Neuromodulation using non-invasive stimulation techniques in humans is one of the most promising advances in treatment of neurological damage. While extensive work has been done in developing these techniques for therapy targeting the brain, there has been little emphasis on targeting spinal cord directly. We recently a developed a human repetitive stimulation paradigm to target spinal cord that is safe, effective, well tolerated, and results in lasting spinal excitability enhancement. In a small pilot study we showed that this spinal excitability modulation could be replicated in affected lower limb muscles of chronic spinal cord injury patients. Objective: In the present study we aim to: (1) determine if spinal excitability is raised following spinal associative stimulation (SAS) in a larger sample of SCI patients with lower limb paralysis, (2) examine the time-course of after effects, and (3) establish the functional consequences by measuring the change in voluntary motor activation associated with raised spinal excitability, assessed by the presence of background EMG during attempted muscle contraction. Methods: Since our prior work showed that the excitability modulation is contingent upon the paired technique, and not placebo or peripheral stimulation alone, we will provide the real stimulation paradigm in 30 chronic incomplete SCI patients, using a within subjects, pre-post intervention design. The principal outcome measure will be H-reflex threshold as per our previous work in healthy subjects. We will secondarily examine how the effect changes over time by repeating the baseline measures at 0, 15 and 30 minutes post intervention. We additionally be recording surface EMG during attempted maximal voluntary contractions at each of the time points. We expect that spinal excitability will be raised for at least 15 minutes post intervention, and that voluntary activation may be enhanced in association with heightened excitability. Results/Conclusions: If, as predicted, we establish conclusively that our method termed spinal associative stimulation is effective in SCI patients, this could profoundly influence the field of non-invasive stimulation, and open up the potential for a range of techniques for spinal cord targeting, including down-regulating excitability in the presence of spasticity. Significance: Spinal associative stimulation is the first paired non-invasive technique based on known timing-dependent interactions in spinal networks, to modulate spinal excitability. Further, it is one few techniques in humans, ever developed targeting spinal cord, including invasive stimulation.
We have shown for the first time a robust method of modulating spinal excitability in a manner resembling spike-timing dependent plasticity. The significance is that residual corticospinal tract fibers, present even in many of the most severely affected SCI patients, are likely to engage more responsive spinal networks after spinal associative stimulation (SAS), and thus increase voluntary activation of weakened muscles. The combination of neuromodulation protocols (aiming to induce plastic changes at the spinal level) and behavioral training (aiming to promote activity dependent plasticity) may be the future of spinal cord rehabilitation.
|Jannati, Ali; Block, Gabrielle; Oberman, Lindsay M et al. (2017) Interindividual variability in response to continuous theta-burst stimulation in healthy adults. Clin Neurophysiol 128:2268-2278|
|Oliveira-Maia, Albino J; Press, Daniel; Pascual-Leone, Alvaro (2017) Modulation of motor cortex excitability predicts antidepressant response to prefrontal cortex repetitive transcranial magnetic stimulation. Brain Stimul 10:787-794|
|Brys, Miroslaw; Fox, Michael D; Agarwal, Shashank et al. (2016) Multifocal repetitive TMS for motor and mood symptoms of Parkinson disease: A randomized trial. Neurology 87:1907-1915|
|Manor, Brad; Zhou, Junhong; Jor'dan, Azizah et al. (2016) Reduction of Dual-task Costs by Noninvasive Modulation of Prefrontal Activity in Healthy Elders. J Cogn Neurosci 28:275-81|
|Murray, Lynda M; Edwards, Dylan J; Ruffini, Giulio et al. (2015) Intensity dependent effects of transcranial direct current stimulation on corticospinal excitability in chronic spinal cord injury. Arch Phys Med Rehabil 96:S114-21|
|Shafi, Mouhsin M; Vernet, Marine; Klooster, Debby et al. (2015) Physiological consequences of abnormal connectivity in a developmental epilepsy. Ann Neurol 77:487-503|
|Edwards, D J; Cortes, M; Thickbroom, G W et al. (2014) Reply: evidence against volume conduction to explain normal MEPs in muscles with low motor power in SCI. Spinal Cord 52:718|
|Edwards, D J; Cortes, M; Thickbroom, G W et al. (2013) Preserved corticospinal conduction without voluntary movement after spinal cord injury. Spinal Cord 51:765-7|