scholarly journals Cervical Epidural Electrical Stimulation Restores Voluntary Arm Control In Paralyzed Monkeys

2020 ◽  
Author(s):  
Marco Capogrosso ◽  
Beatrice Barra ◽  
Sara Conti ◽  
Matthew Perich ◽  
Katie Zhuang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Motor Control ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Three Dimensional ◽  
Sensory Afferents ◽  
Reach And Grasp ◽  
Cervical Spinal Injury ◽  
Stimulation Of

Abstract Regaining arm motor control is critical for people with paralysis. Despite promising results on grasping, no technology could restore effective arm control. Here, we show that electrical stimulation of the cervical spinal cord enabled three monkeys with cervical spinal injury to execute functional arm movements. We designed an epidural interface that engaged surviving spinal circuits via the recruitment of large sensory afferents to produce movement. Simple stimulation bursts produced sustained joint movements which, triggered by movement-related intracortical signals, enabled monkeys with arm paralysis to perform an unconstrained, three-dimensional reach and grasp task. This restoration of voluntary motor control was enabled by the synergistic integration of spared descending commands and electrical stimulation within the spinal cord. The simplicity of this technology promises realistic clinical translation.

scholarly journals Electrical Stimulation Of The Cervical Dorsal Roots Enables Functional Arm And Hand Movements In Monkeys With Cervical Spinal Cord Injury

2020 ◽  
Author(s):  
B. Barra ◽  
S. Conti ◽  
M.G. Perich ◽  
K. Zhuang ◽  
G. Schiavone ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Motor Control ◽  
Cervical Spinal Cord ◽  
Three Dimensional ◽  
Arm Movements ◽  
Cervical Spinal Cord Injury ◽  
Cord Injury ◽  
Stimulation Of

SUMMARYRegaining arm motor control is a high priority for people with cervical spinal cord injury1. Unfortunately, no therapy can reverse upper limb paralysis. Promising neurotechnologies stimulating muscles to bypass the injury enabled grasping in humans with SCI2,3 but failed to sustain whole arm functional movements that are necessary for daily living activities. Here, we show that electrical stimulation of the cervical spinal cord enabled three monkeys with cervical SCI to execute functional, three-dimensional, arm movements. We designed a lateralized epidural interface that targeted motoneurons through the recruitment of sensory afferents within the dorsal roots and was adapted to the specific anatomy of each monkey. Simple stimulation bursts engaging single roots produced selective joint movements. We then triggered these bursts using movement-related intracortical signals, which enabled monkeys with arm motor deficits to perform an unconstrained, three-dimensional reach and grasp task. Our technology increased muscle activity, forces, task performance and quality of arm movements. Finally, analysis of intra-cortical neural data showed that a synergistic interaction between spared descending pathways and electrical stimulation enabled this restoration of voluntary motor control. Spinal cord stimulation is a mature clinical technology4–7, which suggests a realistic path for our approach to clinical applications.

scholarly journals Recruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathan Greiner ◽  
Beatrice Barra ◽  
Giuseppe Schiavone ◽  
Henri Lorach ◽  
Nicholas James ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Motor Control ◽  
Upper Limb ◽  
Cervical Spinal Cord ◽  
Sensory Afferents ◽  
Cord Injury ◽  
Hand Control ◽  
Muscle Responses ◽  
Stimulation Of

AbstractEpidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a computational model of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of upper-limb motoneuron recruitment with EES and characterize the selectivity of cervical interfaces. We show that lateral electrodes produce a segmental recruitment of arm motoneurons mediated by the direct activation of sensory afferents, and that muscle responses to EES are modulated during movement. Intraoperative recordings suggested similar properties in humans at rest. These modelling and experimental results can be applied for the development of neurotechnologies designed for the improvement of arm and hand control in humans with quadriplegia.

Recruitment of Upper-Limb Motoneurons with Epidural Electrical Stimulation of the Primate Cervical Spinal Cord

2020 ◽  
Author(s):  
Nathan Greiner ◽  
Beatrice Barra ◽  
Giuseppe Schiavone ◽  
Nicholas James ◽  
Florian Fallegger ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Motor Control ◽  
Upper Limb ◽  
Cervical Spinal Cord ◽  
Target Individual ◽  
Cord Injury ◽  
Hand Control ◽  
Cervical Stimulation ◽  
Stimulation Of

ABSTRACTEpidural electrical stimulation (EES) of lumbosacral sensorimotor circuits improves leg motor control in animals and humans with spinal cord injury (SCI). Upper-limb motor control involves similar circuits, located in the cervical spinal cord, suggesting that EES could also improve arm and hand movements after quadriplegia. However, the ability of cervical EES to selectively modulate specific upper-limb motor nuclei remains unclear. Here, we combined a realistic computational model of EES of the cervical spinal cord with experiments in macaque monkeys to explore the mechanisms of this modulation and characterize the recruitment selectivity of cervical stimulation interfaces. Our results indicate that interfaces with lateral electrodes can target individual posterior roots and achieve selective modulation of arm motoneurons via the direct recruitment of pre-synaptic pathways. Intraoperative recordings suggested similar properties in humans. These results provide a framework for the design of neuro-technologies to improve arm and hand control in humans with quadriplegia.

scholarly journals Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat

2019 ◽  
Vol 126 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Tidal Volume ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Breathing Patterns ◽  
Cord Injury ◽  
Spinal Contusion ◽  
Cervical Spinal Injury

The present study was designed to investigate breathing patterns across the sleep-wake state following a high cervical spinal injury in rats. The breathing patterns (e.g., respiratory frequency, tidal volume, and minute ventilation), neck electromyogram, and electroencephalography of unanesthetized adult male rats were measured at the acute (i.e., 1 day), subchronic (i.e., 2 wk), and/or chronic (i.e., 6 wk) injured stages after unilateral contusion of the second cervical spinal cord. Cervical spinal cord injury caused a long-term reduction in the tidal volume but did not influence the sleep-wake cycle duration. The minute ventilation during sleep was usually lower than that during the wake period in uninjured animals due to a decrease in respiratory frequency. However, this sleep-induced reduction in respiratory frequency was not observed in contused animals at the acute injured stage. By contrast, the tidal volume was significantly lower during sleep in contused animals but not uninjured animals from the acute to the chronic injured stage. Moreover, the frequency of sigh and postsigh apnea was elevated in acutely contused animals. These results indicated that high cervical spinal contusion is associated with exacerbated sleep-induced attenuation of the tidal volume and higher occurrence of sleep apnea, which may be detrimental to respiratory functional recovery after cervical spinal cord injury. NEW & NOTEWORTHY Cervical spinal injury is usually associated with sleep-disordered breathing. The present study investigated breathing patterns across sleep-wake state following cervical spinal injury in the rat. Unilateral cervical spinal contusion significantly impacted sleep-induced alteration of breathing patterns, showing a blunted frequency response and exacerbated attenuated tidal volume and occurrence of sleep apnea. The result enables us to investigate effects of cervical spinal injury on the pathogenesis of sleep-disordered breathing and evaluate potential therapies to improve respiration.

Effects of serotonergic agents on respiratory recovery after cervical spinal injury

2015 ◽  
Vol 119 (10) ◽  
pp. 1075-1087 ◽  
Author(s):  
Shih-Hui Hsu ◽  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Tidal Volume ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Serotonergic System ◽  
Chronic Injury ◽  
Adult Rats ◽  
Respiratory Impairment ◽  
Cord Injury ◽  
Cervical Spinal Injury

Unilateral cervical spinal cord hemisection (i.e., C2Hx) usually interrupts the bulbospinal respiratory pathways and results in respiratory impairment. It has been demonstrated that activation of the serotonin system can promote locomotor recovery after spinal cord injury. The present study was designed to investigate whether serotonergic activation can improve respiratory function during the chronic injury state. Bilateral diaphragm electromyogram and tidal volume were measured in anesthetized and spontaneously breathing adult rats at 8 wk post-C2Hx or C2laminectomy. A bolus intravenous injection of a serotonin precursor [5-hydroxytryptophan (5-HTP), 10 mg/kg], a serotonin reuptake inhibitor (fluoxetine, 10 mg/kg), or a potent agonist for serotonin 2A receptors (TCB-2, 0.05 mg/kg) was used to activate the serotonergic system. Present results demonstrated that 5-HTP and TCB-2, but not fluoxetine, significantly increased the inspiratory activity of the diaphragm electromyogram ipsilateral to the lesion for at least 30 min in C2Hx animals, but not in animals that received sham surgery. However, the tidal volume was not increased after administration of 5-HTP or TCB-2, indicating that the enhancement of ipsilateral diaphragm activity is not associated with improvement of the tidal volume. These results suggest that exogenous activation of the serotonergic system can specifically enhance the ipsilateral diaphragmatic motor outputs, but this approach may not be sufficient to improve respiratory functional recovery following chronic cervical spinal injury.

scholarly journals Epidural Electrical Stimulation Of The Cervical Dorsal Roots Restores Voluntary Arm Control In Paralyzed Monkeys

2021 ◽  
Author(s):  
Marco Capogrosso ◽  
Beatrice Barra ◽  
Sara Conti ◽  
Matthew Perich ◽  
Katie Zhuang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Functional Organization ◽  
Three Dimensional ◽  
Spinal Reflexes ◽  
Neural Function ◽  
Sensory Afferents ◽  
Dorsal Roots ◽  
Cord Injury ◽  
Spinal Segments

Abstract Recovering arm control is a top priority for people with paralysis. Unfortunately, the complexity of the neural mechanisms underlying arm control practically limited the effectiveness of neurotechnology approaches. Here, we exploited the neural function of surviving spinal circuits to restore voluntary arm and hand control in three monkeys with spinal cord injury using spinal cord stimulation. Our neural interface leverages the functional organization of the dorsal roots to convey artificial excitation via electrical stimulation to relevant spinal segments at appropriate movement phases. Stimulation bursts, triggered by intracortical signals produced sustained arm movements enabling monkeys with arm paralysis to perform an unconstrained, three-dimensional reach-and-grasp task. Stimulation specifically improved strength, task performances and movement quality. Electrophysiology suggested that artificial recruitment of the sensory afferents was synergistically integrated with spared descending inputs and spinal reflexes to produce coordinated movements. The efficacy and reliability of our approach hold realistic promises of clinical translation.

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