# Can spinal cord epidural stimulation increase the efficacy of midbrain excitation of locomotor circuits?

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $191,875

## Abstract

Project summary
Spinal cord injury (SCI) interrupts motor control pathways between supraspinal and spinal sensorimotor
networks. This disruption results in impairment of gait and sensation, chronic decreased quality of life (QOL),
and numerous medical complications. In human studies of chronic SCI, lumbar electrical epidural stimulation
(EES) based rehabilitation has allowed weight-bearing and unprecedented voluntary stepping in motor complete
patients. These results establish that even severe complete SCIs have intact axons spared through the injury
site. EES activates dorsal sensory roots to raise excitability of residual intact locomotor circuitry in the spinal
cord. This allows otherwise silent descending inputs to become effective, permitting voluntary motion. Although
impressive, ES based rehabilitation has not been adequate to restore balanced independent gait in the
community setting. If applied during subacute rehabilitation, a period of increased neuroplasticity, this strategy
may engender a greater level of permanent recovery. To address inadequate supraspinal drive we will use deep
brain stimulation (DBS) of the mesencephalic locomotor region (MLR) to “overdrive” the stepping initiation center.
We have previously developed protocols for MLR DBS and EES in a porcine contusion SCI model but have not
combined them. In this project with 2:1 treatment:controls, we propose testing DBS and ES, together with
developing a closed-loop perturbation and response protocol, to provide feedback driven stability and balance
during weight supported stepping. In Aim 1, Yucatan minipigs with severe T9 SCI will be implanted with both
MLR DBS and lumbar ES electrodes and undergo intensive rehabilitation for 3 months. In Aim 2 we test to what
extent postural correction can be achieved by asymmetric modification of stimulus parameters in response to a
posterior pelvic mounted inertial measurement unit coupled to a PID controller. Primary outcome measures
include extent recovery of locomotion, time-walked testing, capacity to achieve unassisted weight support and
structural plasticity of the reticulospinal tract. Measures will be acquired using state of the art kinematic analysis
and telemetry-electromyography. In histological analysis after neuroanatomical tracing we determine if MLR-
DBS causes axonal structural plasticity. Our aims align with the NIBIB mission statement by testing a
multidisciplinary bioengineering approach in a clinically relevant and translational paraplegia model. ES and DBS
technology has been applied in other clinical conditions including neuropathic pain and Parkinson’s disease.
Thus, if successful, the translational path would be accelerated. The combined neuromodulation and
rehabilitative intervention is relevant to public health, as it may fundamentally improve recovery from SCI and
render subacute neurorehabilitation more effective allowing allow community-setting ambulation, supplanting
wheelchair use and increasing QOL for ind...

## Key facts

- **NIH application ID:** 10020796
- **Project number:** 5R21NS115185-02
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** James David Guest
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,875
- **Award type:** 5
- **Project period:** 2019-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020796

## Citation

> US National Institutes of Health, RePORTER application 10020796, Can spinal cord epidural stimulation increase the efficacy of midbrain excitation of locomotor circuits? (5R21NS115185-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020796. Licensed CC0.

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