scholarly journals Vagus Nerve Stimulation Paired With Rehabilitative Training Enhances Motor Recovery After Bilateral Spinal Cord Injury to Cervical Forelimb Motor Pools

2020 ◽  
Vol 34 (3) ◽  
pp. 200-209 ◽  
Author(s):  
Michael J. Darrow ◽  
Miranda Torres ◽  
Maria J. Sosa ◽  
Tanya T. Danaphongse ◽  
Zainab Haider ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Vagus Nerve ◽  
Motor Neurons ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Closed Loop ◽  
Neurological Injury ◽  
Injury Model ◽  
Cord Injury

Closed-loop vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a strategy to enhance recovery after neurological injury. Previous studies demonstrate that brief bursts of closed-loop VNS paired with rehabilitative training substantially improve recovery of forelimb motor function in models of unilateral and bilateral contusive spinal cord injury (SCI) at spinal level C5/6. While these findings provide initial evidence of the utility of VNS for SCI, the injury model used in these studies spares the majority of alpha motor neurons originating in C7-T1 that innervate distal forelimb muscles. Because the clinical manifestation of SCI in many patients involves damage at these levels, it is important to define whether damage to the distal forelimb motor neuron pools limits VNS-dependent recovery. In this study, we assessed recovery of forelimb function in rats that received a bilateral incomplete contusive SCI at C7/8 and underwent extensive rehabilitative training with or without paired VNS. The study design, including planned sample size, assessments, and statistical comparisons, was preregistered prior to beginning data collection ( https://osf.io/ysvgf/ ). VNS paired with rehabilitative training significantly improved recovery of volitional forelimb strength compared to equivalent rehabilitative training without VNS. Additionally, VNS-dependent enhancement of recovery generalized to 2 similar, but untrained, forelimb tasks. These findings indicate that damage to alpha motor neurons does not prevent VNS-dependent enhancement of recovery and provides additional evidence to support the evaluation of closed-loop VNS paired with rehabilitation in patients with incomplete cervical SCI.

scholarly journals Neuromodulation of pelvic nerve during early phase of spinal cord injury in rats using implantable prototype devices - a preliminary study

2019 ◽  
Author(s):  
Wendy Yen Xian Peh ◽  
Monzurul Alam ◽  
Rakib Uddin Ahmed ◽  
Sanghoon Lee ◽  
Li Jing Ong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nerve Stimulation ◽  
Early Phase ◽  
Closed Loop ◽  
Intravesical Pressure ◽  
External Urethral Sphincter ◽  
Pelvic Nerve ◽  
Cord Injury ◽  
Bladder Management

AbstractObjectivesThe bladder becomes retentive during the early phase of spinal cord injury, and requires proper bladder management to prevent damage to the lower urinary tract and kidney. We investigated the effects of on-demand pelvic nerve stimulation on the areflexive bladder during the earliest phase of complete spinal cord injury in rats and the use of pelvic nerve signals as a proxy to estimate intravesical pressure for closed-loop applications.Materials and MethodsIn order to stimulate the pelvic nerves in female Sprague-Dawley rats with complete spinal cord transection (T7 level), a flexible electrode was implanted unilaterally on pelvic nerve, and electrical stimulation was provided by a custom-built nerve stimulator. Stimulation-evoked voiding was monitored in the awake state while size, capacity and spontaneous contractions of the bladder were analysed under anaesthesia. Separately, recordings of the pelvic nerve signals, external urethral sphincter activity and intravesical pressure were performed in animals with intact and transected spinal cord under anaesthesia.ResultsSuccessful pelvic nerve stimulation enabled more frequent voiding, reduced overdistension of bladder, and preserved non-voiding spontaneous bladder contractions. Typical bladder management protocol for SCI rats (manual expression every 8 – 12 hours) resulted in more severe bladder overdistention. Signal processing of the recorded extraneural pelvic nerve signals successfully reconstructed changes in intravesical pressure, demonstrating their use in estimating the fullness and contractions of the bladder.ConclusionsThe preliminary results suggest that pelvic nerve stimulators can serve as an alternative method for frequent emptying of the areflexive bladder. Simultaneous recording of the same pelvic nerve will be useful for development of a closed-loop neuroprosthesis.

scholarly journals Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Patrick D Ganzer ◽  
Michael J Darrow ◽  
Eric C Meyers ◽  
Bleyda R Solorzano ◽  
Andrea D Ruiz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Closed Loop ◽  
Neural Circuits ◽  
Corrective Feedback ◽  
Network Connectivity ◽  
Neurological Injury ◽  
Adaptive Plasticity ◽  
Cord Injury ◽  
Neurological Insult

Recovery from serious neurological injury requires substantial rewiring of neural circuits. Precisely-timed electrical stimulation could be used to restore corrective feedback mechanisms and promote adaptive plasticity after neurological insult, such as spinal cord injury (SCI) or stroke. This study provides the first evidence that closed-loop vagus nerve stimulation (CLV) based on the synaptic eligibility trace leads to dramatic recovery from the most common forms of SCI. The addition of CLV to rehabilitation promoted substantially more recovery of forelimb function compared to rehabilitation alone following chronic unilateral or bilateral cervical SCI in a rat model. Triggering stimulation on the most successful movements is critical to maximize recovery. CLV enhances recovery by strengthening synaptic connectivity from remaining motor networks to the grasping muscles in the forelimb. The benefits of CLV persist long after the end of stimulation because connectivity in critical neural circuits has been restored.

scholarly journals Restoration of breathing after opioid overdose and spinal cord injury using temporal interference stimulation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Michael D. Sunshine ◽  
Antonino M. Cassarà ◽  
Esra Neufeld ◽  
Nir Grossman ◽  
Thomas H. Mareci ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Drug Overdose ◽  
Cervical Spinal Cord ◽  
Opioid Overdose ◽  
Electrode Position ◽  
Spinal Motor Neurons ◽  
Cord Injury ◽  
Low Amplitude

AbstractRespiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.

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