Electrical Stimulation and Motor Recovery

Abstract

In recent years, several investigators have successfully regenerated axons in animal spinal cords without locomotor recovery. One explanation is that the animals were not trained to use the regenerated connections. Intensive locomotor training improves walking recovery after spinal cord injury (SCI) in people, and >90% of people with incomplete SCI recover walking with training. Although the optimal timing, duration, intensity, and type of locomotor training are still controversial, many investigators have reported beneficial effects of training on locomotor function. The mechanisms by which training improves recovery are not clear, but an attractive theory is available. In 1949, Donald Hebb proposed a famous rule that has been paraphrased as "neurons that fire together, wire together." This rule provided a theoretical basis for a widely accepted theory that homosynaptic and heterosynaptic activity facilitate synaptic formation and consolidation. In addition, the lumbar spinal cord has a locomotor center, called the central pattern generator (CPG), which can be activated nonspecifically with electrical stimulation or neurotransmitters to produce walking. The CPG is an obvious target to reconnect after SCI. Stimulating motor cortex, spinal cord, or peripheral nerves can modulate lumbar spinal cord excitability. Motor cortex stimulation causes long-term changes in spinal reflexes and synapses, increases sprouting of the corticospinal tract, and restores skilled forelimb function in rats. Long used to treat chronic pain, motor cortex stimuli modify lumbar spinal network excitability and improve lower extremity motor scores in humans. Similarly, epidural spinal cord stimulation has long been used to treat pain and spasticity. Subthreshold epidural stimulation reduces the threshold for locomotor activity. In 2011, Harkema et al. reported lumbosacral epidural stimulation restores motor control in chronic motor complete patients. Peripheral nerve or functional electrical stimulation (FES) has long been used to activate sacral nerves to treat bladder and pelvic dysfunction and to augment motor function. In theory, FES should facilitate synaptic formation and motor recovery after regenerative therapies. Upcoming clinical trials provide unique opportunities to test the theory. INTRODUCTIONIn the past decade, several prominent laboratories have shown axonal regeneration in animal spinal cord injury (SCI) models, but locomotor recovery did not follow regeneration (277). For example Lu et al. (159,160) and He's group (156,282) regenerated many axons that synapsed with neurons in the lower spinal cord, but the animals did not recover walking. To explain the lack of locomotor recovery, the investigators assume that insufficient numbers of regenerated axons have formed synapses with appropriate neurons in the lower spinal cord to support locomotion. Another explanation for the lack of locomotor recovery after complete SCI and regeneration is that the animals did not learn to use their newly regrown connections.Regenerated fibe...

A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats

“…Epidural stimulation of the spinal cord has been used frequently in both animal models and human subjects to restore some motor control even after neurologically complete SCI. Proposed mechanisms include activation of lumbar neuronal networks that are known as central pattern generators (Cazalets, Borde et al 1995, Young 2015), direct or indirect activation of motor neuron pools (Angeli, Edgerton et al 2014), or stimulation of afferent fibers in the dorsal roots (Harkema, Gerasimenko et al 2011). …”

Tail Nerve Electrical Stimulation and Electro-Acupuncture Can Protect Spinal Motor Neurons and Alleviate Muscle Atrophy after Spinal Cord Transection in Rats

“…This ultimately leads to atrophy of the innervated muscles. Giving exterior intervention to reactivate the lumbar segments may be a feasible treatment strategy for relieving the muscle atrophy [39]. There is available evidence demonstrating the beneficial effect of electrical stimulation (ES) on muscle atrophy treatment [7, 32, 40].…”

Effect of Treadmill Training Protocols on Locomotion Recovery in Spinalized Rats

“…[8] Hebbian theory proposes an explanation for the adaptation of neurons in the brain during a learning process. [9] When an axon of a neural cell is placed near enough to excite another cell repeatedly, some growth process (new axonal and/or dendritic projections) or metabolic change can develop in one or both cells like increasing the efficiency of the firing cell. [9] These synaptic changes are well-known as synaptic plasticity.…”