A Prospective Multi-Institutional Study Comparing the Brain Development in the Third Trimester between Opioid-Exposed and Nonexposed Fetuses Using Advanced Fetal MR Imaging Techniques.

BACKGROUND AND PURPOSE: While the adverse neurodevelopmental effects of prenatal opioid exposure on infants and children in the United States are well described, the underlying causative mechanisms have yet to be fully understood. This study aims to compare quantitative volumetric and surface-based features of the fetal brain between opioid-exposed fetuses and unexposed controls by using advanced MR imaging processing techniques. MATERIALS AND METHODS: This is a multi-institutional IRB-approved study in which pregnant women with and without opioid use during the current pregnancy were prospectively recruited to undergo fetal MR imaging. A total of 14 opioid-exposed (31.4 ± 2.3 weeks of gestation) and 15 unexposed (31.4 ± 2.4 weeks) fetuses were included. Whole brain volume, cortical plate volume, surface area, sulcal depth, mean curvature, and gyrification index were computed as quantitative features by using our fetal brain MR imaging processing pipeline. RESULTS: After correcting for gestational age, fetal sex, maternal education, polysubstance use, high blood pressure, and MR imaging acquisition site, all of the global morphologic features were significantly lower in the opioid-exposed fetuses compared with the unexposed fetuses, including brain volume, cortical volume, cortical surface area, sulcal depth, cortical mean curvature, and gyrification index. In regional analysis, the opioid-exposed fetuses showed significantly decreased surface area and sulcal depth in the bilateral Sylvian fissures, central sulci, parieto-occipital fissures, temporal cortices, and frontal cortices. CONCLUSIONS: In this small cohort, prenatal opioid exposure was associated with altered fetal brain development in the third trimester. This adds to the growing body of literature demonstrating that prenatal opioid exposure affects the developing brain.

Maternal Diet Quality during Pregnancy Is Associated with Neonatal Brain White Matter Development.

Maternal diet and nutrient intake are important for fetal growth and development. In this study, we aim to evaluate whether there are associations between maternal diet quality and the offspring's brain white matter development. Healthy pregnant women's (N = 44) nutrition intake was assessed by the Healthy Eating Index-2015 (HEI-2015) during the first, second, and third trimesters, respectively. Correlations between MRI diffusion tensor imaging measured fractional anisotropy (FA) of the neonatal brain and the HEI-2015 scores were evaluated using voxel-wise analysis with appropriate multiple comparisons correction and post hoc analysis based on regions of interest. Significant correlations were found between sodium scores at the first trimester of pregnancy and mean neonatal FA values in parietal white matter (R = 0.39, p = 0.01), anterior corona radiata (R = 0.43, p = 0.006), posterior limb of internal capsule (R = 0.53, p < 0.001), external capsule (R = 0.44, p = 0.004), and temporal white matter (R = 0.50, p = 0.001) of the left hemisphere. No other correlations were identified. In conclusion, the relationships between the maternal sodium intake score and the neonatal white matter microstructural development indicate sodium intake patterns better aligned with the Dietary Guidelines for Americans during early pregnancy are associated with greater white matter development in the offspring's brain.

Effects of short-term supervised exercise training on liver fat in adolescents with obesity: a randomized controlled trial.

OBJECTIVE: The objective of this study was to quantify the effects of a 4-week, supervised, high-intensity interval training (HIIT) on intrahepatic triglyceride content (IHTG, percentage), cardiorespiratory fitness (CRF), and cardiometabolic markers in adolescents with obesity. METHODS: A total of 40 adolescents (age 13-18 y, BMI 36.7 ± 5.8 kg/m2 ) at risk for metabolic dysfunction-associated steatotic liver disease (MASLD) based on obesity and elevated Fibroscan measured controlled attenuation parameter (CAP) scores were randomized to HIIT three times a week for 4 weeks (n = 34) or observation (control; n = 6). Liver magnetic resonance imaging proton-density fat-fraction (MRI-PDFF), CAP, oral glucose tolerance test, serum alanine aminotransferase, dual-energy x-ray absorptiometry, and CRF tests were performed before and after intervention. Within- and between-group differences were compared. RESULTS: A total of 13 (38%) and 4 (66%) children had MASLD by MRI-PDFF (IHTG ≥ 5%) in the HIIT and control groups, respectively. The implemented HIIT protocol had no impact on CRF or IHTG (baseline 5.26%, Δ = -0.31 percentage points, 95% CI: -0.77 to 0.15; p = 0.179), but it decreased the 2-h glucose concentration (baseline 116 mg/dL, Δ = -11 mg/dL; 95% CI: -17.6 to -5.5; p < 0.001). When limiting the analysis to participants with MASLD (n = 17), HIIT decreased IHTG (baseline 8.81%, Δ = -1.05 percentage points, 95% CI: -2.08 to -0.01; p = 0.048). Between-group comparisons were not different. CONCLUSIONS: The implemented exercise protocol did not reduce IHTG, but it led to modest improvement in markers of cardiometabolic health.

Associations between mother's depressive symptoms during pregnancy and newborn's brain functional connectivity.

Depression during pregnancy is common and the prevalence further increased during the COVID pandemic. Recent findings have shown potential impact of antenatal depression on children's neurodevelopment and behavior, but the underlying mechanisms are unclear. Nor is it clear whether mild depressive symptoms among pregnant women would impact the developing brain. In this study, 40 healthy pregnant women had their depressive symptoms evaluated by the Beck Depression Inventory-II at ~12, ~24, and ~36 weeks of pregnancy, and their healthy full-term newborns underwent a brain MRI without sedation including resting-state fMRI for evaluation of functional connectivity development. The relationships between functional connectivities and maternal Beck Depression Inventory-II scores were evaluated by Spearman's rank partial correlation tests using appropriate multiple comparison correction with newborn's gender and gestational age at birth controlled. Significant negative correlations were identified between neonatal brain functional connectivity and mother's Beck Depression Inventory-II scores in the third trimester, but not in the first or second trimester. Higher depressive symptoms during the third trimester of pregnancy were associated with lower neonatal brain functional connectivity in the frontal lobe and between frontal/temporal lobe and occipital lobe, indicating a potential impact of maternal depressive symptoms on offspring brain development, even in the absence of clinical depression.

MRI Findings in Third-Trimester Opioid-Exposed Fetuses, With Focus on Brain Measurements: A Prospective Multicenter Case-Control Study.

BACKGROUND. The opioid epidemic has profoundly affected infants born in the United States, as in utero opioid exposure increases the risk of cognitive and behavioral problems in childhood. Scarce literature has evaluated prenatal brain development in fetuses with opioid exposure in utero (hereafter opioid-exposed fetuses). OBJECTIVE. The purpose of this study is to compare opioid-exposed fetuses and fetuses without opioid exposure (hereafter unexposed fetuses) in terms of 2D biometric measurements of the brain and additional pregnancy-related assessments on fetal MRI. METHODS. This prospective case-control study included patients in the third trimester of pregnancy who underwent investigational fetal MRI at one of three U.S. academic medical centers from July 1, 2020, through December 31, 2021. Fetuses were classified as opioid exposed or unexposed in utero. Fourteen 2D biometric measurements of the fetal brain were manually assessed and used to derive four indexes. Measurements and indexes were compared between the two groups by use of multivariable linear regression models, which were adjusted for gestational age (GA), fetal sex, and nicotine exposure. Additional pregnancy-related findings on MRI were evaluated. RESULTS. The study included 65 women (mean age, 29.0 ± 5.5 [SD] years). A total of 28 fetuses (mean GA at the time of MRI, 32.2 ± 2.5 weeks) were opioid-exposed, and 37 fetuses (mean GA at the time of MRI, 31.9 ± 2.7 weeks) were unexposed. In the adjusted models, seven measurements were smaller (p < .05) in opioid-exposed fetuses than in unexposed fetuses: cerebral frontooccipital diameter (93.8 ± 7.4 vs 95.0 ± 8.6 mm), bone biparietal diameter (79.0 ± 6.0 vs 80.3 ± 7.1 mm), brain biparietal diameter (72.9 ± 7.7 vs 74.1 ± 8.6 mm), corpus callosum length (37.7 ± 4.0 vs 39.4 ± 3.7 mm), vermis height (18.2 ± 2.7 vs 18.8 ± 2.6 mm), anteroposterior pons measurement (11.6 ± 1.4 vs 12.1 ± 1.4 mm), and transverse cerebellar diameter (40.4 ± 5.1 vs 41.4 ± 6.0 mm). In addition, in the adjusted model, the frontoocccipital index was larger (p = .02) in opioid-exposed fetuses (0.04 ± 0.02) than in unexposed fetuses (0.04 ± 0.02). Remaining measures and indexes were not significantly different between the two groups (p > .05). Fetal motion, cervical length, and deepest vertical pocket of amniotic fluid were not significantly different (p > .05) between groups. Opioid-exposed fetuses, compared with unexposed fetuses, showed higher frequencies of both breech position (21% vs 3%, p = .03) and increased amniotic fluid volume (29% vs 8%, p = .04). CONCLUSION. Fetuses with opioid exposure in utero had a smaller brain size and altered fetal physiology. CLINICAL IMPACT. The findings provide insight into the impact of prenatal opioid exposure on fetal brain development.

Mother's physical activity during pregnancy and newborn's brain cortical development.

Background: Physical activity is known to improve mental health, and is regarded as safe and desirable for uncomplicated pregnancy. In this novel study, we aim to evaluate whether there are associations between maternal physical activity during pregnancy and neonatal brain cortical development. Methods: Forty-four mother/newborn dyads were included in this longitudinal study. Healthy pregnant women were recruited and their physical activity throughout pregnancy were documented using accelerometers worn for 3-7 days for each of the 6 time points at 4-10, ∼12, ∼18, ∼24, ∼30, and ∼36 weeks of pregnancy. Average daily total steps and daily total activity count as well as daily minutes spent in sedentary/light/moderate/vigorous activity modes were extracted from the accelerometers for each time point. At ∼2 weeks of postnatal age, their newborns underwent an MRI examination of the brain without sedation, and 3D T1-weighted brain structural images were post-processed by the iBEAT2.0 software utilizing advanced deep learning approaches. Cortical surface maps were reconstructed from the segmented brain images and parcellated to 34 regions in each brain hemisphere, and mean cortical thickness for each region was computed for partial correlation analyses with physical activity measures, with appropriate multiple comparison corrections and potential confounders controlled. Results: At 4-10 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left caudal middle frontal gyrus (rho = 0.48, P = 0.04), right medial orbital frontal gyrus (rho = 0.48, P = 0.04), and right transverse temporal gyrus (rho = 0.48, P = 0.04); mother's daily time in moderate activity mode positively correlated with newborn's cortical thickness in the right transverse temporal gyrus (rho = 0.53, P = 0.03). At ∼24 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left (rho = 0.56, P = 0.02) and right isthmus cingulate gyrus (rho = 0.50, P = 0.05). Conclusion: We identified significant relationships between physical activity in healthy pregnant women during the 1st and 2nd trimester and brain cortical development in newborns. Higher maternal physical activity level is associated with greater neonatal brain cortical thickness, presumably indicating better cortical development.

C-section increases cecal abundance of the archetypal bile acid and glucocorticoid modifying Lachnoclostridium [clostridium] scindens in mice.

In humans and animal models, Cesarean section (C-section) has been associated with alterations in the taxonomic structure of the gut microbiome. These changes in microbiota populations are hypothesized to impact immune, metabolic, and behavioral/neurologic systems and others. It is not clear if birth mode inherently changes the microbiome, or if C-section effects are context-specific and involve interactions with environmental and other factors. To address this and control for potential confounders, cecal microbiota from ~3 week old mice born by C-section (n = 16) versus natural birth (n = 23) were compared under matched conditions for housing, cross-fostering, diet, sex, and genetic strain. A total of 601 unique species were detected across all samples. Alpha diversity richness (i.e., how many species within sample; Chao1) and evenness/dominance (i.e., Shannon, Simpson, Inverse Simpson) metrics revealed no significant differences by birth mode. Beta diversity (i.e., differences between samples), as estimated with Bray-Curtis dissimilarities and Aitchison distances (using log[x + 1]-transformed counts), was also not significantly different (Permutational Multivariate ANOVA [PERMANOVA]). Only the abundance of Lachnoclostridium [Clostridium] scindens was found to differ using a combination of statistical methods (ALDEx2, DESeq2), being significantly higher in C-section mice. This microbe has been implicated in secondary bile acid production and regulation of glucocorticoid metabolism to androgens. From our results and the extant literature we conclude that C-section does not inherently lead to large-scale shifts in gut microbiota populations, but birth mode could modulate select bacteria in a context-specific manner: For example, involving factors associated with pre-, peri-, and postpartum environments, diet or host genetics.

Track-weighted imaging analysis of white matter microstructures in healthy children: Sex and hemispheric differences.

Structural substrates of sex differences in human function and behavior have been elucidated in previous studies. Diffusion weighted magnetic resonance imaging (DW-MRI) is a widely used non-invasive imaging technique in studying human brain white matter structural organization. While many DW-MRI studies reporting sex differences in WM structure are based on diffusion tensor imaging (DTI) measures, tract specific microstructural differences require further investigation. In this study, we aim to investigate sex differences and sex-specific hemispheric differences in white matter microstructural development in healthy 8-year-old children based on novel track weighted imaging (TWI) analysis. Average pathlength map (APM) is a TWI contrast in which the average length of fibers passing through a voxel is utilized. In this study, we employed tract specific APM measures to evaluate sex differences in WM microstructural development. A total of 37 WM tracts were analyzed including 7 commissural tracts, 9 bilateral association tracts and 6 bilateral projection tracts. APM maps were generated for each tract. Tract-wise group tests were done using the mean values of APM maps. Sex differences were tested using general linear model based group comparisons. Age and total brain volume were included as covariates in the group analysis. Sex specific hemispheric differences were performed for the 15 bilateral tracts. One sample t-tests were done independently for left>right and right>left cases and the APM measures were controlled for age and total cerebral hemispheric volume. P-values<0.05 were considered significant after correcting for multiple comparisons accounting for the total number of tracts. Significant sex differences were revealed in APM measures between boys and girls in 11 WM tracts including rostral body of corpus callosum (CC), left inferior fronto-occipital fasciculus (IFOF), right cingulum, bilateral first and second segments of superior longitudinal fasciculus (SLF), right middle longitudinal fasciculus (MLF), bilateral fronto-pontine (FPT) and right parieto-occipital pontine tracts (POPT). The sex differences showed higher APM values for these 11 tracts in boys as compared to that of girls. In hemispheric differences analysis for both boys and girls, 2 tracts, arcuate fasciculus and optic radiation showed higher APM in left tracts as compared right; 5 tracts, IFOF, MLF, third segment of SLF, FPT and superior thalamic radiation showed higher APM in right tracts as compared to left. This indicates that boys and girls possess similar lateral asymmetries in these 7 tracts. Additionally, anterior thalamic radiation (ATR) showed higher APM in left tract and 4 tracts, first segment of SLF, POPT, inferior longitudinal fasciculus and cortico-spinal tract showed higher APM in right for boys. In girls, second segment of SLF and uncinate fasciculus showed higher APM in right hemisphere. These results indicate different lateral asymmetries between boys and girls for 7 tracts. Overall, boys showed higher average fiber length in most of the tracts, even after controlling for total brain volume.

Circulating microRNAs Are Associated With Metabolic Markers in Adolescents With Hepatosteatosis.

Background: Altered hepatic microRNA (miRNA) expression may play a role in the development of insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). Circulating miRNAs could mirror the liver metabolism. Objective: This study aimed to assess the relationship between serum miRNA profile in children with obesity, IR, and NAFLD. Methods: Adolescents with obesity (n = 31) were stratified based on insulin resistance and NAFLD status. One-hundred seventy-nine miRNAs were determined in the serum by quantitative RT-PCR. Differentially expressed miRNAs were compared between groups, and log-transformed levels correlated with metabolic markers and intrahepatic triglyceride. Results: Serum miR-21-5p, -22-3p, -150-5p, and -155-5p levels were higher in children with IR and NAFLD, and their expression levels correlated with hepatic fat and serum triglyceride. In patients with NAFLD, miR-155-5p correlated with ALT (r = 0.68, p<0.01) and AST (r = 0.64, p<0.01) and miR-21-5p and -22-3p levels correlated with plasma adiponectin (r = -0.71 and r = -0.75, respectively, p<0.05) and fibroblast growth factor-21 (r = -0.73 and r = -0.89, respectively, p<0.01). miR-27-3a level was higher in children without IR and NAFLD. Conclusions: Several miRNAs are differentially expressed in children with IR and NAFLD. Determining their mechanistic roles may provide newer diagnostic tools and therapeutic targets for pediatric NAFLD.

Associations Between White Matter Microstructures and Cognitive Functioning in 8-Year-Old Children: A Track-Weighted Imaging Study.

PURPOSE: Quantitative tractography using diffusion-weighted magnetic resonance imaging data is widely used in characterizing white matter microstructure throughout childhood, but more studies are still needed to investigate comprehensive brain-behavior relationships between tract-specific white matter measures and multiple cognitive functions in children. METHODS: In this study, we analyzed diffusion-weighted MRI data of 71 healthy 8-year-old children utilizing white matter tract-specific quantitative measures derived from diffusion-weighted MRI tractography based on a novel track-weighted imaging approach. Track density imaging, average path length map and 4 track-weighted diffusion tensor imaging measures including: mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for 63 white matter tracts. The track-weighted imaging measures were then correlated with a comprehensive set of neuropsychological test scores in different cognitive domains including intelligence, language, memory, academic skills, and executive functions to identify tract-specific brain-behavior relationships. RESULTS: Significant correlations (P < .05, false discovery rate corrected; r = 0.27-0.57) were found in multiple white matter tracts, with a total of 40 correlations identified between various track-weighted imaging measures including average path length map, track-weighted imaging-fractional anisotropy, and neuropsychological test scores and subscales. Specifically, track-weighted imaging measures indicative of better white matter connectivity and/or microstructural development significantly correlated with higher IQ and better language abilities. CONCLUSION: Our findings demonstrate the ability of track-weighted imaging measures in establishing associations between white matter and cognitive functioning in healthy children and can serve as a reference for normal brain/cognition relationships in young school-age children and further aid in identifying imaging biomarkers predictive of adverse neurodevelopmental outcomes.

Neural correlates of sleep quality in children: Sex-specific associations shown by brain diffusion tractography.

BACKGROUND AND PURPOSE: Sleep quality is important for healthy growth and development of children. We aimed to identify associations between sleep disturbances in healthy children without clinical diagnosis of sleep disorders and brain white matter (WM) microstructure using an advanced diffusion-weighted magnetic resonance imaging (DW-MRI) based tractography analysis, and to explore whether there are sex differences in these associations. METHODS: Brain DW-MRI data were collected from sixty-two 8-year-old children (28 boys, 34 girls) whose parents also completed Children's Sleep Habits Questionnaire (CSHQ). Track-weighted imaging (TWI) measures were computed from the DW-MRI data for 37 WM tracts in each subject. Sex-specific partial correlation analyses were performed to evaluate correlations between TWI measures and a set of sleep disturbance scores derived from the CSHQ. RESULTS: Significant correlations (P < .05, FDR-corrected; r: .48-.67) were identified in 13 WM tracts between TWI and sleep disturbance scores. Sexually dimorphic differences in correlations between sleep disturbance scores and WM microstructure measurements were observed. Specifically, in boys, daytime sleepiness positively correlated with track-weighted mean or radial diffusivity in 10 WM tracts (bilateral arcuate fasciculus, left cingulum, right middle longitudinal fasciculus, and three bilateral segments of superior longitudinal fasciculus). In girls, total CSHQ score, night walking, or sleep onset delay negatively correlated with track-weighted fractional anisotropy or axial diffusivity in 4 WM tracts (bilateral inferior longitudinal fasciculus and uncinate fasciculus). CONCLUSIONS: The findings suggest that sleep disturbances without clinical diagnosis of sleep disorders are associated with lower WM microstructural integrity in children. Additionally, the associations possess unique patterns in boys and girls.

Associations between Cortical Asymmetry and Domain Specific Cognitive Functions in Healthy Children.

Cortical asymmetry and functional lateralization form intriguing and fundamental features of human brain organization, and is complicated by individual differences and evolvement with age. While many studies have investigated neuroanatomical differences between hemispheres as well as functional lateralization of the brain for different age groups, few have looked into the associations between cortical asymmetry and development of cognitive functions in children. In this study, we aimed to identify relationships between hemispheric asymmetry in brain cortex measured by MRI and cognitive development in healthy young children evaluated by a comprehensive battery of neuropsychological tests. Structural MRI data were obtained from 71 children in the age range of 7.5 to 8.5 years. Structural lateralization index (SLI), a reflection of the brain asymmetry, was computed for each of the 3 cortical morphometry measurements: cortical thickness, surface area and gray matter volume. A total of 34 bilateral regions were studied for the whole brain cortex as defined by the Desikan atlas. Region-wise SLI was correlated with domain specific cognitive scores using partial correlation analysis controlled for the potential confounding effects of age and sex. Significant correlations were identified between test scores of multiple cognitive domains and SLI of several cortical regions. Specifically, SLI of total surface area of precuneus and insula significantly correlated with measures of executive function behavior; significant relationships were also found between SLI of mean cortical thickness of superior parietal cortex and memory and language tests scores; in addition, SLI of parahippocampal gyrus also showed significant correlations with language test scores for all 3 morphometry features. These findings revealed regional hemispheric asymmetries that may be linked to specific cognitive abilities in children.Clinical relevance- This study shows associations between structural lateralization in different brain cortical regions and variations in specific cognitive functions in healthy children.

Fibroblast Growth Factor-21 to Adiponectin Ratio: A Potential Biomarker to Monitor Liver Fat in Children With Obesity.

Background: There is a pressing need for effective and non-invasive biomarkers to track intrahepatic triglyceride (IHTG) in children at-risk for non-alcoholic fatty liver disease (NAFLD), as standard-of-care reference tools, liver biopsy and magnetic resonance imaging (MRI), are impractical to monitor the course disease. Objective: We aimed to examine the association between serum fibroblast growth factor (FGF)-21 to adiponectin ratio (FAR) and IHTG as assessed by MRI in children with obesity. Methods: Serum FGF21 and adiponectin levels and IHTG were measured at two time points (baseline, 6 months) in obese children enrolled in a clinical weight loss program. The association between percent change in FAR and IHTG at final visit was examined using a multiple linear regression model. Results: At baseline, FAR was higher in the subjects with NAFLD (n = 23, 35.8 ± 41.9 pg/ng) than without NAFLD (n = 35, 19.8 ± 13.7 pg/ng; p = 0.042). Forty-eight subjects completed both visits and were divided into IHTG loss (≥1% reduction than baseline), no change (within ±1% change), and gain (≥1% increase than baseline) groups. At 6 months, the percent change in FAR was different among the three groups (p = 0.005). Multiple linear regression showed a positive relationship between percent change in FAR and the final liver fat percent in sex and pubertal stage-similar subjects with NAFLD at baseline (slope coefficient 6.18, 95% CI 1.90-10.47, P = 0.007), but not in those without NAFLD. Conclusions: Higher value in percent increase in FAR is positively associated with higher level of IHTG percent value at 6 months in children with baseline NAFLD. FAR could be a potential biomarker to monitor the changes in IHTG in children with NAFLD.

Cortical Morphometry is Associated with Neuropsychological Function in Healthy 8-Year-Old Children.

BACKGROUND AND PURPOSE: Cortical development is essential for children's neurocognition. In this study, we evaluated how variations in cortical morphometry in normal children are associated with outcome differences in multiple domains of cognition. METHODS: Eight-year-old children were recruited for a brain MRI followed by a battery of neuropsychological assessments. The MRI scan included 3D-T1-weighted imaging for cortical morphometry in 34 regions defined by the Desikan atlas. The neuropsychological assessments included the Reynolds Intellectual Assessment Scales (RIAS) for IQ, Clinical Evaluation of Language Fundamentals (CELF-4) for language, Children's Memory Scale (CMS) for memory, Wide Range Achievement Test (WRAT-4) for academic skills, and Behavior Rating Inventory of Executive Function (BRIEF) for executive functions. The relationships between MRI measured cortical features, including gray matter volume, surface area, and cortical thickness for different brain regions and neuropsychological test scores, were evaluated using partial correlation analyses controlled for age and sex. RESULTS: RIAS/CELF-4/CMS/WRAT-4/BRIEF scores showed significant correlations (R: [.38-.44], P: [.005-.046]) with gray matter volume, surface area, or cortical thickness in multiple brain regions. Gray matter volume in the medial orbitofrontal/ventromedial prefrontal cortex appeared to be a sensitive marker for overall neurocognition as it significantly correlated with IQ, language, memory, and executive function behaviors. The superior temporal gyrus and banks of superior temporal sulcus appeared to be most sensitive to reflect overall language function as their cortical features consistently correlated with language-related test scores. CONCLUSIONS: Cortical morphometry significantly correlated with neuropsychological function in healthy children; certain regions/features may serve as sensitive imaging markers.

Diffusion Tensor MRI of White Matter of Healthy Full-term Newborns: Relationship to Neurodevelopmental Outcomes.

Background It is well known that white matter injuries observed at birth are associated with adverse neurodevelopmental outcomes later in life. Whether white matter developmental variations in healthy newborns are also associated with changes in later neurodevelopment remains to be established. Purpose To evaluate whether developmental variations of white matter microstructures identified by MRI correlate with neurodevelopmental outcomes in healthy full-term infants. Materials and Methods In this prospective study, pregnant women were recruited and their healthy full-term newborns underwent a brain MRI including diffusion tensor imaging at approximately 2 weeks of age. These infants were tested at approximately 2 years of age with the Bayley Scales of Infant Development (BSID). Voxel-wise correlation analyses of fractional anisotropy (FA), measured with diffusion tensor MRI, and neurodevelopmental test scores, measured by using BSID, were performed by using tract-based spatial statistics (TBSS), followed by region-of-interest (ROI) analyses of correlations between mean FA in selected white matter ROIs and each BSID subscale score. Results Thirty-eight full-term infants (20 boys, 18 girls) underwent MRI examination at 2 weeks of age (14.3 days ± 1.6) and BSID measurement at 2 years of age (732 days ± 6). TBSS analyses showed widespread clusters in major white matter tracts, with positive correlations (P ≤ .05, corrected for the voxel-wise multiple comparisons) between FA values and multiple BSID subscale scores. These correlations were largely independent of several demographic parameters as well as family environment. Gestational age at birth appeared to be a confounding factor as TBSS-observed correlations weakened when it was included as a covariate; however, after controlling for gestational age at birth, ROI analyses still showed positive correlations (P ≤ .05, R = 0.35 to 0.48) between mean FA in many white matter ROIs and BSID cognitive, language, and motor scores. Conclusion There were significant associations between white matter microstructure developmental variations in healthy full-term newborns and their neurodevelopmental outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Hu and McAllister in this issue.

White Matter Microstructure Correlates with Memory Performance in Healthy Children: A Diffusion Tensor Imaging Study.

BACKGROUND AND PURPOSE: The complex function of memory has been linked to both brain gray and white matter (WM). WM abnormalities are associated with memory impairment in pathological conditions. We investigated whether variation in WM microstructure in healthy children also correlates with memory performance. METHODS: Sixty-five 7.5 to 8.5-year-old healthy children had a brain MRI scan using diffusion tensor imaging (DTI). They were also assessed for memory performance using the Children's Memory Scale (CMS). Eight indices that evaluate verbal and visual memory (immediate and delayed) were measured. DTI parameters reflecting WM microstructure, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), were calculated and correlated with memory indices. RESULTS: Tract-based spatial statistics analysis showed multiple WM tracts in which DTI parameters correlated with CMS indices. Specifically, FA (a reflection of WM integrity) and RD values (a reflection of myelination) in multiple projecting, association, and commissural WM tracts correlated with verbal delayed index (P < .05, corrected for voxel-wise multiple comparisons). Also, FA values in several WM tracts, including superior longitudinal fasciculus and posterior corona radiata, positively correlated with delayed recognition index (P < .05, corrected). Region of interest analyses showed similar correlations between FA/RD and CMS scores in WM regions involving these tracts and additionally in the cingulum, and detected additional MD-CMS correlations in several regions. CONCLUSIONS: Significant correlations between DTI parameter values and CMS indices in multiple WM tracts in healthy children indicate that neuroimaging can sensitively detect brain WM changes associated with variations of memory function, even for that in the normal range.

Brain activation to high-calorie food images in healthy normal weight and obese children: a fMRI study.

BACKGROUND: Understanding how normal weight and obese young children process high-calorie food stimuli may provide information relevant to the neurobiology of eating behavior contributing to childhood obesity. In this study, we used fMRI to evaluate whether brain activation to high-calorie food images differs between normal weight and obese young children. METHODS: Brain activation maps in response to high-calorie food images and non-food images for 22 healthy, 8-10-years-old children (N = 11/11 for normal weight/obese respectively) were generated and compared between groups. RESULTS: When comparing brain activation differences in response to viewing high-calorie food versus non-food images between normal weight and obese children, group differences were observed in areas related to memory and cognitive control. Specifically, normal weight children showed higher activation of posterior parahippocampal gyri (PPHG) and dorsomedial prefrontal cortex (DMPFC). Further ROI analyses indicated higher activation strength (Z scores) in the right PPHG (p = 0.01) and higher activation strength (p < 0.001) as well as a larger activation area (p = 0.02) in the DMPFC in normal weight than obese children. CONCLUSIONS: Normal weight and obese children process high-calorie food stimuli differently even from a young age. Normal weight children exhibit increased brain activation in regions associated with memory and cognitive control when viewing high-calorie food images.

Maternal Adiposity Influences Neonatal Brain Functional Connectivity.

The neural mechanisms associated with obesity have been extensively studied, but the impact of maternal obesity on fetal and neonatal brain development remains poorly understood. In this study of full-term neonates, we aimed to detect potential neonatal functional connectivity alterations associated with maternal adiposity, quantified via body-mass-index (BMI) and body-fat-mass (BFM) percentage, based on seed-based and graph theoretical analysis using resting-state fMRI data. Our results revealed significant neonatal functional connectivity alterations in all four functional domains that are implicated in adult obesity: sensory cue processing, reward processing, cognitive control, and motor control. Moreover, some of the detected areas showing regional functional connectivity alterations also showed global degree and efficiency differences. These findings provide important clues to the potential neural basis for cognitive and mental health development in offspring of obese mothers and may lead to the derivation of imaging-based biomarkers for the early identification of risks for timely intervention.

Maternal adiposity negatively influences infant brain white matter development.

OBJECTIVE: To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants. METHODS: Diffusion tensor imaging (DTI) was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age (AGA) infants from uncomplicated pregnancies of normal-weight (BMI < 25 at conception) or obese ( BMI = 30 at conception) and otherwise healthy mothers. Tract-based spatial statistics (TBSS) analyses were used for voxel-wise group comparison of fractional anisotropy (FA), a sensitive measure of white matter integrity. DNA methylation analyses of umbilical cord tissue focused on genes known to be important in CNS development were also performed. RESULTS: Newborns from obese women had significantly lower FA values in multiple white matter regions than those born of normal-weight mothers. Global and regional FA values negatively correlated (P < 0.05) with maternal fat mass percentage. Linear regression analysis followed by gene ontology enrichment showed that methylation status of 68 CpG sites representing 57 genes with GO terms related to CNS development was significantly associated with maternal adiposity status. CONCLUSIONS: These results suggest a negative association between maternal adiposity and white matter development in offspring.

Brain gray and white matter differences in healthy normal weight and obese children.

PURPOSE: To compare brain gray and white matter development in healthy normal weight and obese children. METHODS: Twenty-four healthy 8- to 10-year-old children whose body mass index was either <75(th) percentile (normal weight) or >95(th) percentile (obese) completed an MRI examination which included T1-weighted three-dimensional structural imaging and diffusion tensor imaging (DTI). Voxel-based morphometry was used to compare the regional gray and white matter between the normal weight and obese children, and tract-based spatial statistics was used to compare the water diffusion parameters in the white matter between groups. RESULTS: Compared with normal weight children, obese children had significant (P < 0.05, family wise error corrected) regional gray matter reduction in the right middle temporal gyrus, left and right thalami, left superior parietal gyrus, left pre/postcentral gyri, and left cerebellum. Obese children also had higher white matter (P < 0.05, corrected) in multiple regions in the brain and higher DTI measured fractional anisotropy (FA) values (P < 0.05, corrected) in part of the left brain association and projection fibers. There was no difference in mean diffusivity at P < 0.05, corrected. DTI eigenvalues suggested that the FA differences were likely from decreased radial diffusivity (P < 0.1, corrected) and there was no change in axial diffusivity (corrected P > 0.35 for all voxels). CONCLUSION: Our results indicated that obese but otherwise healthy children have different regional gray and white matter development in the brain and differences in white matter microstructures compared with healthy normal weight children.