Tapping into rhythm generation circuitry in humans during simulated weightlessness conditions

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

Tapping into rhythm generation circuitry in humans during simulated weightlessness conditions

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 circuitry in humans, which may be important for developing gait rehabilitation strategies in individuals with spinal cord and brain injuries

Higher Responsiveness of Pattern Generation Circuitry to Sensory Stimulation in Healthy Humans Is Associated with a Larger Hoffmann Reflex

Simple Summary Individual differences in the sensorimotor circuitry play an important role for understanding the nature of behavioral variability and developing personalized therapies. While the spinal network likely requires relatively rigid organization, it becomes increasingly evident that adaptability and inter-individual variability in the functioning of the neuronal circuitry is present not only in the brain but also in the spinal cord. In this study we investigated the relationship between the excitability of pattern generation circuitry and segmental reflexes in healthy humans. We found that the high individual responsiveness of pattern generation circuitries to tonic sensory input in both the upper and lower limbs was related to larger H-reflexes. The results provide further evidence for the importance of physiologically relevant assessments of spinal cord neuromodulation and the individual physiological state of reflex pathways. The state and excitability of pattern generators are attracting the increasing interest of neurophysiologists and clinicians for understanding the mechanisms of the rhythmogenesis and neuromodulation of the human spinal cord. It has been previously shown that tonic sensory stimulation can elicit non-voluntary stepping-like movements in non-injured subjects when their limbs were placed in a gravity-neutral unloading apparatus. However, large individual differences in responsiveness to such stimuli were observed, so that the effects of sensory neuromodulation manifest only in some of the subjects. Given that spinal reflexes are an integral part of the neuronal circuitry, here we investigated the extent to which spinal pattern generation excitability in response to the vibrostimulation of muscle proprioceptors can be related to the H-reflex magnitude, in both the lower and upper limbs. For the H-reflex measurements, three conditions were used: stationary limbs, voluntary limb movement and passive limb movement. The results showed that the H-reflex was considerably higher in the group of participants who demonstrated non-voluntary rhythmic responses than it was in the participants who did not demonstrate them. Our findings are consistent with the idea that spinal reflex measurements play important roles in assessing the rhythmogenesis of the spinal cord

Electrical spinal stimulation, and imagining of lower limb movements to modulate brain-spinal connectomes that control locomotor-like behavior

© 2018 Gerasimenko, Sayenko, Gad, Kozesnik, Moshonkina, Grishin, Pukhov, Moiseev, Gorodnichev, Selionov, Kozlovskaya and Edgerton. Neuronal control of stepping movement in healthy human is based on integration between brain, spinal neuronal networks, and sensory signals. It is generally recognized that there are continuously occurring adjustments in the physiological states of supraspinal centers during all routines movements. For example, visual as well as all other sources of information regarding the subject's environment. These multimodal inputs to the brain normally play an important role in providing a feedforward source of control. We propose that the brain routinely uses these continuously updated assessments of the environment to provide additional feedforward messages to the spinal networks, which provides a synergistic feedforwardness for the brain and spinal cord. We tested this hypothesis in 8 non-injured individuals placed in gravity neutral position with the lower limbs extended beyond the edge of the table, but supported vertically, to facilitate rhythmic stepping. The experiment was performed while visualizing on the monitor a stick figure mimicking bilateral stepping or being motionless. Non-invasive electrical stimulation was used to neuromodulate a wide range of excitabilities of the lumbosacral spinal segments that would trigger rhythmic stepping movements. We observed that at the same intensity level of transcutaneous electrical spinal cord stimulation (tSCS), the presence or absence of visualizing a stepping-like movement of a stick figure immediately initiated or terminated the tSCS-induced rhythmic stepping motion, respectively. We also demonstrated that during both voluntary and imagined stepping, the motor potentials in leg muscles were facilitated when evoked cortically, using transcranial magnetic stimulation (TMS), and inhibited when evoked spinally, using tSCS. These data suggest that the ongoing assessment of the environment within the supraspinal centers that play a role in planning a movement can routinely modulate the physiological state of spinal networks that further facilitates a synergistic neuromodulation of the brain and spinal cord in preparing for movements

Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0 mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion

Electrical spinal stimulation, and imagining of lower limb movements to modulate brain-spinal connectomes that control locomotor-like behavior

© 2018 Gerasimenko, Sayenko, Gad, Kozesnik, Moshonkina, Grishin, Pukhov, Moiseev, Gorodnichev, Selionov, Kozlovskaya and Edgerton. Neuronal control of stepping movement in healthy human is based on integration between brain, spinal neuronal networks, and sensory signals. It is generally recognized that there are continuously occurring adjustments in the physiological states of supraspinal centers during all routines movements. For example, visual as well as all other sources of information regarding the subject's environment. These multimodal inputs to the brain normally play an important role in providing a feedforward source of control. We propose that the brain routinely uses these continuously updated assessments of the environment to provide additional feedforward messages to the spinal networks, which provides a synergistic feedforwardness for the brain and spinal cord. We tested this hypothesis in 8 non-injured individuals placed in gravity neutral position with the lower limbs extended beyond the edge of the table, but supported vertically, to facilitate rhythmic stepping. The experiment was performed while visualizing on the monitor a stick figure mimicking bilateral stepping or being motionless. Non-invasive electrical stimulation was used to neuromodulate a wide range of excitabilities of the lumbosacral spinal segments that would trigger rhythmic stepping movements. We observed that at the same intensity level of transcutaneous electrical spinal cord stimulation (tSCS), the presence or absence of visualizing a stepping-like movement of a stick figure immediately initiated or terminated the tSCS-induced rhythmic stepping motion, respectively. We also demonstrated that during both voluntary and imagined stepping, the motor potentials in leg muscles were facilitated when evoked cortically, using transcranial magnetic stimulation (TMS), and inhibited when evoked spinally, using tSCS. These data suggest that the ongoing assessment of the environment within the supraspinal centers that play a role in planning a movement can routinely modulate the physiological state of spinal networks that further facilitates a synergistic neuromodulation of the brain and spinal cord in preparing for movements

Electrical Spinal Stimulation, and Imagining of Lower Limb Movements to Modulate Brain-Spinal Connectomes That Control Locomotor-Like Behavior

Neuronal control of stepping movement in healthy human is based on integration between brain, spinal neuronal networks, and sensory signals. It is generally recognized that there are continuously occurring adjustments in the physiological states of supraspinal centers during all routines movements. For example, visual as well as all other sources of information regarding the subject's environment. These multimodal inputs to the brain normally play an important role in providing a feedforward source of control. We propose that the brain routinely uses these continuously updated assessments of the environment to provide additional feedforward messages to the spinal networks, which provides a synergistic feedforwardness for the brain and spinal cord. We tested this hypothesis in 8 non-injured individuals placed in gravity neutral position with the lower limbs extended beyond the edge of the table, but supported vertically, to facilitate rhythmic stepping. The experiment was performed while visualizing on the monitor a stick figure mimicking bilateral stepping or being motionless. Non-invasive electrical stimulation was used to neuromodulate a wide range of excitabilities of the lumbosacral spinal segments that would trigger rhythmic stepping movements. We observed that at the same intensity level of transcutaneous electrical spinal cord stimulation (tSCS), the presence or absence of visualizing a stepping-like movement of a stick figure immediately initiated or terminated the tSCS-induced rhythmic stepping motion, respectively. We also demonstrated that during both voluntary and imagined stepping, the motor potentials in leg muscles were facilitated when evoked cortically, using transcranial magnetic stimulation (TMS), and inhibited when evoked spinally, using tSCS. These data suggest that the ongoing assessment of the environment within the supraspinal centers that play a role in planning a movement can routinely modulate the physiological state of spinal networks that further facilitates a synergistic neuromodulation of the brain and spinal cord in preparing for movements

Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0 mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion

Activation of spinal locomotor circuits in the decerebrated cat by spinal epidural and/or intraspinal electrical stimulation

The present study was designed to further compare the stepping-like movements generated via epidural (ES) and/or intraspinal (IS) stimulation. We examined the ability to generate stepping-like movements in response to ES and/or IS of spinal lumbar segments L1-L7 in decerebrate cats. ES (5-10 Hz) of the dorsal surface of the spinal cord at L3-L7 induced hindlimb stepping-like movements on a moving treadmill belt, but with no rhythmic activity in the forelimbs. IS (60 Hz) of the dorsolateral funiculus at L1-L3 (depth of 0.5-1.0 mm from the dorsal surface of the spinal cord) induced quadrupedal stepping-like movements. Forelimb movements appeared first, followed by stepping-like movements in the hindlimbs. ES and IS simultaneously enhanced the rhythmic performance of the hindlimbs more robustly than ES or IS alone. The differences in the stimulation parameters, site of stimulation, and motor outputs observed during ES vs. IS suggest that different neural mechanisms were activated to induce stepping-like movements. The effects of ES may be mediated more via dorsal structures in the lumbosacral region of the spinal cord, whereas the effects of IS may be mediated via more ventral propriospinal networks and/or brainstem locomotor areas. Furthermore, the more effective facilitation of the motor output during simultaneous ES and IS may reflect some convergence of pathways on the same interneuronal populations involved in the regulation of locomotion