Regional Brain Development Research Articles

Abnormal prenatal brain development in Chiari II malformation.

The Chiari II is a relatively common birth defect that is associated with open spinal abnormalities and is characterized by caudal migration of the posterior fossa contents through the foramen magnum. The pathophysiology of Chiari II is not entirely known, and the neurobiological substrate beyond posterior fossa findings remains unexplored. We aimed to identify brain regions altered in Chiari II fetuses between 17 and 26 GW. We used in vivo structural T2-weighted MRIs of 31 fetuses (6 controls and 25 cases with Chiari II). The results of our study indicated altered development of diencephalon and proliferative zones (ventricular and subventricular zones) in fetuses with a Chiari II malformation compared to controls. Specifically, fetuses with Chiari II showed significantly smaller volumes of the diencephalon and significantly larger volumes of lateral ventricles and proliferative zones. We conclude that regional brain development should be taken into consideration when evaluating prenatal brain development in fetuses with Chiari II.

Longitudinal Associations between Peer and Family Relationships, Emotional Symptoms, and Regional Brain Volume across Adolescence

The period of adolescence brings with it a dynamic interaction between social context and behaviour, structural brain development, and anxiety and depressive symptoms. The rate of volumetric change in the ventromedial prefrontal cortex (vmPFC) and amygdala have been implicated in socioemotional development in adolescence; typically, there is thinning of grey matter volume (GMV) in the vmPFC and growth in the amygdala during this time. The directionality of the associations between social, emotional, and neuroanatomical factors has yet to be untangled, such as the degree to which social variables impact regional brain development, and vice versa. To add, the differences between sexes are still up for debate. In this study, longitudinal associations between peer problems, family support, socioeconomic stress, emotional symptoms, amygdala volume, and vmPFC GMV were investigated for both sexes using latent change score models. Data from a multi-site European study at baseline (mean (SD) age = 14.40 (0.38) years; % female = 53.19) and follow-up 2 (mean (SD) age = 18.90 (0.69) years, % female = 53.19) were used. Results revealed that peer problems did not predict emotional symptoms, rather they changed together over time. For males only, there was positive correlated change between vmPFC GMV, peer problems and emotional symptoms, indicating that slower vmPFC GMV thinning was associated with poorer social and emotional functioning. Additionally, greater family support at age 14 years was associated with slower growth of amygdala volume between ages 14 and 19 years for males; previous research has related slower amygdala growth to resilience to mental health disorders. The findings have extended understanding of mutual social, emotional and brain development, and avenues to protect mental health.

Early life adversity ablates sex differences in active versus passive threat responding in mice

Early life adversity (ELA) heightens the risk for anxiety disorders (which are characterized by heightened fear and avoidance behaviors), with females being twice as likely as males to develop pathology. Pavlovian fear conditioning tasks have been used to study possible mechanisms supporting endophenotypes of pathology. Identification of sex and ELA selective effects on the nature of behavioral responding in these paradigms may provide a unique window into coping strategies in response to learned fear to guide more mechanistic studies. The goals of this study were two-fold; First, to test if male and female mice employed different coping strategies in response to threat learning using different conditioning parameters (low, medium, and high intensity foot shocks). Second, to test if ELA in the form of limited bedding and nesting (LBN) altered the behavioral response of mice to conditioning. Mice received 6 tone/foot-shock pairings at one of three different foot-shock intensities (0.35 mA; 0.57 mA; 0.7 mA). Freezing, darting, and foot-shock reactivity were measured across trials. During conditioning, control-reared female mice exhibited significantly higher rates of darting behavior compared to control males at nearly all shock intensities tested. LBN rearing decreased the proportion of darting females to levels observed in males. Thus, ELA in the form of LBN significantly diminished the recruitment of active versus passive coping strategies in female mice but did not generally change male responding. Additional work will be required to understand the neural basis of these behavioral effects. Findings extending from this work have the potential to shed light on how ELA impacts trajectories of regional brain development with implications for sex-selective risk for behavioral endophenotypes associated with pathology and possibly symptom presentation.

AUTOMATIC SEGMENTATION OF INFANT BRAIN MRI USING SOFT COMPUTING TECHNIQUES

This article is concerned with exploration and diagnostic implementation of an effective neo-anatomical brain MRI classification method to classify primal cognitive development and investigate neuro-anatomical intellectual disability correlations. A crucial stage in the research as well as appraisal of the newborn brain growth is neonatal brain tissue classification. Owing to the major variations in anatomy and tissues among neonate and mature brains, the largest proportion of developing technology for the classification and segmentation of the adult brain really aren''''t sufficient for newborns brain. The existing brain tissue classification strategies for MRIs rely either on manual interactions or involve the use of atlases or models, which ultimately skew the findings from the population used to extract atlas. This article, focuses on atlas free soft computing approach to classify the neonatal brain tissue. Classification of brain tissue is the main process in which regional brain tissue examination is conducted. This helps the regional brain development to be characterized and the correspondence with therapeutic conditions to be studied. The modified BM3D approach is utilized for image enhancement along with 32 Gabor filter bank based feature extraction. The innovative aspect of this research is the multistage classification methodology, which produces higher dice coefficients and lower MHD values when compared to existing approaches.

Regional brain development in fetuses with Dandy-Walker malformation: A volumetric fetal brain magnetic resonance imaging study.

Dandy-Walker malformation (DWM) is a common prenatally diagnosed cerebellar malformation, characterized by cystic dilatation of the fourth ventricle, upward rotation of the hypoplastic vermis, and posterior fossa enlargement with torcular elevation. DWM is associated with a broad spectrum of neurodevelopmental abnormalities such as cognitive, motor, and behavioral impairments, which cannot be explained solely by cerebellar malformations. Notably, the pathogenesis of these symptoms remains poorly understood. This study investigated whether fetal structural developmental abnormalities in DWM extended beyond the posterior fossa to the cerebrum even in fetuses without apparent cerebral anomalies. Post-acquisition volumetric fetal magnetic resonance imaging (MRI) analysis was performed in 12 fetuses with DWM and 14 control fetuses. Growth trajectories of the volumes of the cortical plate, subcortical parenchyma, cerebellar hemispheres, and vermis between 18 and 33 weeks of gestation were compared. The median (interquartile range) gestational ages at the time of MRI were 22.4 (19.4–24.0) and 23.9 (20.6–29.2) weeks in the DWM and control groups, respectively (p = 0.269). Eight of the 12 fetuses with DWM presented with associated cerebral anomalies, including hydrocephalus (n = 3), cerebral ventriculomegaly (n = 3), and complete (n = 2) and partial (n = 2) agenesis of the corpus callosum (ACC); 7 presented with extracerebral abnormalities. Chromosomal abnormalities were detected by microarray analysis in 4 of 11 fetuses with DWM, using amniocentesis. Volumetric analysis revealed that the cortical plate was significantly larger in fetuses with DWM than in controls (p = 0.040). Even without ACC, the subcortical parenchyma, whole cerebrum, cerebellar hemispheres, and whole brain were significantly larger in fetuses with DWM (n = 8) than in controls (p = 0.004, 0.025, 0.033, and 0.026, respectively). In conclusion, volumetric fetal MRI analysis demonstrated that the development of DWM extends throughout the brain during the fetal period, even without apparent cerebral anomalies.

Structural abnormalities in paediatric moyamoya disease revealed by clinical magnetic resonance imaging, regionally distributed relative signal intensities and volumes.

Moyamoya disease (MMD) is a rare, progressive cerebrovascular disorder, with an unknown aetiology and pathogenesis. It is characterized by steno-occlusive changes at the terminal portion of the internal carotid artery (ICA), which is accompanied by variable development of the basal collaterals called moyamoya vessels. In this study, we investigate the potential for structural T1 magnetic resonance imaging (MRI) to help characterize MMD clinically, with the help of regionally distributed relative signal intensities (RRSIs) and volumes (RRVs). These RRSIs and RRVs provide the ability to characterize aspects of regional brain development and represent an extension to existing automated biomarker extraction technologies. This study included 269 MRI examinations from MMD patients and 993 MRI examinations from neurotypical controls, with regional biomarkers compared between groups with the area under the receiver operating characteristic curve (AUC). Results demonstrate abnormal presentation of RRSIs and RRVs in the insula (15- to 20-year old cohort, left AUC: 0.74, right AUC: 0.71) and the lateral orbitofrontal region (5- to 10-year old cohort, left AUC: 0.67; 15-20 year cohort, left AUC: 0.62, right AUC: 0.65). Results indicate that RRSIs and RRVs may help in characterizing brain development, assist in the assessment of the presentation of the brains of children with MMD and help overcome standardization challenges in multiprotocol clinical MRI. Further investigation of the potential for RRSIs and RRVs in clinical imaging is warranted and supported through the release of open-source software.

Male and Female, Prenatal Brain Development Differs in Response to the Maternal Omega 3 and 6 Nutritional Status

ObjectivesTo establish why prenatal brain growth in male fetuses responded to an omega-3-rich supplement but the females did not. MethodsIn a study of maternal lipid status during pregnancy in relation to regional fetal brain development a supplement containing long chain polyenoic fatty acids (300 mg of docosahexaenoic acid DHA, 42 mg eicosapentaenoic (EPA), 8.4 mg arachidonic and placebo 721 mg of oleic acid). Magnetic resonance images were obtained of newborn brains. Quantitative analysis of regions of the brain showed the supplement enhanced brain volume, with and without CSF, cortex, whole grey matter, and corpus callosum but only boys. ResultsWe wish to report correlations for arachidonic and stearic acids with several regions of brain growth in girls but not boys: for example, maternal RBC stearic acid at recruitment correlated with whole cortex (0.85 p < 0.0002), grey matter (0.847 p < 0.0002), corpus callosum (0.699 p < 0.008), whole brain (0.792 p < 0.001), brain plus CSF (0.733 p < 0.004, n = 13). Correlations with arachidonic acid at delivery reflected its index of arachidonic biomagnification and linoleic bioreduction. This measure of placental efficiency for arachidonic was for cortex (0.748 p < 0. 0034), deep grey matter (0.659 p < 0.014), whole grey matter (0.753 p < 0.003), hippocampus (0.611 p < 0.03), lentiform (0.774 p < 0.002), thalami (0.654 p < 0.015), corpus callosum (0.640 p < 0.018), brain (0.685 p < 0.0098), brain with CSF (0.774 p < 0.0019 n = 12). None were seen with the placebo boys (n = 22). Following embryogenesis, the placenta develops ahead of the demands of fetal growth. The fetal cardiovascular system is required to develop to support organogenesis and the brain growth thrust. The fetal immune system is required to help maintain pregnancy and for birth. All these systems are rich in arachidonic acid with little omega 3. The placenta biomagnifies arachidonic acid for the fetus: (typically maternal plasma lecithin 8.76% ± 1.49 CFD fetal cord 17.5% ± 3.22 p < 0.0001 (n = 44), whereas DHA in the same mothers was 4.13% ± 0.98 vs 5.79% ± 1.69 p < 0.0001. ConclusionsWe conclude that arachidonic acid is playing an as yet, unseen role, and female physiology is more focused on arachidonic acid to serve the basics of reproduction. Funding SourcesThe Mother and Child Foundation, Waterloo Foundation and the BORNE Charity.

Regional brain development analysis through registration using anisotropic similarity, a constrained affine transformation.

We propose a novel method to quantify brain growth in 3 arbitrary orthogonal directions of the brain or its sub-regions through linear registration. This is achieved by introducing a 9 degrees of freedom (dof) transformation called anisotropic similarity which is an affine transformation with constrained scaling directions along arbitrarily chosen orthogonal vectors. This gives the opportunity to extract scaling factors describing brain growth along those directions by registering a database of subjects onto a common reference. This information about directional growth brings insights that are not usually available in longitudinal volumetric analysis. The interest of this method is illustrated by studying the anisotropic regional and global brain development of 308 healthy subjects betwen 0 and 19 years old. A gender comparison of those scaling factors is also performed for four age-intervals. We demonstrate through these applications the stability of the method to the chosen reference and its ability to highlight growth differences accros regions and gender.

Plasma cholesterol levels and brain development in preterm newborns.

Objective:To assess whether postnatal plasma cholesterol levels are associated with microstructural and macrostrucural regional brain development in preterm newborns.Methods:Sixty preterm newborns (born 24-32 weeks gestational age) were assessed using MRI studies soon after birth and again at term-equivalent age. Blood samples were obtained within 7 days of each MRI scan to analyze for plasma cholesterol and lathosterol (a marker of endogenous cholesterol synthesis) levels. Outcomes were assessed at 3 years using the Bayley Scales of Infant Development, 3rd edition.Results:Early plasma lathosterol levels were associated with increased axial and radial diffusivity, and increased volume of the subcortical white matter. Early plasma cholesterol levels were associated with increased volume of the cerebellum. Early plasma lathosterol levels were associated with a 2-point decrease in motor scores at 3 years.Conclusions:Higher early endogenous cholesterol synthesis is associated with worse microstructural measures and larger volumes in the subcortical white matter which may signify regional edema, and worse motor outcomes. Higher early cholesterol is associated with improved cerebellar volumes. Further work is needed to better understand how the balance of cholesterol supply and endogenous synthesis impacts preterm brain development, especially if these may be modifiable factors to improve outcomes.

Physical activity and dentate gyrus volume in pediatric acquired demyelinating syndromes.

ObjectiveTo assess the association between daily moderate-to-vigorous physical activity (MVPA) and dentate gyrus volume (DGv) in pediatric patients with acquired demyelinating syndromes (ADSs) of the CNS.MethodsCross-sectional analysis of accelerometry (7 days) and research protocol MRI data from 12 pediatric MS and 18 children with monophasic ADS (monoADS). Total brain and DGv were quantified using standardized methods. The association of daily minutes of MVPA with normalized DGv (nDGv) was assessed using multivariable generalized linear models.ResultsMedian (interquartile range) MVPA was lower in MS patients [9.5 (14)] and exhibited less variation than in monoADS patients [24.5 (47)]. nDGv did not differ significantly between groups [mean nDGv (SD) [cm3]: MS 0.34 (0.1); monoADS 0.4 (0.1); p = 0.100]. In the monoADS group, every 1-minute increase in MVPA was associated with a 2.4-mm3 increase in nDGv (p = 0.0017), an association that was independent of age at incident demyelination, time from incident demyelination, sex, and brain white matter T2 lesion volume. No significant association was found between MVPA and nDGv (−2.6 mm3/min, p = 0.16) in the MS group.ConclusionsHigher MVPA associates with greater nDGv in children who have recovered from monophasic demyelination. Larger studies are required to determine whether MVPA can promote regional brain development, or limit tissue damage, in youth with MS.

Longitudinal Regional Brain Development and Clinical Risk Factors in Extremely Preterm Infants

To investigate third-trimester extrauterine brain growth and correlate this with clinical risk factors in the neonatal period, using serially acquired brain tissue volumes in a large, unselected cohort of extremely preterm born infants. Preterm infants (gestational age <28 weeks) underwent brain magnetic resonance imaging (MRI) at around 30 weeks postmenstrual age and again around term equivalent age. MRIs were segmented in 50 different regions covering the entire brain. Multivariable regression analysis was used to determine the influence of clinical variables on volumes at both scans, as well as on volumetric growth. MRIs at term equivalent age were available for 210 infants and serial data were available for 131 infants. Growth over these 10 weeks was greatest for the cerebellum, with an increase of 258%. Sex, birth weight z-score, and prolonged mechanical ventilation showed global effects on brain volumes on both scans. The effect of brain injury on ventricular size was already visible at 30 weeks, whereas growth data and volumes at term-equivalent age revealed the effect of brain injury on the cerebellum. This study provides data about third-trimester extrauterine volumetric brain growth in preterm infants. Both global and local effects of several common clinical risk factors were found to influence serial volumetric measurements, highlighting the vulnerability of the human brain, especially in the presence of brain injury, during this period.

Structural brain development between childhood and adulthood: Convergence across four longitudinal samples

Longitudinal studies including brain measures acquired through magnetic resonance imaging (MRI) have enabled population models of human brain development, crucial for our understanding of typical development as well as neurodevelopmental disorders. Brain development in the first two decades generally involves early cortical grey matter volume (CGMV) increases followed by decreases, and monotonic increases in cerebral white matter volume (CWMV). However, inconsistencies regarding the precise developmental trajectories call into question the comparability of samples. This issue can be addressed by conducting a comprehensive study across multiple datasets from diverse populations. Here, we present replicable models for gross structural brain development between childhood and adulthood (ages 8–30years) by repeating analyses in four separate longitudinal samples (391 participants; 852 scans). In addition, we address how accounting for global measures of cranial/brain size affect these developmental trajectories. First, we found evidence for continued development of both intracranial volume (ICV) and whole brain volume (WBV) through adolescence, albeit following distinct trajectories. Second, our results indicate that CGMV is at its highest in childhood, decreasing steadily through the second decade with deceleration in the third decade, while CWMV increases until mid-to-late adolescence before decelerating. Importantly, we show that accounting for cranial/brain size affects models of regional brain development, particularly with respect to sex differences. Our results increase confidence in our knowledge of the pattern of brain changes during adolescence, reduce concerns about discrepancies across samples, and suggest some best practices for statistical control of cranial volume and brain size in future studies.

Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study

Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study.

SY07-5AGE, SEX, DRINKING, AND THE ADOLESCENT BRAIN CORTEX: INITIAL FINDINGS FROM NATIONAL CONSORTIUM ON ALCOHOL &amp; NEURODEVELOPMENT IN ADOLESCENCE

The National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) is a longitudinal study, designed to track trajectories of regional brain development during a time of high risk for initiating alcohol consumption. We present baseline MRI 3T data from the five, U.S.A. participating sites on 674 adolescents (age 12-22) who met …

Estimating the age of healthy infants from quantitative myelin water fraction maps.

The trajectory of the developing brain is characterized by a sequence of complex, nonlinear patterns that occur at systematic stages of maturation. Although significant prior neuroimaging research has shed light on these patterns, the challenge of accurately characterizing brain maturation, and identifying areas of accelerated or delayed development, remains. Altered brain development, particularly during the earliest stages of life, is believed to be associated with many neurological and neuropsychiatric disorders. In this work, we develop a framework to construct voxel-wise estimates of brain age based on magnetic resonance imaging measures sensitive to myelin content. 198 myelin water fraction (VFM) maps were acquired from healthy male and female infants and toddlers, 3 to 48 months of age, and used to train a sigmoidal-based maturational model. The validity of the approach was then established by testing the model on 129 different VFM datasets. Results revealed the approach to have high accuracy, with a mean absolute percent error of 13% in males and 14% in females, and high predictive ability, with correlation coefficients between estimated and true ages of 0.945 in males and 0.94 in females. This work represents a new approach toward mapping brain maturity, and may provide a more faithful staging of brain maturation in infants beyond chronological or gestation-corrected age, allowing earlier identification of atypical regional brain development. Hum Brain Mapp 36:1233–1244, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

児童虐待が脳に及ぼす影響 : 脳科学と子どもの発達, 行動

児童虐待が脳に及ぼす影響 : 脳科学と子どもの発達, 行動

Longitudinal volumetric brain changes in autism spectrum disorder ages 6-35 years.

Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality magnetic resonance imaging [MRI] scans; mean inter-scan interval 2.7 years) compared to 56 typically developing controls (TDCs) (117 high-quality scans; mean inter-scan interval 2.6 years) from childhood into adulthood, for a total of 156 participants scanned over an 8-year period. This initial analysis includes between one and three high-quality scans per participant that have been processed and segmented to date, with 21% having one scan, 27% with two scans, and 52% with three scans in the ASD sample; corresponding percentages for the TDC sample are 30%, 30%, and 40%. The proportion of participants with multiple scans (79% of ASDs and 68% of TDCs) was high in comparison to that of large longitudinal neuroimaging studies of typical development. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Mean ventricular volume was increased in the ASD sample relative to the TDCs across the broad age range studied. Decreases in regional mean volumes in the ASD sample most often were due to decreases during late adolescence and adulthood. The growth curve of whole brain volume over time showed increased volumes in young children with autism, and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood.

Delayed Cortical Development in Fetuses with Complex Congenital Heart Disease

Neurologic impairment is a major complication of complex congenital heart disease (CHD). A growing body of evidence suggests that neurologic dysfunction may be present in a significant proportion of this high-risk population in the early newborn period prior to surgical interventions. We recently provided the first evidence that brain growth impairment in fetuses with complex CHD has its origins in utero. Here, we extend these observations by characterizing global and regional brain development in fetuses with hypoplastic left heart syndrome (HLHS), one of the most severe forms of CHD. Using advanced magnetic resonance imaging techniques, we compared in vivo brain growth in 18 fetuses with HLHS and 30 control fetuses from 25.4-37.0 weeks of gestation. Our findings demonstrate a progressive third trimester fall-off in cortical gray and white matter volumes (P < 0.001), and subcortical gray matter (P < 0.05) in fetuses with HLHS. Significant delays in cortical gyrification were also evident in HLHS fetuses (P < 0.001). In the HLHS fetus, local cortical folding delays were detected as early as 25 weeks in the frontal, parietal, calcarine, temporal, and collateral regions and appear to precede volumetric brain growth disturbances, which may be an early marker of elevated risk for third trimester brain growth failure.

Regional Cerebral Development at Term Relates to School-Age Social–Emotional Development in Very Preterm Children

Preterm children are at risk for social-emotional difficulties, including autism and attention-deficit/hyperactivity disorder. We assessed the relationship of regional brain development in preterm children, evaluated via magnetic resonance imaging (MRI) at term-equivalent postmenstrual age (TEA), to later social-emotional difficulties. MR images obtained at TEA from 184 very preterm infants (gestation <30 weeks or birth weight <1,250 g) were analyzed for white matter abnormalities, hippocampal volume, and brain metrics. A total of 111 infants underwent diffusion tensor imaging, which provided values for fractional anisotropy and apparent diffusion coefficient. Social-emotional development was assessed with the Infant Toddler Social and Emotional Assessment (ITSEA) at age 2 and the Strengths and Difficulties Questionnaire (SDQ) at age 5 years. Higher apparent diffusion coefficient in the right orbitofrontal cortex was associated with social-emotional problems at age 5 years (peer problems, p < .01). In females, smaller hippocampal volume was associated with increased hyperactivity (p < .01), peer problems (p < .05), and SDQ total score (p < .01). In males, a smaller frontal region was associated with poorer prosocial (p < .05) scores. Many of the hippocampal findings remained significant after adjusting for birthweight z score, intelligence, social risk, immaturity at birth, and parental mental health. These associations were present in children who had social-emotional problems in similar domains at age 2 and those who did not. Early alterations in regional cerebral development in very preterm infants relate to specific deficits in social-emotional performance by school-age. These results vary by gender. Our results provide further evidence for a neuroanatomical basis for behavioral challenges found in very preterm children.

Abnormal anterior cingulum integrity in first episode, early-onset schizophrenia: A diffusion tensor imaging study

Adolescents with early-onset schizophrenia (EOS) provide a unique opportunity to examine regional and disease-specific early abnormal brain development in schizophrenia. There is currently a general agreement that clinical symptoms and cognitive dysfunctions of schizophrenia may arise from a failure of adequate communication between different brain regions. This disturbed connectivity may be related to alterations in the numbers, distribution, and ultrastructural integrity of oligodendrocytes of white matter. Diffusion tensor imaging provides a relatively new approach for quantifying possible connectivity of white matter in vivo. In this study, thirty-eight adolescents with early-onset schizophrenia (EOS; onset of psychotic symptoms by age 18 years) and 38 age- and gender-matched healthy volunteers received diffusion tensor imaging examinations. Fractional anisotropy images were compared between groups in the white matter using a voxelwise analysis after inter-subject registration to standard Montreal Neurological Institute (MNI) space. Adolescents with EOS demonstrated significantly reduced fractional anisotropy in right anterior cingulum compared to healthy volunteers. Increased fractional anisotropy was not observed in any brain region in patients compared to controls. ROI analysis also reported a trend-level negative correlation between mean regional FA in right anterior cingulum and PANSS positive symptom score. These findings indicate that white matter abnormalities in the anterior cingulum are associated with adolescent EOS.