Heidi Furre Østgård

Executive function relates to surface area of frontal and temporal cortex in very-low-birth-weight late teenagers

BACKGROUND Being born with very low birth weight (VLBW; birth weight (BW) ≤1500 g) is associated with increased risk of maldevelopment of the immature brain which may affect neurological functioning. Deficits in attention and executive function problems have been reported in VLBW survivors compared with healthy subjects. AIMS The aim of this study was to evaluate attention and executive functions and to relate the clinical test results to cortical morphometry findings in VLBW young adults compared with term-born controls. STUDY DESIGN Prospective follow-up study of three year cohorts of VLBW and control children from birth to adulthood. OUTCOME MEASURES A comprehensive neuropsychological test battery was administered to 55 VLBW subjects born preterm (mean BW: 1217 g) and 81 term-born controls (mean BW: 3707 g) at age 19-20. Cerebral MRI was successfully obtained in 46 VLBW subjects and 61 controls. The FreeSurfer software package was applied for the cortical analyses based on T1-weighted MRI images. RESULTS The VLBW group obtained inferior scores on 15 of the 29 neuropsychological measures assessing attention and executive function and on both the attention and executive function domain scores. We found positive correlations between the executive function domain score and cortical surface area, especially in the antero-medial frontal and the temporal lobes of the brain in the VLBW group. CONCLUSION Young adults born with VLBW show deficits in attention and executive function compared with controls. The executive problems were related to smaller cortical surface area in brain regions known to be involved in higher order cognitive functioning.

Limited microstructural and connectivity deficits despite subcortical volume reductions in school-aged children born preterm with very low birth weight

Preterm birth and very low birth weight (VLBW, ≤1500 g) are worldwide problems that burden survivors with lifelong cognitive, psychological, and physical challenges. In this multimodal structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) study, we investigated differences in subcortical brain volumes and white matter tract properties in children born preterm with VLBW compared to term-born controls (mean age=8 years). Subcortical brain structure volumes and cortical thickness estimates were obtained, and fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were generated for 18 white matter tracts. We also assessed structural relationships between white matter tracts and cortical thickness of the tract endpoints. Compared to controls, the VLBW group had reduced volumes of thalamus, globus pallidus, corpus callosum, cerebral white matter, ventral diencephalon, and brain stem, while the ventricular system was larger in VLBW subjects, after controlling for age, sex, IQ, and estimated total intracranial volume. For the dMRI parameters, group differences were not significant at the whole-tract level, though pointwise analysis found shorter segments affected in forceps minor and left superior longitudinal fasciculus - temporal bundle. IQ did not correlate with subcortical volumes or dMRI measures in the VLBW group. While the deviations in subcortical volumes were substantial, there were few differences in dMRI measures between the two groups, which may reflect the influence of advances in perinatal care on white matter development.

Fetal growth, cognitive function, and brain volumes in childhood and adolescence.

OBJECTIVE: To evaluate the association between fetal growth pattern and cognitive function at 5 and 9 years and regional brain volumes at 15 years. METHODS: Eighty-three term-born small-for-gestational-age (SGA) neonates and 105 non-SGA neonates in a control group were available for follow-up. Based on serial fetal ultrasound measurements from gestational weeks 25–37, SGA neonates were classified with fetal growth restriction (n=13) or non–fetal growth restriction (n=36). Cognitive function was assessed at 5 and 9 years, and brain volumes were estimated with cerebral magnetic resonance imaging at 15 years. RESULTS: Small-for-gestational-age children had lower performance intelligence quotient at 5 years compared with those in a control group (107.3 compared with 112.5, P<.05). Although there were no differences between the SGA non–fetal growth restriction and control groups, the SGA fetal growth restriction group had significantly lower performance intelligence quotient at 5 years (103.5 compared with 112.5, P<.05) and 9 years (96.2 compared with 107.5, P<.05) compared with those in the control group. There were some brain volume differences at 15 years between SGA children and those in the control group, but after adjustment for total intracranial volume, age at examination, and sex, there were only significant differences between the SGA fetal growth restriction and control groups for thalamic (17.4 compared with 18.6 cm3, P<.01) and cerebellar white matter volumes (21.5 compared with 24.3 cm3, P<.01). CONCLUSION: Small-for-gestational-age children had lower intelligence quotient scores at 5 and 9 years and smaller brain volumes at 15 years compared with those in the control group, but these findings were only found in those with fetal growth restriction, indicating a possible relationship to decelerated fetal growth. LEVEL OF EVIDENCE: II

Brain Morphometry and Cognition in Young Adults Born Small for Gestational Age at Term

OBJECTIVES To examine brain volumes and cortical surface area and thickness and to relate these brain measures to cognitive function in young adults born small for gestational age (SGA) at term compared with non-SGA control patients. STUDY DESIGN This population-based follow-up study at age 20 years included 58 term-born SGA (birth weight <10th percentile, mean: 2915 g) and 81 non-SGA controls (birth weight ≥ 10th percentile, mean: 3707 g). Brain volumes and cortical surface area and thickness were investigated with magnetic resonance imaging, which was successfully obtained in 47 SGA patients and 61 control patients. Cognitive function was assessed using the Wechsler Adult Intelligence Scale, 3rd edition. A subgroup analysis was performed in the SGA group among subjects diagnosed with fetal growth restriction (FGR) based on repeated fetal ultrasound measurements. RESULTS The SGA group showed regional reductions in cortical surface area, particularly in the frontal, parietal, and temporal lobes. Total brain volume, cortical gray matter, cerebral white matter, and putamen volumes were reduced in the SGA group compared with control patients, but there were no differences in specific subcortical brain structure volumes when correcting for intracranial volume. Reductions were most pronounced among SGA subjects with FGR. No associations were found between brain measures and IQ measures in either group. CONCLUSION Young adults born SGA at term show a global reduction in brain volume as well as regional reductions in cortical surface area. We speculate whether these reductions may be confined to those exposed to FGR. None of the brain measures correlated with cognition.

Cortical morphometry and IQ in VLBW children without cerebral palsy born in 2003-2007.

Children born prematurely with very low birth weight (VLBW: bw ≤ 1500 g) have an increased risk of preterm perinatal brain injury, which may subsequently alter the maturation of the brain, including the cerebral cortex. The aim of study was to assess cortical thickness and surface area in VLBW children compared with term-born controls, and to investigate possible relationships between cortical morphology and Full IQ. In this cross-sectional study, 37 VLBW and 104 term children born between the years 2003–2007 were assessed cognitively at 5–10 years of age, using age appropriate Wechsler tests. The FreeSurfer software was used to obtain estimates of cortical thickness and surface area based on T1-weighted MRI images at 1.5 Tesla. The VLBW children had smaller cortical surface area bilaterally in the frontal, temporal, and parietal lobes. A thicker cortex in the frontal and occipital regions and a thinner cortex in posterior parietal areas were observed in the VLBW group. There were significant differences in Full IQ between groups (VLBW M = 98, SD = 9.71; controls M = 108, SD = 13.57; p < 0.001). There was a positive relationship between IQ and surface area in both groups, albeit significant only in the larger control group. In the VLBW group, reduced IQ was associated with frontal cortical thickening and temporo-parietal thinning. We conclude that cortical deviations are evident in childhood even in VLBW children born in 2003–2007 who have received state of the art medical treatment in the perinatal period and who did not present with focal brain injuries on neonatal ultrasonography. The cortical deviations were associated with reduced cognitive functioning.

Neuropsychological Deficits in Young Adults Born Small-for-Gestational Age (SGA) at Term

Reduced IQ, learning difficulties and poor school performance have been reported in small-for-gestational-age (SGA) subjects. However, few studies include a comprehensive neuropsychological assessment. Our aim was to study neuropsychological functioning in young adults born SGA at term. A comprehensive neuropsychological test battery was administered to 58 SGA subjects (birth weight <10th centile) born at term, and 81 term non-SGA controls (birth weight ≥10th centile). The SGA group obtained significantly (p < .01) lower scores on the attention, executive and memory domains compared to non-SGA controls and showed higher risk of obtaining scores below -1.5 SD on the memory domain (odds ratio = 13.3, 95% confidence interval: 1.57, 112.47). At a subtest level, the SGA group obtained lower scores on most neuropsychological tests, with significant differences on 6 of 46 measures: the Trail Making Test 3 (letter sequencing), the Wechsler Memory Scale mental control and the auditory immediate memory scale, the Design Fluency, the Stroop 3 (inhibition) and the Visual Motor Integration (VMI) motor coordination subtest. Young adults born SGA score more poorly on neuropsychological tests compared with non-SGA controls. Differences were modest, with more significant differences in the memory domain.

The Relationship between Adaptive Behavior and Cognitive Abilities (IQ) in Norwegian Children with Cerebral Palsy (CP): A Multi-Center Study

Results: VABS scores and full IQ scores were lower than in Typically Developing (TD) children. Children with left-sided unilateral CP had higher VABS scores within the communication domain (mean:87, SD:13) than right-sided unilateral CP (mean:72, SD:13, p=0.038), but this was not significant when adjusted for IQ. More than 80% of the CP children obtained scores lower than expected for TD children within daily living skills. In the group with normal IQ (Full IQ 85-115, n=30) 31% obtained scores as expected for age within daily life functioning.

O-058 Brain Morphometry In Young Adults Born Small-for-gestational-age At Term

Background/aims Being born small-for-gestational-age (SGA), a proxy for fetal growth restriction (FGR) has been related to poor school performance, lower academic achievement and cognitive problems. The aim of this study was to investigate whether young adults born SGA at term had reduced brain volumes, cortical surface area and/or cortical thickness, and whether brain morphometry measures were related to cognitive functioning. Methods In this population-based follow-up study at age 20, 58 term-born SGA (birthweight < 10 th centile, mean: 2915 g) and 81 non-SGA controls (birthweight >10 th centile, mean: 3707 g) were included. MRI-examinations at 1.5 T were obtained in 47 SGA and 61 control subjects. Image analysis was performed by the FreeSurfer, version 5.1. IQ was assessed by Wechsler Adult Intelligence Scale 3rd edition (WAIS-III). Results Total brain volume was smaller in the SGA than in the control group (-5.6%; p < 0.001). This reduction included most structures, but relative volumes were the same. Cortical surface area was significantly reduced in the SGA group compared with controls in multiple regions across the cerebral cortex, especially in the frontal, parietal and temporal lobes compared with controls (Figure). The reduction in surface area in the SGA group was most pronounced in the anterior cingulate gyri bilaterally. No associations were found between brain measures and IQ measures in either group. Conclusions Young adults born SGA at term have a global reduction in brain volume and regional reductions in cortical surface area. This may have long term consequences for cognitive functioning. Abstract O-058 Figure 1 Group differences in surface area change between SGA young adults and controls. The mapping of cortical surface area reduction in SGA young adults and controls is shown on the reconstructed cortical surface. Cortical areas with statistically significant difference between groups are shown in colour, and the colour scale shows the dynamic range of the statistically significant changes (in p-values), red to yellow reperesents an increasing expansion of the cortex in SGA group to fit the template, thus surface area reduction in these areas compared with controls. All significant clusters survived FDR correction at p < 0.05. No areas with surface area expansion (blue areas) were found in the SGA group compared with controls