Transforming the Anthropomorphic Passive Free-Flow Foot Prosthesis Into a Powered Foot Prosthesis With Intuitive Control and Sensation (Bionic FFF).

INTRODUCTION: Approximately 89% of all service members with amputations do not return to duty. Restoring intuitive neural control with somatosensory sensation is a key to improving the safety and efficacy of prosthetic locomotion. However, natural somatosensory feedback from lower-limb prostheses has not yet been incorporated into any commercial prostheses. MATERIALS AND METHODS: We developed a neuroprosthesis with intuitive bidirectional control and somatosensation and evoking phase-dependent locomotor reflexes, we aspire to significantly improve the prosthetic rehabilitation and long-term functional outcomes of U.S. amputees. We implanted the skin and bone integrated pylon with peripheral neural interface pylon into the cat distal tibia, electromyographic electrodes into the residual gastrocnemius muscle, and nerve cuff electrodes on the distal tibial and sciatic nerves. Results. The bidirectional neural interface that was developed was integrated into the existing passive Free-Flow Foot and Ankle prosthesis, WillowWood, Mount Sterling, OH. The Free-Flow Foot was chosen because it had the highest Index of Anthropomorphicity among lower-limb prostheses and was the first anthropomorphic prosthesis brought to market. Conclusion. The cats walked on a treadmill with no cutaneous feedback from the foot in the control condition and with their residual distal tibial nerve stimulated during the stance phase of walking.

ROLE OF FORELIMB MORPHOLOGY IN MUSCLE SENSORIMOTOR FUNCTIONS DURING LOCOMOTION IN THE CAT.

Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from 6 cats. These characteristics included muscle attachments, physiological cross-sectional area (PCSA), fascicle length, etc. We also recorded full-body mechanics and EMG activity of forelimb muscles during level overground and treadmill locomotion in 7 and 16 adult cats of either sex, respectively. We computed forelimb muscle forces along with force- and length-dependent sensory signals mapped onto corresponding cervical spinal segments. We found that patterns of computed muscle forces and afferent activities were strongly affected by the muscle's moment arm, PCSA, and fascicle length. Morphology of the shoulder muscles suggests distinct roles of the forelimbs in lateral force production and movements. Patterns of length-dependent sensory activity of muscles with long fibers (brachioradialis, extensor carpi radialis) closely matched patterns of overall forelimb length, whereas the activity pattern of biceps brachii matched forelimb orientation. We conclude that cat forelimb muscle morphology contributes substantially to locomotor function, particularly to control lateral stability and turning, rather than propulsion.

Forelimb movements contribute to hindlimb cutaneous reflexes during locomotion in cats.

During quadrupedal locomotion, interactions between spinal and supraspinal circuits and somatosensory feedback coordinate forelimb and hindlimb movements. How this is achieved is not clear. To determine whether forelimb movements modulate hindlimb cutaneous reflexes involved in responding to an external perturbation, we stimulated the superficial peroneal nerve in six intact cats during quadrupedal locomotion and during hindlimb-only locomotion (with forelimbs standing on stationary platform) and in two cats with a low spinal transection (T12-T13) during hindlimb-only locomotion. We compared cutaneous reflexes evoked in six ipsilateral and four contralateral hindlimb muscles. Results showed similar occurrence and phase-dependent modulation of short-latency inhibitory and excitatory responses during quadrupedal and hindlimb-only locomotion in intact cats. However, the depth of modulation was reduced in the ipsilateral semitendinosus during hindlimb-only locomotion. Additionally, longer-latency responses occurred less frequently in extensor muscles bilaterally during hindlimb-only locomotion, whereas short-latency inhibitory and longer-latency excitatory responses occurred more frequently in the ipsilateral and contralateral sartorius anterior, respectively. After spinal transection, short-latency inhibitory and excitatory responses were similar to both intact conditions, whereas mid- or longer-latency excitatory responses were reduced or abolished. Our results in intact cats and the comparison with spinal-transected cats suggest that the absence of forelimb movements suppresses inputs from supraspinal structures and/or cervical cord that normally contribute to longer-latency reflex responses in hindlimb extensor muscles.NEW & NOTEWORTHY During quadrupedal locomotion, the coordination of forelimb and hindlimb movements involves central circuits and somatosensory feedback. To demonstrate how forelimb movement affects hindlimb cutaneous reflexes during locomotion, we stimulated the superficial peroneal nerve in intact cats during quadrupedal and hindlimb-only locomotion as well as in spinal-transected cats during hindlimb-only locomotion. We show that forelimb movement influences the modulation of hindlimb cutaneous reflexes, particularly the occurrence of long-latency reflex responses.

Changes in intra- and interlimb reflexes from forelimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

In quadrupeds, such as cats, cutaneous afferents from the forepaw dorsum signal external perturbations and send signals to spinal circuits to coordinate the activity in muscles of all four limbs. How these cutaneous reflex pathways from forelimb afferents are reorganized after an incomplete spinal cord injury is not clear. Using a staggered thoracic lateral hemisections paradigm, we investigated changes in intralimb and interlimb reflex pathways by electrically stimulating the left and right superficial radial nerves in seven adult cats and recording reflex responses in five forelimb and ten hindlimb muscles. After the first (right T5-T6) and second (left T10-T11) hemisections, forelimb-hindlimb coordination was altered and weakened. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-, mid- and long-latency homonymous and crossed reflex responses in forelimb muscles and their phase modulation remained largely unaffected after staggered hemisections. The occurrence of homolateral and diagonal mid- and long-latency responses in hindlimb muscles evoked with left and right superficial radial nerve stimulation was significantly reduced at the first time point after the first hemisection, but partially recovered at the second time point with left superficial radial nerve stimulation. These responses were lost or reduced after the second hemisection. When present, all reflex responses, including homolateral and diagonal, maintained their phase-dependent modulation. Therefore, our results show a considerable loss in cutaneous reflex transmission from cervical to lumbar levels after incomplete spinal cord injury, albeit with preservation of phase modulation, likely affecting functional responses to external perturbations.

Operation regimes of spinal circuits controlling locomotion and role of supraspinal drives and sensory feedback.

Locomotion in mammals is directly controlled by the spinal neuronal network, operating under the control of supraspinal signals and somatosensory feedback that interact with each other. However, the functional architecture of the spinal locomotor network, its operation regimes, and the role of supraspinal and sensory feedback in different locomotor behaviors, including at different speeds, remain unclear. We developed a computational model of spinal locomotor circuits receiving supraspinal drives and limb sensory feedback that could reproduce multiple experimental data obtained in intact and spinal-transected cats during tied-belt and split-belt treadmill locomotion. We provide evidence that the spinal locomotor network operates in different regimes depending on locomotor speed. In an intact system, at slow speeds (< 0.4 m/s), the spinal network operates in a non-oscillating state-machine regime and requires sensory feedback or external inputs for phase transitions. Removing sensory feedback related to limb extension prevents locomotor oscillations at slow speeds. With increasing speed and supraspinal drives, the spinal network switches to a flexor-driven oscillatory regime and then to a classical half-center regime. Following spinal transection, the model predicts that the spinal network can only operate in the state-machine regime. Our results suggest that the spinal network operates in different regimes for slow exploratory and fast escape locomotor behaviors, making use of different control mechanisms.

Changes in intra- and interlimb reflexes from hindlimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9- to 13-week interval in seven adult cats (4 males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery. KEY POINTS: Cutaneous afferent inputs coordinate muscle activity in the four limbs during locomotion when the foot dorsum contacts an obstacle. Thoracic spinal cord injury disrupts communication between spinal locomotor centres located at cervical and lumbar levels, impairing balance and limb coordination. We investigated cutaneous reflexes during quadrupedal locomotion by electrically stimulating the superficial peroneal nerve bilaterally, before and after staggered lateral thoracic hemisections of the spinal cord in cats. We showed a loss/reduction of mid- and long-latency responses in all four limbs after staggered hemisections, which correlated with altered coordination of the fore- and hindlimbs and impaired balance. Targeting cutaneous reflex pathways projecting to the four limbs could help develop therapeutic approaches aimed at restoring transmission in ascending and descending spinal pathways.

A sensory signal related to left-right symmetry modulates intra- and interlimb cutaneous reflexes during locomotion in intact cats.

Introduction: During locomotion, cutaneous reflexes play an essential role in rapidly responding to an external perturbation, for example, to prevent a fall when the foot contacts an obstacle. In cats and humans, cutaneous reflexes involve all four limbs and are task- and phase modulated to generate functionally appropriate whole-body responses. Methods: To assess task-dependent modulation of cutaneous interlimb reflexes, we electrically stimulated the superficial radial or superficial peroneal nerves in adult cats and recorded muscle activity in the four limbs during tied-belt (equal left-right speeds) and split-belt (different left-right speeds) locomotion. Results: We show that the pattern of intra- and interlimb cutaneous reflexes in fore- and hindlimbs muscles and their phase-dependent modulation were conserved during tied-belt and split-belt locomotion. Short-latency cutaneous reflex responses to muscles of the stimulated limb were more likely to be evoked and phase-modulated when compared to muscles in the other limbs. In some muscles, the degree of reflex modulation was significantly reduced during split-belt locomotion compared to tied-belt conditions. Split-belt locomotion increased the step-by-step variability of left-right symmetry, particularly spatially. Discussion: These results suggest that sensory signals related to left-right symmetry reduce cutaneous reflex modulation, potentially to avoid destabilizing an unstable pattern.

Spinal Sensorimotor Circuits Play a Prominent Role in Hindlimb Locomotor Recovery after Staggered Thoracic Lateral Hemisections but Cannot Restore Posture and Interlimb Coordination during Quadrupedal Locomotion in Adult Cats.

Spinal sensorimotor circuits interact with supraspinal and peripheral inputs to generate quadrupedal locomotion. Ascending and descending spinal pathways ensure coordination between the forelimbs and hindlimbs. Spinal cord injury (SCI) disrupts these pathways. To investigate the control of interlimb coordination and hindlimb locomotor recovery, we performed two lateral thoracic hemisections on opposite sides of the cord (right T5-T6 and left T10-T11) at an interval of approximately two months in eight adult cats. In three cats, the spinal cord was transected at T12-T13. We collected electromyography (EMG) and kinematic data during quadrupedal and hindlimb-only locomotion before and after spinal lesions. We show that (1) cats spontaneously recover quadrupedal locomotion following staggered hemisections but require balance assistance after the second one, (2) coordination between the forelimbs and hindlimbs displays 2:1 patterns (two cycles of one forelimb within one hindlimb cycle) and becomes weaker and more variable after both hemisections, (3) left-right asymmetries in hindlimb stance and swing durations appear after the first hemisection and reverse after the second, and (4) support periods reorganize after staggered hemisections to favor support involving both forelimbs and diagonal limbs. Cats expressed hindlimb locomotion the day following spinal transection, indicating that lumbar sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered hemisections. These results reflect a series of changes in spinal sensorimotor circuits that allow cats to maintain and recover some level of quadrupedal locomotor functionality with diminished motor commands from the brain and cervical cord, although the control of posture and interlimb coordination remains impaired.

Spinal sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered thoracic lateral hemisections but cannot restore posture and interlimb coordination during quadrupedal locomotion in adult cats.

Spinal sensorimotor circuits interact with supraspinal and peripheral inputs to generate quadrupedal locomotion. Ascending and descending spinal pathways ensure coordination between the fore-and hindlimbs. Spinal cord injury disrupts these pathways. To investigate the control of interlimb coordination and hindlimb locomotor recovery, we performed two lateral thoracic hemisections placed on opposite sides of the cord (right T5-T6 and left T10-T11) at an interval of approximately two months in eight adult cats. In three cats, we then made a complete spinal transection caudal to the second hemisection at T12-T13. We collected electromyography and kinematic data during quadrupedal and hindlimb-only locomotion before and after spinal lesions. We show that 1) cats spontaneously recover quadrupedal locomotion following staggered hemisections but require balance assistance after the second one, 2) coordination between the fore-and hindlimbs displays 2:1 patterns and becomes weaker and more variable after both hemisections, 3) left-right asymmetries in hindlimb stance and swing durations appear after the first hemisection and reverse after the second, and 4) support periods reorganize after staggered hemisections to favor support involving both forelimbs and diagonal limbs. Cats expressed hindlimb locomotion the day following spinal transection, indicating that lumbar sensorimotor circuits play a prominent role in hindlimb locomotor recovery after staggered hemisections. These results reflect a series of changes in spinal sensorimotor circuits that allow cats to maintain and recover some level of quadrupedal locomotor functionality with diminished motor commands from the brain and cervical cord, although the control of posture and interlimb coordination remains impaired. Significance Statement: Coordinating the limbs during locomotion depends on pathways in the spinal cord. We used a spinal cord injury model that disrupts communication between the brain and spinal cord by sectioning half of the spinal cord on one side and then about two months later, half the spinal cord on the other side at different levels of the thoracic cord in cats. We show that despite a strong contribution from neural circuits located below the second spinal cord injury in the recovery of hindlimb locomotion, the coordination between the forelimbs and hindlimbs weakens and postural control is impaired. We can use our model to test approaches to restore the control of interlimb coordination and posture during locomotion after spinal cord injury.

Electrical Stimulation of Distal Tibial Nerve During Stance Phase of Walking May Reverse Effects of Unilateral Paw Pad Anesthesia in the Cat.

Cutaneous feedback from feet is involved in regulation of muscle activity during locomotion, and the lack of this feedback results in motor deficits. We tested the hypothesis that locomotor changes caused by local unilateral anesthesia of paw pads in the cat could be reduced/reversed by electrical stimulation of cutaneous and proprioceptive afferents in the distal tibial nerve during stance. Several split-belt conditions were investigated in four adult female cats. In addition, we investigated the effects of similar distal tibial nerve stimulation on overground walking of one male cat that had a transtibial, bone-anchored prosthesis for 29 months and, thus, had no cutaneous/proprioceptive feedback from the foot. In all treadmill conditions, cats walked with intact cutaneous feedback (control), with right fore- and hindpaw pads anesthetized by lidocaine injections, and with a combination of anesthesia and electrical stimulation of the ipsilateral distal tibial nerve during the stance phase at 1.2× threshold of afferent activation. Electrical stimulation of the distal tibial nerve during the stance phase of walking with anesthetized ipsilateral paw pads reversed or significantly reduced the effects of paw pad anesthesia on several kinematic variables, including lateral center of mass shift, cycle and swing durations, and duty factor. We also found that stimulation of the residual distal tibial nerve in the prosthetic hindlimb often had different effects on kinematics compared with stimulation of the intact hindlimb with paw anesthetized. We suggest that stimulation of cutaneous and proprioceptive afferents in the distal tibial nerve provides functionally meaningful motion-dependent sensory feedback, and stimulation responses depend on limb conditions.

Changes in intra- and interlimb reflexes from hindlimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats.

When the foot dorsum contacts an obstacle during locomotion, cutaneous afferents signal central circuits to coordinate muscle activity in the four limbs. Spinal cord injury disrupts these interactions, impairing balance and interlimb coordination. We evoked cutaneous reflexes by electrically stimulating left and right superficial peroneal nerves before and after two thoracic lateral hemisections placed on opposite sides of the cord at 9-13 weeks interval in seven adult cats (4 males and 3 females). We recorded reflex responses in ten hindlimb and five forelimb muscles bilaterally. After the first (right T5-T6) and second (left T10-T11) hemisections, coordination of the fore- and hindlimbs was altered and/or became less consistent. After the second hemisection, cats required balance assistance to perform quadrupedal locomotion. Short-latency reflex responses in homonymous and crossed hindlimb muscles largely remained unaffected after staggered hemisections. However, mid- and long-latency homonymous and crossed responses in both hindlimbs occurred less frequently after staggered hemisections. In forelimb muscles, homolateral and diagonal mid- and long-latency response occurrence significantly decreased after the first and second hemisections. In all four limbs, however, when present, short-, mid- and long-latency responses maintained their phase-dependent modulation. We also observed reduced durations of short-latency inhibitory homonymous responses in left hindlimb extensors early after the first hemisection and delayed short-latency responses in the right ipsilesional hindlimb after the first hemisection. Therefore, changes in cutaneous reflex responses correlated with impaired balance/stability and interlimb coordination during locomotion after spinal cord injury. Restoring reflex transmission could be used as a biomarker to facilitate locomotor recovery.

Transformation from arm joint coordinates to hand external coordinates explains non-uniform precision of hand position sense in horizontal workspace.

People perceive hand position in horizontal workspace more precisely in radial than in azimuth directions and closer to the body than farther away. Current explanations for this position sense non-uniformity include spatial asymmetry in arm proprioceptive activities and/or cortex maps, experience-dependent learning, arm posture, and others. Here we investigated contributions to this non-uniformity of a posture-dependent transformation from arm joint angles, sensed by arm proprioceptors, to hand position. We measured precision of hand position sense in a bimanual hand mirror-position matching task at four horizontal targets forming a square in front of the body in 11 blindfolded individuals. We found lower hand precision in azimuth than in radial direction, higher azimuth precision at close targets, and higher radial precision at distant targets. We then theoretically analyzed the transformation of random angle errors at shoulder and elbow into hand position random errors in a horizontal plane and obtained similar distributions of hand position errors. The predicted and experimental hand-precision ellipse orientations, but not ellipse shapes or sizes, were highly correlated and were nearly orthogonal to arm stiffness ellipse orientations reported in the literature. We concluded that the joint-to-hand coordinate transformation is responsible for the non-uniform precision of hand position sense.

Modulation of the gait pattern during split-belt locomotion after lateral spinal cord hemisection in adult cats.

Most previous studies investigated the recovery of locomotion in animals and people with incomplete spinal cord injury (SCI) during relatively simple tasks (e.g., walking in a straight line on a horizontal surface or a treadmill). We know less about the recovery of locomotion after incomplete SCI in left-right asymmetric conditions, such as turning or stepping along circular trajectories. To investigate this, we collected kinematic and electromyography data during split-belt locomotion at different left-right speed differences before and after a right thoracic lateral spinal cord hemisection in nine adult cats. After hemisection, although cats still performed split-belt locomotion, we observed several changes in the gait pattern compared with the intact state at early (1-2 wk) and late (7-8 wk) time points. Cats with larger lesions showed new coordination patterns between the fore- and hindlimbs, with the forelimbs taking more steps. Despite this change in fore-hind coordination, cats maintained consistent phasing between the fore- and hindlimbs. Adjustments in cycle and phase (stance and swing) durations between the slow and fast sides allowed animals to maintain 1:1 left-right coordination. Periods of triple support involving the right (ipsilesional) hindlimb decreased in favor of quad support and triple support involving the other limbs. Step and stride lengths decreased with concurrent changes in the right fore- and hindlimbs, possibly to avoid interference. The above adjustments in the gait pattern allowed cats to retain the ability to locomote in asymmetric conditions after incomplete SCI. We discuss potential plastic neuromechanical mechanisms involved in locomotor recovery in these conditions.NEW & NOTEWORTHY Everyday locomotion often involves left-right asymmetries, when turning, walking along circular paths, stepping on uneven terrains, etc. To show how incomplete spinal cord injury affects locomotor control in asymmetric conditions, we collected data before and after a thoracic lateral spinal hemisection on a split-belt treadmill with one side stepping faster than the other. We show that adjustments in kinematics and muscle activity allowed cats to retain the ability to perform asymmetric locomotion after hemisection.

Emergence of Extreme Paw Accelerations During Cat Paw Shaking: Interactions of Spinal Central Pattern Generator, Hindlimb Mechanics and Muscle Length-Depended Feedback.

Cat paw shaking is a spinal reflex for removing an irritating stimulus from paw by developing extremely high paw accelerations. Previous studies of paw shaking revealed a proximal-to-distal gradient of hindlimb segmental velocities/accelerations, as well as complex inter-joint coordination: passive motion-dependent interaction moments acting on distal segments are opposed by distal muscle moments. However, mechanisms of developing extreme paw accelerations during paw shaking remain unknown. We hypothesized that paw-shaking mechanics and muscle activity might correspond to a whip-like mechanism of energy generation and transfer along the hindlimb. We first demonstrated in experiments with five intact, adult, female cats that during paw shaking, energy generated by proximal muscle moments was transmitted to distal segments by joint forces. This energy transfer was mostly responsible for the segmental velocity/acceleration proximal-to-distal gradient. Distal muscle moments mostly absorbed energy of the distal segments. We then developed a neuromechanical model of hindlimb paw shaking comprised a half-center CPG, activating hip flexors and extensors, and passive viscoelastic distal muscles that produced length/velocity-depended force. Simulations reproduced whip-like mechanisms found experimentally: the proximal-to-distal velocity/acceleration gradient, energy transfer by joint forces and energy absorption by distal muscle moments, as well as atypical co-activation of ankle and hip flexors with knee extensors. Manipulating model parameters, including reversal of segmental inertia distal-to-proximal gradient, demonstrated important inertia contribution to developing the segmental velocity/acceleration proximal-to-distal gradient. We concluded that extreme paw accelerations during paw shaking result from interactions between a spinal CPG, hindlimb segmental inertia, and muscle length/velocity-depended feedback that tunes limb viscoelastic properties.

Control of Forelimb and Hindlimb Movements and Their Coordination during Quadrupedal Locomotion across Speeds in Adult Spinal Cats.

Coordinating the four limbs is critical for terrestrial mammalian locomotion. Thoracic spinal transection abolishes neural communication between the brain and spinal networks controlling hindlimb/leg movements. Several studies have shown that animal models of spinal transection (spinalization), such as mice, rats, cats, and dogs recover hindlimb locomotion with the forelimbs stationary or suspended. We know less on the ability to generate quadrupedal locomotion after spinal transection, however. We collected kinematic and electromyography data in four adult cats during quadrupedal locomotion at five treadmill speeds before (intact cats) and after low-thoracic spinal transection (spinal cats). We show that adult spinal cats performed quadrupedal treadmill locomotion and modulated their speed from 0.4 m/sec to 0.8 m/sec but required perineal stimulation. During quadrupedal locomotion, several compensatory strategies occurred, such as postural adjustments of the head and neck and the appearance of new coordination patterns between the forelimbs and hindlimbs, where the hindlimbs took more steps than the forelimbs. We also observed temporal changes, such as shorter forelimb cycle/swing durations and shorter hindlimb cycle/stance durations in the spinal state. Forelimb double support periods occupied a greater proportion of the cycle in the spinal state, and hindlimb stride length was shorter. Coordination between the forelimbs and hindlimbs was weakened and more variable in the spinal state. Changes in muscle activity reflected spatiotemporal changes in the locomotor pattern. Despite important changes in the pattern, our results indicate that biomechanical properties of the musculoskeletal system play an important role in quadrupedal locomotion and offset some of the loss in neural communication between networks controlling the forelimbs and hindlimbs after spinal transection.

State- and Condition-Dependent Modulation of the Hindlimb Locomotor Pattern in Intact and Spinal Cats Across Speeds.

Locomotion after complete spinal cord injury (spinal transection) in animal models is usually evaluated in a hindlimb-only condition with the forelimbs suspended or placed on a stationary platform and compared with quadrupedal locomotion in the intact state. However, because of the quadrupedal nature of movement in these animals, the forelimbs play an important role in modulating the hindlimb pattern. This raises the question: whether changes in the hindlimb pattern after spinal transection are due to the state of the system (intact versus spinal) or because the locomotion is hindlimb-only. We collected kinematic and electromyographic data during locomotion at seven treadmill speeds before and after spinal transection in nine adult cats during quadrupedal and hindlimb-only locomotion in the intact state and hindlimb-only locomotion in the spinal state. We attribute some changes in the hindlimb pattern to the spinal state, such as convergence in stance and swing durations at high speed, improper coordination of ankle and hip joints, a switch in the timing of knee flexor and hip flexor bursts, modulation of burst durations with speed, and incidence of bi-phasic bursts in some muscles. Alternatively, some changes relate to the hindlimb-only nature of the locomotion, such as paw placement relative to the hip at contact, magnitude of knee and ankle yield, burst durations of some muscles and their timing. Overall, we show greater similarity in spatiotemporal and EMG variables between the two hindlimb-only conditions, suggesting that the more appropriate pre-spinal control is hindlimb-only rather than quadrupedal locomotion.

Sensory Perturbations from Hindlimb Cutaneous Afferents Generate Coordinated Functional Responses in All Four Limbs during Locomotion in Intact Cats.

Coordinating the four limbs is an important feature of terrestrial mammalian locomotion. When the foot dorsum contacts an obstacle, cutaneous mechanoreceptors send afferent signals to the spinal cord to elicit coordinated reflex responses in the four limbs to ensure dynamic balance and forward progression. To determine how the locomotor pattern of all four limbs changes in response to a sensory perturbation evoked by activating cutaneous afferents from one hindlimb, we electrically stimulated the superficial peroneal (SP) nerve with a relatively long train at four different phases (mid-stance, stance-to-swing transition, mid-swing, and swing-to-stance transition) of the hindlimb cycle in seven adult cats. The largest functional effects of the stimulation were found at mid-swing and at the stance-to-swing transition with several changes in the ipsilateral hindlimb, such as increased activity in muscles that flex the knee and hip joints, increased joint flexion and toe height, increased stride/step lengths and increased swing duration. We also observed several changes in support periods to shift support from the stimulated hindlimb to the other three limbs. The same stimulation applied at mid-stance and the swing-to-stance transition produced more subtle changes in the pattern. We observed no changes in stride and step lengths in the ipsilateral hindlimb with stimulation in these phases. We did observe some slightly greater flexions at the knee and ankle joints with stimulation at mid-stance and a reduction in double support periods and increase in triple support. Our results show that correcting or preventing stumbling involves functional contributions from all four limbs.

Asymmetric and transient properties of reciprocal activity of antagonists during the paw-shake response in the cat.

Mutually inhibitory populations of neurons, half-center oscillators (HCOs), are commonly involved in the dynamics of the central pattern generators (CPGs) driving various rhythmic movements. Previously, we developed a multifunctional, multistable symmetric HCO model which produced slow locomotor-like and fast paw-shake-like activity patterns. Here, we describe asymmetric features of paw-shake responses in a symmetric HCO model and test these predictions experimentally. We considered bursting properties of the two model half-centers during transient paw-shake-like responses to short perturbations during locomotor-like activity. We found that when a current pulse was applied during the spiking phase of one half-center, let's call it #1, the consecutive burst durations (BDs) of that half-center increased throughout the paw-shake response, while BDs of the other half-center, let's call it #2, only changed slightly. In contrast, the consecutive interburst intervals (IBIs) of half-center #1 changed little, while IBIs of half-center #2 increased. We demonstrated that this asymmetry between the half-centers depends on the phase of the locomotor-like rhythm at which the perturbation was applied. We suggest that the fast transient response reflects functional asymmetries of slow processes that underly the locomotor-like pattern; e.g., asymmetric levels of inactivation across the two half-centers for a slowly inactivating inward current. We compared model results with those of in-vivo paw-shake responses evoked in locomoting cats and found similar asymmetries. Electromyographic (EMG) BDs of anterior hindlimb muscles with flexor-related activity increased in consecutive paw-shake cycles, while BD of posterior muscles with extensor-related activity did not change, and vice versa for IBIs of anterior flexors and posterior extensors. We conclude that EMG activity patterns during paw-shaking are consistent with the proposed mechanism producing transient paw-shake-like bursting patterns found in our multistable HCO model. We suggest that the described asymmetry of paw-shaking responses could implicate a multifunctional CPG controlling both locomotion and paw-shaking.

Control of Mammalian Locomotion by Somatosensory Feedback.

When animals walk overground, mechanical stimuli activate various receptors located in muscles, joints, and skin. Afferents from these mechanoreceptors project to neuronal networks controlling locomotion in the spinal cord and brain. The dynamic interactions between the control systems at different levels of the neuraxis ensure that locomotion adjusts to its environment and meets task demands. In this article, we describe and discuss the essential contribution of somatosensory feedback to locomotion. We start with a discussion of how biomechanical properties of the body affect somatosensory feedback. We follow with the different types of mechanoreceptors and somatosensory afferents and their activity during locomotion. We then describe central projections to locomotor networks and the modulation of somatosensory feedback during locomotion and its mechanisms. We then discuss experimental approaches and animal models used to investigate the control of locomotion by somatosensory feedback before providing an overview of the different functional roles of somatosensory feedback for locomotion. Lastly, we briefly describe the role of somatosensory feedback in the recovery of locomotion after neurological injury. We highlight the fact that somatosensory feedback is an essential component of a highly integrated system for locomotor control. © 2021 American Physiological Society. Compr Physiol 11:1-71, 2021.