ORCID ID

0000-0003-0641-0601

Graduation Date

Spring 5-8-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Neuroscience

First Advisor

Max Kurz

Second Advisor

Tony Wilson

Third Advisor

Dawn Venema

Fourth Advisor

David Warren, Elizabeth Heinrichs-Graham (fifth advisor)

Abstract

Cerebral palsy (CP) results from an insult to the developing brain, and it is one of the most common neurodevelopmental disorders in the United States. The insult produces a cascade of activity-dependent plastic changes within the neurophysiology and structure of the brain and spinal cord that ultimately leads to sensorimotor and mobility impairments that may increase in severity throughout the lifespan. Despite this phenomenon, there are a lack of neuroimaging studies in adults with CP, generating a knowledge gap in determining how brain and spinal cord activity and structure may be altered throughout the transition into adulthood. Furthermore, the specific microstructural changes in the spinal cord and the relationship between how the brain and spinal cord interact to produce these impairments remains poorly understood. We sought to address these knowledge gaps by employing a series of studies utilizing a combination of magnetoencephalography (MEG), MRI, and genetic methodologies during a variety of simple sensorimotor tasks. Overall, we uncovered aberrant sensorimotor cortical activity in both children and adults with CP in comparison to their healthy peers. Furthermore, we demonstrated specific structural deficiencies within the somatosensory cortex and the upper spinal cord of adults with CP, and these alterations were related to the aberrant sensorimotor cortical activity. Finally, we found that a polymorphism at the gene coding for brain derived neurotrophic factor (BDNF) contributed to more significant aberrancies in cortical activity in individuals with CP. Ultimately, these findings provide support for the notion that aberrant activity within the brain of individuals with CP, which is exacerbated by a polymorphism at the BDNF gene, results in neuroplastic changes along the spinal cord that may ultimately contribute to the clinical sensorimotor impairments seen within this population.

Available for download on Saturday, April 29, 2023

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