White matter alterations and their associations with motor function in young adults born preterm with very low birth weight

Abstract

Very low birth weight (VLBW: ≤ 1500 g) individuals have an increased risk of white matter alterations and neurodevelopmental problems, including fine and gross motor problems. In this hospital-based follow-up study, the main aim was to examine white matter microstructure and its relationship to fine and gross motor function in 31 VLBW young adults without cerebral palsy compared with 31 term-born controls, at mean age 22.6 ± 0.7 years. The participants were examined with tests of fine and gross motor function (Trail Making Test-5: TMT-5, Grooved Pegboard, Triangle from Movement Assessment Battery for Children-2: MABC-2 and High-level Mobility Assessment Tool: HiMAT) and diffusion tensor imaging (DTI). Probabilistic tractography of motor pathways of the corticospinal tract (CST) and corpus callosum (CC) was performed. Fractional anisotropy (FA) was calculated in non-crossing (capsula interna in CST, body of CC) and crossing (centrum semiovale) fibre regions along the tracts and examined for group differences. Associations between motor test scores and FA in the CST and CC were investigated with linear regression. Tract-based spatial statistics (TBSS) was used to examine group differences in DTI metrics in all major white matter tracts. The VLBW group had lower scores on all motor tests compared with controls, however, only statistically significant for TMT-5. Based on tractography, FA in the VLBW group was lower in non-crossing fibre regions and higher in crossing fibre regions of the CST compared with controls. Within the VLBW group, poorer fine motor function was associated with higher FA in crossing fibre regions of the CST, and poorer bimanual coordination was additionally associated with lower FA in crossing fibre regions of the CC. Poorer gross motor function was associated with lower FA in crossing fibre regions of the CST and CC. There were no associations between motor function and FA in non-crossing fibre regions of the CST and CC within the VLBW group. In the TBSS analysis, the VLBW group had lower FA and higher mean diffusivity compared with controls in all major white matter tracts. The findings in this study may indicate that the associations between motor function and FA are caused by other tracts crossing the CST and CC, and/or by alterations in the periventricular white matter in the centrum semiovale. Some of the associations were in the opposite direction than hypothesized, thus higher FA does not always indicate better function. Furthermore, widespread white matter alterations in VLBW individuals persist into young adulthood.

Keywords: AD, axial diffusivity; Brain; CC, corpus callosum; CST, corticospinal tract; DTI, diffusion tensor imaging; Diffusion tensor imaging; FA, fractional anisotropy; HiMAT, high-level mobility assessment tool; MABC-2, movement assessment battery for children-2; MD, mean diffusivity; MNI, Montreal neurological institute; MRI, magnetic resonance imaging; Motor function; NICU, neonatal intensive care unit; Preterm; RD, radial diffusivity; ROI, region-of-interest; SES, socioeconomic status; TBSS, tract-based spatial statistics; TMT-5, Trail Making Test-5; Tractography; VLBW, very low birth weight; VOI, volume-of-interest; Young adulthood.

Fig. 1

A) ROIs used for the probabilistic tractography of the left and right corticospinal tract (CST): Seed ROI in the cerebral peduncles (green) and target ROIs in the hand area in the primary motor cortex (red), foot area in the primary motor cortex (blue) and premotor cortex (yellow). B) Probabilistic tractography results of the CST_hand (red), CST_foot (blue) and CST_premotor (yellow). Underlying coronal, sagittal and axial gray scaled image is the FA map for one of the participants in the study in individual space. Abbreviations: ROI, region-of-interest; CST, corticospinal tract; FA, fractional anisotropy. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

A) ROIs used for probabilistic tractography of the corpus callosum (CC): Seed ROIs in the CC corresponding to areas connecting the primary motor (green) and premotor cortices (yellow), target ROIs in the primary motor cortex (green) and premotor cortex (yellow). B) Probabilistic tractography results of the CC_motor (green) and CC_premotor (yellow). Underlying coronal, sagittal and axial gray scaled image is the FA map for one of the participants in the study in individual space. Abbreviations: ROI, region-of-interest; CC, corpus callosum; FA, fractional anisotropy. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Segmentation of the corticospinal tract (CST) and the corpus callosum (CC) are shown in MNI template space in the first row. The graphs show fractional anisotropy (FA) (y-axis) in the contralateral CST to the dominant hand and CC slice-wise along the tracts (x-axis) in MNI template space for the VLBW group (solid lines) and the control group (dashed lines). Blue and green areas are volumes of interest indicating regions of the tracts with predominantly non-crossing and crossing fibres, respectively.

Fig. 4

TBSS analysis demonstrated significantly lower fractional anisotropy (red) and higher mean diffusivity (blue) in the VLBW group compared with the control group (p < 0.05, nonparametric permutation test, corrected for multiple comparisons, sex and age at MRI). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)