Date of Award

January 2018

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Laura R. Ment

Abstract

Premature birth is a major public health concern of increasing scope, with far-reaching consequences for children and families. Survival has increased with little improvement in the high incidence of lifelong neurodevelopmental disabilities. Critical among the difficulties resulting in poor academic performance for preterm children are deficits in both visual memory and fine motor skills, but the relationship between these two functions and the neural systems subserving them is relatively unexplored in this population. We tested the hypothesis that deficits in fine motor ability mediate deficits in visual memory as previous research suggests that motor ability is key to the development of visual-spatial processing. Magnetic resonance diffusion tensor imaging (MRI-DTI) was used to assess white matter coherence in 40 preterm adolescents (PT) with no neonatal brain injury compared to 40 term controls to document possible impaired white matter tract development as well as target neuro-correlates of the cognitive findings, particularly in the cerebellum, a developmentally vulnerable region in preterm neonates.

The Rey-Osterrieth Complex Figure Test, the Beery visual-motor integration (VMI), the Grooved Pegboard Test, the Wechsler Intelligence Scale for Children and Wide Range Achievement Test were collected for a PT cohort with no brain injury (N=190) and term controls (N=92) at age 16 years. PT performed more poorly than terms on all measures of fine motor, visual memory, and arithmetic achievement (all p <0.05). Mediation analysis showed fine motor skill significantly mediated the difference in visual memory ability between PTs and terms (all p <0.001), while visual memory ability mediated differences in arithmetic (all p <0.01) even when controlling for subject race and parental education. Visual-motor integration links fine motor ability with these higher-order skills as VMI score mediated the relationship between fine motor ability and arithmetic skill or visual memory among all participants. PTs showed a negative correlation (p < 0.05, corrected) between fractional anisotropy (FA), a measure of white matter integrity, in the right superior cerebellar peduncle and visual memory scores. They also showed a negative correlation (p < 0.05, corrected) between FA in the bilateral middle cerebellar peduncles and time to completion of a fine motor task, such that higher FA correlated with lower time to task completion (indicating improved fine motor ability). PTs also had a positive correlation (p < 0.05, corrected) between visual-motor integration and left middle cerebellar peduncle FA. These novel findings demonstrate for the first time that fine motor skills and the cerebellar systems supporting them subserve visual memory in the prematurely born and in turn contribute to impaired academic achievement in mathematics. Innovative strategies to train their low-level fine motor skills and target the cerebellum during its developmental period may have far-reaching implications for academic performance and help preterm-born adolescents achieve their full potential.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 06/25/2100

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