigated the feasibility of tibialis anterior (TA) motor-evoked potential (MEP) operant conditioning and whether it can enhance corticospinal excitability and alleviate locomotor problems in people with chronic stable MS. The protocol consisted of 6 baseline and 24 up-conditioning sessions over 10 weeks. In all sessions, TA MEPs were elicited at 10% above active threshold while the sitting subject provided 30-35% maximum voluntary contraction (MVC) level of TA background EMG. During baseline sessions, MEPs were simply measured. During conditioning trials of the conditioning sessions, the subject was encouraged to increase MEP and was given immediate feedback indicating whether MEP size was above a criterion. In 3/4 subjects, TA MEP increased 32-75%, MVC increased 28-52%, locomotor EMG modulation improved in multiple leg muscles, and foot drop became less severe. In one of them, MEP and MVC increases were maintained throughout 3 years of extensive follow-up sessions. These initial results support a therapeutic possibility of MEP operant conditioning for improving locomotion in people with MS or other CNS disorders, such as spinal cord injury and stroke.

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 < 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 < 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.

Targeted neuroplasticity for rehabilitation.

An operant-conditioning protocol that bases reward on the electromyographic response produced by a specific CNS pathway can change that pathway. For example, in both animals and people, an operant-conditioning protocol can increase or decrease the spinal stretch reflex or its electrical analog, the H-reflex. Reflex change is associated with plasticity in the pathway of the reflex as well as elsewhere in the spinal cord and brain. Because these pathways serve many different behaviors, the plasticity produced by this conditioning can change other behaviors. Thus, in animals or people with partial spinal cord injuries, appropriate reflex conditioning can improve locomotion. Furthermore, in people with spinal cord injuries, appropriate reflex conditioning can trigger widespread beneficial plasticity. This wider plasticity appears to reflect an iterative process through which the multiple behaviors in the individual's repertoire negotiate the properties of the spinal neurons and synapses that they all use. Operant-conditioning protocols are a promising new therapeutic method that could complement other rehabilitation methods and enhance functional recovery. Their successful use requires strict adherence to appropriately designed procedures, as well as close attention to accommodating and engaging the individual subject in the conditioning process.

Restoring walking after spinal cord injury: operant conditioning of spinal reflexes can help.

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.