Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury

Abstract

Epidural electrical stimulation of lumbar segments facilitates standing and walking in animal models and humans with spinal cord injury. However, the mechanisms through which this neuromodulation therapy engages spinal circuits remain enigmatic. Using computer simulations and behavioral experiments, we provide evidence that epidural electrical stimulation interacts with muscle spindle feedback circuits to modulate muscle activity during locomotion. Hypothesis-driven strategies emerging from simulations steered the design of stimulation protocols that adjust bilateral hindlimb kinematics throughout gait execution. These stimulation strategies corrected subject-specific gait and balance deficits in rats with incomplete and complete spinal cord injury. The conservation of muscle spindle feedback circuits across mammals suggests that the same mechanisms may facilitate motor control in humans. These results provide a conceptual framework to improve stimulation protocols for clinical applications.

Myelin status and oligodendrocyte lineage cells over time after spinal cord injury: What do we know and what still needs to be unwrapped?

“…Indeed, recent evidence suggests that increased physical activity after SCI may promote remyelination. Currently there is much excitement in the SCI field over the remarkable results being obtained with activity‐based training and epidural stimulation in SCI individuals (Capogrosso et al, ; Formento et al, ; Gill et al, ; Moraud et al, ; Wagner et al, ; Wenger et al, ). The most common form of activity‐based therapy is body weight supported treadmill training in which SCI subjects are placed in a harness and trainers move their limbs to provide sufficient input to the neuromuscular system (Dobkin et al, ).…”

Intrinsic Axonal Growth and the Drive for Regeneration

“…Interestingly, these studies revealed significant interspecies differences in the mechanisms of corticospinal tract regeneration during motor recovery when comparing rodents to primates and humans. Finally, combinatorial and holistic approaches that incorporate rehabilitation, pharmacology, neuromodulation (Moraud et al, 2016; Wenger et al, 2016) as well as emerging technologies like the exoskeleton (Gad et al, 2015; Miller et al, 2016) raise hopes that meaningful, functional recovery is achievable in the foreseeable future.…”

Electronic Dura Mater Meddling in the Central Nervous System

“…Previous studies 13,14 found that the stimulation engages spinal circuits through the modulation of proprioceptive feedback circuits located in the dorsal roots. This framework guided the design of e-dura implants that integrated spatially selective electrodes.…”