Date on Master's Thesis/Doctoral Dissertation

5-2023

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Behrman, Andrea

Committee Co-Chair (if applicable)

Depue, Brendan

Committee Member

Depue, Brendan

Committee Member

Hubscher, Charles

Committee Member

Boakye, Maxwell

Committee Member

Lorenz, Doug

Author's Keywords

Pediatric spinal cord injury; supraspinal reorganization; magnetic resonance imaging (MRI); spinal pathways electrophysiology; functional connectivity; neuroimaging

Abstract

Pediatric spinal cord injury (SCI) disrupts the efferent and afferent flow of the developing brain, leading to devastating functional impairments below the injury site, yet our understanding of its impact on the brain remains limited. This study examines supraspinal reorganization in children with SCI using electrophysiology and neuroimaging techniques to understand the relationship between residual spinal transmission and supraspinal reorganization. Chapter 2 discusses the development of a child-centric approach using ‘learn, play, and practice’ to foster a trusting relationship with each child and increase compliance with experimental protocols. Chapter 3 evaluates the residual neural transmission of three spinal pathways in children with SCI, revealing that supraspinal inputs onto spinal motor circuitry persist despite a clinical diagnosis of complete SCI. This finding supports the concept of discomplete injuries and suggests that clinical assessments may not fully capture the extent of residual sensorimotor function in this population. The neural conduction of the corticospinal tract (CST), the primary mediator of volitional motor function, was assessed via functional neurophysiological assessment (FNPA). Reticulospinal tract (RST) activity, crucial for movement coordination, was evaluated using acoustic startle response (ASR). Finally, the functional transmission of the dorsal column-medial lemniscus (DCML) pathway, which conveys touch information from the periphery to the brain, was evaluated by analyzing somatosensory evoked potentials (SSEP). In Chapter 4, the impact of SCI on the pediatric brain was investigated using neuroimaging techniques. Analysis of 8 children with SCI and 18 age- and gender-matched typically developing controls showed reduced gray matter morphometry and functional connectivity in cortical and subcortical sensorimotor structures and lower CST microstructural integrity in the brains of children with SCI. Additional analysis reveals that higher cortical and subcortical neuroimaging measures were associated with a higher probability of volitional muscle activation, and higher RST activity levels were correlated with better measurements of subcortical morphometry and functional connectivity. These findings provide valuable insights into the effects of pediatric SCI on the brain and their underlying relationships to motor pathways activity, suggesting the potential of supraspinal neuroimaging to serve as biomarkers to assess recovery and track the efficacy of interventions targeting spinal translesional connectivity.

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