Cortical thinning in young adolescents born preterm with very low birth weight
Tsung-Han Wu1, Tzu-chao Chuang1, Ming-Ting Wu2,3, and Pinchen Yang4

1Electrical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan, 2School of Medicine, National Yang-Ming University, Taipei, Taiwan, 3Radiology, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan, 4Psychiatry, Kaohsiung Medical University and Kaohsiung Medical University Hospital, Kaohsiung, Taiwan


By using a surface-based method (FreeSurfer), the cortical thickness measurement was performed on young adolescents born preterm with very low birth weight (n = 15, birth weight < 1500 g) and age-matched term born controls (n = 17). The preterms, who present no brain injuries, showed a thicker cortex in parietal, occipital, and temporal regions compared to the controls, suggesting the delay of cortical thinning.


Preterm born neonates with very low birth weight (VLBW, birth weight < 1500g) have a high risk of brain injury, and the encephalopathy of prematurity could influence the process of cortical maturation during childhood and affect brain function. To investigate the abnormality of gray matter, the cerebral cortical thickness is considered as an important biomarker of neuroanatomical development. The growth pattern of healthy children, which could vary at different cortical regions, is generally composed of an initial increase that reaches to the peak at around 8 to 10 years, followed by a decrease due to pruning of inefficient synaptic connection. 1 In comparison with age-matched controls, both regional cortical thinning and thickening in preterms have been reported in several MRI-based studies, 2-6 and diverse results are found at different scan ages. For example, regions with thinner cortex is more prominent in preterm born teenagers with VLBW 2-3 while a thicker cortex is found at more regions in school-aged children. 4-6 Also, the presence of focal brain injury, such as periventricular leukomalacia and intraventricular hemorrhage, may lead to a distinct pattern of cortical thickness. 4 To our knowledge, previous investigations in preterm born adolescents did not exclude those preterms with brain injuries. 2-3 Therefore, the aim of this study is to explore the cortical development by comparing the cortical thickness between young adolescents born preterm with VLBW and age-matched controls.


The MPRAGE sequence (TE/TR = 2.07/2000 ms, TI = 900 ms, flip angle = 9°, FOV = 256 mm, voxel size = 1mm3) is performed on a 3-T scanner (Magnetom Skyra, Siemens, Erlangen, Germany) to obtain three-dimensional T1-weighted MRI of 15 young adolescents born preterm (mean age = 12.8 years, SD = 1.4, five females) and 17 term born controls (mean age = 13.8 years, SD = 1.7, six females). Neither periventricular leukomalacia nor neonatal cerebral lesion was found in the preterm group. The cortical thickness is estimated by using a fully-automated surface-based method 7 (FreeSurfer software package, version 5.3.0), which is one of the most widely used techniques at its field. 2, 4-6 In brief, this method reconstructs the white matter surface (white matter-gray matter interface) and the pial surface (gray matter-CSF interface) by a topological mesh model, and the cortical thickness is calcualted as the average of the distance from a given point on gray/white boundary to the closest point on pial surface and from that point back to the closest point on white matter surface again. All values of cortical thickness can be mapped the inflated cortex, and the global or regional statistics of thickness can be computed. To reduce noise-induced error in segmentation and registration, a Gaussian kernel with a full width at half maximum of 30 mm is used for smoothing. Unpaired two-sample t-test is used for group comparison between preterms and controls. A two-tailed p value less than 0.05 is considered statistically significant.


The pretem group shows significantly thicker cortex at parietal (post central gyrus, superior parietal lobule, and precuneus), temporal (superior temporal gyrus), and occipital lobes (lateral occipital cortex) compared to the normal control (Figure 1, Table 1). No region indicates that the preterm group has thinner cortical thickness than control. In addition, no significant difference is found on global thickness between groups.


Previous studies examing cortical thickness in school-aged children with no 6 or possibly mild 5 brain injuries report a thicker cortex at frontal, occipital, and parietal regions and a thinner cortex at a more limited area in preterm born subjects. Besides, age is found correlated negatively with global and regional cortical thickness in preterms, but not in controls, suggesting the delay of cortical thinning in children born preterm. 5 In this study, data were acquired at early adolescence when the growth of cortical thickness has already reached its peak and pruning is taking place in healthy term born subjects. As a result, our finding of a thicker cortex in preterms is consistent with the hypothesis of delayed maturation, 5, 6 yet the possibility of permenant cortical change can not be ruled out. The main limitation of this study is the small number of participants, limiting the statistical power. Further longitudinal investigation is required to provide more insight of cortical maturation in preterm born survivors.


This work was funded by Ministry of Science and Technology at Taiwan (MOST 104-2221-E-110-039).


1. Shaw P, Kabani NJ, Lerch JP, et al. Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci. 2008; 28(14): 3586-3594.

2. Martinussen M, Fischl B, Larsson HB, et al. Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method. Brain. 2005; 128(Pt 11): 2588-2596.

3. Nagy Z, Lagercrantz H, Hutton C. Effects of preterm birth on cortical thickness measured in adolescence. Cereb Cortex. 2011; 21(2): 300-306.

4. Zubiaurre-Elorza L, Soria-Pastor S, Junque C, et al. Cortical Thickness and Behavior Abnormalities in Children Born Preterm. PLoS One. 2012; 7(7): e42148.

5. Murner-Lavanchy I, Steinlin M, Nelle M, et al. Delay of cortical thinning in very preterm born children. Early Hum Dev. 2014; 90(9): 443-450.

6. Sølsnes AE, Grunewaldt KH, Bjuland KJ, et al. Cortical morphometry and IQ in VLBW children without cerebral palsy born in 2003-2007. Neuroimage Clin. 2015; 8: 193-201.

7. Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc. Natl. Acad. Sci. U. S. A. 2000; 97 (20), 11050–11055.


Figure 1 Significant differences in cortical thickness between young adolescents born preterm with VLBW and controls are shown on the inflated brain. Dark to light blue indicates a thicker cortex in the preterm group.

Table 1 Anatomical regions with significant differences in mean cortical thickness in unit of mm. In comparison with controls, thicker cortex is found at all five regions in preterms. The difference in percentage ranges from 4.5% to 6.5%.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)