Corticospinal Excitability Quantification During a Visually-Guided Precision Walking Task in Humans: Potential for Neurorehabilitation.

The corticospinal tract has been shown to be involved in normal walking in humans. However, its contribution during more challenging locomotor tasks is still unclear. As the corticospinal tract can be a potential target to promote gait recovery after neurological injury, it is of primary importance to quantify its use during human walking. The aims of the current study were to: (1) quantify the effects of precision walking on corticospinal excitability as compared to normal walking; (2) assess if corticospinal modulation is related to task difficulty or participants' performance. Sixteen healthy participants walked on a treadmill during 2 tasks: regular walking (simple task) and stepping onto virtual targets (precision task). Virtual targets appeared randomly at 3 different step lengths: preferred, and ±20%. To assess corticospinal excitability, 25 motor evoked potentials (MEPs) were recorded from the tibialis anterior muscle in each task during walking. Performance for each participant (global success score; % of target hit) and task difficulty related to step length adjustments (success score for each step length) were also calculated. MEP size was larger during the precision task in all participants (mean increase of 93% ± 72%; P < .05) compared to the simple task. There was a correlation between MEP facilitation and individual performance (r = -.64; P < .05), but no difference in MEP size associated with task difficulty (P > .05). In conclusion, corticospinal excitability exhibits a large increase during the precision task. This effect needs to be confirmed in neurological populations to potentially provide a simple and non-invasive approach to increase corticospinal drive during gait rehabilitation.

Systematic review of motor control and somatosensation assessment tests for the ankle.

BACKGROUND/AIM: Ankle sprains are frequent musculoskeletal injuries that can lead to sensorimotor deficits provoking long-term instability at the ankle joint. A broad variety of clinical tests currently exist to assess sensorimotor processing, and are commonly clinically referred to as proprioceptive tests. However, there is a discrepancy in the use of the term proprioception when looking at the main outcome of these tests. As identifying specific deficits is important for motor recovery, it is critical for clinicians to select the most appropriate tests. METHODS: A systematic review of four databases was performed to provide an up-to-date review of the psychometric properties of available tests referred to as proprioceptive tests. Seventy-nine articles on eight ankle proprioceptive tests were included and critically appraised. Data on validity, reliability and responsiveness were extracted from the included articles and synthesised. The tests reviewed were then divided into two categories based on their main outcome: motor control or somatosensation. RESULTS: Strong evidence showed that the Star Excursion Balance Test, a motor control test, is capable of differentiating between stable and unstable ankles. Moderate evidence suggests that somatosensation tests, such as Joint Position Sense, are also valid and reliable, but their responsiveness has yet to be evaluated. CONCLUSIONS: Together, these findings indicate that the Star Excursion Balance Test can be used in the clinic to assess motor control based on its excellent psychometric properties. However, as ankle stability control involves complex sensorimotor interactions, care has to be taken regarding the use of this test as a specific tool for proprioception assessment.

Ankle proprioception during gait in individuals with incomplete spinal cord injury.

INTRODUCTION: Proprioception is known to be affected after a spinal cord injury (SCI). However, it is currently assessed during simple tasks that do not reflect activities of daily living. To better understand how proprioception affects movement, assessing it during a functional sensorimotor task such as walking is therefore of primary importance. Therefore, the objectives of this study were as follows: (a) measure the protocol reliability of a new robotic test in nondisabled controls; (b) evaluate the effect nonlesion-related factors such as sex, age, pain, and gait speed on ankle proprioception; and (c) assess ankle proprioception during walking in individuals with SCI. METHODS: In the current study, ankle proprioception was assessed during gait in individuals with an incomplete spinal cord injury (iSCI; n = 15) using an electrohydraulic robotized ankle-foot orthosis (rAFO). Ankle proprioceptive threshold was quantified as the participants' ability to detect torque perturbations of varied amplitude applied during swing by the rAFO. In addition, test-retest reliability and the potential effect of nonlesion-related factors (sex, age, pain, and gait speed) were evaluated in nondisabled (ND; n = 65) participants. RESULTS: During gait, individuals with iSCI had a 53% poorer proprioceptive threshold than ND controls (p < .05). Test-retest reliability was good (ICC = 0.78), and only gait speed affected proprioceptive threshold (p = .018). CONCLUSION: This study is the first to show that ankle proprioception assessed during gait is impaired in individuals with an iSCI. The developed test can now be used to better characterize proprioception in population with other neurological conditions and has potential to maximize functional recovery during gait training in those populations.

Intralimb and Interlimb Cutaneous Reflexes during Locomotion in the Intact Cat.

When the foot contacts an obstacle during locomotion, cutaneous inputs activate spinal circuits to ensure dynamic balance and forward progression. In quadrupeds, this requires coordinated reflex responses between the four limbs. Here, we investigated the patterns and phasic modulation of cutaneous reflexes in forelimb and hindlimb muscles evoked by inputs from all four limbs. Five female cats were implanted to record muscle activity and to stimulate the superficial peroneal and superficial radial nerves during locomotion. Stimulating these nerves evoked short-, mid-, and longer-latency excitatory and/or inhibitory responses in all four limbs that were phase-dependent. The largest responses were generally observed during the peak activity of the muscle. Cutaneous reflexes during mid-swing were consistent with flexion of the homonymous limb and accompanied by modification of the stance phases of the other three limbs, by coactivating flexors and extensors and/or by delaying push-off. Cutaneous reflexes during mid-stance were consistent with stabilizing the homonymous limb by delaying and then facilitating its push-off and modifying the support phases of the homolateral and diagonal limbs, characterized by coactivating flexors and extensors, reinforcing extensor activity and/or delaying push-off. The shortest latencies of homolateral and diagonal responses were consistent with fast-conducting disynaptic or trisynaptic pathways. Descending homolateral and diagonal pathways from the forelimbs to the hindlimbs had a higher probability of eliciting responses compared with ascending pathways from the hindlimbs to the forelimbs. Thus, in quadrupeds, intralimb and interlimb reflexes activated by cutaneous inputs ensure dynamic coordination of the four limbs, producing a whole-body response.SIGNIFICANCE STATEMENT The skin contains receptors that, when activated, send inputs to spinal circuits, signaling a perturbation. Rapid responses, or reflexes, in muscles of the contacted limb and opposite homologous limb help maintain balance and forward progression. Here, we investigated reflexes during quadrupedal locomotion in the cat by electrically stimulating cutaneous nerves in each of the four limbs. Functionally, responses appear to modify the trajectory or stabilize the movement of the stimulated limb while modifying the support phase of the other limbs. Reflexes between limbs are mediated by fast-conducting pathways that involve excitatory and inhibitory circuits controlling each limb. The comparatively stronger descending pathways from cervical to lumbar circuits controlling the forelimbs and hindlimbs, respectively, could serve a protective function.

Lack of adaptation during prolonged split-belt locomotion in the intact and spinal cat.

KEY POINTS: During split-belt locomotion in humans where one leg steps faster than the other, the symmetry of step lengths and double support periods of the slow and fast legs is gradually restored. When returning to tied-belt locomotion, there is an after-effect, with a reversal in the asymmetry observed in the early split-belt period, indicating that the new pattern was stored within the central nervous system. In this study, we investigated if intact and spinal-transected cats show a similar pattern of adaptation to split-belt locomotion by measuring kinematic variables and electromyography before, during and after 10 min of split-belt locomotion. The results show that cats do not adapt to prolonged split-belt locomotion. Our results suggest an important physiological difference in how cats and humans respond to prolonged asymmetric locomotion. ABSTRACT: In humans, gait adapts to prolonged walking on a split-belt treadmill, where one leg steps faster than the other, by gradually restoring the symmetry of interlimb kinematic variables, such as double support periods and step lengths, and by reducing muscle activity (EMG, electromyography). The adaptation is also characterized by reversing the asymmetry of interlimb variables observed during the early split-belt period when returning to tied-belt locomotion, termed an after-effect. To determine if cats adapt to prolonged split-belt locomotion and to assess if spinal locomotor circuits participate in the adaptation, we measured interlimb variables and EMG in intact and spinal-transected cats before, during and after 10 min of split-belt locomotion. In spinal cats, only the hindlimbs performed stepping with the forelimbs stationary. In intact and spinal cats, step lengths and double support periods were, on average, symmetric, during tied-belt locomotion. They became asymmetric during split-belt locomotion and remained asymmetric throughout the split-belt period. Upon returning to tied-belt locomotion, symmetry was immediately restored. In intact cats, the mean EMG amplitude of hindlimb extensors increased during split-belt locomotion and remained increased throughout the split-belt period, whereas in spinal cats, EMG amplitude did not change. Therefore, the results indicate that the locomotor pattern of cats does not adapt to prolonged split-belt locomotion, suggesting an important physiological difference in the control of locomotion between cats and humans. We propose that restoring left-right symmetry is not required to maintain balance during prolonged asymmetric locomotion in the cat, a quadruped, as opposed to human bipedal locomotion.

Nonlinear Modulation of Cutaneous Reflexes with Increasing Speed of Locomotion in Spinal Cats.

Cutaneous reflexes are important for responding rapidly to perturbations, correcting limb trajectory, and strengthening support. During locomotion, they are modulated by phase to generate functionally appropriate responses. The goal of the present study was to determine whether cutaneous reflexes and their phase-dependent modulation are altered with increasing speed and if this is accomplished at the spinal level. Four adult cats that recovered stable hindlimb locomotion after spinal transection were implanted with electrodes to record hindlimb muscle activity chronically and to stimulate the superficial peroneal nerve electrically to evoke cutaneous reflexes. The speed-dependent modulation of cutaneous reflexes was assessed by evoking and characterizing ipsilateral and contralateral responses in semitendinosus, vastus lateralis, and lateral gastrocnemius muscles at four treadmill speeds: 0.2, 0.4, 0.6, and 0.8 m/s. The amplitudes of ipsilateral and contralateral responses were largest at intermediate speeds of 0.4 and 0.6 m/s, followed by the slowest and fastest speeds of 0.2 and 0.8 m/s, respectively. The phase-dependent modulation of reflexes was maintained across speeds, with ipsilateral and contralateral responses peaking during the stance-to-swing transition and swing phase of the ipsilateral limb or midstance of the contralateral limb. Reflex modulation across speeds also correlated with the spatial symmetry of the locomotor pattern, but not with temporal symmetry. That the cutaneous reflex amplitude in all muscles was similarly modulated with increasing speed independently of the background level of muscle activity is consistent with a generalized premotoneuronal spinal control mechanism that could help to stabilize the locomotor pattern when changing speed.SIGNIFICANCE STATEMENT When walking, receptors located in the skin respond to mechanical pressure and send signals to the CNS to correct the trajectory of the limb and to reinforce weight support. These signals produce different responses, or reflexes, if they occur when the foot is contacting the ground or in the air. This is known as phase-dependent modulation of reflexes. However, when walking at faster speeds, we do not know if and how these reflexes are changed. In the present study, we show that reflexes from the skin are modulated with speed and that this is controlled at the level of the spinal cord. This modulation could be important in preventing sensory signals from destabilizing the walking pattern.

Interlimb Coordination during Tied-Belt and Transverse Split-Belt Locomotion before and after an Incomplete Spinal Cord Injury.

Coordination between the arms/forelimbs and legs/hindlimbs is often impaired in humans and quadrupedal mammals after incomplete spinal cord injury. In quadrupeds, the forelimbs often take more steps than the hindlimbs, producing a two-to-one forelimb-hindlimb (2-1 FL-HL) coordination. In locomotor performance scales, this is generally considered a loss of FL-HL coordination. Here, FL-HL coordination was quantified before and 8 weeks after a lateral spinal hemisection at the sixth thoracic segment in six adult cats. Cats were tested during tied-belt locomotion (equal front and rear speeds) and transverse split-belt locomotion with the forelimbs or hindlimbs stepping faster. The results show that consistent phasing between forelimb and hindlimb movements was maintained after hemisection, even with the appearance of 2-1 FL-HL coordination, indicating that new stable forms of coordination emerge. Moreover, transverse split-belt locomotion potently modulated interlimb coordination and was capable of restoring a one-to-one FL-HL coordination with a faster treadmill speed for the hindlimbs. In conclusion, the results suggest that neural communication persists after an incomplete spinal cord injury, despite an unequal number of steps between the forelimbs and hindlimbs, and that interlimb coordination can be modulated by having the forelimbs or hindlimbs move at a faster frequency. We propose that locomotor recovery scales incorporate more sensitive methods to quantify FL-HL coordination, to better reflect residual functional capacity and possible cervicolumbar neural communication. Lastly, devising training protocols that make use of the bidirectional influences of the cervical and lumbar locomotor pattern generators could strengthen interlimb coordination and promote locomotor recovery.

Left-right coordination from simple to extreme conditions during split-belt locomotion in the chronic spinal adult cat.

KEY POINTS: Coordination between the left and right sides is essential for dynamic stability during locomotion. The immature or neonatal mammalian spinal cord can adjust to differences in speed between the left and right sides during split-belt locomotion by taking more steps on the fast side. We show that the adult mammalian spinal cord can also adjust its output so that the fast side can take more steps. During split-belt locomotion, only certain parts of the cycle are modified to adjust left-right coordination, primarily those associated with swing onset. When the fast limb takes more steps than the slow limb, strong left-right interactions persist. Therefore, the adult mammalian spinal cord has a remarkable adaptive capacity for left-right coordination, from simple to extreme conditions. ABSTRACT: Although left-right coordination is essential for locomotion, its control is poorly understood, particularly in adult mammals. To investigate the spinal control of left-right coordination, a spinal transection was performed in six adult cats that were then trained to recover hindlimb locomotion. Spinal cats performed tied-belt locomotion from 0.1 to 1.0 m s-1 and split-belt locomotion with low to high (1:1.25-10) slow/fast speed ratios. With the left hindlimb stepping at 0.1 m s-1 and the right hindlimb stepping from 0.2 to 1.0 m s-1 , 1:1, 1:2, 1:3, 1:4 and 1:5 left-right step relationships could appear. The appearance of 1:2+ relationships was not linearly dependent on the difference in speed between the slow and fast belts. The last step taken by the fast hindlimb displayed longer cycle, stance and swing durations and increased extensor activity, as the slow limb transitioned to swing. During split-belt locomotion with 1:1, 1:2 and 1:3 relationships, the timing of stance onset of the fast limb relative to the slow limb and placement of both limbs at contact were invariant with increasing slow/fast speed ratios. In contrast, the timing of stance onset of the slow limb relative to the fast limb and the placement of both limbs at swing onset were modulated with slow/fast speed ratios. Thus, left-right coordination is adjusted by modifying specific parts of the cycle. Results highlight the remarkable adaptive capacity of the adult mammalian spinal cord, providing insight into spinal mechanisms and sensory signals regulating left-right coordination.

Adaptive muscle plasticity of a remaining agonist following denervation of its close synergists in a model of complete spinal cord injury.

Complete spinal cord injury (SCI) alters the contractile properties of skeletal muscle, and although exercise can induce positive changes, it is unclear whether the remaining motor system can produce adaptive muscle plasticity in response to a subsequent peripheral nerve injury. To address this, the nerve supplying the lateral gastrocnemius (LG) and soleus muscles was sectioned unilaterally in four cats that had recovered hindlimb locomotion after spinal transection. In these spinal cats, kinematics and electromyography (EMG) were collected before and for 8 wk after denervation. Muscle histology was performed on LG and medial gastrocnemius (MG) bilaterally in four spinal and four intact cats. In spinal cats, cycle duration for the hindlimb ipsilateral or contralateral to the denervation could be significantly increased or decreased compared with predenervation values. Stance duration was generally increased and decreased for the contralateral and ipsilateral hindlimbs, respectively. The EMG amplitude of MG was significantly increased bilaterally after denervation and remained elevated 8 wk after denervation. In spinal cats the ipsilateral LG was significantly smaller than the contralateral LG, whereas the ipsilateral MG weighed significantly more than the contralateral MG. Histological characterizations revealed significantly larger fiber areas for type IIa fibers of the ipsilateral MG in three of four spinal cats. Microvascular density in the ipsilateral MG was significantly higher than in the contralateral MG. In intact cats, no differences were found for muscle weight, fiber area, or microvascular density between homologous muscles. Therefore, the remaining motor system after complete SCI retains the ability to produce adaptive muscle plasticity.

The spinal control of locomotion and step-to-step variability in left-right symmetry from slow to moderate speeds.

When speed changes during locomotion, both temporal and spatial parameters of the pattern must adjust. Moreover, at slow speeds the step-to-step pattern becomes increasingly variable. The objectives of the present study were to assess if the spinal locomotor network adjusts both temporal and spatial parameters from slow to moderate stepping speeds and to determine if it contributes to step-to-step variability in left-right symmetry observed at slow speeds. To determine the role of the spinal locomotor network, the spinal cord of 6 adult cats was transected (spinalized) at low thoracic levels and the cats were trained to recover hindlimb locomotion. Cats were implanted with electrodes to chronically record electromyography (EMG) in several hindlimb muscles. Experiments began once a stable hindlimb locomotor pattern emerged. During experiments, EMG and bilateral video recordings were made during treadmill locomotion from 0.1 to 0.4 m/s in 0.05 m/s increments. Cycle and stance durations significantly decreased with increasing speed, whereas swing duration remained unaffected. Extensor burst duration significantly decreased with increasing speed, whereas sartorius burst duration remained unchanged. Stride length, step length, and the relative distance of the paw at stance offset significantly increased with increasing speed, whereas the relative distance at stance onset and both the temporal and spatial phasing between hindlimbs were unaffected. Both temporal and spatial step-to-step left-right asymmetry decreased with increasing speed. Therefore, the spinal cord is capable of adjusting both temporal and spatial parameters during treadmill locomotion, and it is responsible, at least in part, for the step-to-step variability in left-right symmetry observed at slow speeds.

Effect of stimulating the lumbar skin caudal to a complete spinal cord injury on hindlimb locomotion.

Sensory feedback is a potent modulator of the locomotor pattern generated by spinal networks. The purpose of this study was to assess the effect of cutaneous inputs from the back on the spinal-generated locomotor pattern. The spinal cord of six adult cats was transected at low thoracic levels. Cats were then trained to recover hindlimb locomotion. During experiments, the skin overlying lumbar vertebrae L2 to L7 was mechanically stimulated by a small calibrated clip or by manual pinching. Trials without and with cutaneous stimulation were performed at a treadmill speed of 0.4 m/s. Although manually pinching the skin completely stopped hindlimb locomotion and abolished weight support, cutaneous stimulation with the calibrated clip produced smaller effects. Specifically, more focalized cutaneous stimulation with the clip reduced flexor and extensor muscle activity and led to a more caudal positioning of the paw at contact and liftoff. Moreover, cutaneous stimulation with the clip led to a greater number of steps with improper nonplantigrade paw placements at contact and paw drag at the stance-to-swing transition. The most consistent effects on the hindlimb locomotor pattern were observed with cutaneous stimulation at midlumbar levels, from L3 to L5. The results indicate that cutaneous stimulation of the skin modulates the excitability of spinal circuits involved in generating locomotion and weight support, particularly at spinal segments thought to be critical for rhythm generation.

Modulation of phase durations, phase variations, and temporal coordination of the four limbs during quadrupedal split-belt locomotion in intact adult cats.

Stepping along curvilinear paths produces speed differences between the inner and outer limb(s). This can be reproduced experimentally by independently controlling left and right speeds with split-belt locomotion. Here we provide additional details on the pattern of the four limbs during quadrupedal split-belt locomotion in intact cats. Six cats performed tied-belt locomotion (same speed bilaterally) and split-belt locomotion where one side (constant side) stepped at constant treadmill speed while the other side (varying side) stepped at several speeds. Cycle, stance, and swing durations changed in parallel in homolateral limbs with shorter and longer stance and swing durations on the fast side, respectively, compared with the slow side. Phase variations were quantified in all four limbs by measuring the slopes of the regressions between stance and cycle durations (rSTA) and between swing and cycle durations (rSW). For a given limb, rSTA and rSW were not significantly different from one another on the constant side whereas on the varying side rSTA increased relative to tied-belt locomotion while rSW became more negative. Phase variations were similar for homolateral limbs. Increasing left-right speed differences produced a large increase in homolateral double support on the slow side, while triple-support periods decreased. Increasing left-right speed differences altered homologous coupling, homolateral coupling on the fast side, and coupling between the fast hindlimb and slow forelimb. Results indicate that homolateral limbs share similar control strategies, only certain features of the interlimb pattern adjust, and spinal locomotor networks of the left and right sides are organized symmetrically.

Speed-dependent modulation of phase variations on a step-by-step basis and its impact on the consistency of interlimb coordination during quadrupedal locomotion in intact adult cats.

It is well established that stance duration changes more than swing duration for a given change in cycle duration. Small variations in cycle duration are also observed at any given speed on a step-by-step basis. To evaluate the step-by-step effect of speed on phase variations, we measured the slopes of the linear regressions between the phases (i.e., stance, swing) and cycle duration during individual episodes at different treadmill speeds in five adult cats. We also determined the pattern of dominance, defined as the phase that varies most with cycle duration. We found a significant effect of speed on hindlimb phase variations, with significant differences observed between the slowest speed of 0.3 m/s compared with faster speeds. Moreover, although patterns of phase dominance were primarily stance/extensor dominated at the slowest speeds, as speed increased the patterns were increasingly categorized as covarying, whereby both stance/extensor and swing/flexor phases changed in approximately equal proportion with cycle duration. Speed significantly affected the relative duration of support periods as well as interlimb phasing between homolateral and diagonal pairs of limbs but not between homologous pairs of limbs. Speed also significantly affected the consistency of interlimb coordination on a step-by-step basis, being less consistent at the slowest speed of 0.3 m/s compared with faster speeds. We found a strong linear relationship between hindlimb phase variations and the consistency of interlimb coordination. Therefore, results show that phase variations on a step-by-step basis are modulated by speed, which appears to influence the consistency of interlimb coordination.