20 Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as ... more 20 Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as 21 stepping, scratching and swimming. Based on an observed rostrocaudal wave of activity in the 22 motoneuronal firing during locomotor tasks, the traveling-wave hypothesis proposes that spinal 23 interneuronal firing follows a similar rostrocaudal pattern of activation, suggesting the presence 24 of spatially organized interneuronal modules within the spinal motor system. In this study, we 25 examined if the spatial organization of the lumbar interneuronal activity patterns during 26 locomotor activity in the adult mammalian spinal cord was consistent with a traveling wave 27 organizational scheme. The activity of spinal interneurons within the lumbar intermediate zone 28 was examined during air-stepping in sub-chronic spinal cats. The preferred phase of 29 interneuronal activity during a step cycle was determined using circular statistics. We found that 30 the preferred phases of lumba...
We explored the relationship between population interneuronal network activation and motor output... more We explored the relationship between population interneuronal network activation and motor output in the adult, in-vivo, air stepping, spinal cat. By simultaneously measuring the activity of large numbers of spinal interneurons, we explored ensembles of coherently firing interneurons and their relation to motor output. Additionally, the networks were analyzed in relation to their spatial distribution along the lumbar enlargement for evidence of localized groups driving particular phases of the locomotor step cycle. We simultaneously recorded hindlimb EMG activity during stepping and extracellular signals from 128 channels across two polytrodes inserted within lamina V-VII of two separate lumbar segments. Results indicated that spinal interneurons participate in one of two ensembles that are highly correlated with the flexor or the extensor muscle bursts during stepping. Interestingly, less than half of the isolated single units were significantly unimodally tuned during the step cyc...
In spinal cats, locomotor recovery without rehabilitation is limited, but weight-bearing stepping... more In spinal cats, locomotor recovery without rehabilitation is limited, but weight-bearing stepping returns with treadmill training. We investigated whether neurotrophins administered to the injury site also restores locomotion in untrained spinal cats, and whether combining both neurotrophins and training further improves recovery. Ordinary rat fibroblasts or a mixture of fibroblasts secreting Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) (Fb-NTF) were grafted into T12 spinal transection sites. Cats with each type of transplant were divided into two groups: one receiving daily training and the other no training. As expected, trained cats with/without neurotrophin-producing transplants could step on the treadmill. Untrained cats without neurotrophin-producing transplants could not locomote. However, untrained cats with neurotrophin-secreting transplants performed plantar weight bearing stepping at speeds up to 0.8 m/s as early as 2 weeks posttransection. Locomotor...
Objective: H-Reflex is a test that is carried out to measure the relative excitability of reflex ... more Objective: H-Reflex is a test that is carried out to measure the relative excitability of reflex pathways. Although reliable, conventional methods consist of performing many small steps, which requires a high level of attentiveness, and thus can carry an elevated risk of human error, despite proper training. Equipment that is available to perform those tests with different levels of automation are typically proprietary, inextensible by the user, and expensive. Here we present a novel MATLAB application that can accurately and reliably perform automated H-Reflex measurements, test the stimulating electrodes, and carry out typical subsequent analyses. Methods: This application is a Graphical User Interface that works with inexpensive equipment and offers many important features such as measuring electrode impedance in-situ, automating lengthy measurements like recruitment curves and frequency response trials, standardizing electric stimulation properties, automatic exporting of digital data and metadata, and immediately analyzing acquired data with single-click events. Results: Our new method was validated against conventional H-Reflex measurement methods with 2 anesthetized rats. The difference between acquired data using both methods was negligible (mean difference=0.0038; std=0.0121). Our app also detected electrode impedance with high accuracy (94%). Conclusion: The method presented here allows reliable and efficient automated H-reflex measurements and can accurately analyze the collected data.
IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2020
Delivery of neurotrophins to the spinal injury site via cellular transplants or viral vectors adm... more Delivery of neurotrophins to the spinal injury site via cellular transplants or viral vectors administration has been shown to promote recovery of locomotion in the absence of locomotor training in adult spinalized animals. These delivery methods involved risks of secondary injury to the cord and do not allow for precise and controlled dosing making them unsuitable for clinical applications. The present study was aimed at evaluating the locomotor recovery efficacy and safety of the neurotrophin BDNF delivered intrathecally to the lumbar locomotor centers using an implantable and programmable infusion mini-pump. Results showed that BDNF treated spinal cats recovered weight-bearing plantar stepping at all velocities tested (0.3-0.8 m/s). Spinal cats treated with saline did not recover stepping ability, especially at higher velocities, and dragged their hind paws on the treadmill. Histological evaluation showed minimal catheter associated trauma and tissue inflammation, underlining that intrathecal delivery by an implantable/programmable pump is a safe and effective method for delivery of a controlled BDNF dosage; it poses minimal risks to the cord and is clinically translational.
Sensorimotor training providing motion-dependent somatosensory feedback to spinal locomotor netwo... more Sensorimotor training providing motion-dependent somatosensory feedback to spinal locomotor networks restores treadmill weight-bearing stepping on flat surfaces in spinal cats. In this study, we examined if locomotor ability on flat surfaces transfers to sloped surfaces and the contribution of length-dependent sensory feedback from lateral gastrocnemius (LG) and soleus (Sol) to locomotor recovery after spinal transection and locomotor training. We compared kinematics and muscle activity at different slopes (±10° and ±25°) in spinalized cats ( n = 8) trained to walk on a flat treadmill. Half of those animals had their right hindlimb LG/Sol nerve cut and reattached before spinal transection and locomotor training, a procedure called muscle self-reinnervation that leads to elimination of autogenic monosynaptic length feedback in spinally intact animals. All spinal animals trained on a flat surface were able to walk on slopes with minimal differences in walking kinematics and muscle act...
Adult cats show limited spontaneous locomotor capabilities following spinal transection, but reco... more Adult cats show limited spontaneous locomotor capabilities following spinal transection, but recover treadmill stepping with body-weight-supported training. Delivery of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT-3) can substitute for body-weight-supported training, and promotes a similar recovery in a shorter period of time. Autologous cell grafts would negate the need for the immunosuppressive agents currently used with most grafts, but have not shown functional benefits in incomplete spinal cord injury models and have never been tested in complete transection or chronic injury models. In this study, we explored the effects of autologous fibroblasts, prepared from the individual cats and modified to produce BDNF and NT-3, on the recovery of locomotion in acute, sub-chronic and chronic full-transection models of spinal injury. Fourteen female cats underwent complete spinal transection at T11/T12. Cats were separated into four ...
While it is well established that the axons of adult neurons have a lower capacity for regrowth, ... more While it is well established that the axons of adult neurons have a lower capacity for regrowth, some regeneration of certain CNS populations after spinal cord injury (SCI) is possible if their axons are provided with a permissive substrate, such as an injured peripheral nerve. While some axons readily regenerate into a peripheral nerve graft (PNG), these axons almost always stall at the distal interface and fail to re-innervate spinal cord tissue. Treatment of the glial scar at the distal graft interface with chondroitinase ABC (ChABC) can improve regeneration, but most regenerated axons need further stimulation to extend beyond the interface. Previous studies demonstrate that pharmacologically inhibiting kinesin-5, a motor protein best known for its essential role in mitosis but also expressed in neurons, with the pharmacological agent monastrol increases axon growth on inhibitory substrates in vitro. We sought to determine if monastrol treatment after a SCI improves functional axon regeneration. Animals received complete thoracic level 7 (T7) transections and PNGs and were treated intrathecally with ChABC and either monastrol or DMSO vehicle. We found that combining ChABC with monastrol significantly enhanced axon regeneration. However, there were no further improvements in function or enhanced c-Fos induction upon stimulation of spinal cord rostral to the transection. This indicates that monastrol improves ChABC-mediated axon regeneration but that further treatments are needed to enhance the integration of these regrown axons.
The lumbar spinal cord circuitry can autonomously generate locomotion, but it remains to be deter... more The lumbar spinal cord circuitry can autonomously generate locomotion, but it remains to be determined which types of neurons constitute the locomotor generator and how their population activity is organized spatially in the mammalian spinal cord. In this study, we investigated the spatiotemporal dynamics of the spinal interneuronal population activity in the intermediate zone of the adult mammalian cord. Segmental interneuronal population activity was examined via multiunit activity (MUA) during air-stepping initiated by perineal stimulation in subchronic spinal cats. In contrast to single-unit activity, MUA provides a continuous measure of neuronal activity within a ∼100-μm volume around the recording electrode. MUA was recorded during air-stepping, along with hindlimb muscle activity, from segments L3 to L7 with two multichannel electrode arrays placed into the left and right hemicord intermediate zones (lamina V–VII). The phasic modulation and spatial organization of MUA dynamic...
Sensory feedback plays a crucial role in the control of locomotion and in the recovery of functio... more Sensory feedback plays a crucial role in the control of locomotion and in the recovery of function after spinal cord injury. Investigations in reduced preparations have shown that the locomotor cycle can be modified through the activation of afferent feedback at various phases of the gait cycle. We investigated the effect of phase-dependent electrical stimulation of a cutaneous afferent nerve on the locomotor pattern of trained spinal cord-injured cats. Animals were first implanted with chronic nerve cuffs on the sural and sciatic nerves and electromyographic electrodes in different hindlimb muscles. Cats were then transected at T12 and trained daily to locomote on a treadmill. We found that electrical stimulation of the sural nerve can enhance the ongoing flexion phase, producing higher (+129%) and longer (+17.4%) swing phases of gait even at very low threshold of stimulation. Sural nerve stimulation can also terminate an ongoing extension and initiate a flexion phase. A higher pre...
Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as ste... more Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as stepping, scratching, and swimming. Based on an observed rostrocaudal wave of activity in the motoneuronal firing during locomotor tasks, the traveling-wave hypothesis proposes that spinal interneuronal firing follows a similar rostrocaudal pattern of activation, suggesting the presence of spatially organized interneuronal modules within the spinal motor system. In this study, we examined if the spatial organization of the lumbar interneuronal activity patterns during locomotor activity in the adult mammalian spinal cord was consistent with a traveling-wave organizational scheme. The activity of spinal interneurons within the lumbar intermediate zone was examined during air-stepping in subchronic spinal cats. The preferred phase of interneuronal activity during a step cycle was determined using circular statistics. We found that the preferred phases of lumbar interneurons from both sides of...
Degree Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering, 1995 . Abst... more Degree Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering, 1995 . Abstract This research investigated the feasibility of providing wrist flexion/extension control to C5 tetraplegics, and forearm pronosupination to C5 and C6 tetraplegics, using ...
Cutaneous feedback from feet is involved in regulation of muscle activity during locomotion, and ... more Cutaneous feedback from feet is involved in regulation of muscle activity during locomotion, and the lack of this feedback results in motor deficits. We tested the hypothesis that locomotor changes caused by local unilateral anesthesia of paw pads in the cat could be reduced/reversed by electrical stimulation of cutaneous and proprioceptive afferents in the distal tibial nerve during stance. Several split-belt conditions were investigated in four adult female cats. In addition, we investigated the effects of similar distal tibial nerve stimulation on overground walking of one male cat that had a transtibial, bone-anchored prosthesis for 29 months and, thus, had no cutaneous/proprioceptive feedback from the foot. In all treadmill conditions, cats walked with intact cutaneous feedback (control), with right fore- and hindpaw pads anesthetized by lidocaine injections, and with a combination of anesthesia and electrical stimulation of the ipsilateral distal tibial nerve during the stance...
[PDF] [Full Text] [Abstract] , April , 2010; 103 (4): 2285-2300. J Neurophysiol Irina N. Beloozer... more [PDF] [Full Text] [Abstract] , April , 2010; 103 (4): 2285-2300. J Neurophysiol Irina N. Beloozerova, Bradley J. Farrell, Mikhail G. Sirota and Boris I. Prilutsky Between Accurate and Nonaccurate Stepping Differences in Movement Mechanics, Electromyographic, and Motor Cortex Activity [PDF] [Full Text] [Abstract] , December , 2010; 104 (6): 3189-3202. J Neurophysiol John Martin Curtis Oware Asante, Amy Chu, Mark Fisher, Leora Benson, Asim Beg, Peter Scheiffele and 2-Chimaerin α the Ephrin-Eph Effector Protein Cortical Control of Adaptive Locomotion in Wild-Type Mice and Mutant Mice Lacking [PDF] [Full Text] [Abstract] , January , 2011; 105 (1): 388-409. J Neurophysiol Sergiy Yakovenko, Nedialko Krouchev and Trevor Drew During Reaching in the Cat by Modulating Muscle Synergies Sequential Activation of Motor Cortical Neurons Contributes to Intralimb Coordination [PDF] [Full Text] [Abstract] , March , 2011; 105 (3): 1011-1022. J Neurophysiol Nicholas AuYong, Karen Ollivier-Lanvin and Michel A. Lemay subchronic spinal cats Preferred locomotor phase of activity of lumbar interneurons during air-stepping in [PDF] [Full Text] [Abstract] , March 23, 2011; 31 (12): 4636-4649. J. Neurosci. Namrata M. Dasgupta, Mikhail G. Sirota and Irina N. Beloozerova Pavel V. Zelenin, Tatiana G. Deliagina, Grigori N. Orlovsky, Anastasia Karayannidou, during Locomotion Contribution of Different Limb Controllers to Modulation of Motor Cortex Neurons
Spinal cord injury (SCI) often results in lifelong sensorimotor impairment. Spontaneous recovery ... more Spinal cord injury (SCI) often results in lifelong sensorimotor impairment. Spontaneous recovery from SCI is limited, as supraspinal fibers cannot spontaneously regenerate to form functional networks below the level of injury. Despite this, animal models and humans exhibit many motor behaviors indicative of recovery when electrical stimulation is applied epidurally to the dorsal aspect of the lumbar spinal cord. In 1976, epidural stimulation was introduced to alleviate spasticity in Multiple Sclerosis. Since then, epidural electrical stimulation (EES) has been demonstrated to improve voluntary mobility across the knee and/or ankle in several SCI patients, highlighting its utility in enhancing motor activation. The mechanisms that EES induces to drive these improvements in sensorimotor function remain largely unknown. In this review, we discuss several sensorimotor plasticity mechanisms that we hypothesize may enable epidural stimulation to promote recovery, including changes in local lumbar circuitry, propriospinal interneurons, and the internal model. Finally, we discuss genetic tools for afferent modulation as an emerging method to facilitate the search for the mechanisms of action.
20 Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as ... more 20 Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as 21 stepping, scratching and swimming. Based on an observed rostrocaudal wave of activity in the 22 motoneuronal firing during locomotor tasks, the traveling-wave hypothesis proposes that spinal 23 interneuronal firing follows a similar rostrocaudal pattern of activation, suggesting the presence 24 of spatially organized interneuronal modules within the spinal motor system. In this study, we 25 examined if the spatial organization of the lumbar interneuronal activity patterns during 26 locomotor activity in the adult mammalian spinal cord was consistent with a traveling wave 27 organizational scheme. The activity of spinal interneurons within the lumbar intermediate zone 28 was examined during air-stepping in sub-chronic spinal cats. The preferred phase of 29 interneuronal activity during a step cycle was determined using circular statistics. We found that 30 the preferred phases of lumba...
We explored the relationship between population interneuronal network activation and motor output... more We explored the relationship between population interneuronal network activation and motor output in the adult, in-vivo, air stepping, spinal cat. By simultaneously measuring the activity of large numbers of spinal interneurons, we explored ensembles of coherently firing interneurons and their relation to motor output. Additionally, the networks were analyzed in relation to their spatial distribution along the lumbar enlargement for evidence of localized groups driving particular phases of the locomotor step cycle. We simultaneously recorded hindlimb EMG activity during stepping and extracellular signals from 128 channels across two polytrodes inserted within lamina V-VII of two separate lumbar segments. Results indicated that spinal interneurons participate in one of two ensembles that are highly correlated with the flexor or the extensor muscle bursts during stepping. Interestingly, less than half of the isolated single units were significantly unimodally tuned during the step cyc...
In spinal cats, locomotor recovery without rehabilitation is limited, but weight-bearing stepping... more In spinal cats, locomotor recovery without rehabilitation is limited, but weight-bearing stepping returns with treadmill training. We investigated whether neurotrophins administered to the injury site also restores locomotion in untrained spinal cats, and whether combining both neurotrophins and training further improves recovery. Ordinary rat fibroblasts or a mixture of fibroblasts secreting Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) (Fb-NTF) were grafted into T12 spinal transection sites. Cats with each type of transplant were divided into two groups: one receiving daily training and the other no training. As expected, trained cats with/without neurotrophin-producing transplants could step on the treadmill. Untrained cats without neurotrophin-producing transplants could not locomote. However, untrained cats with neurotrophin-secreting transplants performed plantar weight bearing stepping at speeds up to 0.8 m/s as early as 2 weeks posttransection. Locomotor...
Objective: H-Reflex is a test that is carried out to measure the relative excitability of reflex ... more Objective: H-Reflex is a test that is carried out to measure the relative excitability of reflex pathways. Although reliable, conventional methods consist of performing many small steps, which requires a high level of attentiveness, and thus can carry an elevated risk of human error, despite proper training. Equipment that is available to perform those tests with different levels of automation are typically proprietary, inextensible by the user, and expensive. Here we present a novel MATLAB application that can accurately and reliably perform automated H-Reflex measurements, test the stimulating electrodes, and carry out typical subsequent analyses. Methods: This application is a Graphical User Interface that works with inexpensive equipment and offers many important features such as measuring electrode impedance in-situ, automating lengthy measurements like recruitment curves and frequency response trials, standardizing electric stimulation properties, automatic exporting of digital data and metadata, and immediately analyzing acquired data with single-click events. Results: Our new method was validated against conventional H-Reflex measurement methods with 2 anesthetized rats. The difference between acquired data using both methods was negligible (mean difference=0.0038; std=0.0121). Our app also detected electrode impedance with high accuracy (94%). Conclusion: The method presented here allows reliable and efficient automated H-reflex measurements and can accurately analyze the collected data.
IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2020
Delivery of neurotrophins to the spinal injury site via cellular transplants or viral vectors adm... more Delivery of neurotrophins to the spinal injury site via cellular transplants or viral vectors administration has been shown to promote recovery of locomotion in the absence of locomotor training in adult spinalized animals. These delivery methods involved risks of secondary injury to the cord and do not allow for precise and controlled dosing making them unsuitable for clinical applications. The present study was aimed at evaluating the locomotor recovery efficacy and safety of the neurotrophin BDNF delivered intrathecally to the lumbar locomotor centers using an implantable and programmable infusion mini-pump. Results showed that BDNF treated spinal cats recovered weight-bearing plantar stepping at all velocities tested (0.3-0.8 m/s). Spinal cats treated with saline did not recover stepping ability, especially at higher velocities, and dragged their hind paws on the treadmill. Histological evaluation showed minimal catheter associated trauma and tissue inflammation, underlining that intrathecal delivery by an implantable/programmable pump is a safe and effective method for delivery of a controlled BDNF dosage; it poses minimal risks to the cord and is clinically translational.
Sensorimotor training providing motion-dependent somatosensory feedback to spinal locomotor netwo... more Sensorimotor training providing motion-dependent somatosensory feedback to spinal locomotor networks restores treadmill weight-bearing stepping on flat surfaces in spinal cats. In this study, we examined if locomotor ability on flat surfaces transfers to sloped surfaces and the contribution of length-dependent sensory feedback from lateral gastrocnemius (LG) and soleus (Sol) to locomotor recovery after spinal transection and locomotor training. We compared kinematics and muscle activity at different slopes (±10° and ±25°) in spinalized cats ( n = 8) trained to walk on a flat treadmill. Half of those animals had their right hindlimb LG/Sol nerve cut and reattached before spinal transection and locomotor training, a procedure called muscle self-reinnervation that leads to elimination of autogenic monosynaptic length feedback in spinally intact animals. All spinal animals trained on a flat surface were able to walk on slopes with minimal differences in walking kinematics and muscle act...
Adult cats show limited spontaneous locomotor capabilities following spinal transection, but reco... more Adult cats show limited spontaneous locomotor capabilities following spinal transection, but recover treadmill stepping with body-weight-supported training. Delivery of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT-3) can substitute for body-weight-supported training, and promotes a similar recovery in a shorter period of time. Autologous cell grafts would negate the need for the immunosuppressive agents currently used with most grafts, but have not shown functional benefits in incomplete spinal cord injury models and have never been tested in complete transection or chronic injury models. In this study, we explored the effects of autologous fibroblasts, prepared from the individual cats and modified to produce BDNF and NT-3, on the recovery of locomotion in acute, sub-chronic and chronic full-transection models of spinal injury. Fourteen female cats underwent complete spinal transection at T11/T12. Cats were separated into four ...
While it is well established that the axons of adult neurons have a lower capacity for regrowth, ... more While it is well established that the axons of adult neurons have a lower capacity for regrowth, some regeneration of certain CNS populations after spinal cord injury (SCI) is possible if their axons are provided with a permissive substrate, such as an injured peripheral nerve. While some axons readily regenerate into a peripheral nerve graft (PNG), these axons almost always stall at the distal interface and fail to re-innervate spinal cord tissue. Treatment of the glial scar at the distal graft interface with chondroitinase ABC (ChABC) can improve regeneration, but most regenerated axons need further stimulation to extend beyond the interface. Previous studies demonstrate that pharmacologically inhibiting kinesin-5, a motor protein best known for its essential role in mitosis but also expressed in neurons, with the pharmacological agent monastrol increases axon growth on inhibitory substrates in vitro. We sought to determine if monastrol treatment after a SCI improves functional axon regeneration. Animals received complete thoracic level 7 (T7) transections and PNGs and were treated intrathecally with ChABC and either monastrol or DMSO vehicle. We found that combining ChABC with monastrol significantly enhanced axon regeneration. However, there were no further improvements in function or enhanced c-Fos induction upon stimulation of spinal cord rostral to the transection. This indicates that monastrol improves ChABC-mediated axon regeneration but that further treatments are needed to enhance the integration of these regrown axons.
The lumbar spinal cord circuitry can autonomously generate locomotion, but it remains to be deter... more The lumbar spinal cord circuitry can autonomously generate locomotion, but it remains to be determined which types of neurons constitute the locomotor generator and how their population activity is organized spatially in the mammalian spinal cord. In this study, we investigated the spatiotemporal dynamics of the spinal interneuronal population activity in the intermediate zone of the adult mammalian cord. Segmental interneuronal population activity was examined via multiunit activity (MUA) during air-stepping initiated by perineal stimulation in subchronic spinal cats. In contrast to single-unit activity, MUA provides a continuous measure of neuronal activity within a ∼100-μm volume around the recording electrode. MUA was recorded during air-stepping, along with hindlimb muscle activity, from segments L3 to L7 with two multichannel electrode arrays placed into the left and right hemicord intermediate zones (lamina V–VII). The phasic modulation and spatial organization of MUA dynamic...
Sensory feedback plays a crucial role in the control of locomotion and in the recovery of functio... more Sensory feedback plays a crucial role in the control of locomotion and in the recovery of function after spinal cord injury. Investigations in reduced preparations have shown that the locomotor cycle can be modified through the activation of afferent feedback at various phases of the gait cycle. We investigated the effect of phase-dependent electrical stimulation of a cutaneous afferent nerve on the locomotor pattern of trained spinal cord-injured cats. Animals were first implanted with chronic nerve cuffs on the sural and sciatic nerves and electromyographic electrodes in different hindlimb muscles. Cats were then transected at T12 and trained daily to locomote on a treadmill. We found that electrical stimulation of the sural nerve can enhance the ongoing flexion phase, producing higher (+129%) and longer (+17.4%) swing phases of gait even at very low threshold of stimulation. Sural nerve stimulation can also terminate an ongoing extension and initiate a flexion phase. A higher pre...
Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as ste... more Spinal locomotor circuits are intrinsically capable of driving a variety of behaviors such as stepping, scratching, and swimming. Based on an observed rostrocaudal wave of activity in the motoneuronal firing during locomotor tasks, the traveling-wave hypothesis proposes that spinal interneuronal firing follows a similar rostrocaudal pattern of activation, suggesting the presence of spatially organized interneuronal modules within the spinal motor system. In this study, we examined if the spatial organization of the lumbar interneuronal activity patterns during locomotor activity in the adult mammalian spinal cord was consistent with a traveling-wave organizational scheme. The activity of spinal interneurons within the lumbar intermediate zone was examined during air-stepping in subchronic spinal cats. The preferred phase of interneuronal activity during a step cycle was determined using circular statistics. We found that the preferred phases of lumbar interneurons from both sides of...
Degree Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering, 1995 . Abst... more Degree Doctor of Philosophy, Case Western Reserve University, Biomedical Engineering, 1995 . Abstract This research investigated the feasibility of providing wrist flexion/extension control to C5 tetraplegics, and forearm pronosupination to C5 and C6 tetraplegics, using ...
Cutaneous feedback from feet is involved in regulation of muscle activity during locomotion, and ... more Cutaneous feedback from feet is involved in regulation of muscle activity during locomotion, and the lack of this feedback results in motor deficits. We tested the hypothesis that locomotor changes caused by local unilateral anesthesia of paw pads in the cat could be reduced/reversed by electrical stimulation of cutaneous and proprioceptive afferents in the distal tibial nerve during stance. Several split-belt conditions were investigated in four adult female cats. In addition, we investigated the effects of similar distal tibial nerve stimulation on overground walking of one male cat that had a transtibial, bone-anchored prosthesis for 29 months and, thus, had no cutaneous/proprioceptive feedback from the foot. In all treadmill conditions, cats walked with intact cutaneous feedback (control), with right fore- and hindpaw pads anesthetized by lidocaine injections, and with a combination of anesthesia and electrical stimulation of the ipsilateral distal tibial nerve during the stance...
[PDF] [Full Text] [Abstract] , April , 2010; 103 (4): 2285-2300. J Neurophysiol Irina N. Beloozer... more [PDF] [Full Text] [Abstract] , April , 2010; 103 (4): 2285-2300. J Neurophysiol Irina N. Beloozerova, Bradley J. Farrell, Mikhail G. Sirota and Boris I. Prilutsky Between Accurate and Nonaccurate Stepping Differences in Movement Mechanics, Electromyographic, and Motor Cortex Activity [PDF] [Full Text] [Abstract] , December , 2010; 104 (6): 3189-3202. J Neurophysiol John Martin Curtis Oware Asante, Amy Chu, Mark Fisher, Leora Benson, Asim Beg, Peter Scheiffele and 2-Chimaerin α the Ephrin-Eph Effector Protein Cortical Control of Adaptive Locomotion in Wild-Type Mice and Mutant Mice Lacking [PDF] [Full Text] [Abstract] , January , 2011; 105 (1): 388-409. J Neurophysiol Sergiy Yakovenko, Nedialko Krouchev and Trevor Drew During Reaching in the Cat by Modulating Muscle Synergies Sequential Activation of Motor Cortical Neurons Contributes to Intralimb Coordination [PDF] [Full Text] [Abstract] , March , 2011; 105 (3): 1011-1022. J Neurophysiol Nicholas AuYong, Karen Ollivier-Lanvin and Michel A. Lemay subchronic spinal cats Preferred locomotor phase of activity of lumbar interneurons during air-stepping in [PDF] [Full Text] [Abstract] , March 23, 2011; 31 (12): 4636-4649. J. Neurosci. Namrata M. Dasgupta, Mikhail G. Sirota and Irina N. Beloozerova Pavel V. Zelenin, Tatiana G. Deliagina, Grigori N. Orlovsky, Anastasia Karayannidou, during Locomotion Contribution of Different Limb Controllers to Modulation of Motor Cortex Neurons
Spinal cord injury (SCI) often results in lifelong sensorimotor impairment. Spontaneous recovery ... more Spinal cord injury (SCI) often results in lifelong sensorimotor impairment. Spontaneous recovery from SCI is limited, as supraspinal fibers cannot spontaneously regenerate to form functional networks below the level of injury. Despite this, animal models and humans exhibit many motor behaviors indicative of recovery when electrical stimulation is applied epidurally to the dorsal aspect of the lumbar spinal cord. In 1976, epidural stimulation was introduced to alleviate spasticity in Multiple Sclerosis. Since then, epidural electrical stimulation (EES) has been demonstrated to improve voluntary mobility across the knee and/or ankle in several SCI patients, highlighting its utility in enhancing motor activation. The mechanisms that EES induces to drive these improvements in sensorimotor function remain largely unknown. In this review, we discuss several sensorimotor plasticity mechanisms that we hypothesize may enable epidural stimulation to promote recovery, including changes in local lumbar circuitry, propriospinal interneurons, and the internal model. Finally, we discuss genetic tools for afferent modulation as an emerging method to facilitate the search for the mechanisms of action.
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Papers by Michel Lemay