Altered frontal‐parietal functioning during verbal working memory in children and adolescents with heavy prenatal alcohol exposure

This study evaluated the neural basis of verbal working memory (WM) function in a group of 20 children and adolescents with fetal alcohol spectrum disorders (FASDs) and 20 typically developing comparison participants using functional magnetic resonance imaging (fMRI). Both groups showed prominent activation in the frontal‐parietal‐cerebellar network known to be important for verbal WM. Despite equivalent behavioral performance between groups, alcohol‐exposed individuals showed increased activation relative to typically developing individuals in left dorsal frontal and left inferior parietal cortices, and bilateral posterior temporal regions during verbal WM. These effects remained even when group differences on IQ were statistically controlled. This pattern of increased activation coupled with equivalent behavioral performance between groups suggests that individuals with FASD recruit a more extensive network of brain regions during verbal WM relative to typically developing individuals. These findings may suggest that frontal‐parietal processing during verbal WM is less efficient in alcohol‐exposed individuals. Hum Brain Mapp 2009. © 2009 Wiley‐Liss, Inc.     

Trajectories of brain white matter development in young children with prenatal alcohol exposure

Prenatal alcohol exposure (PAE) is associated with alterations to brain white matter microstructure. Previous studies of PAE have demonstrated different findings in young children compared to older children and adolescents, suggesting altered developmental trajectories and highlighting the need for longitudinal research. 122 datasets in 54 children with PAE (27 males) and 196 datasets in 89 children without PAE (45 males) were included in this analysis. Children underwent diffusion tensor imaging between 2 and 8 years of age, returning approximately every 6 months. Mean fractional anisotropy (FA) and mean diffusivity (MD) were obtained for 10 major brain white matter tracts and examined for age‐related changes using linear mixed effects models with age, sex, group (PAE vs. control) and an age‐by‐group interaction. Children with PAE had slower decreases of MD over time in the genu of the corpus callosum, inferior fronto‐occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. No significant age‐by‐group interactions were noted for FA. These findings show slower white matter development in young children with PAE than in unexposed controls. This connects previous cross‐sectional findings of lower MD in young children with PAE to findings of higher MD in older children and adolescents with PAE, and further helps to understand brain development in children with PAE. This deviation from typical development trajectories may reflect altered brain plasticity, which has implications for cognitive and behavioral learning in children with PAE.     

Sensorimotor network alterations in children and youth with prenatal alcohol exposure

Children with prenatal alcohol exposure (PAE) often have impaired sensorimotor function. While altered brain structure has been noted in sensorimotor areas, the functional brain alterations remain unclear. This study aims to investigate sensorimotor brain networks in children and youth with PAE using resting‐state functional magnetic resonance imaging (rs‐fMRI). A parcellation‐based network analysis was performed to identify brain networks related to hand/lower limb and face/upper limb function in 59 children and youth with PAE and 50 typically developing controls. Participants with PAE and controls had similar organization of the hand and face areas within the primary sensorimotor cortex, but participants with PAE had altered functional connectivity (FC) between the sensorimotor regions and the rest of the brain. The sensorimotor regions in the PAE group showed less connectivity to certain hubs of the default mode network and more connectivity to areas of the salience network. Overall, our results show that despite similar patterns of organization in the sensorimotor network, subjects with PAE have increased FC between this network and other brain areas, perhaps suggesting overcompensation. These alterations in the sensorimotor network lay the foundation for future studies to evaluate interventions and treatments to improve motor function in children with PAE.     

Volume changes and brain‐behavior relationships in white matter and subcortical gray matter in children with prenatal alcohol exposure

Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1–15.9 years) each received two structural magnetic resonance scans, ～2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC‐IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group‐by‐age interactions and group‐score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group‐score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain‐behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE. Hum Brain Mapp 36:2318–2329, 2015. © 2015 Wiley Periodicals, Inc.     

Preserved cortical asymmetry despite thinner cortex in children and adolescents with prenatal alcohol exposure and associated conditions

Prenatal alcohol exposure (PAE) is associated with reduced overall brain volume. Although this has been reported consistently across studies, the status of cortical thickness after PAE is more variable. The cortex is asymmetric in typical controls, but it is unclear whether the left and right counter parts of the cortical gray matter are unevenly influenced in postpartum brain development after PAE. Brain MRI was acquired in a newly recruited sample of 157 participants (PAE: N = 78, 5.5–18.9 years, 40 females and controls: N = 79, 5.8–18.5 years, 44 females) across four Canadian sites in the NeuroDevNet project. The PAE group had other confounds such as psychiatric co‐morbidity, different living environment, and so on, not present in the control group. In agreement with previous studies, the volumes of all brain structures were reduced in PAE compared to controls, including gray and white matter of cerebrum and cerebellum, and all deep gray matter including the hippocampus, amygdala, thalamus, caudate, putamen, and pallidum. The PAE group showed reductions in global and regional cortical thickness, while the pattern and degree of cortical thickness asymmetry were preserved in PAE participants with the greatest rightward asymmetry in the lateral parietal lobe and the greatest leftward asymmetry in the lateral frontal cortex. This persistent asymmetry reflects that the homologous left and right cortical regions followed typical relative developmental patterns in the PAE group despite being thinner bilaterally than controls. Hum Brain Mapp 39:72–88, 2018. © 2017 Wiley Periodicals, Inc.     

White matter deficits mediate effects of prenatal alcohol exposure on cognitive development in childhood

Fetal alcohol spectrum disorders comprise the spectrum of cognitive, behavioral, and neurological impairments caused by prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) was performed on 54 children (age 10.1 ± 1.0 years) from the Cape Town Longitudinal Cohort, for whom detailed drinking histories obtained during pregnancy are available: 26 with full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 15 nonsyndromal heavily exposed (HE), and 13 controls. Using voxelwise analyses, children with FAS/PFAS showed significantly lower fractional anisotropy (FA) in four white matter (WM) regions and higher mean diffusivity (MD) in seven; three regions of FA and MD differences (left inferior longitudinal fasciculus (ILF), splenium, and isthmus) overlapped, and the fourth FA cluster was located in the same WM bundle (right ILF) as an MD cluster. HE children showed lower FA and higher MD in a subset of these regions. Significant correlations were observed between three continuous alcohol measures and DTI values at cluster peaks, indicating that WM damage in several regions is dose dependent. Lower FA in the regions of interest was attributable primarily to increased radial diffusivity rather than decreased axonal diffusivity, suggesting poorer axon packing density and/or myelination. Multiple regression models indicated that this cortical WM impairment partially mediated adverse effects of PAE on information processing speed and eyeblink conditioning. Hum Brain Mapp 37:2943–2958, 2016. © 2016 Wiley Periodicals, Inc .     

Binge‐like postnatal alcohol exposure triggers cortical gliogenesis in adolescent rats

The long‐term effects of binge‐like postnatal alcohol exposure on cell proliferation and differentiation in the adolescent rat neocortex were examined. Unlike the hippocampal dentate gyrus, where proliferation of progenitors results primarily in addition of granule cells in adulthood, the vast majority of newly generated cells in the intact mature rodent neocortex appear to be glial cells. The current study examined cytogenesis in the motor cortex of adolescent and adult rats that were exposed to 5.25 g/kg/day of alcohol on postnatal days (PD) 4–9 in a binge manner. Cytogenesis was examined at PD50 (through bromodeoxyuridine [BrdU] labeling) and survival of these newly generated cells was evaluated at PD80. At PD50, significantly more BrdU‐positive cells were present in the motor cortex of alcohol‐exposed rats than controls. Confocal analysis revealed that the majority (>60%) of these labeled cells also expressed NG2 chondroitin sulfate proteoglycan (NG2 glia). Additionally, survival of these newly generated cortical cells was affected by neonatal alcohol exposure, based on the greater reduction in the number of BrdU‐labeled cells from PD50 to PD80 in the alcohol‐exposed animals compared to controls. These findings demonstrate that neonatal alcohol exposure triggers an increase in gliogenesis in the adult motor cortex. J. Comp. Neurol. 514:259–271, 2009. © 2009 Wiley‐Liss, Inc.     

Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task

OBJECTIVES: Several lines of evidence suggest that deficits in cognition persist in bipolar patients during periods of euthymia. Working memory impairment has been observed in euthymic bipolar patients and noted to be a significant source of functional deficits in psychiatric disorders. Functional changes associated with these cognitive deficits however, remain poorly understood. We hypothesized that patients with bipolar disorder would demonstrate changes in neuronal activation in specific regions forming part of the working memory network. METHODS: Fifteen euthymic bipolar patients and fifteen age- and gender-matched healthy controls were recruited. Subjects participated in fMRI scans during which a two-back working memory task alternated with a zero-back control/attention task using a block-design paradigm. Groups were analyzed separately, and intergroup comparisons were made using an exploratory, voxel-by-voxel analysis. RESULTS: Bipolar patients performed more poorly on the cognitive tasks than did healthy controls (F = 3.77, p = 0.04). After covarying for task performance and reaction time, bipolar patients demonstrated significantly greater activation than healthy subjects in several regions including the fronto-polar prefrontal cortex, temporal cortex, basal ganglia, thalamus, and posterior parietal cortex. No areas showed a significant decrease in activation, compared with healthy controls. CONCLUSIONS: Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.     

The association between parental attributions of misbehavior and parenting practices in caregivers raising children with prenatal alcohol exposure: A mixed-methods study

Background and aimsLimited research has focused on parenting practices used by caregivers raising children with fetal alcohol spectrum disorders (FASD). The current study hypothesized that parental attributions of children’s misbehavior would relate to the parenting strategies caregivers utilize with children with FASD. This study also aimed to develop a coding scheme to allow quantification of these treatment-relevant constructs in future intervention trials.MethodsThirty-one caregivers of children with FASD (age 4–8) were interviewed with the Parenting Practices Interview (PPI), a study-developed qualitative interview. Quantitative measures of FASD knowledge, parenting sense of competence and stress, and child behavior problems were included. Mixed-method analyses assessed the relationship between parental attributions of misbehavior and parenting practices.ResultsCaregivers who attributed their child’s misbehavior to underlying neurodevelopmental disabilities were more likely to use antecedent strategies and feel more confident in managing their child’s behavior. Parents who attributed their child’s misbehavior to willful disobedience were more likely to rely on consequence strategies and feel more ineffective.ConclusionsResults are consistent with theoretical models for FASD parent training interventions. Assessment of theorized mechanisms of change in intervention trials is needed; the development of the PPI and quantitative coding system will facilitate this type of research.     

Lasting changes induced by mild alcohol exposure during embryonic development in BDNF,NCAM and synaptophysin‐positive neurons quantified in adult zebrafish

Fetal alcohol spectrum disorder is one of the leading causes of mental health issues worldwide. Analysis of zebrafish exposed to alcohol during embryonic development confirmed that even low concentrations of alcohol for a short period of time may have lasting behavioral consequences at the adult or old age. The mechanism of this alteration has not been studied. Here, we immersed zebrafish embryos into 1% alcohol solution (vol/vol%) at 24 hr post‐fertilization (hpf) for 2 hr and analyzed potential changes using immunohistochemistry. We measured the number of BDNF (brain‐derived neurotrophic factor) and NCAM (neuronal cell adhesion molecule)‐positive neurons and the intensity of synaptophysin staining in eight brain regions: lateral zone of the dorsal telencephalic area, medial zone of the dorsal telencephalic area, dorsal nucleus of the ventral telencephalic area, ventral nucleus of the ventral telencephalic area, parvocellular preoptic nucleus, ventral habenular nucleus, corpus cerebella and inferior reticular formation. We found embryonic alcohol exposure to significantly reduce the number of BDNF‐ and NCAM‐positive cells in all brain areas studied as compared to control. We also found alcohol to significantly reduce the intensity of synaptophysin staining in all brain areas except the cerebellum and preoptic area. These neuroanatomical changes correlated with previously demonstrated reduction of social behavior in embryonic alcohol‐exposed zebrafish, raising the possibility of a causal link. Given the evolutionary conservation across fish and mammals, we emphasize the implication of our current study for human health: even small amount of alcohol consumption may be unsafe during pregnancy.     

Impaired cerebellar learning in children with prenatal alcohol exposure: a comparative study of eyeblink conditioning in children with ADHD and dyslexia

Neuroanatomical and behavioral evidence indicate that the cerebellum is particularly vulnerable to the toxic effects of prenatal alcohol exposure. Recent research has shown impairments in eyeblink conditioning in rats following binge-like neonatal ethanol exposure. The neural substrates of eyeblink conditioning have been localized to the cerebellum and related brainstem mechanisms. The present study considered whether heavy prenatal alcohol exposure would result in similar impairments in eyeblink conditioning in children. A related purpose was to determine if eyeblink conditioning could discriminate between children with prenatal alcohol exposure and children diagnosed with attention deficit hyperactive disorder or developmental dyslexia. Fifty-three age-matched children [10 prenatal alcohol exposure (FAE), 16 attention deficit hyperactive disordered (ADHD), 14 children with dyslexia (DYS), 13 normal controls] were assessed on eyeblink conditioning in the delay paradigm. Children in the FAE and DYS groups failed to learn the conditioned response, producing longer latencies and poorly timed responses to the conditioning stimulus. Children with ADHD were impaired on measures of adaptively timed responses, although conditioned responses matched normal controls. The results suggest that children prenatally exposed to alcohol have deficits in cerebellar processing similar to those with dyslexia, and that these functional deficits are related to disabilities in learning.     

Longitudinal MRI reveals impaired cortical thinning in children and adolescents prenatally exposed to alcohol

Brain imaging studies suggest that cortical thickness decreases during childhood and adolescence, in concert with underlying structural and synaptic changes required for cognitive maturation and regional specialization of function. Abnormalities of this protracted developmental process may provide key insights into the cognitive and behavioral deficits that emerge in individuals with fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cortical thickness differences in children and adolescents who were prenatally exposed to alcohol, though all have been cross sectional, limiting conclusions about cortical development with age. In this study, we analyze serially collected T₁‐weighted MRI from 11 children with FASD and 21 controls, scanned twice each ～2 to 4 years apart. Mixed‐models analysis of cortical thickness measurements revealed age‐by‐group interactions in cortical thinning, with FASD participants undergoing less developmental thinning than controls across many regions of the cortex, particularly in medial frontal and parietal areas. These results provide further longitudinal evidence in humans that prenatal alcohol exposure is associated with altered patterns of brain development that persist during childhood and adolescence. Hum Brain Mapp 35:4892–4903, 2014. © 2014 Wiley Periodicals, Inc .     

Functional connectivity of the attention networks is altered and relates to neuropsychological outcomes in children with prenatal alcohol exposure

Cognitive and functional brain alterations can occur in children with prenatal alcohol exposure (PAE). We examined the functional connectivity (FC) among regions within and between attention networks, and whether inter- and intranetwork FC moderated cognition in children with PAE (n = 37; age 12.8 ± 2.8 years) and nonexposed controls (n = 40; age 13.2 ± 2.8 years). Participants completed standardized attention and executive functioning tasks and resting state functional MRI. Inter- and intra-network FC and graph-theoretical metrics were calculated among attention network regions. Relative to controls, PAE was associated with reduced FC between the left temporoparietal junction and left ventral frontal cortex and anterior insula/frontal operculum (aI/fO), and between the left intraparietal sulcus and bilateral aI/fO. PAE was associated with increased FC between the right precuneus and intraparietal lobes, the right anterior prefrontal cortex and left ventral frontal cortex and aI/fO, and the left thalamus and dorsal frontal cortex. Graph-theoretical metrics did not differ by group. FC predicted cognitive performance, negatively in the children with PAE and positively in controls. Increased intra-network together with reduced internetwork FC suggests inefficient network specialization and impaired long-range FC among attention network regions after PAE. Results further suggest that those alterations may underlie attention and executive dysfunction in children with PAE.     

Localized reductions in resting‐state functional connectivity in children with prenatal alcohol exposure

Fetal alcohol spectrum disorders (FASD) are characterized by impairment in cognitive function that may or may not be accompanied by craniofacial anomalies, microcephaly, and/or growth retardation. Resting‐state functional MRI (rs‐fMRI), which examines the low‐frequency component of the blood oxygen level dependent (BOLD) signal in the absence of an explicit task, provides an efficient and powerful mechanism for studying functional brain networks even in low‐functioning and young subjects. Studies using independent component analysis (ICA) have identified a set of resting‐state networks (RSNs) that have been linked to distinct domains of cognitive and perceptual function, which are believed to reflect the intrinsic functional architecture of the brain. This study is the first to examine resting‐state functional connectivity within these RSNs in FASD. Rs‐fMRI scans were performed on 38 children with FASD (19 with either full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 nonsyndromal heavily exposed (HE)), and 19 controls, mean age 11.3 ± 0.9 years, from the Cape Town Longitudinal Cohort. Nine resting‐state networks were generated by ICA. Voxelwise group comparison between a combined FAS/PFAS group and controls revealed localized dose‐dependent functional connectivity reductions in five regions in separate networks: anterior default mode, salience, ventral and dorsal attention, and R executive control. The former three also showed lower connectivity in the HE group. Gray matter connectivity deficits in four of the five networks appear to be related to deficits in white matter tracts that provide intra‐RSN connections. Hum Brain Mapp 38:5217–5233, 2017. © 2017 Wiley Periodicals, Inc.     

Brain connectivity during verbal working memory in children and adolescents

Working memory (WkM) is a fundamental cognitive process that serves as a building block for higher order cognitive functions. While studies have shown that children and adolescents utilize similar brain regions during verbal WkM, there have been few studies that evaluate the developmental differences in brain connectivity. Our goal was to study the development of brain connectivity related to verbal WkM in typically developing children and adolescents. Thirty‐five healthy children and adolescents, divided into three groups: 9–12 (children), 13–16 (young adolescents), and 17–19 (older adolescents) years, were included in this functional magnetic resonance imaging (fMRI) study. The verbal WkM task involved a modified Sternberg item recognition paradigm using three different loads. Brain connectivity analysis was performed using independent component analyses and regressing the components with the design matrix to determine task‐related networks. Connectivity analyses resulted in four components associated solely with encoding, four solely with recognition and two with both. Two networks demonstrated age‐related differences with respect to load, (1) the left motor area and right cerebellum, and 2) the left prefrontal cortex, left parietal lobe, and right cerebellum. Post hoc analyses revealed that the first network showed significant effects of age between children and the two older groups. There was increasing connectivity with increasing load for adolescents. The second network demonstrated age‐related differences between children and older adolescents. Children have higher task‐related connectivity at lower loads, but they tend to equalize with the adolescents with higher loads. Finally, a non‐load related network involving the orbital frontal and anterior cingulate cortices showed less connectivity in children. Hum Brain Mapp 35:698–711, 2014. © 2012 Wiley Periodicals, Inc.     

Visuospatial working memory in children and adolescents with 22q11.2 deletion syndrome; an fMRI study

22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with a microdeletion of chromosome 22q11. In addition to high rates of neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder, children with 22q11DS have a specific neuropsychological profile with particular deficits in visuospatial and working memory. However, the neurobiological substrate underlying these deficits is poorly understood. We investigated brain function during a visuospatial working memory (SWM) task in eight children with 22q11DS and 13 healthy controls, using fMRI. Both groups showed task-related activation in dorsolateral prefrontal cortex (DLPFC) and bilateral parietal association cortices. Controls activated parietal and occipital regions significantly more than those with 22q11DS but there was no significant between-group difference in DLPFC. In addition, while controls had a significant age-related increase in the activation of posterior brain regions and an age-related decrease in anterior regions, the 22q11DS children showed the opposite pattern. Genetically determined differences in the development of specific brain systems may underpin the cognitive deficits in 22q11DS, and may contribute to the later development of neuropsychiatric disorders.     

Diffusion tensor imaging of white matter and correlates to eye movement control and psychometric testing in children with prenatal alcohol exposure

Prenatal alcohol exposure (PAE) can cause central nervous system dysfunction and widespread structural anomalies as detected by magnetic resonance imaging (MRI). This study focused on diffusion tensor imaging (DTI) of white matter in a large sample of PAE participants that allowed us to examine correlations with behavioral outcomes. Participants were confirmed PAE (n = 69, mean age = 12.5 ± 3.2 years) or typically developing control children (n = 67, mean age = 12.1 ± 3.2 years) who underwent brain MRI, eye movement tasks, and psychometric tests. A semi‐automated tractography method extracted fractional anisotropy (FA) and mean diffusivity (MD) values from 15 white matter tracts. The PAE group displayed decreased FA compared with controls in multiple tracts including 3 corpus callosum regions, right corticospinal tract, and 3 left hemisphere tracts connecting to the frontal lobe (cingulum, uncinate fasciculus, and superior longitudinal fasciculus). Significant group by sex interactions were found for the genu, left superior longitudinal fasciculus, and the left uncinate, with females in the PAE group exhibiting lower FA compared with control females. Correlations were found between DTI and eye movement measures in the control group, but these same relationships were absent in the PAE group. In contrast, no correlations were found between DTI and any of the psychometric tests used in this study. These findings support the hypothesis that measures of eye movement control may be valuable functional biomarkers of the brain injury induced by PAE as these tasks reveal group differences that appear to be linked to deficits in white matter integrity in the brain. Hum Brain Mapp 38:444–456, 2017. © 2016 Wiley Periodicals, Inc.     

White matter microstructure in fetal alcohol spectrum disorders: A systematic review of diffusion tensor imaging studies

Diffusion tensor imaging (DTI) has revolutionized our understanding of the neural underpinnings of alcohol teratogenesis. This technique can detect alterations in white matter in neurodevelopmental disorders, such as fetal alcohol spectrum disorder (FASD). Using Prisma guidelines, we identified 23 DTI studies conducted on individuals with prenatal alcohol exposure (PAE). These studies confirm the widespread nature of brain damage in PAE by reporting diffusivity alterations in commissural, association, and projection fibers; and in relation to increasing cognitive impairment. Reduced integrity in terms of lower fractional anisotropy (FA) and higher mean diffusivity (MD) and radial diffusivity (RD) is reported more consistently in the corpus callosum, cerebellar peduncles, cingulum, and longitudinal fasciculi connecting frontal and temporoparietal regions. Although these interesting results provide insight into FASD neuropathology, it is important to investigate the clinical diversity of this disorder for better treatment options and prediction of progression. The aim of this review is to provide a summary of different patterns of neural structure between PAE and typically developed individuals. We further discuss the association of alterations in diffusivity with demographic features and symptomatology of PAE. With the accumulated knowledge of the neural correlates of FASD presenting symptoms, a comprehensive understanding of the heterogeneity in FASD will potentially improve the disease management and will highlight the diagnostic challenges and potential areas of future research avenues, where neural markers may be beneficial.     

Different brain profiles in children with prenatal alcohol exposure with or without early adverse exposures

Prenatal alcohol exposure (PAE) can alter brain development and impact mental health outcomes, and often occurs in conjunction with postnatal adversity (e.g., maltreatment). However, it is unclear how postnatal adverse exposures may moderate mental health and brain outcomes in children with PAE. T1‐weighted and diffusion magnetic resonance imaging were obtained from 66 participants aged 7–16 years. Twenty‐one participants had PAE and adverse postnatal exposures (PAE+), 12 had PAE without adverse postnatal exposures (PAE?), and 33 were age‐ and gender‐matched controls unexposed to either prenatal alcohol or postnatal adversity. Internalizing and externalizing mental health symptoms were assessed using the Behavioral Assessment System for Children II, Parent‐Rating Scale. ANCOVAs were used to compare mental health symptoms, limbic and prefrontal cortical volumes, and diffusion parameters of cortico‐limbic white matter tracts between groups, and to assess brain‐mental health relationships. Both PAE groups had worse externalizing behavior (higher scores) than controls. The PAE? group had lower fractional anisotropy (FA) in the bilateral cingulum and left uncinate fasciculus, and smaller volumes in the left anterior cingulate cortex than controls and the PAE+ group. The PAE? group also had higher mean diffusivity (MD) in the left uncinate than the PAE+ group, and smaller right anterior cingulate and superior frontal gyrus volumes than controls. These findings show different brain structure and mental health symptom profiles in children with PAE with and without postnatal adversity, highlighting the need to consider adverse postnatal exposures in individuals with PAE.     

A DTI‐based tractography study of effects on brain structure associated with prenatal alcohol exposure in newborns

Prenatal alcohol exposure (PAE) is known to have severe, long‐term consequences for brain and behavioral development already detectable in infancy and childhood. Resulting features of fetal alcohol spectrum disorders include cognitive and behavioral effects, as well as facial anomalies and growth deficits. Diffusion tensor imaging (DTI) and tractography were used to analyze white matter (WM) development in 11 newborns (age since conception <45 weeks) whose mothers were recruited during pregnancy. Comparisons were made with nine age‐matched controls born to abstainers or light drinkers from the same Cape Coloured (mixed ancestry) community near Cape Town, South Africa. DTI parameters, T1 relaxation time, proton density and volumes were used to quantify and investigate group differences in WM in the newborn brains. Probabilistic tractography was used to estimate and to delineate similar tract locations among the subjects for transcallosal pathways, cortico‐spinal projection fibers, and cortico‐cortical association fibers. In each of these WM networks, the axial diffusivity was the parameter that showed the strongest association with maternal drinking. The strongest relations were observed in medial and inferior WM, regions in which the myelination process typically begins. In contrast to studies of older individuals with PAE, fractional anisotropy did not exhibit a consistent and significant relation with alcohol exposure. To our knowledge, this is the first DTI‐tractography study of prenatally alcohol exposed newborns. Hum Brain Mapp, 36:170–186, 2015. © 2014 Wiley Periodicals, Inc.