Epidural Electrical Stimulation of the Cervical Dorsal Roots Restores Voluntary Upper Limb Control in Paralyzed Monkeys

Abstract

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.

High-density spinal cord stimulation selectively activates lower urinary tract afferents

“…Improvements in LUT control may therefore be driven either indirectly or through direct recruitment of afferents innervating the bladder. In the case of limb motion, cervical and lumbar SCS can recruit muscles of the upper and lower limbs 12,13 by activating reflexes 14,15 , demonstrating that focal stimulation of the afferent system can control motor behaviors 16,17 .…”

Epidural stimulation of the cervical spinal cord improves voluntary motor control in post-stroke upper limb paresis

“…Clinical SCS leads are intended to be placed along the midline to broadly stimulate dorsal columns and block pain signals 39 . However, we have shown previously in monkeys and humans that selective recruitment or primary afferent fibers in the cervical dorsal rootlets can be achieved by positioning the clinical SCS leads laterally, near the dorsal root entry zone 8,10,38 . These primary afferents innervate motoneuron pools according to a well-defined rostro-caudal somatotopy 40 , and we predicted that stimulating specific nerve roots would lead to excitation of the corresponding motoneurons.…”

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A large proportion of cerebral strokes disrupt descending commands from motor cortical areas to the spinal cord which can results in permanent motor deficits of the arm and hand 1,2 . However, below the lesion, the spinal circuits that control movement 5 remain intact and could be targeted by neurotechnologies to restore movement [6][7][8][9] . Here we demonstrate that by engaging spinal circuits with targeted electrical stimulation we immediately improved voluntary motor control in two participants with chronic post-stroke hemiparesis.

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Intraoperative electrical stimulation of the human dorsal spinal cord reveals a map of arm and hand muscle responses

“…Importantly, anesthetic conditions had reached a steady state during recording, and no changes were made during the experiment. Participants were tested in an immobilized prone position, so we were not able to address how epidural stimulation can be used to generate movement (Greiner et al 2021; Kato, Nishihara, and Nishimura 2020; Barra et al 2021) or how MEPs interact with body position (Marsden, Merton, and Morton 1981; Knikou 2006; Knikou et al 2009; Danner et al 2016). In future studies these limitations may be addressed in alternative experimental settings either non-invasively or with implanted leads.…”