Spasticity is a debilitating condition which emerges in up to ~75% of individuals with spinal cord injury (SCI), with
most experiencing spastic episodes one year after injury. Current pharmacological approaches to decrease
spasticity (i.e. baclofen, tizanidine, botulinum toxin) lead to significant undesirable side effects such as sedation
and dizziness. More importantly, they also induce a profound depression of spinal reflex excitability which
significantly reduces muscle activity and impedes conventional rehabilitative efforts. There is therefore a critical
need to identify alternate avenues. The last decade has seen a critical breakthrough in the SCI field with the use
of stimulation-based therapies, in particular epidural stimulation, to further modulate the excitability of spinal
networks and enhance functional recovery after SCI. Although promising, these treatments are invasive, costly,
and require highly skilled and specialized teams. In contrast, non-invasive transcutaneous spinal cord stimulation
(tSCS) has the potential to be rapidly adapted in clinical rehabilitation settings. This project is designed to
advance our understanding of the neuroplasticity triggered by 6 weeks of repeated lumbar tSCS initiated acutely,
to prevent the development of spasticity, or chronically, to decrease spasticity once spinal hyperexcitability has
fully developed. Aim 1 will determine if tSCS contributes to decrease spasticity/hyperreflexia through restoring
spinal inhibition in lumbar spinal networks. Behavioral correlates of spasticity will be monitored over time. In a
terminal experiment, the effect of tSCS on spinal inhibitory pathways (homosynaptic depression, reciprocal
inhibition, and presynaptic inhibition) will be correlated to the reorganization of inhibitory/excitatory inputs to
motoneurons and primary afferents. Aim 2 will determine if tSCS restores motor-evoked potentials (MEPs)
originating from above and below the injury after SCI. During a terminal experiment, MEPs initiated by a
stimulation to the spinal cord below or above the injury will be recorded as well as synaptic transmission in the
cortico-reticulospinal pathway. The modulatory effect of proprioceptive feedback on the MEPs of various origin
will also be evaluated. The contribution of primary afferents (VGlut1+/paravalbumin) and descending tracts (vGi)
to increased motor output and normalization of the SCI-induced facilitation of proprioceptive afferents will be
evaluated. Because spastic symptoms, such as spasms and uncontrollable reflexes, render rehabilitation and
activity-based therapies such as locomotor training challenging and less effective, Aim 3 will determine if
decreasing spasticity with tSCS prior to the initiation of a step-training program improves locomotor recovery.
Spasticity and locomotor recovery will be evaluated over time and will be correlated to the return of spinal
inhibition and cortico-reticulospinal transmission. The proposed research project is consistent with the goals of
the NIH/NINDS by addressing a current gap in knowledge and delineating the mechanisms of tSCS.
Understanding the mechanisms underlying the beneficial effect of non-invasive interventions is critical to optimize
evidence-based clinical practice and fast-track its use in the SCI community.
