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Sherlock Holmes and the Curious Case of the Human Locomotor Central Pattern Generator
Abstract
Evidence first described in reduced animal models over 100 years ago led to deductions about the control of locomotion through spinal locomotor central pattern generating (CPG) networks. These discoveries in nature were contemporaneous with another form of deductive reasoning found in popular culture-that of Arthur Conan Doyle's detective "Sherlock Holmes". Since the invasive methods used in reduced non-human animal preparations are not amenable to study in humans, we are left instead with deducing from other measures and observations. Using the deductive reasoning approach of Sherlock Holmes as a metaphor for framing research into human CPGs, we speculate and weigh the evidence that should be observable in humans based on knowledge from other species. This review summarizes indirect inference to assess "observable evidence" of pattern generating activity which leads to the logical deduction of CPG contributions to arm and leg activity during locomotion in humans. The question of where a CPG may be housed in the human nervous system remains incompletely resolved at this time. Ongoing understanding, elaboration and application of functioning locomotor CPGs in humans is important for gait rehabilitation strategies in those with neurological injuries.
... Thus, this study proposed gait training in which people first train their arm swing rhythm in the sitting position using the WMR, resulting in improved gait after removing the WMR. The rhythmic muscle activation of the limbs in arm and leg swings during walking is controlled by neural networks in the spine called central pattern generators (CPGs) with instructions from the central nervous system 32,33 . Arm and leg swings are controlled by different CPGs (cervical and lumbar generators, respectively), and coordination between the upper and lower limbs is achieved through the mutual connection of these CPGs, through which the arm swing is considered to affect leg movement during gait [32][33][34][35] . ...
... The rhythmic muscle activation of the limbs in arm and leg swings during walking is controlled by neural networks in the spine called central pattern generators (CPGs) with instructions from the central nervous system 32,33 . Arm and leg swings are controlled by different CPGs (cervical and lumbar generators, respectively), and coordination between the upper and lower limbs is achieved through the mutual connection of these CPGs, through which the arm swing is considered to affect leg movement during gait [32][33][34][35] . Additionally, using EMG measurements, Klimstra et al. found the same basic rhythmic pattern in arm movement when swinging arms while walking and when swinging arms, suggesting that the same neural mechanisms could be involved in arm swinging in both cases 34 . ...
Although various walking training robots have been developed and their effectiveness has been recognised, operating these robots requires the implementation of safety measures to avoid the risk of falling. This study aimed to confirm whether arm swing rhythm training in the sitting position using an arm swing rhythm-assisted robot, WMR, improved subsequent walking. Healthy older adults (N = 20) performed arm swing rhythm training in a sitting position for 1 min × three times while being presented with tactile stimulation synchronised with the arm swing rhythm from a robot. An increase in walking performance was observed with increases in stride length and speed. In addition, the stabilisation of the gait pattern was observed, with a decrease in the proportion of the double-foot support phase and an increase in the proportion of the swing phase in one gait cycle. These results suggest that arm swing rhythm training in a sitting position using WMR improves gait in older adults. This will lead to the realisation of safe and low-cost robot-based walking training in sitting position.
... Another notable framework for explaining motor redundancy is the concept of central pattern generators (CPG). Rhythmic movement like respiration, walking, and swimming, is attributed to CPGs in the spinal cord [50][51][52]. These CPGs generate muscle activations modulated by higher-level centres, producing synergistic muscle contractions based on sensory responses from the agent-environment interactions [53]. ...
... These CPGs generate muscle activations modulated by higher-level centres, producing synergistic muscle contractions based on sensory responses from the agent-environment interactions [53]. Although some evidence indicates that certain rhythmic human movements persist after neurotrauma [54], a larger impairment is found in discrete reaching than cyclic movements, implying distinct areas in the CNS govern rhythmic and nonrhythmic movement [52]. ...
Vertebrates possess a biomechanical structure with redundant muscles, enabling adaptability in uncertain and complex environments. Harnessing this inspiration, musculoskeletal systems offer advantages like variable stiffness and resilience to actuator failure and fatigue. Despite their potential, the complex structure presents modelling challenges that are difficult to explicitly formulate and control. This difficulty arises from the need for comprehensive knowledge of the musculoskeletal system, including details such as muscle arrangement, and fully accessible muscle and joint states. Whilst existing model-free methods do not need explicit formulations, they also underutilise the benefits of muscle redundancy. Consequently, they necessitate retraining in the event of muscle failure and require manual tuning of parameters to control joint stiffness limiting their applications under unknown payloads. Presented here is a model-free local inverse statics controller for musculoskeletal systems, employing a feedforward neural network trained on motor babbling data. Experiments with a musculoskeletal leg model showcase the controller’s adaptability to complex structures, including mono and bi-articulate muscles. The controller can compensate for changes such as weight variations, muscle failures, and environmental interactions, retaining reasonable accuracy without the need for any additional retraining.
... For example, a study by Lamont, et al. found an enhancement of this TA "reflex reversal" during stair climbing compared to normal gait which was attributed to the increased stability threat posed by the task (Lamont & Zehr, 2006). During these rhythmic activities, cutaneous reflex modulation is thought to be coordinated by human central pattern generation (CPG) which integrates all sensory and positional information at the spinal and supraspinal levels to prompt an appropriate, interlimb motor response across muscle groups (Klarner & Zehr, 2018;MacKay-Lyons, 2002;Zehr, 2005). Spinal-level collaboration between cutaneous reflexes and CPGs is evidenced by bilateral reflexes following unilateral stimulation and coordinated upper and lower extremity reflexes during a variety of rhythmic activities (Haridas & Zehr, 2003;Lamont & Zehr, 2006;Sasada et al., 2010Sasada et al., , 2021Van Wezel et al., 1997;Zehr et al., 2004Zehr et al., , 2009. ...
... Previous literature has shown that BF and VL also contribute to cutaneous reflex modulation during the stance phase of gait in healthy individuals to increase joint stiffness and reduce stumbling risk (Lamont & Zehr, 2006;Tax et al., 1995;Zehr et al., 1998). Additionally, considering the evidence for spinal level control of cutaneous reflex modulation via CPG, we can be confident that stimulation to one limb will likely result in modulation bilaterally (Dietz et al., 2001;Klarner & Zehr, 2018;Tax et al., 1995). Exploring cutaneous reflexes in bilateral musculature of the knee, hip, or upper extremity in the context of perceived instability would reveal the extent of this relationship in both healthy and CAI populations. ...
Cutaneous reflex modulation during rhythmic ambulation is an important motor control mechanism to help minimize stumbling following an unexpected perturbation. Previous literature found individuals with chronic ankle instability (CAI) experience altered reflex patterns compared to healthy controls. Considering CAI is characterized by intermittent feelings of ankle instability, researchers have speculated that these alterations are related to perceived instability. Our purpose was to determine whether variability and magnitude of cutaneous reflex amplitudes can predict perceived instability levels following sural nerve stimulation during gait. Forty subjects walked while receiving random stimulations and reported their perceived instability. Middle latency reflexes among lower leg muscles were calculated using data derived from surface electromyography. Hierarchical logistical regressions revealed a positive relationship between reflex variability of the peroneus longus and lateral gastrocnemius muscles and perceived instability during midstance. This suggests subjects with consistent reflexes following sural nerve stimulation develop a certain level of perceptual expectation resulting in generally lower feelings of ankle instability, while subjects with more variable motor outputs perceive greater instability at the supraspinal level. Cutaneous reflex variability during stance may be an important objective outcome measure to monitor neuromuscular recovery throughout a rehabilitation or as a potential predictor of future lateral ankle sprains.
... In order to match the perturbation training approach for these people, aiming to speci cally train the reactive trunk, hip, and arm balance response, designing and developing a mechatronic system that provides balance training that includes perturbations while in place walking can be valuable. We were also inspired by the in-place walking and regular walking are lower-extremity rhythmic tasks with similar re ex modulation, and related neural circuitry may be operating in both tasks [30,31]. In order to match the perturbation training approach for older adults with lower limb osteoarthritis, aiming to speci cally train the reactive arms, trunk, as well as legs balance response, designing and developing a mechatronic system that provides balance training that includes perturbations while walking in place can be valuable. ...
... Moreover, elliptical training improves gait parameters in older adults with lower limb Osteoarthritis [36], people with stroke [37], Parkinson's [38], multiple sclerosis [39], and people with cardio-respiratory disease [40,41]. This is not surprising since in place walking is a rhythmic task with similar re ex modulation to a regular walking [30,42,43], and related neural circuitry may be operating in both tasks [31,44]. ...
Background: ‘Perturbation-based balance training’ (PBBT) is a training method that was developed to improve balance reactive responses to unexpected balance loss. This training method is more effective in reducing fall rates than traditional balance training methods. Many PBBTs are performed during standing or treadmill walking which targeted specifically step reactive responses, we however, aimed to develop and build a mechatronic system that can provide unexpected perturbation during in-place walking the Elliptical Perturbation System (the EPES system), with the aim of improving specifically the trunk and upper limbs balance reactive control.
Methods: This paper describes the development, and building of the EPES system, using a stationary Elliptical Exercise device, which allows training of trunk and upper limbs balance reactive responses in older adults.
Results: The EPES system provides 3-dimensional small, controlled, and unpredictable sudden perturbations during stationary in-place walking. We developed software that is able to identify a trainee's trunk and arms reactive balance responses using a stereo camera. After identifying an effective trunk and arms reactive balance response, the software controls the EPES system motors to return the system to its horizontal baseline position after the perturbation. The system thus provides closed-loop feedback for a person's counterbalancing trunk and arm responses, helping to implement implicit motor learning for the trainee. The pilot results show that the EPES software is able to successfully identify balance reactive responses among participants who are exposed to a sudden unexpected perturbation during in-place walking on the EPES system.
Conclusions: EPES trigger reactive balance responses involving counter-rotation action of body segments and simultaneously evoke arms, and trunk reactive response, thus reactive training effects should be expected.
... In order to match the perturbation training approach for these people, aiming to specifically train the reactive trunk, hip, and arm balance response, designing and developing a mechatronic system that provides balance training that includes perturbations while elliptical walking can be valuable. We were also inspired by the fact that in-place walking, elliptical walking, and regular overground walking are lowerextremity rhythmic tasks with similar reflex modulation, and related neural circuitry may be operating in these tasks [45,46]. In order to match the perturbation training approach for older adults with lower limb osteoarthritis, aiming to specifically train the reactive arms, trunk, as well as legs balance response, designing and developing a mechatronic system that provides balance training that includes perturbations while elliptical walking can be valuable. ...
... Moreover, elliptical training improves gait parameters in older adults with lower limb Osteoarthritis [51], people with stroke [52], Parkinson's [53], multiple sclerosis [54], and people with cardio-respiratory disease [55,56]. This is not surprising since elliptical walking is a rhythmic task with similar reflex modulation to a regular walking [45,57,58], and related neural circuitry may be operating in both tasks [46,59]. ...
Background
‘Perturbation-based balance training’ (PBBT) is a training method that was developed to improve balance reactive responses to unexpected balance loss. This training method is more effective in reducing fall rates than traditional balance training methods. Many PBBTs are performed during standing or treadmill walking which targeted specifically step reactive responses, we however, aimed to develop and build a mechatronic system that can provide unexpected perturbation during elliptical walking the Elliptical Perturbation System (the EPES system), with the aim of improving specifically the trunk and upper limbs balance reactive control.
Methods
This paper describes the development, and building of the EPES system, using a stationary Elliptical Exercise device, which allows training of trunk and upper limbs balance reactive responses in older adults.
Results
The EPES system provides 3-dimensional small, controlled, and unpredictable sudden perturbations during stationary elliptical walking. We developed software that can identify a trainee’s trunk and arms reactive balance responses using a stereo camera. After identifying an effective trunk and arms reactive balance response, the software controls the EPES system motors to return the system to its horizontal baseline position after the perturbation. The system thus provides closed-loop feedback for a person’s counterbalancing trunk and arm responses, helping to implement implicit motor learning for the trainee. The pilot results show that the EPES software can successfully identify balance reactive responses among participants who are exposed to a sudden unexpected perturbation during elliptical walking on the EPES system.
Conclusions
EPES trigger reactive balance responses involving counter-rotation action of body segments and simultaneously evoke arms, and trunk reactive response, thus reactive training effects should be expected.
... Walking in humans is mainly produced by the combined roles of the reflex circuit, which produces motor patterns triggered by sensory feedback, and the central pattern generators (CPGs), which is a network of neurons capable of generating rhythmic pattern movements even in the absence of command from the higher motor centers (36,37,(54)(55)(56)(57). The CPGs innervate mainly the muscles of the lower limb (54); and they may not be affected following stroke. ...
... Similarly, the role the CPGs play in the generation of rhythmic movement pattern such as the steps required for walking, may aid with the faster recovery of the lower limb (37,54). Thus, considering the roles play by bipedal locomotion in humans, where the unaffected limb forces the affected limb into activity during propulsion and limb advancement; and the potential role of the CPGs in lower limb recovery, use of rhythmic bilateral movement training and bilateral upper limb exercise may help promote recovery of upper limb motor function through use-dependent plasticity (88,89). ...
Background
Stroke results in impairment of motor function of both the upper and lower limbs. However, although it is debatable, motor function of the lower limb is believed to recover faster than that of the upper limb. The aim of this paper is to propose some hypotheses to explain the reasons for that, and discuss their implications for research and practice.
Method
We searched PubMED, Web of Science, Scopus, Embase and CENTRAL using the key words, stroke, cerebrovascular accident, upper extremity, lower extremity, and motor recovery for relevant literature.
Result
The search generated a total of 2,551 hits. However, out of this number, 51 duplicates were removed. Following review of the relevant literature, we proposed four hypotheses: natural instinct for walking hypothesis, bipedal locomotion hypothesis, central pattern generators (CPGs) hypothesis and role of spasticity hypothesis on the subject matter.
Conclusion
We opine that, what may eventually account for the difference, is the frequency of use of the affected limb or intensity of the rehabilitation intervention. This is because, from the above hypotheses, the lower limb seems to be used more frequently. When limbs are used frequently, this will result in use-dependent plasticity and eventual recovery. Thus, rehabilitation techniques that involve high repetitive tasks practice such as robotic rehabilitation, Wii gaming and constraint induced movement therapy should be used during upper limb rehabilitation.
... The modulation of interlimb spinal reflexes suggests the presence of intersegmental linkages between the cervical and lumbar spinal cord regions through proprio-spinal connections [4][5][6]11,77,78]. After A&L cycling training in persons with stroke, increased suppression of cutaneous reflex pathways in the soleus, posterior deltoid, and tibialis anterior muscles of the more affected limbs was evident [28,66]. ...
The ability to walk is often lost after neural injury, leading to multiple secondary complications that reduce quality of life and increase healthcare costs. The current rehabilitation interventions primarily focus on restoring leg movements through intensive training on a treadmill or using robotic devices, but ignore engaging the arms. Several groups have recently shown that simultaneous arm and leg (A&L) cycling improves walking function and interlimb connectivity. These findings highlight the importance of neuronal pathways between the arm (cervical) and leg (lumbar) control regions in the spinal cord during locomotion, and emphasize the need for activating these pathways to improve walking after neural injury or disease. While the findings to date provide important evidence about actively including the arms in walking rehabilitation, these strategies have yet to be optimized. Moreover, improvements beyond A&L cycling alone may be possible with conjunctive targeted strategies to enhance spinal interlimb connectivity. The aim of this review is to highlight the current evidence for improvements in walking function and neural interlimb connectivity after neural injury or disease with cycling-based rehabilitation paradigms. Furthermore, strategies to enhance the outcomes of A&L cycling as a rehabilitation strategy are explored. These include the use of functional electrical stimulation-assisted cycling in acute care settings, utilizing non-invasive transcutaneous spinal cord stimulation to activate previously inaccessible circuitry in the spinal cord, and the use of paired arm and leg rehabilitation robotics. This review aims to consolidate the effects of exercise interventions that incorporate the arms on improved outcomes for walking, functional mobility, and neurological integrity, underscoring the importance of integrating the arms into the rehabilitation of walking after neurological conditions affecting sensorimotor function.
... There is no doubt that CPGs also exist in humans [62,63] . However, the detailed organization of the locomotor network in the spinal cord in humans has yet to be examined. ...
Bipedal gait involves moving the body while maintaining an upright posture under gravity. Throughout vertebrate evolution and postnatal development, humans acquired antigravity functions that allow one to achieve biped gait. While walking, our attention is focused on purposeful, intentional movements such as dexterous arm-hand finger movements or searching for the target. On the other hand, postural control comes to our awareness only when we need to alter gait patterns, such as facing demanding conditions. Nonetheless, our body and brain control gait so as not to fall by anticipatorily adjusting posture that optimally achieves multi-tasks consisting of purposeful movements and walking. Accordingly, we have developed the working hypothesis that postural control is achieved by plans and programs that accomplish purposeful actions. Key questions to verify this hypothesis are (1) how higher brain functions brought about by evolution enabled us to acquire a bipedal standing posture that resists gravity and (2) how the frontal cortex, the most developed neocortical area, enabled us to acquire multi-tasks consisting of gait and intentional movements. We postulate that the frontoparietal networks that contribute to planning and programming based on cognitive information and corticofugal pathways that issue command signals to the subcortical structures, particularly the brainstem and spinal cord in which core systems of posture and gait control exist, play central roles in solving these questions. These mechanisms may be declined in older adults and impaired in patients with degenerative neurological disorders, resulting in posture-gait disturbance such as freezing of gait (FOG) and falling.
... There is no doubt that CPGs also exist in humans [62,63] . However, the detailed organization of the locomotor network in the spinal cord in humans has yet to be examined. ...
Bipedal gait involves moving the body while maintaining an upright posture under gravity. Throughout vertebrate evolution and postnatal development, humans acquired antigravity functions that allow one to achieve biped gait. While walking, our attention is focused on purposeful, intentional movements such as dexterous arm-hand finger movements or searching for the target. On the other hand, postural control comes to our awareness only when we need to alter gait patterns, such as facing demanding conditions. Nonetheless, our body and brain control gait so as not to fall by anticipatorily adjusting posture that optimally achieves multi-tasks consisting of purposeful movements and walking. Accordingly, we have developed the working hypothesis that postural control is achieved by plans and programs that accomplish purposeful actions. Key questions to verify this hypothesis are (1) how higher brain functions brought about by evolution enabled us to acquire a bipedal standing posture that resists gravity and (2) how the frontal cortex, the most developed neocortical area, enabled us to acquire multi-tasks consisting of gait and intentional movements. We postulate that the frontoparietal networks that contribute to planning and programming based on cognitive information and corticofugal pathways that issue command signals to the subcortical structures, particularly the brainstem and spinal cord in which core systems of posture and gait control exist, play central roles in solving these questions. These mechanisms may be declined in older adults and impaired in patients with degenerative neurological disorders, resulting in posture-gait disturbance such as freezing of gait (FOG) and falling.
... Therefore, a more supine sleep position in patients with POSA could decrease the threshold, enhance the response to spinal cord stimulation, and ultimately trigger more PLMS.Finally, activation of the central pattern generator (CPG) may also explain PLMS. Patients with POSA spend more time than others in supine sleep,[41] which can trigger involuntary lower extremity movements via activation of the CPG[42,43]. As PLMS may be activated by the CPG,[44] more supine sleep may be associated with more involuntary lower extremity movements attributable to CPG activation. ...
Objectives:
The relationships among positional obstructive sleep apnea (POSA), obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) are unclear. We analyzed these relationships according to OSA severity and explored the underlying mechanisms.
Methods:
We retrospectively reviewed 6,140 eligible participants who underwent full-night diagnostic polysomnography in four clinical centers over a period of 5 years with eventsynchronized analysis. The PLMS index (PLMI) and periodic limb movements with arousal index (PLMAI) were evaluated. The effects of POSA on the PLMI, PLMAI, and PLMS were analyzed according to OSA severity.
Results:
The mean PLMI and PLMAI, as well as PLMS prevalence, were significantly lower in those with severe OSA than in those with mild and moderate OSA. The mean PLMI was higher in mild OSA group than in control group. The mean PLMI (4.80 ± 12.71 vs. 2.59 ± 9.82 events/h, p < 0.001) and PLMAI (0.89 ± 3.66 vs. 0.53 ± 3.33 events/h, p < 0.001), and the prevalence of PLMS (11% vs. 5.3%, p < 0.001) were higher in patients with POSA than patients with non-POSA. This trend was particularly marked in severe OSA group (OR 1.55, 95%CI [1.07-2.27]) and less so in mild (OR 0.56, 95%CI [0.30-1.03]) and moderate (OR 1.82, 95%CI [0.99-3.34]) OSA groups.
Conclusion:
The POSA group tended to have a higher prevalence of PLMS, particularly in those with severe OSA. If PLMS is prominent, diagnosis and treatment of POSA and OSA may be considered.
... One of the most well-studied examples of a CPG is the locomotor network that controls walking and running. This network is composed of interconnected neurons that produce a rhythmic pattern of muscle activation in a coordinated manner to produce locomotion [2]. CPGs produce coordinated sequences of muscle activation without requiring continuous input from higher brain centers, enabling rhythmic movements even in the absence of sensory feedback [3]. ...
... Many rhythmic motor behaviours such as locomotion, ventilation and mastication are evoked by neural circuits, located in the vertebrate spinal cord or in the invertebrate ganglia, which are termed central pattern generators (CPGs; [1][2][3][4][5]). As a consequence of their properties and connectivity, CPGs can generate and regulate the rhythmic output also 2 of 20 in the absence of afferent input, even though both rhythmic and non-rhythmic sensory activity are important for output compensation [5,6]. ...
Simple Summary
Female moths display a rhythmic motor pattern, a “calling behaviour”, to release sex pheromones and attract of conspecific males for mating. Pheromone release occurs through a squeezing mechanism consisting of turtleneck-like folding and unfolding of the ovipositor cuticle during its rhythmic extensions and retractions. They are under the control of the terminal abdominal ganglion (TAG). The physiology of the production and release of sex pheromones in moths has been an object of great interest. In the present study we investigate the anatomical and physiological basis of calling by using the female spongy moth Lymantria dispar as a model insect. Our results show that the three terminal abdominal segments S7, S8 and S9 (ovipositor) are specialized structures, containing cuticular appendages, hinges, apodemes and several large muscles, innervated by TAG nerves N4 and especially by N5. N6 mainly innervates the oviduct. We also identified a number of specific motor units from nerves N4 and N5 responsible for the ovipositor movements observed during calling. Overall, extensions and retractions of the ovipositor leading to pheromone release are sustained by a coordinated motor program, which involves the activity of a few motor units under the control of TAG nerves N4 and N5.
Abstract
“Calling behaviour” is a stereotyped rhythmic motor pattern displayed by female moths, by which they emit the sex pheromone to attract of conspecific males. Calling occurs through a squeezing mechanism based on the turtleneck-like folding and unfolding of the ovipositor cuticle during its telescopic extensions and retractions. This mechanism is under the control of the terminal abdominal ganglion (TAG). By combining anatomical and electrophysiological approaches, here we studied the morpho-functional organisation of the abdominal muscles and the activity of motoneurons from TAG nerve N4-N6 as correlated to the ovipositor movements during calling in the female spongy moth Lymantria dispar. Our results show that the three abdominal segments S7, S8 and S9 (ovipositor) are highly specialized structures containing cuticular appendages, hinges, apodemes and several large muscles, innervated by N4 and especially by N5. N6 mainly innervates the oviductal tract. We also identified a number of motor units from N4 and N5, the spike activity of which is correlated with the ovipositor movements during calling. In conclusion, the release of sex pheromones in the female spongy moth is obtained by extensions and retractions of the ovipositor operated by a coordinated motor program, which is mainly sustained by the activity of a few motor units under the control of TAG nerves N4 and N5.
... So far, the coordination patterns of locomotor activities without gravity constraints have never been documented. These rhythmic activities are generated by innate spinal generators 27 , and are permanently adapted to the different constraints encountered in terrestrial life 28,29 . However, is the "free" expression of the spinal generators, i.e., without any enforced cadence or constraint, different from that encountered on earth? ...
This study investigates the impact of gravity on lower limb muscle coordination during pedaling. It explores how pedaling behaviors, kinematics, and muscle activation patterns dynamically adapts to changes in gravity and resistance levels. The experiment was conducted in parabolic flights, simulating microgravity, hypergravity (1.8 g), and normogravity conditions. Participants pedaled on an ergometer with varying resistances. The goal was to identify potential changes in muscle synergies and activation strategies under different gravitational contexts. Results indicate that pedaling cadence adjusted naturally in response to both gravity and resistance changes. Cadence increased with higher gravity and decreased with higher resistance levels. Muscular activities were characterized by two synergies representing pull and push phases of pedaling. The timing of synergy activation was influenced by gravity, with a delay in activation observed in microgravity compared to other conditions. Despite these changes, the velocity profile of pedaling remained stable across gravity conditions. The findings strongly suggest that the CNS dynamically manages the shift in body weight by finely tuning muscular coordination, thereby ensuring the maintenance of a stable motor output. Furthermore, electromyography analysis suggest that neuromuscular discharge frequencies were not affected by gravity changes. This implies that the types of muscle fibers recruited during exercise in modified gravity are similar to those used in normogravity. This research has contributed to a better understanding of how the human locomotor system responds to varying gravitational conditions, shedding light on the potential mechanisms underlying astronauts’ gait changes upon returning from space missions.
... One of his own lab members, Thomas Brown, showed in 1911 that a decerebrate cat with spinal sensory nerves cut could still produce walking patterns on a treadmill, without brain or sensory input. The power of Sherrington's research reputation and personality quashed the spread of Brown's research and ideas (Wickens, 2014;Klarner and Zehr, 2018). It was only in the 1970s that Brown's CPG idea was resurrected by the work of Donald Wilson and others on locust flight (Marder and Bucher, 2001). ...
Feeding in pond snails has long been a model system for central pattern generation and its modulation. The pattern is generated by a small set of neurons in the buccal ganglia, which innervate the buccal mass, esophagus, and salivary glands. In this exercise, students observe feeding behavior and then record and quantify rhythmic motor activity and its response to feeding stimulants and neuromodulators. In a standard three-hour class period, students do a dissection, record from several nerves, and perform experimental manipulations such as adding feeding stimulants, serotonin, or dopamine to the preparation. Depending on the course goals, data can be presented qualitatively or cyclic measurements and spike-rate analysis can be done. This exercise leads to discussion of neural circuitry and intrinsic properties that support pattern generation for rhythmic activities such as feeding, locomotion, and respiration.
... Based on our findings, we also suggest that the fast executions of TUG and arm-movement test may challenge the motor system by making similar demands. Thus, walking and armmovement parameters may reflect two facets of the same motor degradation of coordinated rhythmic movements [45,47,48]. This might be surprising given the fact that walking, another than arm movements, comprises equilibrium capacity. ...
Background
There is ample evidence that mobility abilities between healthy young and elderly people differ. However, we do not know whether these differences are based on different lower leg motor capacity or instead reveal a general motor condition that could be detected by monitoring upper-limb motor behavior. We therefore captured body movements during a standard mobility task, namely the Timed Up and Go test (TUG) with subjects following different instructions while performing a rapid, repetitive goal-directed arm-movement test (arm-movement test). We hypothesized that we would be able to predict gait-related parameters from arm motor behavior, even regardless of age.
Methods
Sixty healthy individuals were assigned to three groups (young: mean 26 ± 3 years, middle-aged 48 ± 9, old 68 ± 7). They performed the arm-movement and TUG test under three conditions: preferred (at preferred movement speed), dual-task (while counting backwards), and fast (at fast movement speed). We recorded the number of contacts within 20 s and the TUG duration. We also extracted TUG walking sequences to analyze spatiotemporal gait parameters and evaluated the correlation between arm-movement and TUG results.
Results
The TUG condition at preferred speed revealed differences in gait speed and step length only between young and old, while dual-task and fast execution increased performance differences significantly among all 3 groups. Our old group’s gait speed decreased the most doing the dual-task, while the young group’s gait speed increased the most during the fast condition. As in our TUG results, arm-movements were significant faster in young than in middle-aged and old. We observed significant correlations between arm movements and the fast TUG condition, and that the number of contacts closely predicts TUG timefast and gait speedfast. This prediction is more accurate when including age.
Conclusion
We found that the age-related decline in mobility performance that TUG reveals strongly depends on the test instruction: the dual-task and fast condition clearly strengthened group contrasts. Interestingly, a fast TUG performance was predictable by the performance in a fast repetitive goal-directed arm-movements test, even beyond the age effect. We assume that arm movements and the fast TUG condition reflect similarly reduced motor function.
Trial registration
German Clinical Trials Register (DRKS) number: DRKS00016999, prospectively registered on March, 26, 2019.
... Moreover, rhythmic lower limb movements and sensory inputs in the lower limbs could contribute to motor learning [29]. In this sense, the BWS system could activate the central pattern generator (CPG) in the spinal cord through rhythmic and cyclic gait movements, thus promoting a faster gait and an increased hip extension [30]. The CPG further allows the compensatory cortical excitation of supplementary motor and premotor areas, boosting the functional reorganization of neuronal circuits [31]. ...
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor alterations. Typical motor symptoms include resting tremors, bradykinesia (hypokinesia or akinesia), muscular stiffness, gait alterations, and postural instability. In this context, neurorehabilitation may have a pivotal role in slowing the progression of PD, using both conventional and innovative rehabilitation approaches. Thirty patients (15 males and 15 females) affected by PD were enrolled in our study. We randomly divided the patients into two groups, an experimental group (EG) and a control group (CG). In particular, the EG performed gait and balance training using the Rysen system, which is an innovative body weight support (BWS) system, whilst the CG received conventional physiotherapy. Both groups underwent 20 sessions, five times weekly, with each session lasting about 40 min. At the end of the training sessions (T1), we found that both groups (EG and CG) achieved clinical improvements, although the EG showed better scores for post-treatment regarding global motor functioning and postural stability compared to the CG. In conclusion, our results suggest that the Rysen system, which is an innovative BWS tool, could be considered a valid device for improving postural control and global motor functions, when compared to conventional gait training, in patients affected by PD.
... Such works use an SNN as a central pattern generator [36,37] that controls the contraction and expansion of simulated robot muscles similarly to the voxels in the VSRs. However, the network of a central pattern generator is manually designed and consists of inhibitory cycles between groups of neurons for creating a rhythmic activation of the muscles [38]. In addition, Nadizar et al. [39] applied SNNs to VSRs in a distributed manner, then each voxel is controlled by a single network that can communicate with its neighboring voxels network. ...
... Lampreys, as an early representative of vertebrate evolution, have been a classic model for understanding the detailed structure and operation of vertebrate CPGs in swimming (Grillner and El Manira 2020). Across vertebrates, locomotion encompasses a wide operational range, from swimming to limb-based flight and bipedal locomotion, and it is generally accepted that CPGs are operational across this range (Klarner and Zehr 2018). It is also evident that swimming CPGs are largely understood, but that the operation of limb CPGs, particularly in bipedal locomotion, remains enigmatic (Grillner and Kozlov 2021). ...
Within vertebrates, central pattern generators drive rhythmical behaviours, such as locomotion and ventilation. Their pattern generation is also influenced by sensory input and various forms of neuromodulation. These capabilities arose early in vertebrate evolution, preceding the evolution of the cerebellum in jawed vertebrates. This later evolution of the cerebellum is suggestive of subsumption architecture that adds functionality to a pre-existing network. From a central-pattern-generator perspective, what additional functionality might the cerebellum provide? The suggestion is that the adaptive filter capabilities of the cerebellum may be able to use error learning to appropriately repurpose pattern output. Examples may include head and eye stabilization during locomotion, song learning, and context-dependent alternation between learnt motor-control sequences.
... In the last few years, advances in neurobiology and in the neurorehabilitation field have led to a better understanding of the effects of SCI on gait function and, therefore, in developing treatments to ameliorate the outcomes [11]. Lately, the most relevant mechanism of walking recovery in humans with SCI was related to the concept of central pattern generators (CPGs) [12]. Following this theory, gait can be recovered through rhythmic stimulation, which is a substantial part of different rehabilitation methods [13]. ...
Gait recovery is a fundamental goal in patients with spinal cord injury to attain greater autonomy and quality of life. Robotics is becoming a valid tool in improving motor, balance, and gait function in this patient population. Moreover, other innovative approaches are leading to promising results. The aim of this study was to investigate new rehabilitative methods for gait recovery in people who have suffered spinal cord injuries. A systematic review of the last 10 years of the literature was performed in three databases (PubMed, PEDro, andCochrane). We followed this PICO of the review: P: adults with non-progressive spinal cord injury; I: new rehabilitative methods; C: new methods vs. conventional methods; and O: improvement of gait parameters. When feasible, a comparison through ES forest plots was performed. A total of 18 RCTs of the 599 results obtained were included. The studies investigated robotic rehabilitation (n = 10), intermittent hypoxia (N = 3) and external stimulation (N = 5). Six studies of the first group (robotic rehabilitation) were compared using a forest plot for 10MWT, LEMS, WISCI-II, and SCIM-3. The other clinical trials were analyzed through a narrative review of the results. We found weak evidence for the claim that robotic devices lead to better outcomes in gait independence compared to conventional rehabilitation methods. External stimulation and intermittent hypoxia seem to improve gait parameters associated with other rehabilitation methods. Research investigating the role of innovative technologies in improving gait and balance is needed since walking ability is a fundamental issue in patients with SCI.
... Performance in the regular ladder rung test showed a trend toward improvement that, however, did not reach significance. This is in line with previous observations demonstrating that rhythmic locomotion, as the one necessary for the regular ladder rung test, is known to be essentially under the control of spinal central pattern-generating networks, relying also on afferent cutaneous and proprioceptive feedback (Pearson, 1995;Gerasimenko et al, 2010;Klarner & Zehr, 2018). The findings that some improvement was observed here as well might indicate that rewiring of local circuits is enhanced by FGF22 therapy as well. ...
Functional recovery following incomplete spinal cord injury (SCI) depends on the rewiring of motor circuits during which supraspinal connections form new contacts onto spinal relay neurons. We have recently identified a critical role of the presynaptic organizer FGF22 for the formation of new synapses in the remodeling spinal cord. Here, we now explore whether and how targeted overexpression of FGF22 can be used to mitigate the severe functional consequences of SCI. By targeting FGF22 expression to either long propriospinal neurons, excitatory interneurons, or a broader population of interneurons, we establish that FGF22 can enhance neuronal rewiring both in a circuit-specific and comprehensive way. We can further demonstrate that the latter approach can restore functional recovery when applied either on the day of the lesion or within 24 h. Our study thus establishes viral gene transfer of FGF22 as a new synaptogenic treatment for SCI and defines a critical therapeutic window for its application.
... Côté et al. 2018;Gosgnach et al. 2017;Haque and Gosgnach 2019;Kiehn 2016;Rancic and Gosgnach 2021;Steuer and Guertin 2019; Ziskind-Conhaim and Hochman 2017), but also in cats. CPGs most probably exist in man, but are much less known than in mice and other mammals(Grillner and El Manira 2020;Klarner and Zehr 2018;Minassian et al. 2017). ...
In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in particular spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and predominantly spinal cord injury (SCI) with occasional relations to stroke. Especially the changes in SCI (and stroke) depend on the cause, site and extent of the afflicted damage and are therefore multifarious. At the end, we will briefly summarize results indicating that operant, classical and instrumental conditioning can be used to produce plastic changes in healthy people, with potentials for applications to patients with spinal cord injury. In order not to overload the article, we will not delve deeply into sub-cellular processes.
... Hindlimbs locomotion is controlled by spinal circuits in the lumbar spinal cord, while forelimbs movements are driven by cervical spinal circuits. The lumbar locomotor CPG has received a lot of attention over the years and appears to be very much conserved amongst vertebrates -see for review (Kiehn, 2006;Frigon, 2017;Grillner and El Manira, 2020) -and likely in humans (Minassian et al., 2017;Klarner and Zehr, 2018). Like for investigating the respiratory rhythm, reduced ex vivo preparations were extensively used to isolate the spinal cord circuits and study their organization, function and development (Smith and Feldman, 1987;Branchereau et al., 2000;Clarac et al., 2004). ...
During running, ventilation increases to match the augmented energetic demand. Yet the presumed neuronal substrates for this running hyperpnea have remained elusive. To fill this gap, we have, in mice, examined the interactions between i) limb movements and respiratory cycles, and ii) locomotor and respiratory neural networks. First, by combining electromyographic recordings (EMG) of the diaphragm with limb video-tracking in running mice, we show that, for a wide range of trotting speeds on a treadmill, breathing rate increases to a fixed value, irrespective of running speeds. Importantly, breaths are never temporally synchronized to strides, highlighting that exercise hyperpnea can operate without phasic signals from limb sensory feedbacks. We next sought to identify candidate trigger neurons in the locomotor central network, and their partners in respiratory centers. Combining EMG recordings, viral tracing, and activity interference tools, we first show that the prime supraspinal center for locomotor initiation (the mesencephalic locomotor region, MLR) can upregulate breathing during, and even before, running. Indeed, the MLR contacts directly and modulates the main inspiratory generator, the preBötzinger complex. We show that the lumbar locomotor circuits also have an excitatory action onto respiratory activity, but that this ascending drive targets another essential respiratory group, the retrotrapezoid nucleus. This work highlights the multifunctional nature of locomotor command and executive centers, and points to multiple neuronal pathways capable of upregulating breathing during, or possibly even prior to, running.
... Fifth, within the spinal cord, inter-neuronal networks play a role in the control of locomotion [4,5]. Evidence of a "central pattern generator" (CPG) within the spinal cord is evident across mammalian species [6]. The CPG in humans is believed to be at the level of the second lumbar vertebra (L2) in the posterior spinal cord [7] and is a rhythmogenic circuit kernel partially controlling locomotor movements, based on an open loop system that does not require sensory feedback [8]. ...
The central nervous system (CNS) control of human gait is complex, including descending cortical control, affective ascending neural pathways, interhemispheric communication, whole brain networks of functional connectivity, and neural interactions between the brain and spinal cord. Many important studies were conducted in the past, which administered gait training using externally targeted methods such as treadmill, weight support, over-ground gait coordination training, functional electrical stimulation, bracing, and walking aids. Though the phenomenon of CNS activity-dependent plasticity has served as a basis for more recently developed gait training methods, neurorehabilitation gait training has yet to be precisely focused and quantified according to the CNS source of gait control. Therefore, we offer the following hypotheses to the field: Hypothesis 1. Gait neurorehabilitation after stroke will move forward in important ways if research studies include brain structural and functional characteristics as measures of response to treatment. Hypothesis 2. Individuals with persistent gait dyscoordination after stroke will achieve greater recovery in response to interventions that incorporate the current and emerging knowledge of CNS function by directly engaging CNS plasticity and pairing it with peripherally directed, plasticity-based motor learning interventions. These hypotheses are justified by the increase in the study of neural control of motor function, with emerging research beginning to elucidate neural factors that drive recovery. Some are developing new measures of brain function. A number of groups have developed and are sharing sophisticated, curated databases containing brain images and brain signal data, as well as other types of measures and signal processing methods for data analysis. It will be to the great advantage of stroke survivors if the results of the current state-of-the-art and emerging neural function research can be applied to the development of new gait training interventions.
... To begin with, in human walking locomotion, CPGs coordinate and control the many skeletal muscles that participate in the movement. Although the neural basis of running locomotion has not been widely discussed, its control mechanism is not considered to be significantly different from that of locomotion control during walking, in which spinal nerves are involved [35]. On the other hand, considering the fact that stroke patients have gait disorders, it is clear that the cerebral cortex contributes to locomotion. ...
The purpose of this study was to clarify the lower limb joint motor coordination of para-athletes during running motion from frequency characteristics and to propose this as a method for evaluating their performance. The subject used was a 43-year-old male para-athlete who had suffered a left cerebral infarction. Using a three-dimensional motion analysis system, the angles of the hip, knee, and ankle joints were measured during 1 min of running at a speed of 8 km/h on a treadmill. Nine inter- and intra-limb joint angle pairs were analyzed by coherence and phase analyses. The main characteristic of the stroke patient was that there were joint pairs with absent or increased coherence peaks in the high-frequency band above 4 Hz that were not found in healthy subjects. Interestingly, these features were also observed on the non-paralyzed side. Furthermore, a phase analysis showed different phase differences between the joint motions of the stroke patient and healthy subjects in some joint pairs. Thus, we concluded there was a widespread functional impairment of joint motion in the stroke patient that has not been revealed by conventional methods. The coherence analysis of joint motion may be useful for identifying joint motion problems in para-athletes.
... During this phase of the gait cycle, the subject is experiencing the inversion of load from one leg to the other, and this phenomenon is cortically modulated. The rhythmic motion of human lower limbs is controlled by neural circuits (i.e., central pattern generators) that produce rhythmic activation of muscles that control the limbs (Klarner and Zehr, 2018). Stroke and central nervous system lesions can damage the descending motor pathways. ...
The recovery of symmetric and efficient walking is one of the key goals of a rehabilitation program in patients with stroke. The use of overground exoskeletons alongside conventional gait training might help foster rhythmic muscle activation in the gait cycle toward a more efficient gait. About twenty-nine patients with subacute stroke have been recruited and underwent either conventional gait training or experimental training, including overground gait training using a wearable powered exoskeleton alongside conventional therapy. Before and after the rehabilitation treatment, we assessed: (i) gait functionality by means of clinical scales combined to obtain a Capacity Score, and (ii) gait neuromuscular lower limbs pattern using superficial EMG signals. Both groups improved their ability to walk in terms of functional gait, as detected by the Capacity Score. However, only the group treated with the robotic exoskeleton regained a controlled rhythmic neuromuscular pattern in the proximal lower limb muscles, as observed by the muscular activation analysis. Coherence analysis suggested that the control group (CG) improvement was mediated mainly by spinal cord control, while experimental group improvements were mediated by cortical-driven control. In subacute stroke patients, we hypothesize that exoskeleton multijoint powered fine control overground gait training, alongside conventional care, may lead to a more fine-tuned and efficient gait pattern.
... Looking at the results of these studies, we cannot find anything that contradicts the global entrainment hypothesis that human gait is generated by the dynamic interaction between the neural system including the CPG, the body, and the environment, even 30 years after the proposal. However, there is still debate about the magnitude of relative contributions of the higher center, CPG, and sensory input when gait is generated (Minassian et al. 2017;Klarner and Zehr 2018). Gaining complete proof may be difficult unless we can directly verify the workings of all the elements of the neural and musculoskeletal system when walking in a real environment. ...
We celebrate the 60th anniversary of Biological Cybernetics. It has also been 30 years since “Self-organized control of bipedal locomotion by neural oscillators in unpredictable environment” was published in Biological Cybernetics (Taga et al. in Biol Cybern 65(3):147–159, 1991). I would like to look back on the creation of this paper and discuss its subsequent development and future perspectives. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
... Recent evidence suggests that plasticity changes of some CPG elements may contribute to the development of specific pathophysiological conditions associated with impaired locomotion or spontaneous locomotor-like movements [4]. Despite the relevance of the topic and substantial progress in the field, including proposed mechanisms of pattern generation [5,6], genesis of the motor patterns is still not fully understood [7][8][9]. ...
A minimalistic model of the half-center oscillator is proposed. Within it, we consider dynamics of two excitable neurons interacting by means of the excitatory coupling. In the parameter space of the model, we identify the regions of dynamics, characteristic for central pattern generators: respectively, in-phase, anti-phase synchronous oscillations and quiescence, and study various bifurcation transitions between all these states. Suggested model can serve as a building block of specific complex central pattern generators for studies of rhythmic activity and information processing in animals and humans.
... Stereotyped rhythmic movement can be generated by a tripartite interplay between descending drive; rhythm-generating spinal neural networks, termed central pattern generators (CPGs); and sensory feedback (Duysens & Van de Crommert, 1998;Klarner & Zehr, 2018;Minassian et al., 2017;Zehr, 2005). The knowledge on CPGs and the involvement of these in rhythm generation are, to a large extent, based on animal studies and have been described in a number of excellent reviews from which merely a few are referred to here (Fougère, Flaive, Frigon, & Ryczko, 2019;Grillner & El Manira, 2020;Slawinska & Jordan, 2019). ...
Investigations of behavior and control of voluntary stereotyped rhythmic movement contribute to the enhancement of motor function and performance of disabled, sick, injured, healthy, and exercising humans. The present article presents examples of unprompted alteration of freely chosen movement rate during voluntary stereotyped rhythmic movements. The examples, in the form of both increases and decreases of movement rate, are taken from activities of cycling, finger tapping, and locomotion. It is described that, for example, strength training, changed power output, repeated bouts, and changed locomotion speed can elicit an unprompted alteration of freely chosen movement rate. The discussion of the examples is based on a tripartite interplay between descending drive, rhythm-generating spinal neural networks, and sensory feedback, as well as terminology from dynamic systems theory.
... This multi-limb coordination has its origin at spinal, subcortical and cortical levels. At spinal level, central pattern generators (CPG) generate tightly coupled patterns of neural activity that drive stereotyped motor behaviours including gait (Klarner & Zehr, 2018). Propriospinal pathways interconnect these CPGs from cervical and lumbar levels that control the individual limbs, providing an important contribution in generating coordinated interlimb movements (Gernandt & Megirian, 1961;Forssberg et al. 1980;Meinck & Piesiur-Strehlow, 1981;Cazalets & Bertrand, 2000). ...
Key points
Gait‐related arm swing in humans supports efficient lower limb muscle activation, indicating a neural coupling between the upper and lower limbs during gait.
Intermuscular coherence analyses of gait‐related electromyography from upper and lower limbs in 20 healthy participants identified significant coherence in alpha and beta/gamma bands indicating that upper and lower limbs share common subcortical and cortical drivers that coordinate the rhythmic four‐limb gait pattern.
Additional directed connectivity analyses revealed that upper limb muscles drive and shape lower limb muscle activity during gait via subcortical and cortical pathways and to a lesser extent vice versa.
The results provide a neural underpinning that arm swing may serve as an effective rehabilitation therapy concerning impaired gait in neurological diseases.
Abstract
Human gait benefits from arm swing, as it enhances efficient lower limb muscle activation in healthy participants as well as patients suffering from neurological impairment. The underlying neuronal mechanisms of such coupling between upper and lower limbs remain poorly understood. The aim of the present study was to examine this coupling by intermuscular coherence analysis during gait. Additionally, directed connectivity analysis of this coupling enabled assessment of whether gait‐related arm swing indeed drives lower limb muscles. To that end, electromyography recordings were obtained from four lower limb muscles and two upper limb muscles bilaterally, during gait, of 20 healthy participants (mean (SD) age 67 (6.8) years). Intermuscular coherence analysis revealed functional coupling between upper and lower limb muscles in the alpha and beta/gamma band during muscle specific periods of the gait cycle. These effects in the alpha and beta/gamma bands indicate involvement of subcortical and cortical sources, respectively, that commonly drive the rhythmic four‐limb gait pattern in an efficiently coordinated fashion. Directed connectivity analysis revealed that upper limb muscles drive and shape lower limb muscle activity during gait via subcortical and cortical pathways and to a lesser extent vice versa. This indicates that gait‐related arm swing reflects the recruitment of neuronal support for optimizing the cyclic movement pattern of the lower limbs. These findings thus provide a neural underpinning for arm swing to potentially serve as an effective rehabilitation therapy concerning impaired gait in neurological diseases.
... Moreover, bicycling training improves gait parameters in older people [21], people with stroke [22], Parkinson's [21], multiple sclerosis [23], and heart disease [19]. This is not surprising since pedaling and walking are lower-extremity rhythmic tasks with similar reflex modulation [24][25][26], and related neural circuitry may be operating in both tasks [27,28]. We were also motivated by recent works that found that older people who bicycle outdoors regularly have better balance control than age-matched controls [29,30], and the amount of outdoor bicycling was associated with the degree of balance control [31]. ...
Background
Balance control, and specifically balance reactive responses that contribute to maintaining balance when balance is lost unexpectedly, is impaired in older people. This leads to an increased fall risk and injurious falls. Improving balance reactive responses is one of the goals in fall-prevention training programs. Perturbation training during standing or treadmill walking that specifically challenges the balance reactive responses has shown very promising results; however, only older people who are able to perform treadmill walking can participate in these training regimes. Thus, we aimed to develop, build, and pilot a mechatronic Perturbation Stationary Bicycle Robotic system (i.e., PerStBiRo) that can challenge balance while sitting on a stationary bicycle, with the aim of improving balance proactive and reactive control.
Methods
This paper describes the development, and building of the PerStBiRo using stationary bicycles. In addition, we conducted a pilot randomized control trial (RCT) with 13 older people who were allocated to PerStBiRo training ( N = 7) versus a control group, riding stationary bicycles ( N = 6). The Postural Sway Test, Berg Balance Test (BBS), and 6-min Walk Test were measured before and after 3 months i.e., 20 training sessions.
Results
The PerStBiRo System provides programmed controlled unannounced lateral balance perturbations during stationary bicycling. Its software is able to identify a trainee’s proactive and reactive balance responses using the Microsoft Kinect™ system. After a perturbation, when identifying a trainee’s trunk and arm reactive balance response, the software controls the motor of the PerStBiRo system to stop the perturbation. The pilot RCT shows that, older people who participated in the PerStBiRo training significantly improved the BBS (54 to 56, p = 0.026) and Postural Sway velocity (20.3 m/s to 18.3 m/s, p = 0.018), while control group subject did not (51.0 vs. 50.5, p = 0.581 and 15 m/s vs. 13.8 m/s, p = 0.893, respectively), 6MWT tended to improve in both groups.
Conclusions
Our participants were able to perform correct balance proactive and reactive responses, indicating that older people are able to learn balance trunk and arm reactive responses during stationary bicycling. The pilot study shows that these improvements in balance proactive and reactive responses are generalized to performance-based measures of balance (BBS and Postural Sway measures).
... Similar patterns of activation occur following electrical stimuli applied to the heel (Zehr et al., 2014). This phase-dependency of cutaneous reflexes during gait is thought to be driven by central pattern generator activity (Klarner and Zehr, 2018). While all four types of cutaneous mechanoreceptors found in the glabrous skin of the foot can generate cutaneous reflex responses (Fallon et al., 2005;Bent and Lowrey, 2013), fast adapting type-I (FAI) receptors are believed to be particularly important for the maintenance of balance. ...
Reflex responses generated by cutaneous mechanoreceptors of the plantar foot are important for the maintenance of balance during postural tasks and gait. With aging, reflex generation, particularly from fast adapting type I receptors, is reduced, which likely contributes to impaired postural stability in this population. Therefore, improving reflex generation from these receptors may serve as a tool to improve balance performance. A mechanism to enhance reflexes may lie in the phenomenon of stochastic resonance, whereby the addition of certain intensities and frequencies of noise stimuli improves the performance of a system. This study was conducted to determine whether tactile noise stimuli could improve cutaneous reflex generation. In 12 healthy young adults, we evoked cutaneous reflex responses using a 0–50 Hz Gaussian noise vibration applied to the plantar heel. Concurrently, we applied one of six subthreshold intensities of electrical tactile noise to the plantar heel [0%, 20%, 40%, 60%, 80% or 100% (threshold)] and were able to analyze data from 0%, 20% and 40% trials. Across participants, it was found that the addition of a 20% perceptual threshold (PT) noise resulted in enhanced reflex responses when analyzed in both the time and frequency domains. These data provide evidence that cutaneous reflex generation can be enhanced via a stochastic resonance effect and that 20% PT is the optimal intensity of noise to do so. Therefore, the addition of noise stimuli may be a valuable clinical intervention to improve reflex responses associated with postural balance in populations with impairments.
Model organisms (MO) are widely used in neuroscience to study brain processes, behavior, and the biological foundation of human diseases. However, the use of MO has also been criticized for low reliability and insufficient success rate in the development of therapeutic approaches, because the success of MO use also led to overoptimistic and simplistic applications, which sometimes resulted in wrong conclusions. Here, we develop a conceptual framework of MO to support scientists in their practical work and to foster discussions about their power and limitations. For this purpose, we take advantage of concepts developed in the philosophy of science and adjust them for practical application by neuroscientists. We suggest that MO can be best understood as tools that are used to gain information about a group of species or a phenomenon in a species of interest. These learning processes are made possible by some properties of MO, which facilitate the process of acquisition of understanding or provide practical advantages, and the possibility to transfer information between species. However, residual uncertainty in the reliability of information transfer remains, and incorrect generalizations can be side‐effects of epistemic benefits, which we consider as representational and epistemic risks. This suggests that to use MO most effectively, scientists should analyze the similarity relation between the involved species, weigh advantages and risks of certain epistemic benefits, and invest in carefully designed validation experiments. Altogether, our analysis illustrates how scientists can benefit from philosophical concepts for their research practice.
Non-linear and dynamic systems analysis of human movement has recently become increasingly widespread with the intention of better reflecting how complexity affects the adaptability of motor systems, especially after a stroke. The main objective of this scoping review was to summarize the non-linear measures used in the analysis of kinetic, kinematic, and EMG data of human movement after stroke. PRISMA-ScR guidelines were followed, establishing the eligibility criteria, the population, the concept, and the contextual framework. The examined studies were published between 1 January 2013 and 12 April 2023, in English or Portuguese, and were indexed in the databases selected for this research: PubMed®, Web of Science®, Institute of Electrical and Electronics Engineers®, Science Direct® and Google Scholar®. In total, 14 of the 763 articles met the inclusion criteria. The non-linear measures identified included entropy (n = 11), fractal analysis (n = 1), the short-term local divergence exponent (n = 1), the maximum Floquet multiplier (n = 1), and the Lyapunov exponent (n = 1). These studies focused on different motor tasks: reaching to grasp (n = 2), reaching to point (n = 1), arm tracking (n = 2), elbow flexion (n = 5), elbow extension (n = 1), wrist and finger extension upward (lifting) (n = 1), knee extension (n = 1), and walking (n = 4). When studying the complexity of human movement in chronic post-stroke adults, entropy measures, particularly sample entropy, were preferred. Kinematic assessment was mainly performed using motion capture systems, with a focus on joint angles of the upper limbs.
In the past, the spinal cord was considered a hard-wired network responsible for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic structure that has the potential to adapt to changing environments. While such changes occur under physiological conditions, the most dramatic alterations take place in response to pathological events. Many of the changes that occur following such pathological events are maladaptive, but some appear to help adapt to the new conditions. Although a number of studies have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases impacting the spinal cord are still not well understood. In this review, we summarize current understanding and outstanding challenges for a number of diseases, including spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and spinal cord injury (SCI), with occasional relations to stroke. In particular, we focus on changes resulting from SCI (and stroke), and various influencing factors such as cause, site and extent of the afflicted damage.
Spasticity is characterized by an enhanced size and reduced threshold for activation of stretch reflexes and is associated with "positive signs" such as clonus and spasms, as well as "negative features" such as paresis and a loss of automatic postural responses. Spasticity develops over time after a lesion and can be associated with reduced speed of movement, cocontraction, abnormal synergies, and pain. Spasticity is caused by a combination of damage to descending tracts, reductions in inhibitory activity within spinal cord circuits, and adaptive changes within motoneurons. Increased tone, hypertonia, can also be caused by changes in passive stiffness due to, for example, increase in connective tissue and reduction in muscle fascicle length. Understanding the cause of hypertonia is important for determining the management strategy as nonneural, passive causes of stiffness will be more amenable to physical rather than pharmacological interventions. The management of spasticity is determined by the views and goals of the patient, family, and carers, which should be integral to the multidisciplinary assessment. An assessment, and treatment, of trigger factors such as infection and skin breakdown should be made especially in people with a recent change in tone. The choice of management strategies for an individual will vary depending on the severity of spasticity, the distribution of spasticity (i.e., whether it affects multiple muscle groups or is more prominent in one or two groups), the type of lesion, and the potential for recovery. Management options include physical therapy, oral agents; focal therapies such as botulinum injections; and peripheral nerve blocks. Intrathecal baclofen can lead to a reduction in required oral antispasticity medications. When spasticity is severe intrathecal phenol may be an option. Surgical interventions, largely used in the pediatric population, include muscle transfers and lengthening and selective dorsal root rhizotomy.
Interference between a walking task (target speeds on a self-paced treadmill) and dual visual and tactile-visual response time task was investigated. Ambulatory dual-task scenarios reveal how attention is divided between walking and additional tasks, but the impact of walking speed and dual-task modality on gait characteristics and dual-task performance is unclear. The purpose of this study was to evaluate the effect of visual and tactile-visual dual-task on gait performance. Participants (n=15) targeted four speeds (0.5, 1.0, 1.3, and 1.5 m/s) on a self-paced treadmill with a visual speed indicator (a green region centered at the target speed). Participants completed the same speed profile on the treadmill without (Self-Paced) and with a response time dual task (Self-Paced with Dual Task) requiring finger-tap responses to go/no-go cues. Six gait characteristics were calculated: proportion of time in the desired speed green region (GTP), speed ratio (ratio of mean to target speed), time to green region after target speed change (NRT), normalized stride width (NSW), normalized stride length (NSL), and stride time (ST). Both stride length and width were normalized by participant leg length. Lower GTP and greater speed ratio at slower speeds during dual tasking indicate speed-dependent changes in gait characteristics. Changes in NSL and ST were more affected by speed than dual task. These findings support that when speed is a parameter that is tracked, participants do not universally decrease speed in the presence of a dual task. These findings can support the decisions made when designing new wearable technologies that support navigation, communication, and mobility.
Motor neurons in the spinal cord brainstem motor nuclei (motoneurons) are the final effectors of central motor control and provide the output to skeletal muscles, forming motor units. The activity of spinal motoneurons is controlled by descending cortical and brainstem inputs largely via premotor circuits involving excitatory or inhibitory interneurons. These circuits elicit specific patterns of motoneuron activation controlling muscle synergies under the influence of descending corticospinal and brainstem motor pathways. Central pattern generators are interneuron circuits that can autonomously generate activation of motoneurons in the absence of descending commands or afferent feedback and include those involved in locomotion, respiration, and swallowing. Disorders affecting motor neurons or their control by afferent, cortical, or cerebellar influences constitute a large proportion of neurological diseases.
Objective:
To examine the role of primary motor cortex in gait through exploring the dissociation of impaired voluntary leg muscle contraction and preserved rhythmic activities during gait in a patient who had a stroke.
Subject and methods:
A 49-year-old man with an infarct in the primary motor cortex exhibited automatic-voluntary dissociation in the paretic leg. Functional studies were conducted using surface electromyography (EMG) and near-infrared spectroscopy (NIRS).
Results:
The patient was incapable of voluntary contraction of individual leg muscles on the paretic right side but was able to walk automatically while contracting those muscles rhythmically. Surface EMG confirmed the earlier findings objectively. The preserved automatic activities helped recovery of gait capability, but NIRS showed no functional recovery in the corresponding motor cortex during treadmill gait. We considered that the loss of voluntary leg muscle contraction and the preserved gait capacity in this patient represented a form of automatic-voluntary dissociation.
Conclusions:
The preserved gait capability suggests that the leg representation of the primary motor cortex may not play a major functional role in gait, but other components of the nervous system, including the spinal central pattern generator, would serve important functions to maintain gait capability.
Unlike when you do your math homework, you do not usually have to think about walking—it just happens naturally. We master the ability to walk as children, but the control of walking is complex. To walk, many muscles must act together to produce smooth, coordinated movement of the arms and legs. We sometimes think about where we want to step, but sometimes we do not. We may also choose how fast and which direction we want to go, but we do not actually think about the individual movement of each limb—walking seems so simple and does not require much thought. Although our brains help supervise the control of walking, other parts of the nervous system are what make walking automatic. In fact, the basic pattern of walking is produced and adjusted by networks of cells within the spinal cord, known as central pattern generators.
The use of transcranial magnetic stimulation to assess the excitability of the central nervous system to further understand the neural control of human movement is expansive. The majority of the work performed to-date has assessed corticospinal excitability either at rest or during relatively simple isometric contractions. The results from this work are not easily extrapolated to rhythmic, dynamic motor outputs given that corticospinal excitability is task-, phase-, intensity-, direction- and muscle-dependent (Power et al. 2018). Assessing corticospinal excitability during rhythmic motor output, however, involves technical challenges that are to be overcome, or at the minimum considered, when attempting to design experiments and interpret the physiological relevance of the results. The purpose of this narrative review is to highlight research examining corticospinal excitability during a rhythmic motor output and importantly, to provide recommendations regarding the many factors that must be considered when designing and interpreting findings from studies that involve limb movement. To do so, the majority of work described herein refers to work performed using arm cycling (arm pedaling or arm cranking) as a model of a rhythmic motor output used to examine the neural control of human locomotion.
We examined whether repetitive electrical stimulation to discrete foot sole regions that is phase-locked to the step cycle modulates activity patterns of ankle muscles and induces neuronal adaptation during human walking. Non-noxious repetitive foot sole stimulation (STIM; 67 pulses @333 Hz) was given to the medial forefoot (f-M) or heel (HL) regions at (1) the stance-to-swing transition, (2) swing-to-stance transition, or (3) mid-stance, during every step cycle for 10 min. Stance, but not swing, durations were prolonged f-M STIM delivered at stance-to-swing transition, and these changes remained for up to 20-30 min after the intervention. Electromyographic (EMG) burst durations and amplitudes in the ankle extensors were also prolonged and persisted for 20 min after the intervention. Interestingly, STIM to HL was ineffective at inducing modulation, suggesting stimulation location-specific adaptation. In contrast, STIM to HL (but not f-M), at the swing-to-stance phase transition, shortened the step cycle by premature termination of swing. Furthermore, the onset of EMG bursts in the ankle extensors appeared earlier than in the control condition. STIM delivered during the mid-stance phase was ineffective at modulating the step cycle, highlighting phase-dependent adaptation. These effects were absent when STIM was applied while mimicking static postures for each walking phase during standing. Our findings suggest that the combination of walking-related neuronal activity with repetitive sensory inputs from the foot can generate short-term adaptation that is phase-dependent and localized to the site of STIM.
This is the first study to examine the influence of activity in one limb on corticospinal excitability to the contralateral limb during a locomotor output. Corticospinal and spinal excitability to the biceps brachii of the ipsilateral arm were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of corticospinal axons, respectively. Responses were evoked during the mid-elbow extension position of arm cycling across three different cycling tasks: (1) bilateral arm cycling (BL), (2) unilateral, contralateral cycling with the ipsilateral arm moving passively (IP), and (3) unilateral, contralateral cycling with the ipsilateral arm at rest (IR). Each of these three tasks were performed at two cadences: 60 and 90 rpm. TMS-induced motor evoked potential (MEPs) amplitudes were significantly smaller during BL compared to the IP and IR conditions; however, MEP amplitudes were not significantly different between IP and IR. TMES-evoked cervicomedullary MEP (CMEPs) amplitudes followed a similar pattern of task-dependent modulation, with BL having the smallest CMEPs and IR having the largest. In line with our previous findings, MEP amplitudes increased and CMEP amplitudes decreased as the cadence increased from 60 to 90 rpm. We suggest that the higher corticospinal excitability to the ipsilateral limb during the IP and IR conditions was predominantly due to disinhibition at both the cortical and spinal levels.
Robot-aided gait training (RAGT) has been implemented to provide patients with spinal cord injury (SCI) with a physiological limb activation during gait, cognitive engagement, and an appropriate stimulation of peripheral receptors, which are essential to entrain neuroplasticity mechanisms supporting functional recovery. We aimed at assessing whether RAGT by means of an end-effector device equipped with body weight support could improve functional ambulation in patients with subacute, motor incomplete SCI. In this pilot study, 15 patients were provided with six RAGT sessions per week for eight consecutive weeks. The outcome measures were muscle strength, ambulation, going upstairs, and disease burden. Furthermore, we estimated the activation patterns of lower limb muscles during RAGT by means of surface electromyography and the resting state networks' functional connectivity (RSN-FC) before and after RAGT. Patients achieved a clinically significant improvement in the clinical outcome measures substantially up to six months post-treatment. These data were paralleled by an improvement in the stair-climbing cycle and a potentiating of frequency-specific and area-specific RSN-FC patterns. Therefore, RAGT, by means of an end-effector device equipped with body weight support, is promising in improving gait in patients with subacute, motor incomplete SCI, and it could produce additive benefit for the neuromuscular reeducation to gait in SCI when combined with conventional physiotherapy.
ELife digest
Circuits of nerve cells, or neurons, in the spinal cord control movement. After an injury to the spinal cord, the connections between the brain and spinal neurons may be severed, meaning that the spinal circuits can no longer work properly. This loss of communication between the brain and the spinal cord often leads to paralysis below the level of the injury.
There are currently no effective treatments for individuals who have lost the ability to walk following spinal cord injury. However, the spinal cord retains circuits that are sufficient to restore walking and these circuits can be activated with training. That is, rehabilitative training can lead to improvements in movement by promoting spinal cord plasticity – the ability of other neurons in the spinal cord to take over the roles of the severed neurons. By understanding how rehabilitation leads to these improvements following injury, new strategies could be developed to optimize the recovery process.
Previous research showed that spinal neurons called dI3 interneurons are involved in short term adjustments of movement. Could these interneurons also be involved in longer term adaptations?
Bui, Stifani et al. compared normal mice with genetically engineered mice that had dI3 interneurons “removed” from their circuits. This revealed that although dI3 interneurons in mice are integrated with spinal circuits that are involved in walking, they are not necessary for normal walking. Following the severing of the spinal cord, the experimental mice, unlike the normal mice, did not recover the ability to step. Thus, circuits comprising dI3 interneurons are necessary for recovering the ability to move after an injury.
Now that Bui, Stifani et al. have identified this essential circuit, the next step is to investigate how dI3 interneurons promote spinal cord plasticity. Understanding these mechanisms could help to develop therapies that enhance rehabilitation-assisted improvement of movement following spinal cord injury.
DOI: http://dx.doi.org/10.7554/eLife.21715.002
Neural connections remain partially viable after stroke, and access to these residual connections provides a substrate for training-induced plasticity. The objective of this project was to test if reflex excitability could be modified with arm and leg (A & L) cycling training. Nineteen individuals with chronic stroke (more than six months postlesion) performed 30 min of A & L cycling training three times a week for five weeks. Changes in reflex excitability were inferred from modulation of cutaneous and stretch reflexes. A multiple baseline (three pretests) within-subject control design was used. Plasticity in reflex excitability was determined as an increase in the conditioning effect of arm cycling on soleus stretch reflex amplitude on the more affected side, by the index of modulation, and by the modulation ratio between sides for cutaneous reflexes. In general, A & L cycling training induces plasticity and modifies reflex excitability after stroke.
During bipedal locomotor activities, humans use elements of quadrupedal neuronal limb control. Evolutionary constraints can help inform the historical ancestry for preservation of these core control elements support transfer of the huge body of quadrupedal non-human animal literature to human rehabilitation. In particular, this has translational applications for neurological rehabilitation after neurotrauma where interlimb coordination is lost or compromised. The present state of the field supports including arm activity in addition to leg activity as a component of gait retraining after neurotrauma.
Rhythmic arm and leg (A&L) movements share common elements of neural control. The extent to which A&L cycling training can lead to training adaptations which transfer to improved walking function remains untested. The purpose of this study was to test the efficacy of A&L cycling training as a modality to improve locomotor function after stroke. Nineteen chronic stroke (>six months) participants were recruited and performed 30 minutes of A&L cycling training three times a week for five weeks. Changes in walking function were assessed with (1) clinical tests; (2) strength during isometric contractions; and (3) treadmill walking performance and cutaneous reflex modulation. A multiple baseline (3 pretests) within-subject control design was used. Data show that A&L cycling training improved clinical walking status increased strength by ~25%, improved modulation of muscle activity by ~25%, increased range of motion by ~20%, decreased stride duration, increased frequency, and improved modulation of cutaneous reflexes during treadmill walking. On most variables, the majority of participants showed a significant improvement in walking ability. These results suggest that exploiting arm and leg connections with A&L cycling training, an accessible and cost-effective training modality, could be used to improve walking ability after stroke.
Whether interlimb reflexes emerge only after a severe insult to the human spinal cord is controversial. Here the aim was to examine interlimb reflexes at rest in participants with chronic (>1 year) spinal cord injury (SCI, n = 17) and able-bodied control participants (n = 5). Cutaneous reflexes were evoked by delivering up to 30 trains of stimuli to either the superficial peroneal nerve on the dorsum of the foot or the radial nerve at the wrist (5 pulses, 300 Hz, approximately every 30 s). Participants were instructed to relax the test muscles prior to the delivery of the stimuli. Electromyographic activity was recorded bilaterally in proximal and distal arm and leg muscles. Superficial peroneal nerve stimulation evoked interlimb reflexes in ipsilateral and contralateral arm and contralateral leg muscles of SCI and control participants. Radial nerve stimulation evoked interlimb reflexes in the ipsilateral leg and contralateral arm muscles of control and SCI participants but only contralateral leg muscles of control participants. Interlimb reflexes evoked by superficial peroneal nerve stimulation were longer in latency and duration, and larger in magnitude in SCI participants. Interlimb reflex properties were similar for both SCI and control groups for radial nerve stimulation. Ascending interlimb reflexes tended to occur with a higher incidence in participants with SCI, while descending interlimb reflexes occurred with a higher incidence in able-bodied participants. However, the overall incidence of interlimb reflexes in SCI and neurologically intact participants was similar which suggests that the neural circuitry underlying these reflexes does not necessarily develop after central nervous system injury. © 2016 Butler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Recent reports indicate that rhythmic and discrete upper-limb movements are two different motor primitives which recruit, at least partially, distinct neural circuitries. In particular, rhythmic movements recruit a smaller cortical network than discrete movements. The goal of this paper is to compare the levels of disability in performing rhythmic and discrete movements after a stroke. More precisely, we tested the hypothesis that rhythmic movements should be less affected than discrete ones, because they recruit neural circuitries that are less likely to be damaged by the stroke. Eleven stroke patients and eleven age-matched control subjects performed discrete and rhythmic movements using an end-effector robot (REAplan). The rhythmic movement condition was performed with and without visual targets to further decrease cortical recruitment. Movement kinematics was analyzed through specific metrics, capturing the degree of smoothness and harmonicity. We reported three main observations: (1) the movement smoothness of the paretic arm was more severely degraded for discrete movements than rhythmic movements; (2) most of the patients performed rhythmic movements with a lower harmonicity than controls; and (3) visually guided rhythmic movements were more altered than non-visually guided rhythmic movements. These results suggest a hierarchy in the levels of impairment: Discrete movements are more affected than rhythmic ones, which are more affected if they are visually guided. These results are a new illustration that discrete and rhythmic movements are two fundamental primitives in upper-limb movements. Moreover, this hierarchy of impairment opens new post-stroke rehabilitation perspectives.
This is the first study to report the influence of different cadences on the modulation of supraspinal and spinal excitability during arm cycling. Supraspinal and spinal excitability were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the corticospinal tract, respectively. TMS-induced motor evoked potentials (MEPs) and TMES-induced cervicomedullary evoked potentials (CMEPs) were recorded from the biceps brachii at two separate positions corresponding to elbow flexion and extension (6 and 12 o'clock relative to a clock face, respectively) while arm cycling at 30, 60 and 90 rpm. MEP amplitudes increased significantly as cadence increased during both elbow flexion (P < 0.001) and extension (P = 0.027). CMEP amplitudes also increased with cadence during elbow flexion (P < 0.01), however, the opposite occurred during elbow extension (i.e. decreased CMEP amplitude; P = 0.01). The data indicate an overall increase in the excitability of corticospinal neurones which ultimately project to biceps brachii throughout arm cycling as cadence increased. Conversely, changes in spinal excitability as cadence increased were phase-dependent (i.e. increased during elbow flexion and decreased during elbow extension). Phase and cadence-dependent changes in spinal excitability are suggested to be mediated via changes in the balance of excitatory and inhibitory synaptic input to the motor pool as opposed to changes in the intrinsic properties of spinal motoneurones.
Copyright © 2015, Journal of Neurophysiology.
An ability to produce rhythmic activity is ubiquitous for locomotor pattern generation and modulation. The role that the rhythmogenesis capacity of the spinal cord plays in injured populations has become an area of interest and systematic investigation among researchers in recent years, despite its importance being long recognized by neurophysiologists and clinicians. Given that each individual interneuron, as a rule, receives a broad convergence of various supraspinal and sensory inputs and may contribute to a vast repertoire of motor actions, the importance of assessing the functional state of the spinal locomotor circuits becomes increasingly evident. Air-stepping can be used as a unique and important model for investigating human rhythmogenesis since its manifestation is largely facilitated by a reduction of external resistance. This article aims to provide a review on current issues related to the "locomotor" state and interactions between spinal and supraspinal influences on the central pattern generator (CPG) circuitry in humans, which may be important for developing gait rehabilitation strategies in individuals with spinal cord and brain injuries.
The basic pattern of arm and leg movement during rhythmic locomotor tasks is supported by common central neural control from spinal and supraspinal centers in neurologically intact participants. The purpose of this study was to test the hypothesis that following a cerebrovascular accident, shared systems from interlimb cutaneous networks facilitating arm and leg coordination persist across locomotor tasks. Twelve stroke participants (>6 months post CVA) performed arm and leg (A&L) cycling using a stationary ergometer and walking on a motorized treadmill. In both tasks cutaneous reflexes were evoked via surface stimulation of the nerves innervating the dorsum of the hand (superficial radial; SR) and foot (superficial peroneal; SP) of the less affected limbs. Electromyographic (EMG) activity from the tibialis anterior, soleus, flexor carpi radialis, and posterior deltoid were recorded bilaterally with surface electrodes. Full-wave rectified and filtered EMG data were separated into eight equal parts or phases and aligned to begin with maximum knee extension for both walking and A&L cycling. At each phase of movement, background EMG data were quantified as the peak normalized response for each participant and cutaneous reflexes were quantified as the average cumulative reflex over 150 ms following stimulation. In general, background EMG was similar between walking and A&L cycling, seen especially in the distal leg muscles. Cutaneous reflexes were evident and modified in the less and more affected limbs during walking and A&L cycling and similar modulation patterns were observed suggesting activity in related control networks between tasks. After a stroke common neural patterning from conserved subcortical regulation is seen supporting the notion of a common core in locomotor tasks involving arm and leg movement. This has translational implications for rehabilitation where A&L cycling could be usefully applied to improve walking function.
Reduced gravity offers unique opportunities to study motor behavior. This paper aims at providing a review on current issues of the known tools and techniques used for hypogravity simulation and their effects on human locomotion. Walking and running rely on the limb oscillatory mechanics, and one way to change its dynamic properties is to modify the level of gravity. Gravity has a strong effect on the optimal rate of limb oscillations, optimal walking speed, and muscle activity patterns, and gait transitions occur smoothly and at slower speeds at lower gravity levels. Altered center of mass movements and interplay between stance and swing leg dynamics may challenge new forms of locomotion in a heterogravity environment. Furthermore, observations in the lack of gravity effects help to reveal the intrinsic properties of locomotor pattern generators and make evident facilitation of nonvoluntary limb stepping. In view of that, space neurosciences research has participated in the development of new technologies that can be used as an effective tool for gait rehabilitation.
The present work investigated the reliability of locomotion-related physiological measures taken using a repeated test-retest protocol in stroke participants. Data were collected across 3 testing sessions. Measurements of muscle activity and force during maximum isometric dorsiflexion, plantarflexion and hand grip contractions were taken for both the less and more affected limbs. Cardiovascular measures and stretch reflex amplitudes in soleus muscle were evaluated at rest. Background EMG activity and amplitudes of cutaneous reflexes (following stimulation of the superficial peroneal and superficial radial nerves) were evaluated during walking. Intraclass correlation coefficients (ICC) and results from repeated measures ANOVA revealed no significant differences across and between testing sessions and high absolute agreement (ICC = 0.665 to 0.998) of measures within a participant. Our data support the suggestion that multiple baseline measures obtained from the same participants should be considered a valid alternative to the concept of a control group in intervention studies.
Objective
To compare the effectiveness of body weight-supported treadmill training and body weight-supported overground training for improving gait and strength in people with traumatic incomplete tetraplegia.
Design
Assessor blinded randomized trial.
Setting
Rehabilitation institute of a tertiary care teaching hospital in India.
Participants
Sixteen participants with traumatic motor incomplete tetraplegia and within two years of injury.
Interventions
Participants were randomised to one of two groups: body weight-supported overground training on level ground and body weight-supported treadmill training. Both groups received 30 minutes of gait training per day, five days a week for eight weeks. In addition, both groups received regular rehabilitation which included flexibility, strength, balance, self care and functional training.
Outcome measures
The primary outcome measure was the Walking Index for Spinal Cord Injury (/20 points) and the secondary outcome was the Lower Extremity Muscle Score (/50 points).
Results
There was no statistically significant between group differences in the Walking Index for Spinal Cord Injury [mean difference=0.3points; 95% CI (-4.8 to 5.4); p=0.748] or the Lower Extremity Muscle Score [mean difference=0.2 points; 95% CI (-3.8 to 5.1); p=0.749].
Conclusions
Gait training with body weight-supported overground training is comparable to treadmill training for improving locomotion in people with traumatic incomplete tetraplegia.
Human studies have not assessed corticospinal excitability of an upper-limb prime mover during arm cycling. The purpose of the present study was to determine whether supraspinal and/or spinal motoneurone excitability of the biceps brachii was different between arm cycling and an intensity-matched tonic contraction. We hypothesized that spinal motoneurone excitability would be higher during arm cycling than an intensity-matched tonic contraction. Supraspinal and spinal motoneurone excitability were assessed using transcranial magnetic stimulation (TMS) of the motor cortex and transmastoid electrical stimulation (TMES) of the corticospinal tract, respectively. TMS-induced motor evoked potentials (MEPs) and TMES-induced cervicomedullary evoked potentials (CMEPs) were assessed at three separate positions (3, 6 and 12 o'clock relative to a clock face) during arm cycling and an intensity-matched tonic contraction. MEP amplitudes were 7.2 and 8.8% Mmax larger during arm cycling when compared to a tonic contraction at the 3 (P < 0.001) and 6 o'clock (P < 0.001) positions, respectively. There was no difference between tasks during elbow extension (12 o'clock). CMEP amplitudes were 5.2% Mmax larger during arm cycling when compared to a tonic contraction at the 3 o'clock position (P < 0.001) with no differences seen at mid-flexion (6 o'clock) or extension (12 o'clock). The data indicate an increase in supraspinal excitability of the biceps brachii during the elbow flexion portion of arm cycling and increased spinal motoneurone excitability at the onset of elbow flexion during arm cycling. We conclude that supraspinal and spinal motoneurone excitability are phase- and task-dependent.
Objectives: after stroke a typical presentation is exaggerated stretch reflexes (SRs) on the more affected (MA) side. The present study evaluated the contribution of presynaptic inhibition (PSI) induced by arm cycling and homosynaptic depression (HD) to the modulation of hyperreflexia at the ankle after stroke. Possible asymmetry of these effects between the MA and less affected (LA) legs was also assessed. Methods: soleus SR was conditioned by: arm cycling at 1 Hz (to increase Ia PSI); or, a preceding conditioning tendon tap applied 1 s before the test stimulus (to induce HD). The extent of conditioning effects was compared between the MA and the LA legs. Results: for both MA and LA legs, rhythmic arm movement induced a bidirectional effect in different participants, either increasing or decreasing SR amplitude (p < 0.05). HD had a significant effect in both legs (p < 0.05), however, the effect of both a previous muscle stretch and arm cycling was not different between the MA and the LA legs. Conclusion: our data reveal a bidirectional reflex modulation induced by arm cycling that produced facilitation in some and suppression in other participants after stroke. Relative SR amplitude modulation did not differ between the LA and MA legs. We speculate that alterations in SR amplitude modulation after stroke may reflect specific changes in both presynaptic afferent transmission mechanisms and fusimotor control. Significance: the present findings open new perspectives on the characterization of pathophysiology of stroke during the performance of functionally relevant motor tasks.
Motion of the upper limbs is often coupled to that of the lower limbs in human bipedal locomotion. It is unclear, however, whether the functional coupling between upper and lower limbs is bi-directional, i.e. whether arm movements can affect the lumbosacral locomotor circuitry. Here we tested the effects of voluntary rhythmic arm movements on the lower limbs. Participants lay horizontally on their side with each leg suspended in an unloading exoskeleton. They moved their arms on an overhead treadmill as if they walked on their hands. Hand-walking in the antero-posterior direction resulted in significant locomotor-like movements of the legs in 58% of the participants. We further investigated quantitatively the responses in a subset of the responsive subjects. We found that the electromyographic (EMG) activity of proximal leg muscles was modulated over each cycle with a timing similar to that of normal locomotion. The frequency of kinematic and EMG oscillations in the legs typically differed from that of arm oscillations. The effect of hand-walking was direction specific since medio-lateral arm movements did not evoke appreciably leg air-stepping. Using externally imposed trunk movements and biomechanical modelling, we ruled out that the leg movements associated with hand-walking were mainly due to the mechanical transmission of trunk oscillations. EMG activity in hamstring muscles associated with hand-walking often continued when the leg movements were transiently blocked by the experimenter or following the termination of arm movements. The present results reinforce the idea that there exists a functional neural coupling between arm and legs.
ABSTRACT It is well established that remote whole-limb rhythmic movement (e.g., cycling or stepping) induces suppression of the Hoffman (H-) reflex evoked in stationary limbs. However, the dependence of reflex amplitude on the phase of the movement cycle (i.e., phase-dependence) has not been consistent across this previous research. The authors investigated the phase-dependence of flexor carpi radialis (FCR) H-reflex amplitudes during active walking and in kinematically matched static postures across the gait cycle. FCR H-reflexes were elicited in the stationary forearm with electrical stimulation to the median nerve. Significant phase-dependent modulation occurred during walking when the gait cycle was examined with adequate phase resolution. The suppression was greatest during midstance and midswing, suggesting increased ascending communication during these phases. There was no phase-dependent modulation in static standing postures and no correlation between lower limb background electromyography levels and H-reflex amplitude during active walking. This evidence, along with previous research demonstrating no phase modulation during passive walking, suggests that afferent feedback associated with joint position and leg muscle activation levels are not the sole source of the phase modulation seen during active walking. Possible sources of phase modulation include combinations of afferent feedback related to active movement or central motor commands or both.
Presynaptic inhibition of transmission between Ia afferent terminals and alpha motoneurons (Ia PSI) is a major control mechanism associated with soleus H-reflex modulation during human locomotion. Rhythmic arm cycling suppresses soleus H-reflex amplitude by increasing segmental Ia PSI. There is a reciprocal organization in the human nervous system such that arm cycling modulates H-reflexes in leg muscles and leg cycling modulates H-reflexes in forearm muscles. However, comparatively little is known about mechanisms subserving the effects from leg to arm. Using a conditioning-test (C-T) stimulation paradigm, the purpose of this study was to test the hypothesis that changes in Ia PSI underlie the modulation of H-reflexes in forearm flexor muscles during leg cycling. Subjects performed leg cycling and static activation while H-reflexes were evoked in forearm flexor muscles. H-reflexes were conditioned with either electrical stimuli to the radial nerve (to increase Ia PSI; C-T interval = 20 ms) or to the superficial radial (SR) nerve (to reduce Ia PSI; C-T interval = 37-47 ms). While stationary, H-reflex amplitudes were significantly suppressed by radial nerve conditioning and facilitated by SR nerve conditioning. Leg cycling suppressed H-reflex amplitudes and the amount of this suppression was increased with radial nerve conditioning. SR conditioning stimulation removed the suppression of H-reflex amplitude resulting from leg cycling. Interestingly, these effects and interactions on H-reflex amplitudes were observed with subthreshold conditioning stimulus intensities (radial n., ∼0.6×MT; SR n., ∼ perceptual threshold) that did not have clear post synaptic effects. That is, did not evoke reflexes in the surface EMG of forearm flexor muscles. We conclude that the interaction between leg cycling and somatosensory conditioning of forearm H-reflex amplitudes is mediated by modulation of Ia PSI pathways. Overall our results support a conservation of neural control mechanisms between the arms and legs during locomotor behaviors in humans.
Neural networks in the spinal cord known as central pattern generators produce the sequential activation of muscles needed for locomotion. The overall locomotor network architectures in limbed vertebrates have been much debated, and no consensus exists as to how they are structured. Here, we use optogenetics to dissect the excitatory and inhibitory neuronal populations and probe the organization of the mammalian central pattern generator. We find that locomotor-like rhythmic bursting can be induced unilaterally or independently in flexor or extensor networks. Furthermore, we show that individual flexor motor neuron pools can be recruited into bursting without any activity in other nearby flexor motor neuron pools. Our experiments differentiate among several proposed models for rhythm generation in the vertebrates and show that the basic structure underlying the locomotor network has a distributed organization with many intrinsically rhythmogenic modules.
Recent data from this laboratory on differential controls for the shoulder, elbow, and wrist exerted by the thalamo-cortical network during locomotion is presented, based on experiments involving chronically instrumented cats walking on a flat surface and along a horizontal ladder. The activity of the following three groups of neurons is characterized: 1) neurons of the motor cortex that project to the pyramidal tract (PTNs), 2) neurons of the ventrolateral thalamus (VL), many identified as projecting to the motor cortex (thalamo-cortical neurons, TCs), and 3) neurons of the reticular nucleus of thalamus (RE), which inhibit TCs. Neurons were grouped according to their receptive field into shoulder-, elbow-, and wrist/paw-related categories. During simple locomotion, shoulder-related PTNs were most active in the late stance and early swing, and on the ladder, often increased activity and step-related modulation while reducing discharge duration. Elbow-related PTNs were most active during late swing/early stance and typically remained similar on the ladder. Wrist-related PTNs were most active during swing, and on the ladder often decreased activity and increased modulation while reducing discharge duration. In the VL, shoulder-related neurons were more active during transition from swing to stance. Elbow-related cells tended to be more active during transition from stance to swing and on the ladder often decreased their activity and increased modulation. Wrist-related neurons were more active throughout the stance phase. In the RE, shoulder-related cells had low discharge rates and depths of modulation and long periods of activity distributed evenly across the cycle. In contrast, wrist/paw-related cells discharged synchronously during end of stance and swing with short periods of high activity, high modulation, and frequent sleep-type bursting. We conclude that thalamo-cortical network processes information related to different segments of the forelimb differe
Facilitation of leg muscle activity by active arm movements during locomotor tasks could be beneficial during gait rehabilitation after spinal cord injury. The present study explored the effects of arm movements on leg muscle activity during sub-maximal recumbent stepping. Healthy subjects exercised on a recumbent stepping machine both with and without arm movements. Activity of five leg muscles was recorded and compared for stepping with and without arm movements. To determine which arm movements are optimal for leg muscle facilitation, subjects were instructed to step with 1) mechanically coupled vs. decoupled arm and leg movements, 2) synchronous (SYNC) vs. asynchronous (ASYNC) arm movements and 3) at 50 vs. 70 revolutions per minute (RPM). Leg muscle activity was increased by active arm movements in all muscles, except the vastus lateralis (VL) muscle. Activity of other extensors (soleus (SO), medial gastrocnemius (MG) and biceps femoris (BF)) was primarily increased during the extension phase whereas activity of flexors (tibialis anterior (TA)) was also increased during the flexion phase. Facilitation was more or less consistent for both frequencies and for SYNC and ASYNC movements. For coupled arm movements facilitation tended to be diminished or absent. The observed facilitation in the present study is probably of neuromuscular rather than of biomechanical origin, since the arms are probably hardly involved in postural control or weight-bearing during recumbent stepping. Further studies in patients should explore the possibility to integrate neuromuscular facilitation in rehabilitation programs.
Recently there has been a growing interest in the modular organization of leg movements, in particular those related to locomotion. One of the basic modules involves the flexion of the leg during swing and it was shown that this module is already present in neonates (Dominici et al., 2011). In this paper, we question how these finding build upon the original work by Sherrington, who proposed that the flexor reflex is the basic building block of flexion during swing phase. Similarly, the relation between the flexor reflex and the withdrawal reflex modules of Schouenborg and Weng (1994) will be discussed. It will be argued that there is large overlap between these notions on modules and the older concepts of reflexes. In addition, it will be shown that there is a great flexibility in the expression of some of these modules during gait, thereby allowing for a phase-dependent modulation of the appropriate responses. In particular, the end of the stance phase is a period when the flexor synergy is facilitated. It is proposed that this is linked to the activation of circuitry that is responsible for the generation of locomotor patterns (CPG, "central pattern generator"). More specifically, it is suggested that the responses in that period relate to the activation of a flexor burst generator. The latter structure forms the core of a new asymmetric model of the CPG. This activation is controlled by afferent input (facilitation by a broad range of afferents, suppression by load afferent input). Meanwhile, many of these physiologic features have found their way in the control of very flexible walking bipedal robots.
This article provides a perspective on major innovations over the past century in research on the spinal cord and, specifically, on specialized spinal circuits involved in the control of rhythmic locomotor pattern generation and modulation. Pioneers such as Charles Sherrington and Thomas Graham Brown have conducted experiments in the early twentieth century that changed our views of the neural control of locomotion. Their seminal work supported subsequently by several decades of evidence has led to the conclusion that walking, flying, and swimming are largely controlled by a network of spinal neurons generally referred to as the central pattern generator (CPG) for locomotion. It has been subsequently demonstrated across all vertebrate species examined, from lampreys to humans, that this CPG is capable, under some conditions, to self-produce, even in absence of descending or peripheral inputs, basic rhythmic, and coordinated locomotor movements. Recent evidence suggests, in turn, that plasticity changes of some CPG elements may contribute to the development of specific pathophysiological conditions associated with impaired locomotion or spontaneous locomotor-like movements. This article constitutes a comprehensive review summarizing key findings on the CPG as well as on its potential role in Restless Leg Syndrome, Periodic Leg Movement, and Alternating Leg Muscle Activation. Special attention will be paid to the role of the CPG in a recently identified, and uniquely different neurological disorder, called the Uner Tan Syndrome.
Suppression of soleus H-reflex amplitude in stationary legs is seen during rhythmic arm cycling. We examined the influence of various arm cycling parameters on this interlimb reflex modulation in order to determine the origin of the effect. We previously showed the suppression to be graded with the frequency of arm cycling but not largely influenced by changes in peripheral input associated with crank length. Here, we more explicitly explored the contribution of afferent feedback related to arm movement on the soleus H-reflex suppression. We explored the influence of load and rate of muscle stretch by manipulating crank load and arm muscle vibration during arm cycling. Further, internally-driven ("Active") and externally-driven ("Passive") arm cycling were compared. Soleus H-reflexes were evoked with tibial nerve stimulation during stationary control and rhythmic arm cycling conditions including: 1) 6 different loads; 2) with and without vibration to arm muscles; and, 3) Active and Passive conditions. No significant differences were seen in the level of suppression between the different crank loads or between conditions with and without arm muscle vibration. Further, in contrast to the clear effect seen during active cycling, passive arm cycling did not significantly suppress the soleus H- reflex amplitude. Current results, in conjunction with previous findings, suggest that the afferent feedback examined in these studies is not the primary source responsible for soleus H-reflex suppression. Instead it appears that central motor commands ( supraspinal or spinal in origin) associated with frequency of arm cycling are relatively more dominant sources.
A new tool for locomotor circuitry activation in the non-injured human by transcutaneous electrical spinal cord stimulation (tSCS) has been described. We show that continuous tSCS over T11-T12 vertebrae at 5-40 Hz induced involuntary locomotor-like stepping movements in subjects with their legs in a gravity-independent position. The increase of frequency of tSCS from 5 to 30 Hz augmented the amplitude of evoked stepping movements. The duration of cycle period did not depend on frequency of tSCS. During tSCS the hip, knee and ankle joints were involved in the stepping performance. It has been suggested that tSCS activates the locomotor circuitry through the dorsal roots. It appears that tSCS can be used as a non-invasive method in rehabilitation of spinal pathology.
Half of human spinal cord injuries lead to chronic paralysis. Here, we introduce an electrochemical neuroprosthesis and a
robotic postural interface designed to encourage supraspinally mediated movements in rats with paralyzing lesions. Despite
the interruption of direct supraspinal pathways, the cortex regained the capacity to transform contextual information into
task-specific commands to execute refined locomotion. This recovery relied on the extensive remodeling of cortical projections,
including the formation of brainstem and intraspinal relays that restored qualitative control over electrochemically enabled
lumbosacral circuitries. Automated treadmill-restricted training, which did not engage cortical neurons, failed to promote
translesional plasticity and recovery. By encouraging active participation under functional states, our training paradigm
triggered a cortex-dependent recovery that may improve function after similar injuries in humans.
Disordered reflex activity and alterations in the neural control of walking have been observed after stroke. In addition to impairments in leg movement that affect locomotor ability after stroke, significant impairments are also seen in the arms. Altered neural control in the upper limb can often lead to altered tone and spasticity resulting in impaired coordination and flexion contractures. We sought to address the extent to which the neural control of movement is disordered after stroke by examining the modulation pattern of cutaneous reflexes in arm muscles during arm cycling. Twenty-five stroke participants who were at least 6 mo postinfarction and clinically stable, performed rhythmic arm cycling while cutaneous reflexes were evoked with trains (5 × 1.0-ms pulses at 300 Hz) of constant-current electrical stimulation to the superficial radial (SR) nerve at the wrist. Both the more (MA) and less affected (LA) arms were stimulated in separate trials. Bilateral electromyography (EMG) activity was recorded from muscles acting at the shoulder, elbow, and wrist. Analysis was conducted on averaged reflexes in 12 equidistant phases of the movement cycle. Phase-modulated cutaneous reflexes were present, but altered, in both MA and LA arms after stroke. Notably, the pattern was "blunted" in the MA arm in stroke compared with control participants. Differences between stroke and control were progressively more evident moving from shoulder to wrist. The results suggest that a reduced pattern of cutaneous reflex modulation persists during rhythmic arm movement after stroke. The overall implication of this result is that the putative spinal contributions to rhythmic human arm movement remain accessible after stroke, which has translational implications for rehabilitation.
How rudimentary movements evolve into sophisticated ones during development remains unclear. It is often assumed that the primitive patterns of neural control are suppressed during development, replaced by entirely new patterns. Here we identified the basic patterns of lumbosacral motoneuron activity from multimuscle recordings in stepping neonates, toddlers, preschoolers, and adults. Surprisingly, we found that the two basic patterns of stepping neonates are retained through development, augmented by two new patterns first revealed in toddlers. Markedly similar patterns were observed also in the rat, cat, macaque, and guineafowl, consistent with the hypothesis that, despite substantial phylogenetic distances and morphological differences, locomotion in several animal species is built starting from common primitives, perhaps related to a common ancestral neural network.
Arm movements modulate leg activity and improve gait efficiency; however, current rehabilitation interventions focus on improving walking through gait-specific training, and do not actively involve the arms. The goal of this project was to assess the effect of a rehabilitation strategy involving simultaneous arm and leg cycling on improving walking after incomplete spinal cord injury (iSCI). We investigated the effect of 1) non-gait-specific training and 2) active arm involvement during training on changes in over ground walking capacity. Participants with iSCI were assigned to simultaneous arm-leg cycling (A&L) or legs only cycling (Leg) training paradigms, and cycling movements were assisted with electrical stimulation. Overground walking speed significantly increased by 0.0920.022m/s in the Leg group and 0.270.072m/s in the A&L group after training. While the increases in the Leg group were similar to those seen after current locomotor training strategies, increases in the A&L group were significantly larger than those in the Leg group. Walking distance also significantly increased by 32.128.74m in the Leg and 91.5836.24m in the A&L group. Muscle strength, sensation and balance improved in both groups; however, the A&L group had significant improvements in most gait measures, and had more regulated joint kinematics and muscle activity after training compared to the Leg group. We conclude that electrical stimulation-assisted cycling training can produce significant improvements in walking after SCI. Furthermore, active arm involvement during training can produce greater improvements in walking performance. This strategy may also be effective in people with other neural disorders or diseases.
Neuro-Behavioral Determinants of Interlimb Coordination: A multidisciplinary approach focuses on bimanual coordination against the broader context of the coordination between the upper and lower limbs. However, it is also broad in scope in that it reviews recent developments in the study of coordination by means of the latest technologies for the study of brain function, such as functional magnetic resonance imaging, near-infrared spectroscopy, magneto-encephalography, and transcranial magnetic stimulation. In addition, new developments in recovery of interlimb coordination following spinal cord injury and other insults of the central nervous system, such as stroke, are reviewed.
Abstract Training locomotor pattern generating networks (CPGs) through arm and leg cycling improves walking in chronic stroke. These outcomes are presumed to result from enhanced interlimb connectivity and CPG function. The extent to which rhythmic arm training activates interlimb CPG networks for locomotion remains unclear and was assessed by studying chronic stroke participants before and after 5-weeks of arm cycling training. Strength was assessed bilaterally via maximal voluntary isometric contractions in the legs and hands. Muscle activation during arm cycling and transfer to treadmill walking were assessed in the more affected (MA) and less affected (LA) sides via surface electromyography. Changes to interlimb coupling during rhythmic movement were evaluated using modulation of cutaneous reflexes elicited by electrical stimulation of the superficial radial nerve at the wrist. Bilateral soleus stretch reflexes were elicited at rest and during 1Hz arm cycling. Clinical function tests assessed walking, balance and motor function. Results show significant changes in function and neurophysiological integrity. Training increased bilateral grip strength, force during MA plantarflexion and muscle activation. 'Normalization' of cutaneous reflex modulation was found during arm cycling. There was enhanced activity in the dorsiflexor muscles on the MA side during swing phase of walking. Enhanced interlimb coupling was shown by increased modulation of MA soleus stretch reflexes amplitudes during arm cycling after training. Clinical evaluations showed enhanced walking ability and balance. These results are consistent with training-induced changes in CPG function and interlimb connectivity and underscore the need for arm training in the functional rehabilitation of walking after neurotrauma.
The effect of arm movements and movements of individual arm joints on the electrophysiological and kinematic characteristics of voluntary and vibration-triggered stepping-like leg movements was studied under the conditions of horizontal support of the upper and lower limbs. The horizontal support of arms provided a significant increase in the rate of activation of locomotor automatism by noninvasive impact on tonic sensory inputs. The addition of active arm movements during involuntary stepping-like leg movements led to an increase in the EMG activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. Passive arm movements had the same effect on induced leg movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and an increase in the amplitude of movements of knee and hip joints. At the same time, the movement of forearms and wrists had a similar facilitating effect on the physiological and kinematic characteristics of rhythmic stepping-like movements, but influenced the distal segments of legs to a greater extent. Under the conditions of subthreshold vibration of leg muscles, voluntary arm movements led to activation of involuntary rhythmic stepping movements. During voluntary leg movements, the addition of arm movements had a significantly smaller impact on the parameters of rhythmic stepping than during involuntary leg movements. Thus, the simultaneous movements of the upper and lower limbs are an effective method of activation of neural networks connecting the rhythm generators of arms and legs. Under the conditions of arm and leg unloading, the interactions between the cervical and lumbosacral segments of the spinal cord seem to play the major role in the impact of arm movements on the patterns of leg movements. The described methods of activation of interlimb interactions can be used in the rehabilitation of post-stroke patients and patients with spinal cord injuries, Parkinson’s disease, and other neurological diseases.
This chapter discusses interlimb reflexes in cat and human in relation to locomotion. The need for stability requires that the motor program, underlying locomotion, regulate the flow of activity in pathways used in interlimb reflexes to ensure that the evoked responses are appropriate for the phase of the step cycle in a given limb. Following the electrical stimulation of skin or muscle, the main responses, occurring in flexor muscles both ipsi- and contralaterally, are facilitated near the transition from stance to swing. This reinforces the onset of the spontaneous activity in these muscles during this period. At the end swing, however, the gain of these reflexes is often drastically reduced.
Restless legs syndrome (RLS) is a neurological disorder characterized by unpleasant sensations known as dysthesias and an irresistible urge to move the lower limbs. It is a life-long, often progressive condition for which there is currently no cure. RLS is thought to affect approximately 10% of the population. Women are affected twice as often as men, and the prevalence of RLS increases with age. Symptoms usually occur at rest, are worse in the evening, and are relieved by voluntary movement. This article summarizes the diagnostic criteria, genetics, and pathophysiology of RLS, as well as current treatment options and ongoing research on RLS.
Interlimb coordination is presented as a temporal and phase relationship between peak hip extension (HE) in one limb and (1) peak hip extension in the contralateral limb (LHE to RHE), and (2) peak shoulder flexion (SF) and extension (SE) in both the homolateral (e.g., LHE to LSF) and the diagonal (e.g., LHE to RSE) limbs. In the normal subjects studied, a cycle-by-cycle analysis of a series of strides at various rates of free walking reveals an abrupt shift of the frequency relationship between the motion of upper and lower limbs from 1:1 to 2:1 at approximately 0.75 Hz. This relation persists through the complete range of slow frequencies investigated (i.e., 0.5 – 0.75 Hz). The commonly observed characteristics of in-phase coupling between the homo-lateral HE-SF and the diagonal HE-SE limbs and of alternate phase coupling between both upper limbs are altered at frequencies below 0.75 Hz. At these rhythms, HE couples in-phase with homolateral SE and remains coupled in-phase with the diagonal SE. Thus, below 0.75 Hz, each hip extensor peak during a stride cycle is “locked” to SE bilaterally. The analysis of shoulder motion and associated EMG discharges (e.g., M. posterior deltoid, M. anterior deltoid) indicates that each muscle may change its functional role when the rhythm of upper limb motion is altered. Additional investigation of muscle function suggests that one or more muscles with common segmental innervation have differing functional activities during the gait cycle, activities that vary in accordance with the tactics and strategies employed.
We investigated a pattern of involuntary lower extremity stepping-like movements which recently appeared in a subject with a 17-year history of neurologically incomplete injury to the cervical spinal cord. The movements were rhythmic, alternating and forceful, involved all muscles of the lower extremities and could be reliably evoked by lying the subject down (supine) and extending his hips. Once in this position, the movements continued spontaneously, in the absence of external sensory perturbations, with a step-cycle duration of ˜3.5 s (0.3 Hz). This rate could be either increased or temporarily halted by specific sensory inputs. Anaesthetizing the subject's right hip joint, in which we found evidence of pathology, led to a marked attenuation of the stepping movements for a period of ˜15 min. We believe that a combination of (i) preserved but limited supraspinal tonic facilitation, and (ii) abnormal, perhaps noxious afferent inflow from the subject's right hip to the spinal cord may underlie the appearance of this highly unusual and involuntary movement pattern. The striking similarity between the movement and EMG patterns in this subject and those described in many reports using the surgically reduced cat model suggests that we were witnessing the first well-defined example of a central rhythm generator for stepping in the adult human.
A patient with clinically complete cervical spinal cord transection developed rhythmic myoclonic movements of the trunk and lower limbs, demonstrating that, in man, such movements can be generated within the spinal cord itself when deprived of supraspinal control. Electromyographic (EMG) recordings used to define the features of the myoclonus, which had a frequency of 0.3-0.6 Hz, was bilaterally symmetric, and involved extensor muscles. The EMG bursts always appeared in phase in all muscles involved. Peripheral stimulation of flexor reflex afferents (FRA) could induce, slow or interrupt the rhythmic activity. When FRA stimulation induced a flexion reflex, it occurred between extensor EMG bursts and induced alternating flexion-extension activity which could be sustained for several cycles. Soleus and quadriceps monosynaptic reflexes were depressed during the silent period of the rhythmic activity. Several arguments, mainly the great sensitivity of the myoclonus to flexor reflex afferent stimulation, suggest that the myoclonus observed in this patient was due to partial release of a spinal stepping generator.
It has been argued that arm movements are important during human gait because they affect leg activity due to neural coupling between arms and legs. Consequently, one would expect that locomotor-like alternating arm swing is more effective than in-phase swing in affecting the legs' motor output. Other alternating movements such as trunk rotation associated to arm swing could also affect leg reflexes. Here, we assessed how locomotor-like movement patterns would affect soleus H-reflexes in thirteen subjects performing arm swing in the sagittal plane (ipsilateral, contralateral and bilateral in-phase versus locomotor-like anti-phase arm movements) and trunk rotation with the legs stationary, and leg stepping with the arms stationary. Findings revealed that soleus H-reflexes were suppressed for all arm, trunk or leg movements. However, a marked reflex modulation occurred during locomotor-like anti-phase arm swing, as was also the case during leg stepping, and this modulation flattened out during in-phase arm swing. This modulation had a peculiar bell shape and showed maximum suppression at a moment where the heel-strike would occur during a normal walking cycle. Furthermore, this modulation was independent from EMG activity, suggesting a spinal processing at premotoneuronal level. Therefore, trunk movement can affect legs' output, and a special neural coupling occurs between arms and legs when arms move in alternation. This may have implications for gait rehabilitation.
To provide an overview of, and evaluate the current evidence on locomotor training approaches for gait rehabilitation in individuals with incomplete spinal cord injury (SCI) to identify the most effective therapies.
Electronic databases AMED, CINAHL, Cochrane, MEDLINE, PEDro and PubMed were searched systematically from first date of publication until May 2013. References of relevant clinical trials and systematic reviews were also hand searched.
Only randomized controlled trials (RCT) evaluating locomotor therapies after incomplete SCI in an adult population were included. Full-text versions of all relevant articles were selected and evaluated by both authors.
Eligible studies were identified and methodological quality assessed with the PEDro scale. Articles scoring <4 points on this scale were excluded. Sample population, interventions, outcome measures and findings were evaluated with regard to walking capacity, velocity, duration and quality of gait.
Data were analysed by systematic comparison of findings. Eight articles were included in this review. Five compared body weight supported treadmill training (BWSTT) or robotic assisted BWSTT (Lokomat) with conventional gait training in acute/subacute subjects (≤ 1 year post injury). The remaining studies each compared three or four different locomotor interventions in chronic participants (> 1 year post injury). Sample sizes were small and study designs differed considerably impeding comparison. Only minor differences in outcomes measured were found between groups. Gait parameters improved slightly more after BWSTT and robotic gait training for acute participants. For chronic participants, improvements were greater after BWSTT+FES and overground training+FES/BWS compared to BWSTT+manual assistance, robotic gait training or conventional physiotherapy.
Evidence on the effectiveness of locomotor therapy is limited. All approaches show some potential for improvement of ambulatory function without superiority of one approach over another. More research on this topic is required.
In the last years it has become possible to regain some locomotor activity in patients suffering from an incomplete spinal cord injury (SCI) through intense training on a treadmill. The ideas behind this approach owe much to insights derived from animal studies. Many studies showed that cats with complete spinal cord transection can recover locomotor function. These observations were at the basis of the concept of the central pattern generator (CPG) located at spinal level. The evidence for such a spinal CPG in cats and primates (including man) is reviewed in part 1, with special emphasis on some very recent developments which support the view that there is a human spinal CPG for locomotion.
: Neuronal networks in the spinal cord are capable of producing rhythmic movements, such as walking and swimming, when the spinal cord itself is isolated from the brain and sensory inputs. These spinal networks, also called central pattern generators or CPGs, serve as relatively simple model systems for our understanding of brain functions. In this paper we concentrate on spinal CPGs in limbed vertebrates and in particular address the question: Where in the spinal cord, in the longitudinal and transverse planes, are they located? We will review the use of lesions to isolate the rhythm and pattern-generating parts of the CPG network, indirect methods like activity-dependent labeling with [14C]-2-deoxyglucose, c-fos, sulforhodamine 101, and WGA-HRP, which label presumed rhythmically active neurons en bloc, and direct methods such as calcium-imaging, extracellular and intracellular recordings, which identify rhythmically active cells directly. With this review we hope to highlight the scientific disagreements and the consensus, which have emerged from these studies with regard to the distribution of the CPG networks in the spinal cord.
The present study examined upper and lower limb coordination during lower limb asymmetry in a split-belt walking paradigm. Eleven healthy individuals walked on a split-belt treadmill with 4 different speed ratios (2:2, 2:4, 2:6 and 2:8km/h) and the left belt fixed at 2km/h. Spatial (upper and lower limb movement amplitudes) and temporal (correlations between trajectories) aspects of limb movement were analyzed. Results showed that while amplitudes of the right lower limb increased and left lower limb decreased with increasing asymmetry, both upper limb amplitudes increased. Correlations between diagonal upper/lower limb trajectories increased as right belt speed became faster, suggesting increasing cross-body matching regardless of side. As the treadmill asymmetry increased, ipsilateral lower/upper limbs became more out of phase suggesting a more precise gait pattern to regulate timing between limbs. The upper limbs reached maximum horizontal displacement before the lower limbs except between the right upper limb/left lower limb for asymmetrical belt speeds. From these results, it appears the faster moving lower limb drives the motion of both upper limbs. These changes are most likely due to neural mechanisms in which upper and lower limb CPGs regulate full body movement and maintain the rhythmic locomotor pattern.
On the assumption that locomotion is partly produced by a central pattern generator (CPG) in the spinal cord of both cat and man, it is essential to learn more about how such a CPG is controlled by sensory input produced during gait. For the cat there is evidence that load receptor input both from extensor muscles and from cutaneous receptors from the foot, is able to reinforce the ongoing extensor activity in the stance phase and delay the ensuing swing phase. Original data on electrical stimulation of nerves in walking premammillary cats with one hindlimb fixed, support the notion that this type of load afferent input acts directly on the CPG. A second potential source of sensory input on the CPG is derived from sensory signals related to hip position. One would therefore expect that hip position is a more tightly controlled variable than the position of other joints. This was investigated by measuring these angles under conditions of constrained gait (crouch). It was found that cats indeed maintained the maximum excursions of hip flexion and extension within stricter limits than the corresponding angles at other joints. Finally, experiments on hip joint denervation show that there is very little effect on step cycle parameters, thereby supporting the idea that the important hip signal is unlikely to be derived from hip joint afferents. It is suggested that procedures aimed at activating the locomotor CPG in SCI patients could benefit from the use of periodic stimulation of ankle muscle load afferents and hip flexor stretch receptors.
Tackling the question of whether control of human gait is based on that of a quadrupedal locomotion system is of basic and practical relevance. During evolution, the increased influence of a direct cortical-motoneuronal system in parallel with more specialized hand function might have replaced phylogenetically older systems that organized locomotor movements. However, recent research indicates that interlimb coordination during human locomotion is organized in a similar way to that in the cat. Hence, it is hypothesized that during locomotion, corticospinal excitation of upper limb motoneurons is mediated indirectly, via propriospinal neurons in the cervical spinal cord. This allows a task-dependent neuronal linkage of cervical and thoraco-lumbar propriospinal circuits controlling leg and arm movements during human locomotor activities. The persistence of such movement control has consequences for rehabilitation and the applicability of animal research to human patients with spinal cord injury.
• Hip extension and low load in the extensor muscles are important sensory signals that allow a decerebrate or spinal cat to advance from the stance phase to the swing phase during walking. We tested whether the same sensory information controlled the phases of stepping in human infants. • Twenty-two infants between the ages of 5 and 12 months were studied during supported stepping on a treadmill. Forces exerted by the lower limbs, surface electromyography (EMG) from muscles, and the right hip angle were recorded. The whole experimental session was videotaped. • The hip position and the amount of load experienced by the right limb were manipulated during stepping by changing the position of the foot during the stance phase or by applying manual pressure on the pelvic crest. Disturbances with different combinations of hip position and load were used. • The stance phase was prolonged and the swing phase delayed when the hip was flexed and the load on the limb was high. In contrast, stance phase was shortened and swing advanced when the hip was extended and the load was low. The results were remarkably similar to those in reduced preparations of the cat. They thus suggest that the behaviour of the brainstem and spinal circuitry for walking may be similar between human infants and cats. • There was an inverse relationship between hip position and load at the time of swing initiation, indicating the two factors combine to regulate the transition.
Non-patterned electrical stimulation of the posterior structures of the lumbar spinal cord in subjects with complete, long-standing spinal cord injury, can induce patterned, locomotor-like activity. We show that epidural spinal cord stimulation can elicit step-like EMG activity and locomotor synergies in paraplegic subjects. An electrical train of stimuli applied over the second lumbar segment with a frequency of 25 to 60 Hz and an amplitude of 5-9 V was effective in inducing rhythmic, alternating stance and swing phases of the lower limbs. This finding suggests that spinal circuitry in humans has the capability of generating locomotor-like activity even when isolated from brain control, and that externally controlled sustained electrical stimulation of the spinal cord can replace the tonic drive generated by the brain.
Key points It is often assumed that automatic movements such as walking require little conscious attention and it has therefore been argued that these movements require little cortical control.
In humans, however, the gait function is often heavily impaired or completely lost following cortical lesions such as stroke.
In this study we investigated synchrony between cortical signals recorded with electroencephalography (EEG) and electromyographic signals (EMG activity) recorded from the tibialis anterior muscle (TA) during walking.
We found evidence of synchrony in the frequency domain (coherence) between the primary motor cortex and the TA muscle indicating a cortical involvement in human gait function.
This finding underpins the importance of restoration of the activity and connectivity between the motor cortex and the spinal cord in the recovery of gait function in patients with damage of the central nervous system.
Impaired walking is a debilitating consequence of spinal cord injury (SCI). This impairment arises, to some degree, from disruption of supraspinal pathways that activate the spinal locomotor central pattern generator (CPG). Evidence in nondisabled (ND) individuals suggests that vibration activates locomotor CPGs, eliciting involuntary step-like behavior.
To compare vibration-elicited step-like behavior in individuals with chronic SCIs with the responses of ND individuals and to assess the influence of locomotor training on these responses.
Participants included 7 individuals with motor-incomplete SCIs (MISCIs) and 6 with motor-complete SCIs (MCSCIs) who were untrained, 6 individuals with MISCIs who underwent locomotor training, and 8 ND individuals. Kinematic and EMG data were collected while vibration was applied to the quadriceps, hamstrings, or tensor fascia latae (TFL) muscles. Consistency and robustness of vibration-elicited responses was determined from hip and knee angle data.
Consistent and reliable step-like behaviors were elicited in individuals with MISCIs and MCSCIs, although responses were not as robust as those in ND individuals. Vibration to the TFL elicited the most robust responses. Consistency and robustness were not influenced by SCI severity or locomotor training but appeared to increase with repeated testing.
These results confirm that vibration elicits step-like behaviors in individuals with SCIs, even those with no voluntary motor function in the legs. Further research is warranted to investigate the use of vibration as an approach to activating the spinal CPGs associated with stepping, perhaps as an adjunct to locomotor training for individuals with SCIs.
Studies of spinalized animals indicate that some pharmacological agents may act on receptors in the spinal cord, helping to produce coordinated locomotor movement. Other drugs may help to ameliorate the neuropathological changes resulting from spinal cord injury (SCI), such as spasticity or demyelination, to improve walking. The purpose of this study was to systematically review the effects of pharmacological agents on gait in people with SCI. A keyword literature search of articles that evaluated the effects of drugs on walking after SCI was performed using the databases MEDLINE/PubMed, CINAHL, EMBASE, PsycINFO, and hand searching. Two reviewers independently evaluated each study, using the Physiotherapy Evidence Database (PEDro) tool for randomized clinical trials (RCTs), and the modified Downs & Black scale for all other studies. Results were tabulated and levels of evidence were assigned. Eleven studies met the inclusion criteria. One RCT provided Level 1 evidence that GM-1 ganglioside in combination with physical therapy improved motor scores, walking velocity, and distance better than placebo and physical therapy in persons with incomplete SCI. Multiple studies (levels of evidence 1-5) showed that clonidine and cyproheptadine may improve locomotor function and walking speed in severely impaired individuals with incomplete SCI. Gains in walking speed associated with GM-1, cyproheptadine, and clonidine are low compared to those seen with locomotor training. There was also Level 1 evidence that 4-aminopyridine and L-dopa were no better than placebo in helping to improve gait. Two Level 5 studies showed that baclofen had little to no effect on improving walking in persons with incomplete SCI. There is limited evidence that pharmacological agents tested so far would facilitate the recovery of walking after SCI. More studies are needed to better understand the effects of drugs combined with gait training on walking outcomes in people with SCI.