Authors

Dea GaricFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Psychology

First Advisor's Name

Anthony Dick

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Paulo Graziano

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Andy Pham

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Bethany Reeb-Sutherland

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Lucina Uddin

Fifth Advisor's Committee Title

Committee member

Keywords

brain development, ADHD, language, executive function, DWI, density

Date of Defense

6-24-2020

Abstract

The structure and connectivity of the prefrontal cortex has been extensively studied for its contribution to language and executive function (EF) development, but many questions still remain whether its microstructural tissue properties can reliably predict behavioral outcomes in very young typically and atypically developing populations. In particular, the bilateral frontal aslant tract (FAT) has garnered increasing interest with respect to its potential association with both language and EF, but has yet to be examined in childhood attention disorders, such Attention Deficit Hyperactivity Disorder (ADHD). At the same time, with advances in diffusion weighted imaging (DWI), new diffusion models offer more nuanced characterizations of specific tissue properties, namely neurite (axonal and dendritic) density and organization. Restricted diffusion imaging (RDI) and neurite orientation dispersion and density diffusion imaging (NODDI) are two advanced approaches to measuring density \textit{in vivo} that have been tested in animal, infant, and adult studies, but have been sparsely examined in regards to their association with behavioral outcomes in young children. We can now apply these diffusion methods to the analysis of microstructure of the frontal lobe and its association with language and EF. Thus, across three studies, this dissertation aims to answer the following questions: Does the FAT show age-related change during the sensitive developmental period between 4- to 7-years of age, and do age-related differences differ in children diagnosed with ADHD? Can the microstructural properties of the FAT differentially predict language and EF outcomes in ADHD and control samples? Are novel DWI methods capable of reliably mapping neurite density in children and adults and expanding what we currently know about brain microstructure and maturation? And finally, can neurite density and orientation within prefrontal and subcortical brain regions predict behavioral outcomes in typically and atypically developing children? To answer these questions, we used three DWI reconstruction methods to better elucidate neural tissue development, and examined its association to a battery of language and EF measures. We present compelling evidence that the FAT is a potential biomarker for ADHD, capable of differentially predicting aspects of language and EF across these groups. Furthermore, we show that more precise diffusion-weighted imaging methods can inform our understanding of typical and atypical brain development as it relates to behavior in the domains of language and EF.

Identifier

FIDC009025

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