A new age for rehabilitation.
ABSTRACT In this review we will describe newly developed techniques that are being used to recover levels of motor function after a severe spinal cord injury that have not been observed previously. These new approaches include pharmacological neuromodulation and/or epidural stimulation of the spinal cord circuitries in combination with motor training. By combining the increased levels of excitability of the interneuronal spinal circuitries using these interventions and the ability of the spinal circuitries to interpret and respond appropriately to ongoing complex ensembles of sensory input, the peripheral sensory system can become an effective source for the control of motor function. Similar types of neuromodulation have been shown to enable the brain to regain functional connectivity with the spinal cord circuitries below a clinically complete spinal cord lesion. In fact, some level of voluntary control of movement has been observed in subjects with complete paralysis in the presence of epidural stimulation. The biological mechanisms thought to underlie the recovery of motor function after a severe spinal cord injury are based on decades of research on a wide range of animal models. Fortunately the extensive conservation of neural mechanisms of motor control has provided a window for gaining considerable insight into the mechanisms of recovery of motor function in humans.
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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 non-specifically 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, Harkemaet 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.Cell Transplantation 02/2015; 24(3). DOI:10.3727/096368915X686904 · 3.57 Impact Factor
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ABSTRACT: Motor cortex (MCX) motor representation reorganization occurs after injury, learning, and different long-term stimulation paradigms. The neuromodulatory approach trans-spinal direct current stimulation (tsDCS) has been used to promote evoked cortical motor responses. Here we used cathodal tsDCS (c-tsDCS) of the rat cervical cord to determine if spinal cord activation can modify the MCX forelimb motor map. We used a finite element method model based on co-registered high-resolution rat MRI and micro-CT imaging data to predict spinal current density to target stimulation to the caudal cervical enlargement. We examined the effects of cathodal and anodal tsDCS on the H-reflex and c-tsDCS on responses evoked by intra-cortical microstimulation (ICMS). To determine if cervical c-tsDCS also modified MCX somatic sensory processing, we examined sensory evoked potentials (SEP) produced by wrist electrical stimulation and induced changes in ongoing activity. Cervical c-tsDCS enhanced and anodal depressed the H-reflex. Using cathodal stimulation to examine cortical effects, we found that cervical c-tsDCS immediately modified the forelimb MCX motor map, as decreased thresholds and an expanded area. c-tsDCS also increased SEP amplitude in MCX. The magnitude of changes produced by c-tsDCS were greater on the motor than the sensory response. Cervical c-tsDCS more strongly enhanced the forelimb than hind limb motor representation, and had no effect on the vibrissal representation. The finite element model indicated current density localized to caudal cervical segments, informing forelimb motor selectivity. Our results suggest that c-tsDCS augments spinal excitability in a spatially-selective manner and may improve voluntary motor function through MCX representational plasticity. Copyright © 2014, Journal of Neurophysiology.Journal of Neurophysiology 02/2015; 113(7):jn.00784.2014. DOI:10.1152/jn.00784.2014 · 3.04 Impact Factor
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ABSTRACT: Human locomotor movements exhibit considerable variability and are highly complex in terms of both neural activation and biomechanical output. The building blocks with which the central nervous system constructs these motor patterns can be preserved in patients with various sensory-motor disorders. In particular, several studies highlighted a modular burst-like organization of the muscle activity. Here we review and discuss this issue with a particular emphasis on the various examples of adaptation of locomotor patterns in patients (with large fiber neuropathy, amputees, stroke and spinal cord injury). The results highlight plasticity and different solutions to reorganize muscle patterns in both peripheral and central nervous system lesions. The findings are discussed in a general context of compensatory gait mechanisms, spatiotemporal architecture and modularity of the locomotor program.Frontiers in Computational Neuroscience 09/2013; 7:123. DOI:10.3389/fncom.2013.00123 · 2.23 Impact Factor