E. Paul Zehr

Neural regulation of rhythmic arm and leg movement is conserved across human locomotor tasks

It has been proposed that different forms of rhythmic human limb movement have a common central neural control (‘common core hypothesis’), just as in other animals. We compared the modulation patterns of background EMG and cutaneous reflexes during walking, arm and leg cycling, and arm‐assisted recumbent stepping. We hypothesized that patterns of EMG and reflex modulation during cycling and stepping (deduced from mathematical principal components analysis) would be comparable to those during walking because they rely on similar neural substrates. Differences between the tasks were assessed by evoking cutaneous reflexes via stimulation of nerves in the foot and hand in separate trials. The EMG was recorded from flexor and extensor muscles of the arms and legs. Angular positions of the hip, knee and elbow joints were also recorded. Factor analysis revealed that across the three tasks, four principal components explained more than 93% of the variance in the background EMG and middle‐latency reflex amplitude. Phase modulation of reflex amplitude was observed in most muscles across all tasks, suggesting activity in similar control networks. Significant correlations between EMG level and reflex amplitude were frequently observed only during static voluntary muscle activation and not during rhythmic movement. Results from a control experiment showed that strong correlation between EMG and reflex amplitudes was observed during discrete, voluntary leg extension but not during walking. There were task‐dependent differences in reflex modulation between the three tasks which probably arise owing to specific constraints during each task. Overall, the results show strong correlation across tasks and support common neural patterning as the regulator of arm and leg movement during various rhythmic human movements.

The Quadrupedal Nature of Human Bipedal Locomotion

During rhythmic movement, arm activity contributes to the neural excitation of leg muscles. These observations are consistent with the emergence of human bipedalism and nonhuman primate arboreal quadrupedal walking. These neural and biomechanical linkages could be exploited in rehabilitation after neurotrauma to allow the arms to give the legs a helping hand during gait rehabilitation. Summary: Neuronal interactions between arm and leg activity during rhythmic human movement assist in coordinating locomotion and may be usefully exploited in rehabilitation of walking.

A sigmoid function is the best fit for the ascending limb of the Hoffmann reflex recruitment curve

The Hoffmann (H)-reflex has been studied extensively as a measure of spinal excitability. Often, researchers compare the H-reflex between experimental conditions with values determined from a recruitment curve (RC). An RC is obtained experimentally by varying the stimulus intensity to a nerve and recording the peak-to-peak amplitudes of the evoked H-reflex and direct motor (M)-wave. The values taken from an RC may provide different information with respect to a change in reflex excitability. Therefore, it is important to obtain a number of RC parameters for comparison. RCs can be obtained with a measure of current (HCRC) or without current (HMRC). The ascending limb of the RC is then fit with a mathematical analysis technique in order to determine parameters of interest such as the threshold of activation and the slope of the function. The purpose of this study was to determine an unbiased estimate of the specific parameters of interest in an RC through mathematical analysis. We hypothesized that a standardized analysis technique could be used to ascertain important points on an RC, regardless of data presentation methodology (HCRC or HMRC). For both HCRC and HMRC produced using 40 randomly delivered stimuli, six different methods of mathematical analysis [linear regression, polynomial, smoothing spline, general least squares model with custom logistic (sigmoid) equation, power, and logarithmic] were compared using goodness of fit statistics (r-square, RMSE). Behaviour and robustness of selected curve fits were examined in various applications including RCs generated during movement and somatosensory conditioning from published data. Results show that a sigmoid function is the most reliable estimate of the ascending limb of an H-reflex recruitment curve for both HCRC and HMRC. Further, the parameters of interest change differentially with respect to the presentation methodology and the analysis technique. In conclusion, the sigmoid function is a reliable analysis technique which mimics the physiologically based prediction of the input/output relation of the ascending limb of the recruitment curve. Therefore, the sigmoid function should be considered an acceptable and preferable analytical tool for H-reflex recruitment curves obtained with reference to stimulation current or M-wave amplitude.

Ankle position and voluntary contraction alter maximal M waves in soleus and tibialis anterior

Compound muscle action potentials (CMAPs) recorded using surface electrodes are often used to assess the excitability of neural pathways to skeletal muscle. However, the amplitude of CMAPs can be influenced by changes at the recording site, independent of mechanisms within the central nervous system. We quantified how joint angle and background contraction influenced CMAP amplitude. In seven subjects CMAPs evoked by supramaximal transcutaneous electrical stimulation of motor axons (Mmax) were recorded using surface electrodes from soleus and tibialis anterior (TA) at static positions over the full range of ankle movement at 5° intervals. Across subjects the peak‐to‐peak amplitude of Mmax was 155% and 159% larger at the shortest than longest muscle lengths for soleus and TA, respectively. In five subjects the effect of ankle position and voluntary contraction on M‐wave/H‐reflex recruitment curves was assessed in the soleus. Both ankle position and level of contraction significantly influenced Mmax, Hmax, and the Hmax to Mmax ratio, but there were no interactions between the two parameters. These peripheral changes that influence Mmax will also impact other CMAPs such as submaximal M‐waves, H‐reflexes, and responses to transcranial magnetic stimulation. As such, during experimental studies CMAPs evoked at a given joint angle and contraction level should be normalized to Mmax recorded at similar joint angle and contraction strength. Muscle Nerve, 2007

Postural uncertainty leads to dynamic control of cutaneous reflexes from the foot during human walking

Cutaneous reflexes evoked by stimulation of nerves innervating the foot are modulated in a phase-dependent manner during locomotion. The pattern of modulation of these reflexes has been suggested to indicate a functional role of cutaneous reflexes in assisting to maintain stability during walking. We hypothesized that if cutaneous reflexes assist in maintaining stability during gait, then these reflexes should be modulated in a context-dependent manner when subjects are asked to walk in an environment in which stability is challenged. To do this, we asked subjects to walk on a treadmill under five conditions: (1) normally, (2) with the arms crossed, (3) while receiving unpredictable anterior-posterior (AP) perturbations, (4) with the arms crossed while receiving unpredictable AP perturbations, and (5) with the hands holding onto fixed handles. Cutaneous reflexes arising from electrical stimulation of the superficial peroneal (SP; relevant to stumbling) or distal tibial (TIB; relevant to ground contact sensation) nerves were recorded bilaterally, at four points in the step cycle. Reflexes evoked with SP nerve stimulation showed marked facilitation during the most unstable walking condition in 4 of the 7 muscles tested. SP nerve-evoked reflexes in the muscles of the contralateral leg also showed suppression during the most stable walking condition. Reflexes evoked with TIB nerve stimulation were less affected by changes in the walking task. We argue that the specific adaptation of cutaneous reflexes observed with SP nerve stimulation supports the hypothesis that cutaneous reflexes from the foot contribute to the maintenance of stability during walking.

Rhythmic leg cycling modulates forearm muscle H-reflex amplitude and corticospinal tract excitability.

Rhythmic arm cycling leads to suppression of H-reflexes in both leg and arm muscles, and a reduction in the excitability of corticospinal projections to the forearm flexors. It is unknown, however, whether leg cycling modulates excitability in neural projections to the arms. Here we studied the extent to which rhythmic movement of the legs alters reflex (Experiment 1) and corticospinal (Experiment 2) transmission to arm muscles. In experiment 1, flexor carpi radialis (FCR) H-reflex recruitment curves were recorded with the legs static, and during rhythmic leg movement, while the FCR was both contracted and relaxed. The results indicate that rhythmic leg movement suppresses reflex transmission, both when FCR is at rest and during tonic contraction, but that the effect is not phase-dependent. In experiment 2, we used transcranial magnetic stimulation (TMS) to elicit motor-evoked potentials in the contracted and relaxed FCR during static leg, and leg cycling conditions. Sub-threshold TMS was also used to condition H-reflexes in order to provide specific information about cortical excitability during leg cycling. Both resting and tonically contracting arm muscles showed a greater corticospinal excitability during leg cycling than during the static leg condition. The magnitude of TMS facilitation of H-reflexes was similar during leg cycling and rest, suggesting a considerable sub-cortical component to the increased corticospinal excitability. The results suggest a differential regulation of afferent and descending projections to the arms during leg cycling, and are consistent with the idea that there is a loose, but significant, neural coupling between the arms and legs during rhythmic movement.

Task-specific modulation of cutaneous reflexes expressed at functionally relevant gait cycle phases during level and incline walking and stair climbing

Reflexes are exquisitely sensitive to the motor task that is being performed at the time they are evoked; in other words, they are “task-dependent”. The purpose of this study was to investigate the extent to which the pattern of reflex modulation is conserved across three locomotor tasks that differ in muscle activity, joint kinematics, and stability demands. Subjects performed continuous level and incline walking on a treadmill and stair climbing on a stepping mill. Cutaneous reflexes were evoked by delivering trains of electrical stimulation to the sural nerve at the ankle at an intensity of two times the radiating threshold. Electromyographic (EMG) recordings were collected continuously from muscles in the arms, legs and trunk. Results showed that middle-latency reflex modulation patterns were generally conserved across the three locomotor tasks with a few notable exceptions related to specific functional requirements. For example, a reflex reversal was observed for tibialis anterior during stair climbing, which may be indicative of a specific adaptation to the task constraints. Overall our data suggest that the underlying neural mechanisms involved in coordinating level walking can be modified to also coordinate other locomotor tasks such as incline walking and stair climbing. Therefore, there may be considerable overlap in the neural control of different forms of locomotion.

Facilitation of soleus H-reflex amplitude evoked by cutaneous nerve stimulation at the wrist is not suppressed by rhythmic arm movement

Neural connections between the cervical and lumbosacral spinal cord may assist in arm and leg coordination during locomotion. Currently the extent to which arm activity can modulate reflex excitability of leg muscles is not fully understood. We showed recently that rhythmic arm movement significantly suppresses soleus H-reflex amplitude probably via modification of presynaptic inhibition of the IA afferent pathway. Further, during walking reflexes evoked in leg muscles by stimulation of a cutaneous nerve at the wrist (superficial radial nerve; SR) are phase and task dependent. However, during walking both the arms and legs are rhythmically active thus it is difficult to identify the locus of such modulation. Here we examined the influence of SR nerve stimulation on transmission through the soleus H-reflex pathway in the leg during static contractions and during rhythmic arm movements. Nerve stimulation was delivered with the right shoulder in flexion or extension. H-reflexes were evoked alone (unconditioned) or with cutaneous conditioning via stimulation of the SR nerve (also delivered alone without H-reflex in separate trials). SR nerve stimulation significantly facilitated H-reflex amplitude during static contractions with the arm extended and countered the suppression of reflex amplitude induced by arm cycling. The results demonstrate that cutaneous feedback from the hand on to the soleus H-reflex pathway in the legs is not suppressed during rhythmic arm movement. This contrasts with the observation that rhythmic arm movement suppresses facilitation of soleus H-reflex when cutaneous nerves innervating the leg are stimulated. In conjunction with other data taken during walking, this suggests that the modulation of transmission through pathways from the SR nerve to the lumbosacral spinal cord is partly determined by rhythmic activity of both the arms and legs.

Modulation of cutaneous reflexes in human upper limb muscles during arm cycling is independent of activity in the contralateral arm

The amplitudes and signs of cutaneous reflexes are modulated during rhythmic movements of the arms and legs (during walking and arm or leg cycling for instance). This reflex modulation is frequently independent of the background muscle activity and may involve central pattern generator (CPG) circuits. The purpose of the present study was to investigate the nature and degree of coupling between the upper limbs during arm cycling, with regard to the regulation of cutaneous reflexes. Responses to electrical stimulations of the right, superficial radial nerve (five 1 ms pulses, 300 Hz) were recorded bilaterally in six arm muscles of eight participants during arm cycling involving only the limb ipsilateral to the stimulation, only the limb contralateral to the stimulation, and bilateral movement when the limbs were both in-phase and 180° out of phase. The pattern of cutaneous reflex modulation throughout the arm cycle was independent of the functional state of the limb contralateral to the recording site, irrespective of whether recordings were made ipsilateral or contralateral to the stimulation. Furthermore, cutaneous reflexes were significantly (p<0.05) modulated with arm position in only 8% of cases in which the limb containing the responding muscle was either stationary or being moved passively by the experimenter. The results show that there is relatively weak coupling between the arms with regard to the regulation of cutaneous reflexes during rhythmic, cyclical arm movements. This suggests a loose connection between the CPGs for each arm that regulate muscle activity and reflex amplitude during rhythmic movement.

Rhythmic arm cycling suppresses hyperactive soleus H-reflex amplitude after stroke

OBJECTIVE Rhythmic arm cycling movement suppresses the amplitude of soleus H-reflexes in neurologically intact participants. This suppression is greater when the movement frequency is increased. If rhythmic arm movement can still suppress the amplitude of H-reflexes in the legs after stroke, it could potentially be used as a rehabilitation technique to reduce exaggerated reflexes such as those occurring in spasticity. The purpose of this study was to test for maintenance of this suppressive effect after stroke. Since a portion of the effect of arm cycling had previously been ascribed to subcortical and spinal mechanisms, we hypothesized that the suppressive effect of arm cycling would be partially maintained after stroke. METHODS Participants with history of single chronic (> 6 months) stroke performed rhythmic arm cycling at approximately 1 Hz and also at the highest frequency possible ( approximately 1.5 Hz). Soleus H-reflexes were evoked in the more and less affected legs simultaneously and full recruitment curves obtained. RESULTS H-reflex amplitudes in both the more and less affected legs of stroke participants were significantly suppressed during arm cycling. However, the extent of the suppression is weaker compared to neurologically intact and age-matched subjects. CONCLUSIONS Neural activity related to arm cycling can still access interlimb pathways after stroke and activate spinal control mechanisms leading to suppression of H-reflex amplitudes. SIGNIFICANCE The suppressive effect of arm cycling could be exploited in the modification of exaggerated muscle afferent reflexes in leg muscles after stroke. Whether this has a significant effect on modulation of spasticity requires further substantiation.