Knut Jørgen Bjuland

Cortical thickness and cognition in very-low-birth-weight late teenagers

BACKGROUND Preterm born children with very low birth weight (VLBW: bw ≤ 1500 g) have an increased risk of perinatal brain injury which may influence the subsequent maturation of grey and white matter. Aberrant cortical development may have implications for future cognitive functioning. AIMS The aim of this study was to measure deviations in cortical thickness and to investigate the relationship between cortical thickness, perinatal variables and IQ measurements in VLBW late teenagers compared with term-born controls. STUDY DESIGN Prospective follow-up study of three year cohorts of children from birth to early adulthood. SUBJECT Forty-seven VLBW and 61 term born controls were examined at ages 18-21. OUTCOME MEASURES Cognitive function was assessed with the WAIS-III, measuring full IQ and IQ indices. We applied an automated method to reconstruct the cortical surface based on T1-weighted MRI images using the FreeSurfer software. RESULTS We found widespread areas of thinner cerebral cortex in the left parietal and temporal lobes and thicker cortex in frontal areas bilaterally in the VLBW group compared to controls. There were positive correlations between IQ and cortical thickness in areas in ventro-lateral frontal, parietal and temporal lobes in the VLBW group. The most pronounced cortical changes were seen in the VLBW subjects with the lowest birth weight and gestational age, and in those with IQ below 89. CONCLUSION Persistent cortical deviations seen in VLBW late teenagers are associated with immaturity at birth and level of cognitive functioning.

Follow-up at age 10 years in ELBW children — Functional outcome, brain morphology and results from motor assessments in infancy ☆ ☆☆

BACKGROUND Extremely-low-birth-weight (ELBW) children without severe brain injury or CP are at high risk of developing deficits within cognition, attention, behavior and motor function. Assessing the quality of an infants spontaneous motor-repertoire included in Prechtls General-Movement-Assessment (GMA) has been shown to relate to later motor and cognitive functioning in preterm children without CP. AIMS To investigate functional outcome and cerebral MRI morphometry at 10 years in ELBW children without CP compared to healthy controls and to examine any relationship with the quality of infant-motor-repertoire included in the GMA. STUDY DESIGN A cohort-study-design. SUBJECTS 31 ELBW children (mean birth-weight: 773 g, SD 146, mean gestational age 26.1 weeks, SD 1.8) and 33 term-born, age-matched controls. OUTCOME MEASURES GMA was performed in ELBW children at 3 months corrected age. At 10 years the children underwent comprehensive motor, cognitive, behavioral assessments and cerebral MRI. RESULTS The non-CP ELBW children had similar full-IQ but poorer working memory, poorer motor skills, and more attentional and behavioral problems compared to controls. On cerebral MRI reduced volumes of globus pallidus, cerebellar white matter and posterior corpus callosum were found. Cortical surface-area was reduced in temporal, parietal and anterior-medial-frontal areas. Poorer test-results and reduced brain volumes were mainly found in ELBW children with fidgety movements combined with abnormal motor-repertoire in infancy. CONCLUSION Non-CP ELBW children have poorer functional outcomes, reduced brain volumes and cortical surface-area compared with term-born controls at 10 years. ELBW children with abnormal infant motor-repertoire seem to be at increased risk of later functional deficits and brain pathology.

Memory function and hippocampal volumes in preterm born very-low-birth-weight (VLBW) young adults

The hippocampi are regarded as core structures for learning and memory functions, which is important for daily functioning and educational achievements. Previous studies have linked reduction in hippocampal volume to working memory problems in very low birth weight (VLBW; ≤ 1500 g) children and reduced general cognitive ability in VLBW adolescents. However, the relationship between memory function and hippocampal volume has not been described in VLBW subjects reaching adulthood. The aim of the study was to investigate memory function and hippocampal volume in VLBW young adults, both in relation to perinatal risk factors and compared to term born controls, and to look for structure-function relationships. Using Wechsler Memory Scale-III and MRI, we included 42 non-disabled VLBW and 61 control individuals at age 19-20 years, and related our findings to perinatal risk factors in the VLBW-group. The VLBW young adults achieved lower scores on several subtests of the Wechsler Memory Scale-III, resulting in lower results in the immediate memory indices (visual and auditory), the working memory index, and in the visual delayed and general memory delayed indices, but not in the auditory delayed and auditory recognition delayed indices. The VLBW group had smaller absolute and relative hippocampal volumes than the controls. In the VLBW group inferior memory function, especially for the working memory index, was related to smaller hippocampal volume, and both correlated with lower birth weight and more days in the neonatal intensive care unit (NICU). Our results may indicate a structural-functional relationship in the VLBW group due to aberrant hippocampal development and functioning after preterm birth.

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.

Cortical trajectories during adolescence in preterm born teenagers with very low birthweight.

While cross-sectional neuroimaging studies on cortical development predict reductions in cortical volume (surface area and thickness) during adolescence, this is the first study to undertake a longitudinal assessment of cortical surface area changes across the continuous cortical surface during this period. We studied the developmental dynamics of cortical surface area and thickness in adolescents and young adults (aged 15-20) born with very low birth weight (VLBW; <1500 g) as well as in term-born controls. Previous studies have demonstrated brain structural abnormalities in cortical morphology, as well as long-term motor, cognitive and behavioral impairments, in adolescents and young adults with VLBW, but the developmental dynamics throughout adolescence have not been fully explored. T1-weighted MRI scans from 51 VLBW (27 scanned twice) and 79 term-born adolescents (37 scanned twice) were used to reconstruct the cortical surface and produce longitudinal estimates of cortical surface area and cortical thickness. Linear mixed model analyses were performed, and the main effects of time and group, as well as time × group interaction effects, were investigated. In both groups, cortical surface area decreased up to 5% in some regions, and cortical thickness up to 8%, over the five-year period. The most affected regions were located on the lateral aspect of the hemispheres, in posterior temporal, parietal and to some extent frontal regions. There was no significant interaction between time and group for either morphometry variable. In conclusion, cortical thickness decreases from 15 to 20 years of age, in a similar fashion in the clinical and control groups. Moreover, we show for the first time that developmental trajectories of cortical surface area in preterm and term-born adolescents do not diverge during adolescence.

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.

Joint Analysis of Cortical Area and Thickness as a Replacement for the Analysis of the Volume of the Cerebral Cortex

Abstract Cortical surface area is an increasingly used brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided that images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on the joint analysis of thickness and area, we compare an improved, analytic method for measuring cortical volume to a permutation-based nonparametric combination (NPC) method. We use the methods to analyze area, thickness and volume in young adults born preterm with very low birth weight, and show that NPC analysis is a more sensitive option for studying joint effects on area and thickness, giving equal weight to variation in both of these 2 morphological features.

Joint analysis of area and thickness as a replacement for the analysis of cortical volume

A detailed investigation of the surface-based methods for assessment of cortical volume and area from magnetic resonance images shows that volume mostly mirrors variability in surface area, while having little sensitivity to cortical thickness, and this remains the case even when volume is assessed using an improved analytic method. Using data from young adults born with very low birth weight and coetaneous controls, it is demonstrated that the permutation-based non-parametric combination (NPC) of thickness and area is more sensitive than volume for studying joint effects on these two quantities, giving equal weight to variation in both. NPC can replace current analyses of cortical volume altogether, allowing a better characterisation of processes that can concomitantly influence brain anatomy, even when their effects are in opposite directions. The method is remarkably general and can be extended to other indices of brain structure and function.Cortical surface area is an increasingly popular brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on the joint analysis of thickness and area, we compare an improved, analytic method for measuring cortical volume to a permutation based non-parametric combination (npc) method. We analyze area, thickness and volume in young adults born preterm with very low birth weight, using both methods and show that npc analysis is a more sensitive option for studying joint effects on area and thickness, giving equal weight to variation in both of these two morphological features.