Date of Award

January 2016

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Laura R. Ment

Second Advisor

Jeffrey Gruen

Abstract

Preterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated through the weakening of short-range and strengthening of long-range connections. The specific aims of this study are: (1) To use residual fMRI data to investigate intrinsic connectivity development from ages 8 to 16 years in PT vs. T controls; and (2) To correlate intrinsic connectivity to cognitive and language scores. Longitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n = 13) compared to T children (n = 12) at ages 8 vs. 16 years using a Linear Mixed Effects model. Connectivity values in regions generated by the group x age interaction analysis were correlated with scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody Picture Vocabulary Test­Revised (PPVT­R), and Rapid Naming Composite (RDRL_cmp). The group x age analysis revealed significant ICD differences in the following regions: bilateral Brodmann area (BA) 47­BA11­BA10­L BA45 (p=0.0002) and L fusiform­BA18­BA19 (p=0.008). The larger frontal region (bilateral BA47-BA11-BA10-L BA45) was separated into subregions for further analysis, which showed the following significant ICD group x age differences: L and R BA47 (p=0.03 and p=0.0006, respectively), bilateral BA11 (p=0.0008), L and R BA10 (p=0.0005 and 0.005, respectively), and L BA46 (p=0.03). Over time, PT ICD increased in: bilateral BA47­BA11­BA10­L BA45 (p<0.0001), L and R BA47 (p=0.02 and <0.0001, respectively), bilateral BA11 (p<0.0001), L and R BA10 (p<0.0001 for both), and L BA46 (p=0.002). In addition, PT showed decreased ICD in L fusiform­BA18­BA19 (p=0.002). In contrast, the T subjects had no significant changes in ICD values over time. At age 16, PT had greater ICD than T in: bilateral BA47­BA11­BA10­L BA45 (p=0.0002), L & R BA47 (p=0.03 & p=0.0007), bilateral BA11 (p=0.0009), L & R BA10 (p=0.0006 & p=0.005), and L BA46 (p=0.03). PT had less ICD than T in L fusiform­BA18­BA19 (p=0.04). L fusiform­BA18­BA19 ICD positively correlated to scores on VIQ (p=0.021), PIQ (p=0.041), and FSIQ (p=0.015). None of the other regions correlated to scores on the cognitive tasks. The L fusiform-BA18-BA19 region includes the visual word form area, which has long been associated with reading performance and complex visual processing. These data demonstrate for the first time that, over the course of adolescence, prematurely-born children undergo widespread developmental changes in intrinsic connectivity that differ from term-born children. The development of resting state connectivity in prematurely-born children does not reflect compensatory alterations but rather appears to underscore and perpetuate impairment in language and cognitive processing.

Comments

This is an Open Access Thesis.

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