Neuromodulation of the Cortex and Spinal Cord

Overview

Specific Aim 1: To further quantify the difference in the sensorimotor cortical activity, spinal cord activity, and corticospinal coherence of persons with CP. Overall hypotheses: The sensorimotor cortical activity, spinal cord activity, and corticospinal coherence will be uncharacteristic in persons with CP when compared with neurotypical controls. Furthermore, the extent of the alterations in the sensorimotor cortical activity, spinal cord activity, and corticospinal coherence will be tightly linked with the clinical presentations of persons with CP. Specific Aim 2: To investigate the effect of transcutaneous current stimulation applied over the cortex and/or spinal cord on the sensorimotor cortical activity, spinal cord dynamics, and corticospinal coherence. Overall hypotheses: Compared with the sham controls, those receiving the transcutaneous current stimulation will demonstrate alterations in the strength of the sensorimotor cortical activity, spinal cord activity, and corticospinal coherence. Moreover, the extent of the alterations in the sensorimotor cortical activity, spinal cord activity, and corticospinal coherence will be tightly linked with the clinical presentations of persons with CP.

Cerebral palsy (CP) is the most common pediatric motor disability, affecting 3.6 per 1000 children, and is typically a result of an insult to the developing brain. The brain insult impacts the precision of the motor actions and can have a lifelong impact on the precision of the motor actions. Although these motor deficits are vastly documented clinically, the underlying neurophysiological changes responsible for the emergence of these impairments are less understood. Our experimental work over the past decade has been directed at filling this knowledge gap. For example, magnetoencephalographic (MEG) brain imaging results were the first to show that the sensorimotor cortices of persons with CP exhibit abnormal activity when planning and executing a motor action, and that this aberrant activity is tightly coupled with slower reaction times and muscular force production errors. In addition, the investigators have repeatedly found that persons with CP have uncharacteristic activity within the somatosensory cortices following peripheral stimulation of the foot and hand, and that such abnormal cortical activity persists while producing a motor action. More recently, the investigators have evaluated if the altered cortical activity has cascading effects on the spinal cord interneuron dynamics. The logic for this premise was based on prior animal models that have shown that the initial insult to the developing brain impacts the structural organization of the spinal cord. The investigators\' high-resolution structural MRI pipelines have revealed that the spinal cords of persons with CP have less grey and white matter area notable microstructural aberrations in the lemniscal and corticospinal tracts. Furthermore, the investigators\' neurophysiological tests have indicated that persons with CP cannot excite the spinal cord's higher-threshold type II motor units that govern the fast-twitch fibers and the production of larger muscular forces. Altogether the investigators\' body of experimental work suggests that there are unique interactions between the cortex and spinal cord that are likely responsible for the altered motor actions seen in those with CP. Further investigation of the brain and spinal cord connectivity will be important for advancing our understanding of the neurophysiology of persons with CP and the development of personalized therapeutic approaches that specifically target these deficiencies. Transcutaneous current stimulation over the cortex and spinal cord is the most common noninvasive stimulation paradigms being explored with persons with CP in the hope of beneficially altering the neural generators that are involved in the production of a motor action. This approach involves the application of stimulating electrodes that emit a low-grade electrical current that passes through the skull/spine/skin to either excite or inhibit the underlying neural generators. The outcomes from these investigations have largely been mixed with some persons with CP demonstrating beneficial improvements, while others are non-responders. There are several limitations of these prior investigations. For one, there have been no neuroimaging investigations that have been performed to determine how the stimulation impacts the neurophysiology of the targeted cortical or spinal cord neural generators of those with CP. Secondarily, none of these prior investigations have considered whether these neuromodulation techniques impact the spinal cord-cortex connectivity. Lastly, many of the initial investigations have been case series that have not included a sham control group. This makes it difficult to discern if the clinical improvements seen in persons with CP after transcutaneous current stimulation are due to the physical therapy or physical therapy plus the neuromodulation. There are large knowledge gaps in our understanding of how the respective transcutaneous current stimulation approaches influence the neurophysiology of persons with CP and if the stimulation protocols are beneficially altering the neurophysiology. The lion's share of the current research is blindly applying these neuromodulation techniques in hopes of having a beneficial improvement. There is a critical need to robustly evaluate the effect of these neuromodulation techniques on the neurophysiology of those with CP before the investigators are well prepared to launch a clinical trial. The Aims of this investigation are directed at beginning to fill this substantial knowledge gap.