Left-Right Locomotor Coordination in Human Neonates.

Terrestrial locomotion requires coordinated bilateral activation of limb muscles, with left-right alternation in walking or running, and synchronous activation in hopping or skipping. The neural mechanisms involved in interlimb coordination at birth are well known in different mammalian species, but less so in humans. Here, 46 neonates (of either sex) performed bilateral and unilateral stepping with one leg blocked in different positions. By recording EMG activities of lower-limb muscles, we observed episodes of left-right alternating or synchronous coordination. In most cases, the frequency of EMG oscillations during sequences of consecutive steps was approximately similar between the two sides, but in some cases it was considerably different, with episodes of 2:1 interlimb coordination and episodes of activity deletions on the blocked side. Hip position of the blocked limb significantly affected ipsilateral, but not contralateral, muscle activities. Thus, hip extension backward engaged hip flexor muscle, and hip flexion engaged hip extensors. Moreover, the sudden release of the blocked limb in the posterior position elicited the immediate initiation of the swing phase of the limb, with hip flexion and a burst of an ankle flexor muscle. Extensor muscles showed load responses at midstance. The variable interlimb coordination and its incomplete sensory modulation suggest that the neonatal locomotor networks do not operate in the same manner as in mature locomotion, also because of the limited cortical control at birth. These neonatal mechanisms share many properties with spinal mammalian preparations (i.e., independent pattern generators for each limb, and for flexor and extensor muscles, load, and hip position feedback).SIGNIFICANCE STATEMENT Bilateral coupling and reciprocal activation of flexor and extensor burst generators represent the fundamental mechanisms used by mammalian limbed locomotion. Considerable progress has been made in deciphering the early development of the spinal networks and left-right coordination in different mammals, but less is known about human newborns. We compared bilateral and unilateral stepping in human neonates, where cortical control is still underdeveloped. We found neonatal mechanisms that share many properties with spinal mammalian preparations (i.e., independent pattern generators for each limb, the independent generators for flexor and extensor muscles, load, and hip-position feedback. The variable interlimb coordination and its incomplete sensory modulation suggest that the human neonatal locomotor networks do not operate in the same manner as in mature locomotion.

Distinct locomotor precursors in newborn babies.

Mature locomotion involves modular spinal drives generating a set of fundamental patterns of motoneuron activation, each timed at a specific phase of locomotor cycles and associated with a stable muscle synergy. How locomotor modules develop and to what extent they depend on prior experience or intrinsic programs remains unclear. To address these issues, we herein leverage the presence at birth of two types of locomotor-like movements, spontaneous kicking and weight-bearing stepping. The former is expressed thousands of times in utero and postnatally, whereas the latter is elicited de novo by placing the newborn on the ground for the first time. We found that the neuromuscular modules of stepping and kicking differ substantially. Neonates kicked with an adult-like number of temporal activation patterns, which lacked a stable association with systematic muscle synergies across movements. However, on the ground neonates stepped with fewer temporal patterns but all structured in stable synergies. Since kicking and ground-stepping coexist at birth, switching between the two behaviors may depend on a dynamic reconfiguration of the underlying neural circuits as a function of sensory feedback from surface contact. We tracked the development of ground-stepping in 4- to 48-mo-old infants and found that, after the age of 6 mo, the number of temporal patterns increased progressively, reaching adult-like conformation only after independent walking was established. We surmise that mature locomotor modules may derive by combining the multiple patterns of repeated kicking, on the one hand, with synergies resulting from fractionation of those revealed by sporadic weight-bearing stepping, on the other hand.

Evaluation of Spatiotemporal Patterns of the Spinal Muscle Coordination Output during Walking in the Exoskeleton.

Recent advances in the performance and evaluation of walking in exoskeletons use various assessments based on kinematic/kinetic measurements. While such variables provide general characteristics of gait performance, only limited conclusions can be made about the neural control strategies. Moreover, some kinematic or kinetic parameters are a consequence of the control implemented on the exoskeleton. Therefore, standard indicators based on kinematic variables have limitations and need to be complemented by performance measures of muscle coordination and control strategy. Knowledge about what happens at the spinal cord output level might also be critical for rehabilitation since an abnormal spatiotemporal integration of activity in specific spinal segments may result in a risk for abnormalities in gait recovery. Here we present the PEPATO software, which is a benchmarking solution to assess changes in the spinal locomotor output during walking in the exoskeleton with respect to reference data on normal walking. In particular, functional and structural changes at the spinal cord level can be mapped into muscle synergies and spinal maps of motoneuron activity. A user-friendly software interface guides the user through several data processing steps leading to a set of performance indicators as output. We present an example of the usage of this software for evaluating walking in an unloading exoskeleton that allows a person to step in simulated reduced (the Moon's) gravity. By analyzing the EMG activity from lower limb muscles, the algorithms detected several performance indicators demonstrating differential adaptation (shifts in the center of activity, prolonged activation) of specific muscle activation modules and spinal motor pools and increased coactivation of lumbar and sacral segments. The software is integrated at EUROBENCH facilities to benchmark the performance of walking in the exoskeleton from the point of view of changes in the spinal locomotor output.

Backward walking highlights gait asymmetries in children with cerebral palsy.

To investigate how early injuries to developing motor regions of the brain affect different forms of gait, we compared the spatiotemporal locomotor patterns during forward (FW) and backward (BW) walking in children with cerebral palsy (CP). Bilateral gait kinematics and EMG activity of 11 pairs of leg muscles were recorded in 14 children with CP (9 diplegic, 5 hemiplegic; 3.0-11.1 yr) and 14 typically developing (TD) children (3.3-11.8 yr). During BW, children with CP showed a significant increase of gait asymmetry in foot trajectory characteristics and limb intersegmental coordination. Furthermore, gait asymmetries, which were not evident during FW in diplegic children, became evident during BW. Factorization of the EMG signals revealed a comparable structure of the motor output during FW and BW in all groups of children, but we found differences in the basic temporal activation patterns. Overall, the results are consistent with the idea that both forms of gait share pattern generation control circuits providing similar (though reversed) kinematic patterns. However, BW requires different muscle activation timings associated with muscle modules, highlighting subtle gait asymmetries in diplegic children, and thus provides a more comprehensive assessment of gait pathology in children with CP. The findings suggest that spatiotemporal asymmetry assessments during BW might reflect an impaired state and/or descending control of the spinal locomotor circuitry and can be used for diagnostic purposes and as complementary markers of gait recovery. NEW & NOTEWORTHY Early injuries to developing motor regions of the brain affect both forward progression and other forms of gait. In particular, backward walking highlights prominent gait asymmetries in children with hemiplegia and diplegia from cerebral palsy and can give a more comprehensive assessment of gait pathology. The observed spatiotemporal asymmetry assessments may reflect both impaired supraspinal control and impaired state of the spinal circuitry.

Function dictates the phase dependence of vision during human locomotion.

In human and animal locomotion, sensory input is thought to be processed in a phase-dependent manner. Here we use full-field transient visual scene motion toward or away from subjects walking on a treadmill. Perturbations were presented at three phases of walking to test 1) whether phase dependence is observed for visual input and 2) whether the nature of phase dependence differs across body segments. Results demonstrated that trunk responses to approaching perturbations were only weakly phase dependent and instead depended primarily on the delay from the perturbation. Recording of kinematic and muscle responses from both right and left lower limb allowed the analysis of six distinct phases of perturbation effects. In contrast to the trunk, leg responses were strongly phase dependent. Leg responses during the same gait cycle as the perturbation exhibited gating, occurring only when perturbations were applied in midstance. In contrast, during the postperturbation gait cycle, leg responses occurred at similar response phases of the gait cycle over a range of perturbation phases. These distinct responses reflect modulation of trunk orientation for upright equilibrium and modulation of leg segments for both hazard accommodation/avoidance and positional maintenance on the treadmill. Overall, these results support the idea that the phase dependence of responses to visual scene motion is determined by different functional tasks during walking.

Spinal maps of motoneuron activity during human locomotion: neuromechanical considerations.

The spatial segmental location of motoneurons in the human spinal cord is influenced by both evolutionary and functional principles tending to optimize motor control, reflex integration, and adaptation to the demands of movement. Bearing in mind the biomechanics of limb muscles, it is logical to examine how motoneuron activity clusters functionally during typical daily activities like walking. This article provides a summary of advancements in the study of spinal maps of motoneuron activation during human locomotion by reviewing data gathered over ∼20 years. The effects of child development, aging, and neurological disorders show the salient characteristics of spinal segmental activity during different human locomotor tasks and conditions. By exploiting the neuromechanics of the spinal motor circuits, that is, the link between motoneuron activity and gait mechanics, neuroprosthetics and other focused treatments may better help individuals with locomotor impairments.

Muscle Activity during Passive and Active Movements in Preterm and Full-Term Infants.

Manifestation of muscle reactions at an early developmental stage may reflect the processes underlying the generation of appropriate muscle tone, which is also an integral part of all movements. In preterm infants, some aspects of muscular development may occur differently than in infants born at term. Here we evaluated early manifestations of muscle tone by measuring muscle responses to passive stretching (StR) and shortening (ShR) in both upper and lower limbs in preterm infants (at the corrected age from 0 weeks to 12 months), and compared them to those reported in our previous study on full-term infants. In a subgroup of participants, we also assessed spontaneous muscle activity during episodes of relatively large limb movements. The results showed very frequent StR and ShR, and also responses in muscles not being primarily stretched/shortened, in both preterm and full-term infants. A reduction of sensorimotor responses to muscle lengthening and shortening with age suggests a reduction in excitability and/or the acquisition of functionally appropriate muscle tone during the first year of life. The alterations of responses during passive and active movements in preterm infants were primarily seen in the early months, perhaps reflecting temporal changes in the excitability of the sensorimotor networks.

Comparison of the forward and sideways locomotor patterns in children with Cerebral Palsy.

Switching locomotion direction is a common task in daily life, and it has been studied extensively in healthy people. Little is known, however, about the locomotor adjustments involved in changing locomotion direction from forward (FW) to sideways (SW) in children with cerebral palsy (CP). The importance of testing the ability of children with CP in this task lies in the assessment of flexible, adaptable adjustments of locomotion as a function of the environmental context. On the one hand, the ability of a child to cope with novel task requirements may provide prognostic cues as to the chances of modifying the gait adaptively. On the other hand, challenging the child with the novel task may represent a useful rehabilitation tool to improve the locomotor performance. SW is an asymmetrical locomotor task and requires a differential control of right and left limb muscles. Here, we report the results of a cross-sectional study comparing FW and SW in 27 children with CP (17 diplegic, 10 hemiplegic, 2-10 years) and 18 age-matched typically developing (TD) children. We analyzed gait kinematics, joint moments, EMG activity of 12 pairs of bilateral muscles, and muscle modules evaluated by factorization of EMG signals. Task performance in several children with CP differed drastically from that of TD children. Only 2/3 of children with CP met the primary outcome, i.e. they succeeded to step sideways, and they often demonstrated attempts to step forward. They tended to rotate their trunk FW, cross one leg over the other, flex the knee and hip. Moreover, in contrast to TD children, children with CP often exhibited similar motor modules for FW and SW. Overall, the results reflect developmental deficits in the control of gait, bilateral coordination and adjustment of basic motor modules in children with CP. We suggest that the sideways (along with the backward) style of locomotion represents a novel rehabilitation protocol that challenges the child to cope with novel contextual requirements.

Complexity of modular neuromuscular control increases and variability decreases during human locomotor development.

When does modular control of locomotion emerge during human development? One view is that modularity is not innate, being learnt over several months of experience. Alternatively, the basic motor modules are present at birth, but are subsequently reconfigured due to changing brain-body-environment interactions. One problem in identifying modular structures in stepping infants is the presence of noise. Here, using both simulated and experimental muscle activity data from stepping neonates, infants, preschoolers, and adults, we dissect the influence of noise, and identify modular structures in all individuals, including neonates. Complexity of modularity increases from the neonatal stage to adulthood at multiple levels of the motor infrastructure, from the intrinsic rhythmicity measured at the level of individual muscles activities, to the level of muscle synergies and of bilateral intermuscular network connectivity. Low complexity and high variability of neuromuscular signals attest neonatal immaturity, but they also involve potential benefits for learning locomotor tasks.

Age-related changes in the neuromuscular control of forward and backward locomotion.

Previous studies found significant modification in spatiotemporal parameters of backward walking in healthy older adults, but the age-related changes in the neuromuscular control have been considered to a lesser extent. The present study compared the intersegmental coordination, muscle activity and corresponding modifications of spinal montoneuronal output during both forward and backward walking in young and older adults. Ten older and ten young adults walked forward and backward on a treadmill at different speeds. Gait kinematics and EMG activity of 14 unilateral lower-limb muscles were recorded. As compared to young adults, the older ones used shorter steps, a more in-phase shank and foot motion, and the activity profiles of muscles innervated from the sacral segments were significantly wider in each walking condition. These findings highlight age-related changes in the neuromuscular control of both forward and backward walking. A striking feature of backward walking was the differential organization of the spinal output as compared to forward gait. In addition, the resulting spatiotemporal map patterns also characterized age-related changes of gait. Finally, modifications of the intersegmental coordination with aging were greater during backward walking. On the whole, the assessment of backward walk in addition to routine forward walk may help identifying or unmasking neuromuscular adjustments of gait to aging.

Neuromuscular Age-Related Adjustment of Gait When Moving Upwards and Downwards.

Locomotor movements are accommodated to various surface conditions by means of specific locomotor adjustments. This study examined underlying age-related differences in neuromuscular control during level walking and on a positive or negative slope, and during stepping upstairs and downstairs. Ten elderly and eight young adults walked on a treadmill at two different speeds and at three different inclinations (0°, +6°, and -6°). They were also asked to ascend and descend stairs at self-selected speeds. Full body kinematics and surface electromyography of 12 lower-limb muscles were recorded. We compared the intersegmental coordination, muscle activity, and corresponding modifications of spinal motoneuronal output in young and older adults. Despite great similarity between the neuromuscular control of young and older adults, our findings highlight subtle age-related differences in all conditions, potentially reflecting systematic age-related adjustments of the neuromuscular control of locomotion across various support surfaces. The main distinctive feature of walking in older adults is a significantly wider and earlier activation of muscles innervated by the sacral segments. These changes in neuromuscular control are reflected in a reduction or lack of propulsion observed at the end of stance in older adults at different slopes, with the result of a delay in the timing of redirection of the centre-of-mass velocity and of an unanticipated step-to-step transition strategy.

Emergence of Different Gaits in Infancy: Relationship Between Developing Neural Circuitries and Changing Biomechanics.

How does gait-specific pattern generation evolve in early infancy? The idea that neural and biomechanical mechanisms underlying mature walking and running differ to some extent and involve distinct spinal and supraspinal neural circuits is supported by various studies. Here we consider the issue of human gaits from the developmental point of view, from neonate stepping to adult mature gaits. While differentiating features of the walk and run are clearly distinct in adults, the gradual and progressive developmental bifurcation between the different gaits suggests considerable sharing of circuitry. Gaits development and their biomechanical determinants also depend on maturation of the musculoskeletal system. This review outlines the possible overlap in the neural and biomechanical control of walking and running in infancy, supporting the idea that gaits may be built starting from common, likely phylogenetically conserved elements. Bridging connections between movement mechanics and neural control of locomotion could have profound clinical implications for technological solutions to understand better locomotor development and to diagnose early motor deficits. We also consider the neuromuscular maturation time frame of gaits resulting from active practice of locomotion, underlying plasticity of development.

Clinical Relevance of State-of-the-Art Analysis of Surface Electromyography in Cerebral Palsy.

Surface electromyography (sEMG) can be used to assess the integrity of the neuromuscular system and its impairment in neurological disorders. Here we will consider several issues related to the current clinical applications, difficulties and limited usage of sEMG for the assessment and rehabilitation of children with cerebral palsy. The uniqueness of this methodology is that it can determine hyperactivity or inactivity of selected muscles, which cannot be assessed by other methods. In addition, it can assist for intervention or muscle/tendon surgery acts, and it can evaluate integrated functioning of the nervous system based on multi-muscle sEMG recordings and assess motor pool activation. The latter aspect is especially important for understanding impairments of the mechanisms of neural controllers rather than malfunction of individual muscles. Although sEMG study is an important tool in both clinical research and neurorehabilitation, the results of a survey on the clinical relevance of sEMG in a typical department of pediatric rehabilitation highlighted its limited clinical usage. We believe that this is due to limited knowledge of the sEMG and its neuromuscular underpinnings by many physiotherapists, as a result of lack of emphasis on this important methodology in the courses taught in physical therapy schools. The lack of reference databases or benchmarking software for sEMG analysis may also contribute to the limited clinical usage. Despite the existence of educational and technical barriers to a widespread use of, sEMG does provide important tools for planning and assessment of rehabilitation treatments for children with cerebral palsy.

Maturation of the Locomotor Circuitry in Children With Cerebral Palsy.

The first years of life represent an important phase of maturation of the central nervous system, processing of sensory information, posture control and acquisition of the locomotor function. Cerebral palsy (CP) is the most common group of motor disorders in childhood attributed to disturbances in the fetal or infant brain, frequently resulting in impaired gait. Here we will consider various findings about functional maturation of the locomotor output in early infancy, and how much the dysfunction of gait in children with CP can be related to spinal neuronal networks vs. supraspinal dysfunction. A better knowledge about pattern generation circuitries in infancy may improve our understanding of developmental motor disorders, highlighting the necessity for regulating the functional properties of abnormally developed neuronal locomotor networks as a target for early sensorimotor rehabilitation. Various clinical approaches and advances in biotechnology are also considered that might promote acquisition of the locomotor function in infants at risk for locomotor delays.

Development of Locomotor-Related Movements in Early Infancy.

This mini-review focuses on the emergence of locomotor-related movements in early infancy. In particular, we consider multiples precursor behaviors of locomotion as a manifestation of the development of the neuronal networks and their link in the establishment of precocious locomotor skills. Despite the large variability of motor behavior observed in human babies, as in animals, afferent information is already processed to shape the behavior to specific situations and environments. Specifically, we argue that the closed-loop interaction between the neural output and the physical dynamics of the mechanical system should be considered to explore the complexity and flexibility of pattern generation in human and animal neonates.

Muscle Responses to Passive Joint Movements in Infants During the First Year of Life.

Muscle tone represents one of the important concepts for characterizing changes in the state of the developing nervous system. It can be manifested in the level of activity of flexors and extensors and in muscle reactions to its passive stretching (StR) or shortening (ShR). Here we investigated such reactions in a cohort of healthy infants aged from 2 weeks to 12 months. We examined the presence and the characteristics of StR and ShR during slow passive cyclic flexion/extension movements (T~3 s) in the hip, knee, ankle, and elbow joints while awake infants were in the supine position. The results showed that most infants demonstrated prominent ShRs in response to passive joint rotations, although the StR was observed more frequently, suggesting that the ShR is an important component of adaptive motor behavior already at an early developmental stage. Interestingly, the occurrence of both StR and ShR in most muscles significantly decreased throughout the first year of life. Passive cyclic flexion/extension movements could also evoke rhythmic muscle responses in other joints or in the contralateral limb, however, such responses were predominantly observed in younger infants (<6 months). A noticeable manifestation of muscle reactions at an early developmental stage, along with spontaneous motor activity in this period of life, may reflect the processes underlying a formation of appropriate muscle tone and the self-organization of neural circuits. A substantial reduction of ipsilateral and contralateral muscle responses to passive movements with age is consistent with the idea of a functional reorganization of the motor circuitry during early development.

Human-Human Interaction Forces and Interlimb Coordination During Side-by-Side Walking With Hand Contact.

Handholding can naturally occur between two walkers. When people walk side-by-side, either with or without hand contact, they often synchronize their steps. However, despite the importance of haptic interaction in general and the natural use of hand contact between humans during walking, few studies have investigated forces arising from physical interactions. Eight pairs of adult subjects participated in this study. They walked on side-by-side treadmills at 4 km/h independently and with hand contact. Only hand contact-related sensory information was available for unintentional synchronization, while visual and auditory communication was obstructed. Subjects walked at their natural cadences or following a metronome. Limb kinematics, hand contact 3D interaction forces and EMG activity of 12 upper limb muscles were recorded. Overall, unintentional step frequency locking was observed during about 40% of time in 88% of pairs walking with hand contact. On average, the amplitude of contact arm oscillations decreased while the contralateral (free) arm oscillated in the same way as during normal walking. Interestingly, EMG activity of the shoulder muscles of the contact arm did not decrease, and their synergistic pattern remained similar. The amplitude of interaction forces and of trunk oscillations was similar for synchronized and non-synchronized steps, though the synchronized steps were characterized by significantly more regular orientations of interaction forces. Our results further support the notion that gait synchronization during natural walking is common, and that it may occur through interaction forces. Conservation of the proximal muscle activity of the contact (not oscillating) arm is consistent with neural coupling between cervical and lumbosacral pattern generation circuitries ("quadrupedal" arm-leg coordination) during human gait. Overall, the findings suggest that individuals might integrate force interaction cues to communicate and coordinate steps during walking.

Muscle Coordination and Locomotion in Humans.

Locomotion is a semi-automatic daily task. Several studies show that muscle activity is fairly stereotyped during normal walking. Nevertheless, each human leg contains over 50 muscles and locomotion requires flexibility in order to adapt to different conditions as, for instance, different speeds, gaits, turning, obstacle avoidance, altered gravity levels, etc. Therefore, locomotor control has to deal with a certain level of flexibility and non-linearity. In this review, we describe and discuss different findings dealing with both simplicity and variability of the muscular control, as well as with its maturation during development. Despite complexity and redundancy, muscle activity patterns and spatiotemporal maps of spinal motoneuron output during human locomotion show both stereotypical features as well as functional re-organization. Flexibility and different solutions to adjust motor patterns should be considered when considering new rehabilitation strategies to treat disorders involving deficits in gait.

Tonic and Rhythmic Spinal Activity Underlying Locomotion.

In recent years, many researches put significant efforts into understanding and assessing the functional state of the spinal locomotor circuits in humans. Various techniques have been developed to stimulate the spinal cord circuitries, which may include both diffuse and quite specific tuning effects. Overall, the findings indicate that tonic and rhythmic spinal activity control are not separate phenomena but are closely integrated to properly initiate and sustain stepping. The spinal cord does not simply transmit information to and from the brain. Its physiologic state determines reflex, postural and locomotor control and, therefore, may affect the recovery of the locomotor function in individuals with spinal cord and brain injuries. This review summarizes studies that examine the rhythmogenesis capacity of cervical and lumbosacral neuronal circuitries in humans and its importance in developing central pattern generator-modulating therapies.