Preterm birth results in alterations in neural connectivity at age 16 years

Abstract

Very low birth weight preterm (PT) children are at high risk for brain injury. Employing diffusion tensor imaging (DTI), we tested the hypothesis that PT adolescents would demonstrate microstructural white matter disorganization relative to term controls at 16 years of age. Forty-four PT subjects (600-1250 g birth weight) without neonatal brain injury and 41 term controls were evaluated at age 16 years with DTI, the Wechsler Intelligence Scale for Children-III (WISC), the Peabody Picture Vocabulary Test-Revised (PPVT), and the Comprehensive Test of Phonological Processing (CTOPP). PT subjects scored lower than term subjects on WISC full scale (p=0.003), verbal (p=0.043), and performance IQ tests (p=0.001), as well as CTOPP phonological awareness (p=0.004), but scored comparably to term subjects on PPVT and CTOPP Rapid Naming tests. PT subjects had lower fractional anisotropy (FA) values in multiple regions including bilateral uncinate fasciculi (left: p=0.01; right: p=0.004), bilateral external capsules (left: p<0.001; right: p<0.001), the splenium of the corpus callosum (p=0.008), and white matter serving the inferior frontal gyrus bilaterally (left: p<0.001; right: p=0.011). FA values in both the left and right uncinate fasciculi correlated with PPVT scores (a semantic language task) in the PT subjects (left: r=0.314, p=0.038; right: r=0.336, p=0.026). FA values in the left and right arcuate fasciculi correlated with CTOPP Rapid Naming scores (a phonologic task) in the PT subjects (left: r=0.424, p=0.004; right: r=0.301, p=0.047). These data support for the first time that dual pathways underlying language function are present in PT adolescents. The striking bilateral dorsal correlations for the PT group suggest that prematurely born subjects rely more heavily on the right hemisphere than typically developing adults for performance of phonological language tasks. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.

Copyright © 2010 Elsevier Inc. All rights reserved.

Figures

Figure 1

Tri-color fractional anisotropy maps of a control brain are presented in sagittal and axial projections. Colors represent directionality of tracts: blue indicates superior-inferior orientation, green indicates anterior-posterior, and red indicates left-right. Outlines of regions of interest overlie this map: the uncinate fasciculus in white and the arcuate fasciculus in yellow.

Figure 2

Graphs show the relationship between testing scores on the y axis (PPVT in A – D; CTOPP Rapid Naming Composite scores in E – H) and FA values in specific regions on the x axis (left uncinate in A, B; right uncinate in C, D; left arcuate in E, F; right arcuate in G, H). Data are shown for preterm subjects (A, C, E, G) and term subjects (B, D, F, G) separately. The dashed lines represent 95% confidence intervals. Each black dot represents data from a single subject.