Perinatal brain growth and autistic traits in toddlers

Direct and indirect effects of fetal irradiation on cortical gray and white matter volume in the macaque

ObjectiveThis study aims to evaluate the neurodevelopmental outcomes in children with congenital heart disease (CHD) using magnetic resonance imaging (MRI), and to assess the role of brain volume metrics as predictors of neurodevelopmental abnormalities.MethodsIn this retrospective cohort study, 160 children with CHD treated at Children’s Hospital of Nanjing Medical University from January 2020 to December 2023 were analyzed. Patients were classified into normal (DQ ≥ 70, n=106) and abnormal neurodevelopment (DQ < 70, n=54) groups based on Developmental Quotient (DQ) scores. MRI scans were used to measure total brain volume, cortical gray matter, deep gray matter, white matter, and cerebrospinal fluid volumes. Neurodevelopmental assessments focused on adaptive behavior, motor skills, language, and personal-social behavior. ROC analysis was performed to determine the predictive value of brain volume metrics for neurodevelopmental abnormalities.ResultsTotal brain volume in the normal group (341.82 ± 10.43 mL) was significantly higher than in the abnormal group (323.92 ± 10.24 mL) (P < 0.05). Cortical gray matter volume in the normal group (131.47 ± 4.02 mL) was also significantly greater than in the abnormal group (121.63 ± 6.91 mL) (P < 0.05). No significant differences were observed in white matter, deep gray matter, or cerebrospinal fluid volumes. Children in the abnormal group scored significantly lower in all developmental domains (P < 0.05). ROC analysis showed that total brain volume (AUC = 0.968) and cortical gray matter volume (AUC = 0.936) were strong predictors of neurodevelopmental abnormalities (P < 0.001).ConclusionTotal brain volume and cortical gray matter volume, as measured by MRI, are effective predictors of neurodevelopmental abnormalities in children with CHD and can serve as valuable tools for early neurodevelopmental assessment.

Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity (WMH) volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging who were free of stroke and other neurologic disorders that might influence brain volumes and who were members of families with at least 2 Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60 were observed for total brain, WMH, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for WMH, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and WMH volumes. These data extend current knowledge by showing that these 2 different types of magnetic resonance imaging measures do not share underlying genetic or environmental influences.

Executive processes and frontal cortical regions supporting them show notable changes with age. Structural magnetic resonance imaging studies have revealed a positive relationship between cardiorespiratory fitness (CRF) and brain volume in several cortical regions and in the medial temporal lobe. However, previous studies have been mainly focused on cognitively intact subjects. Furthermore, no sex differences have been reported. PURPOSE: To investigate whether CRF is associated with total gray matter (GM) and white matter volumes as well as medial temporal lobe and striatum volumes in a population-based sample of subjects with increased risk of Alzheimer’s disease. We also examined the role of sex in the association of CRF with brain volumes. METHODS: We used baseline data from the FINGER study. Participants had elevated CAIDE Dementia Risk Score. Inclusion criteria was set to select persons with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. Our substudy included 68 randomly selected individuals (39 men and 29 women) with 61-75 years of age. Cardiorespiratory fitness was assessed as peak oxygen consumption (VO2peak, ml/kg/min) measured directly in a symptom-limited maximal exercise test on cycle ergometer. Structural imaging was performed using a 1.5-Tesla scanner. Volumetric segmentation was performed with the Freesurfer automated image analysis suite. All brain volumes were expressed as ratios after normalizing by the total intracranial volume. RESULTS: In whole group, VO2peak was associated with left caudate volume (β=0.32, p=0.03), cortical GM volume (β=0.37, p=0.01) and total GM volume (β=0.40, p=0.007). In men, VO2peak was associated with cortical GM volume (β=0.61, p=0.001) and total GM volume (β=0.59, p=0.001). In women, VO2peak was associated with the left caudate volume (β=0.49, p=0.04). Peak oxygen consumption accounted for 23 and 1 percent of total variance of cortical GM volume in men and women, respectively. Likewise, VO2peak accounted for 25 and 4 percent of total variance of total GM volume in men and women, respectively. CONCLUSION: Cardiorespiratory fitness is associated with cortical and total gray matter volumes in elderly men with increased risk for Alzheimer’s disease.

While postnatal dexamethasone (dex) therapy ameliorates bronchopulmonary dysplasia (BPD) in preterm infants, it also increases rates of neuromotor and cognitive abnormalities. In a study by Murphy et al, dex therapy...

BackgroundPrevious studies showed that there is a positive association between mothers’ and children’s autistic traits. We also tested if this association is more pronounced in mothers with a higher pre-pregnancy body mass index (BMI).MethodThe study was embedded in two cohorts with information available for 4,659 participants from the Generation R and for 179 participants from the Cambridge Ultrasound Siblings and Parents Project (CUSP) cohort. In both cohorts, maternal autistic traits were assessed using the short form of the Autism Spectrum Quotient, and information about maternal height and weight before pregnancy was obtained by questionnaire. Child autistic traits were assessed with the short form of Social Responsiveness Scale in Generation R (M = 13.5 years) and with the Quantitative Checklist for Autism in Toddlers (Q-CHAT) in the CUSP cohort (M = 1.6 years).ResultHigher maternal autistic traits were associated with higher autistic traits in toddlerhood (CUSP cohort; βadjusted = 0.20, p < 0.01), in early childhood (Generation R; βadjusted = 0.19, p < 0.01), and in early adolescence (Generation R; βadjusted = 0.16, p < 0.01). Furthermore, a higher maternal pre-pregnancy BMI was associated with higher child autistic traits, but only in Generation R (βadjusted = 0.03, p < 0.01). There was no significant moderating effect of maternal pre-pregnancy BMI on the association between autistic traits of mothers and children, neither in Generation R nor in CUSP. In addition, child autistic traits scores were significantly higher in mothers who were underweight and in mothers who were overweight compared to mothers with a healthy weight.ConclusionWe confirm the association between maternal and child autistic traits in toddlerhood, early childhood, and early adolescence. Potential interacting neurobiological processes remain to be confirmed.

Genetic Schizophrenia Risk Variants Jointly Modulate Total Brain and White Matter Volume

Despite evidence for a difference in total brain volume between dyslexic and good readers, no previous neuroimaging study examined differences in allometric scaling (i.e. differences in the relationship between regional and total brain volumes) between dyslexic and good readers. The present study aims to fill this gap by testing differences in allometric scaling and regionalbrain volume differences in dyslexic and good readers. Object-based morphometry analysis was used to determine grey and white matter volumes of the four lobes, the cerebellum and limbic structures in 130 dyslexic and 106 good readers aged 8-14years. Data were collected across three countries (France, Poland and Germany). Three methodological approaches were used as follows: principal component analysis (PCA), linear regression and multiple-group confirmatory factor analysis (MGCFA). Difference in total brain volume between good and dyslexic readers was Cohen's d=0.39. We found no difference in allometric scaling, nor in regional brain volume between dyslexic and good readers. Results of our three methodological approaches (PCA, linear regression and MGCFA) were consistent. This study provides evidence for total brain volume differences between dyslexic and control children, but no evidence for differences in the volumes of the four lobes, the cerebellum or limbic structures, once allometry is taken into account. It also finds no evidence for a difference in allometric relationships between the groups. We highlight the methodological interest of the MGCFA approach to investigate such research issues.

This study evaluated childhood brain volumes using voxel-based morphometry and examined their relationships with grey matter, white matter and total brain volume in children diagnosed with intellectual disability (ID) and healthy controls. Sixty children (age range 6-12 years) diagnosed with mild to moderate ID according to DSM-5 and 60 age- and sex-matched healthy controls (age range 6-12 years) were included in the study. Total brain volume (TBV), white matter volume (WMV) and grey matter volume (GMV) were automatically calculated from magnetic resonance images of all participants. Normality was assessed using the Shapiro-Wilk test, group differences were assessed using Welch t-tests and associations were assessed using multiple regression and logistic regression analyses. The Shapiro-Wilk test results indicated that many variables were not normally distributed (TBV: p < 0.001; GMV: p < 0.001). In group comparisons, no significant effect of gender on TBV, WMV and GMV was found (t-values ranged from -0.757 to -0.276, all p > 0.45). Age was a strong predictor of TBV (β = 7.25, 95% CI [3.07, 11.43], p < 0.001), and the regression model had high explanatory power (R2 = 0.977). Logistic regression analyses showed that WMV (OR = 0.82, 95% CI [0.73, 0.92], p = 0.001) and GMV (OR = 1.16, 95% CI [1.06, 1.26], p = 0.0012) significantly predicted diagnostic status. However, the very high odds ratios calculated for the WMVM variable (OR > 1063, p < 0.001) indicate a multicollinearity problem. The findings indicate that white and grey matter volumes may differ in children with MR compared to healthy controls, and these structures have potential as diagnostic biomarkers. The study demonstrates the developmental heterogeneity of the brain during childhood. However, the limited sample size, the presence of outliers and multicollinearity should be considered as limitations.

BackgroundStudies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children.Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old.FindingfT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores.ConclusionsThese preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.

BackgroundProlonged morphine treatment in infancy is associated with a high incidence of opioid tolerance and dependence, but our knowledge of the long-term consequences of this treatment is sparse. Using a rodent model, we examined the (1) short- and (2) long-term effects of prolonged morphine administration in infancy on body weight and brain volume, and (3) we evaluated if subsequent dosing in adulthood poses an increased brain vulnerability.MethodsNewborn rats received subcutaneous injections of either morphine or equal volume of saline twice daily for the first two weeks of life. In adulthood, animals received an additional two weeks of saline or morphine injections before undergoing structural brain MRI. After completion of treatment, structural T2-weigthed MRI images were acquired on a 7 T preclinical scanner (Bruker) using a RARE FSE sequence. Total and regional brain volumes were manually extracted from the MRI images using ITK-SNAP (v.3.6). Regions of interest included the brainstem, the cerebellum, as well as the forebrain and its components: the cerebral cortex, hippocampus, and deep gray matter (including basal ganglia, thalamus, hypothalamus, ventral tegmental area). Absolute (cm3) and normalized (as % total brain volume) values were compared using a one-way ANOVA with Tukey HSD post-hoc test.ResultsProlonged morphine administration in infancy was associated with lower body weight and globally smaller brain volumes, which was not different between the sexes. In adulthood, females had lower body weights than males, but no difference was observed in brain volumes between treatment groups. Our results are suggestive of no long-term effect of prolonged morphine treatment in infancy with respect to body weight and brain size in either sex. Interestingly, prolonged morphine administration in adulthood was associated with smaller brain volumes that differed by sex only in case of previous exposure to morphine in infancy. Specifically, we report significantly smaller total brain volume of female rats on account of decreased volumes of forebrain and cortex.ConclusionsOur study provides insight into the short- and long-term consequences of prolonged morphine administration in an infant rat model and suggests brain vulnerability to subsequent exposure in adulthood that might differ with sex.

Cognitive decline, related at least in part to reduced processing speed and lower working memory, is a major problem in paediatric and adult patients with sickle cell anaemia (SCA)1,2 and affects quality of life. Multiple studies investigating the association between quantitative and qualitative neuroimaging findings and cognition have had mixed results. Hence, the aetiology of cognitive decline in this population is not clearly understood. Cerebral atrophy on magnetic resonance imaging is noted in the literature but few studies have investigated the association between brain volumes and cognition. White matter microstructural integrity and white matter hyperintensities have been associated with reduced processing speed index (PSI).3 However no study has investigated the association between white matter volumes and PSI in the SCA population. Total subcortical volumes have also been noted to be lower in SCA children and adults. Only one study has investigated the association between total subcortical volumes and working memory index (WMI) in adults.4 Moreover, several studies in the past have noted age related decline in total brain volume as well neurodevelopmental delay in grey matter volume growth.5,6 Most of the developmental trajectory data in the literature comes from longitudinal data sets with limited samples and without control groups. Hence, for the purpose of this study, we investigated the association between regional brain volumes (white matter volumes and total subcortical volumes) and cognition (processing speed index and working memory index) in 129 SCA patients aged 8 – 64 years (66 male) and 50 controls (21 males). Participants were enrolled in two studies - the Sleep Asthma Cohort (SAC) and the Prevention of Morbidity in SCA (POMS) trial. We hypothesized that white matter volumes would predict processing speed index and total subcortical volumes would predict working memory index in SCA patients as well as controls. We also hypothesized that the developmental trajectories for regional brain volumes and cognitive variables would differ between patients and controls. Separate multiple linear regression models for males and females revealed that WMV predicted processing speed index(p=.019) and total subcortical volumes predicted working memory index (p=.025) in male patients only. Age (p=.003) and socioeconomic status (p=.03) also independently predicted PSI in male patients. Individual subcortical regions predicting WMI were statistically significant for left and right thalamus only in male patients. Haemoglobin and age emerged as the best predictors of cognitive decline in patients. Comparison of developmental trajectories between patients and controls revealed that only processing speed was significantly delayed at 8 years. The rate of development for all variables was lower in SCA patients and age-related decline was accelerated in patients as compared to controls. We speculate that early cerebral haemodynamic compromise may contribute to long term cognitive decline in patients. We also highlight that male SCA patients are particularly vulnerable to SCA disease severity. Hence, timely intervention to stabilise haemoglobin levels, especially in males, should be considered. Limitations include lack of stratification by SCI and age (adults and children separately) and the possibility that we were underpowered to detect effects in females.

Brain volumes and cerebrovascular lesions on MRI in patients with atherosclerotic disease. The SMART-MR study

This was a project in primary care for young children (1-2 years old). We tested a parent questionnaire on a tablet. This tablet questionnaire asked questions to see whether the child may have autism. We compared the paper and pencil version of the questionnaire to the tablet questionnaire. We read the medical charts for the children until they were 4 years old to see whether they ended up having autism. We found that doctors were more likely to recommend an autism evaluation when a parent used the tablet questionnaire. We think that the tablet's automatic scoring feature helped the doctors. We also think that the doctors benefited from the advice the tablet gave them.

ObjectiveTo quantify total and regional brain damage in subjects with cerebrotendinous xanthomatosis (CTX) using MR based quantitative measures.BackgroundCTX is a rare inherited disorder characterised by progressive neurological impairment. Appropriate therapy...