Passive Exercise of the Hind Limbs after Complete Thoracic Transection of the Spinal Cord Promotes Cortical Reorganization

Abstract

Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes – such as increased cardiovascular fitness, improved circulation and neuroendocrine changes – that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity – specifically ADCY1 and BDNF – increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain.

Dissociating Movement from Movement Timing in the Rat Primary Motor Cortex

“…This is similar to the early work of Olds (1965) andFetz (1969) showing neurons can be trained to modify their activity for a reward (for review, seeGanguly and Carmena, 2009;Manohar et al, 2012;Ganguly et al, 2011 for more recent studies in BMIs). However, after SCI there is an upregulation of proteins associated with plasticity (Endo et al, 2007;Graziano et al, 2013) and, therefore, this training is occurring in a more plastic state, likely supporting the functional reorganization.…”

Passive cycling in neurorehabilitation after spinal cord injury: A review

“…The results illustrated in this review are consistent with the findings of other experimental studies, demonstrating that passive training after spinal cord transection is sufficient to increase the neural responsiveness of the deafferented hindpaw cortex to tactile stimuli delivered to the forepaw/forelimb under deep anesthesia. 33 The authors found that the level of proteins associated with plasticity, in particular BDNF and adenylate cyclase type 1, increased in the somatosensory cortex of adult rats with complete thoracic transection that received passive hindlimb bike exercise compared to transected rats that received sham exercise. Electrophysiological techniques revealed that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received PC exercise compared to transected animals that received sham exercise.…”

“…33 PC may thus represent a low-cost therapeutic intervention with demonstrable motor, sensory and cardiovascular benefits. The results illustrated in this review are consistent with the findings of other experimental studies, demonstrating that passive training after spinal cord transection is sufficient to increase the neural responsiveness of the deafferented hindpaw cortex to tactile stimuli delivered to the forepaw/forelimb under deep anesthesia.…”

“…[47][48][49] These cardiovascular and neuroendocrine systemic effects can boost or simply accelerate the cascade of plasticity-related events that are already occurring in the deafferented somatosensory cortex after SCI. 33 Furthermore, PC exercise was able to elicit sensory inputs that have beneficial effects for functional recovery after stroke. 50,51 Cycling motion itself can activate somatosensory receptors and generate ascending inputs to the central nervous system.…”

Brain-Machine Interfaces beyond Neuroprosthetics

“…To further investigate the relationships between changes in tuning properties and plasticity, it is feasible to propose new paradigms that combine BMI with other techniques that modulate cortical plasticity at a more global level, such as pharmacological interventions (Maya Vetencourt et al, 2008;Ganzer et al, 2013), exercise (Cotman et al, 2007;Graziano et al, 2013), or electromagnetic neuromodulation with either direct current stimulation (Bindman et al, 1964;Má rquez-Ruiz et al, 2012;Filmer et al, 2014) or static magnetic field stimulation (Oliviero et al, 2011;Aguila et al, 2014). With these combined paradigms, the causality of BMI could be exploited to clarify the mechanisms by which interventions inducing changes in plasticity at a broad population level can affect tuning properties at the cellular level and ultimately behavior.…”