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Although prenatal alcohol exposure causes craniofacial anomalies, growth retardation, neurological abnormalities, cognitive impairment, and birth defects, fetal alcohol spectrum disorder is underdiagnosed. Global prevalence of fetal alcohol spectrum disorder is 0·77%, with a higher prevalence of 2-5% in Europe and North America, highlighting the need for increased diagnosis and treatment. However, diagnosis remains challenging because of the poor reliability of self-reported maternal drinking histories, an absence of sensitive biomarkers, and the infrequency of diagnostic dysmorphic facial features among individuals with fetal alcohol spectrum disorder. Different diagnostic systems and disagreements over criteria have slowed progress in the diagnosis and management of the disorder. Neuroimaging shows abnormalities in brain structure, cortical development, white matter microstructure, and functional connectivity in individuals with fetal alcohol spectrum disorder. These abnormalities modify developmental trajectories and are associated with deficits in cognition, executive function, memory, vision, hearing, motor skills, behaviour, and social adaptation. Promising trials of nutritional interventions and cognitive rehabilitation therapies are underway, with the aim of treating cognitive deficits in fetal alcohol spectrum disorders. [ABSTRACT FROM AUTHOR]

Ragan, A.N. and Wozniak, J.R., 2019. Linking hydrologic connectivity in salt marsh ponds to fish assemblages across a heterogenous coastal habitat. Journal of Coastal Research, 35(3), 545–558. Coconut Creek (Florida), ISSN 0749-0208. In estuarine systems, inundation regime plays a vital role in shaping the physical and chemical characteristics of salt marsh ponds. Along the Texas Gulf Coast, salt marsh ponds are scattered across the coastal marsh landscape, with each pond possessing a varying degree of hydrological connectivity to adjacent estuarine waters. The timing, frequency, and magnitude of connection events can directly influence both the abiotic and biotic components of the ponds. To determine how the degree of hydrological connectivity impacts these systems, discriminant function analysis (DFA) was used to test the ability of environmental variables (e.g., pond size, vegetation, soil type, water column salinity, pH, dissolved oxygen, etc.), fish presence–absence data, and fish relative abundances to predict the level of connectivity of a subset of ponds. In addition, canonical correspondence analysis (CCA) was used to determine whether fish assemblage data (collected via seine and minnow traps) could determine whether pond conditions affect the composition of fish assemblages. Results from the DFA for environmental parameters showed that the model classified ponds correctly to their a priori connectivity classifications; however, no more accurately than random chance. Fish presence–absence data were the least accurate for predicting degree of connectivity, but the relative abundances of those species proved to be an accurate method for pond connectivity classification. Many efforts to understand how an altered hydroperiod impacts marsh complexes along the Texas Gulf Coast have focused on tidal creeks and the vegetated portions of open marshes rather than salt marsh ponds, which can be key habitats for both primary and secondary productivity. This study concentrates on salt marsh ponds to provide a better understanding of how these ecosystems function within the greater marsh landscape. [ABSTRACT FROM AUTHOR]

Background: Since the 1970s, a range of facial, neurostructural, and neurocognitive adverse effects have been shown to be associated with prenatal alcohol exposure. Typically, these effects are studied individually and not in combination. Our objective is to improve the understanding of the teratogenic effects of prenatal alcohol exposure by simultaneously considering face–brain morphology and neurocognitive measures. Methods: Participants were categorized as control (n = 47), fetal alcohol syndrome (FAS, n = 22), or heavily exposed (HE) prenatally, but not eligible for a FAS diagnosis (HE, n = 50). Structural brain MRI images and high‐resolution 3D facial images were analyzed using dense surface models of features of the face and surface shape of the corpus callosum (CC) and caudate nucleus (CN). Asymmetry of the CN was evaluated for correlations with neurocognitive measures. Results: (i) Facial growth delineations for FAS, HE, and controls are replicated for the CN and the CC. (ii) Concordance of clinical diagnosis and face‐based control–FAS discrimination improves when the latter is combined with specific brain regions. In particular, midline facial regions discriminate better when combined with a midsagittal profile of the CC. (iii) A subset of HE individuals was identified with FAS‐like CN dysmorphism. The average of this HE subset was FAS‐like in its facial dysmorphism. (iv) Right–left asymmetry found in the CNs of controls is not apparent for FAS, is diminished for HE, and correlates with neurocognitive measures in the combined FAS and HE population. Conclusions: Shape analysis which combines facial regions with the CN, and with the CC, better identify those with FAS. CN asymmetry was reduced for FAS compared to controls and is strongly associated with general cognitive ability, verbal learning, and recall in those with prenatal alcohol exposure. This study further extends the brain–behavior relationships known to be vulnerable to alcohol teratogenesis. [ABSTRACT FROM AUTHOR]

The 2017 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was titled “Prenatal alcohol exposure in the context of multiple factors affecting brain development.” The theme was reflected in the interactions between members of the Teratology Society and the FASDSG this year. The first keynote speaker, Elaine Faustman, Ph.D., was a liaison between the societies and spoke about systems biology and the multiple genetic and environmental influences on development. The second keynote speaker, Rebecca Knickmeyer, Ph.D., discussed population neuroscience and multiple influences on brain development. The conference presented updates from three government agencies and short presentations by junior and senior investigators showcasing late-breaking FASD research. The conference was capped by Dr. John Hannigan, Ph.D., the recipient of the 2017 Henry Rosett award for career-long contributions to the field. [ABSTRACT FROM AUTHOR]

The 2016 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was titled "Rehabilitation in FASD: Potential Interventions and Challenges". During the previous decades, studies with human subjects and animal models have improved much of our understanding of the mechanisms underlying FASD, putting the scientific community in a good position to test hypotheses that can lead to potential therapeutic interventions. During the conference, two keynote speakers addressed potential interventions used in different fields and their applicability to FASD research. The conference also included updates from several government agencies, short presentations by junior and senior investigators that showcased the latest in FASD research, and award presentations. The conference was closed by a talk by Dr. Charles Goodlett, the recipient of the 2016 Henry Rosett award. [ABSTRACT FROM AUTHOR]

The 2017 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was titled "Prenatal alcohol exposure in the context of multiple factors affecting brain development." The theme was reflected in the interactions between members of the Teratology Society and the FASDSG this year. The first keynote speaker, Elaine Faustman, Ph.D., was a liaison between the societies and spoke about systems biology and the multiple genetic and environmental influences on development. The second keynote speaker, Rebecca Knickmeyer, Ph.D., discussed population neuroscience and multiple influences on brain development. The conference presented updates from three government agencies and short presentations by junior and senior investigators showcasing late-breaking FASD research. The conference was capped by Dr. John Hannigan, Ph.D., the recipient of the 2017 Henry Rosett award for career-long contributions to the field. [ABSTRACT FROM AUTHOR]

Forensic taphonomy is an essential research field; however, the decomposition of human cadavers at forensic science facilities may lead to nutrient loading and the introduction of unique biological compounds to adjacent areas. The infrastructure of a water retention system may provide a mechanism for the biogeochemical processing and retention of nutrients and compounds, ensuring the control of runoff from forensic facilities. This work provides a proof of concept for a hydrologic retention system and an autonomous water quality monitoring program designed to mitigate runoff from The Southeast Texas Applied Forensic Science ( STAFS) Facility. Water samples collected along a sample transect were analyzed for total phosphorous, total nitrogen [ABSTRACT FROM AUTHOR]

Brain functional connectivity has been studied by analyzing time series correlations in regional brain activities based on resting-state fMRI data. Brain functional connectivity can be depicted as a network or graph defined as a set of nodes linked by edges. Nodes represent brain regions and an edge measures the strength of functional correlation between two regions. Most of existing work focuses on estimation of such a network. A key but inadequately addressed question is how to test for possible differences of the networks between two subject groups, say between healthy controls and patients. Here we illustrate and compare the performance of several state-of-the-art statistical tests drawn from the neuroimaging, genetics, ecology and high-dimensional data literatures. Both real and simulated data were used to evaluate the methods. We found that Network Based Statistic (NBS) performed well in many but not all situations, and its performance critically depends on the choice of its threshold parameter, which is unknown and difficult to choose in practice. Importantly, two adaptive statistical tests called adaptive sum of powered score (aSPU) and its weighted version (aSPUw) are easy to use and complementary to NBS, being higher powered than NBS in some situations. The aSPU and aSPUw tests can also be applied to adjust for covariates. Between the aSPU and aSPUw tests, they often, but not always, performed similarly with neither one as a uniform winner. On the other hand, Multivariate Matrix Distance Regression (MDMR) has been applied to detect group differences for brain connectivity; with the usual choice of the Euclidean distance, MDMR is a special case of the aSPU test. Consequently NBS, aSPU and aSPUw tests are recommended to test for group differences in functional connectivity. [ABSTRACT FROM AUTHOR]

Abstract: Cerebral involvement in Myotonic Dystrophy Type 1 (DM1) is well-established but not well characterized. This study applied new Diffusion Tensor Imaging (DTI) tractography to characterize white matter disturbance in adults with DM1. Forty-five participants with DM1 and 44 control participants had MRIs on a Siemens 3T TIM Trio scanner. Data were processed with TRActs Constrained by UnderLying Anatomy (TRACULA) and 7 tracts were evaluated. Bilateral disturbances in white matter integrity were seen in all tracts in participants with DM1 compared to controls. There were no right–left hemisphere differences. The resulting DTI metrics were correlated with cognitive functioning, particularly working memory and processing speed. Motor speed was not significantly correlated with white matter microstructural integrity and, thus, was not the core explanation for the working memory and processing speed findings. White matter integrity was correlated with important clinical variables including the muscular impairment rating scale (MIRS). CTG repeat length was moderately associated with white matter status in corticospinal tract and cingulum. Sleepiness (Epworth Sleepiness Scale) was moderately associated with white matter status in the superior longitudinal fasciculus and cingulum. Overall, the results add to an emerging literature showing widespread white matter disturbances in both early-onset and adult-onset DM1. Results suggest that further investigation of white matter pathology is warranted in DM1 and that non-invasive measures such as DTI have a potentially important clinical value in characterizing the status of individuals with DM1. [Copyright &y& Elsevier]

Abstract: There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway. [Copyright &y& Elsevier]

Background Previous studies, including those employing diffusion tensor imaging ( DTI), have revealed significant disturbances in the white matter of individuals with fetal alcohol spectrum disorders ( FASD). Both macrostructural and microstructural abnormalities have been observed across levels of FASD severity. Emerging evidence suggests that these white matter abnormalities are associated with functional deficits. This study used resting-state functional MRI (f MRI) to evaluate the status of network functional connectivity in children with FASD compared with control subjects. Methods Participants included 24 children with FASD, ages 10 to 17, and 31 matched controls. Neurocognitive tests were administered including Wechsler Intelligence Scales, California Verbal Learning Test ( CVLT), and Behavior Rating Inventory of Executive Functioning. High-resolution anatomical MRI data and 6-minute resting-state fMRI data were collected. The resting-state f MRI data were subjected to a graph theory analysis, and 4 global measures of cortical network connectivity were computed: characteristic path length, mean clustering coefficient, local efficiency, and global efficiency. Results Results revealed significantly altered network connectivity in those with FASD. The characteristic path length was 3.1% higher ( p = 0.04, Cohen's d = 0.47), and global efficiency was 1.9% lower ( p = 0.04, d = 0.63) in children with FASD compared with controls, suggesting decreased network capacity that may have implications for integrative cognitive functioning. Global efficiency was significantly positively correlated with cortical thickness in frontal ( r = 0.38, p = 0.005), temporal ( r = 0.28, p = 0.043), and parietal ( r = 0.36, p = 0.008) regions. No relationship between facial dysmorphology and functional connectivity was observed. Exploratory correlations suggested that global efficiency and characteristic path length are associated with capacity for immediate verbal memory on the CVLT ( r = 0.41, p = 0.05 and r = 0.41, p = 0.01, respectively) among those with FASD. Conclusions Resting-state functional connectivity measures provide new insight into the integrity of brain networks in clinical populations such as FASD. Results demonstrate that children with FASD have alterations in core components of network function and that these aspects of brain integrity are related to measures of structure and cognitive functioning. [ABSTRACT FROM AUTHOR]

Abstract: The degree of hydrological connectivity in wetlands plays a vital role in determining the flux of energy, material, and nutrients across these wet landscapes. During the last century, compartmentalization of hydrologic flows in the Florida Everglades by canals and levees has had a profound impact on the natural timing and supply of freshwater and nutrients across the southern Everglades. Nitrogen (N) is an understudied nutrient in the phosphorus-limited Everglades; it plays an important role in many Everglades processes. To gain a better understanding of the overall N-dynamics in southern Everglades’ marshes and the role that canals play in the distribution of N across this landscape, we analyzed δ15N natural abundance data for the primary ecosystem components (the macrophyte Cladium jamaicense, marl soils, peat soils, and periphyton). Three sample transects were established in the three main basins of the southern Everglades: Shark River Slough, Taylor Slough, and the C-111 basin. Each transect included sample sites near canal inflows, in interior marshes, and at the estuarine ecotone. Natural abundance δ15N signatures provided insights into processes that may be enriching the 15N content of ecosystem components across the marsh landscape. We also conducted a combined analysis of δ15N data, tissue N concentrations, and water column N data to provide a broad overview of N cycling in the freshwater marshes of the southern Everglades. The primary trend that emerged from each basin was a significant 15N enrichment of all ecosystem components at near-canal sites, relative to more downstream sample sites. These data suggest that the phosphorus-limited marshes of the southern Everglades are not inactive conduits for N. Rather, these marshes appear to be actively cycling and processing N as it flows from the canal–marsh interface through downstream freshwater marshes. This finding has important implications to downstream coastal estuaries, including Florida Bay, and to nearshore coastal ocean ecosystems, such as coral reefs, where N is the limiting nutrient. [Copyright &y& Elsevier]

Over the past 5 years, Diffusion Tensor Imaging (DTI) has begun to provide new evidence about the effects of prenatal alcohol exposure on white matter development. DTI, which examines microstructural tissue integrity, is sensitive to more subtle white matter abnormalities than traditional volumetric MRI methods. Thus far, the available DTI data suggest that white matter microstructural abnormalities fall on a continuum of severity in Fetal Alcohol Spectrum Disorder (FASD). Abnormalities are prominent in the corpus callosum, but also evident in major anterior-posterior fiber bundles, corticospinal tracts, and cerebellum. These subtle abnormalities are correlated with neurocognitive deficits, especially in processing speed, non-verbal ability, and executive functioning. Future studies using larger samples, increasingly sophisticated DTI methods, and additional functional MRI connectivity measures will better characterize the full range of abnormalities in FASD. Ultimately, these measures may serve as indices of change in future longitudinal studies and in studies of interventions for FASD. [ABSTRACT FROM AUTHOR]

MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual-motor skill, verbal learning, and executive functioning. The goal of this study was to determine whether inter-hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter-hemispheric functional connectivity and disrupted cognition. Twenty-one children with FASD and 23 matched controls underwent a 6-minute resting-state functional MRI scan as well as anatomical imaging and DTI. Using a semi-automated method, we parsed the corpus callosum and delineated 7 inter-hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right-left correlations in resting fMRI signal were computed for these sets of ROIs, and group comparisons were made. Correlations with facial dysmorphology, cognition, and DTI measures were computed. A significant group difference in inter-hemispheric functional connectivity was seen in a posterior set of ROIs, the para-central region. Children with FASD had functional connectivity that was 12% lower than in controls in this region. Subgroup analyses were not possible owing to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para-central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures, and Wechsler perceptual reasoning ability. Inter-hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para-central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions, and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning. [ABSTRACT FROM AUTHOR]

Abstract: Diffusion tensor imaging was used to evaluate cerebral white matter in eight patients (ages 10–17), with myotonic dystrophy type 1 (3 congenital-onset, 5 juvenile-onset) compared to eight controls matched for age and sex. Four regions of interest were examined: inferior frontal, superior frontal, supracallosal, and occipital. The myotonic dystrophy group showed white matter abnormalities compared to controls in all regions. All indices of white matter integrity were abnormal: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. With no evidence of regional variation, correlations between whole cerebrum white matter fractional anisotropy and neurocognitive functioning were examined in the patients. Strong correlations were observed between whole cerebrum fractional anisotropy and full-scale intelligence and a measure of executive functioning. Results indicate that significant white matter abnormality is characteristic of young patients with myotonic dystrophy type 1 and that the white matter abnormality seen with neuroimaging has implications for cognitive functioning. [ABSTRACT FROM AUTHOR]

Background: Several studies have now shown corpus callosum abnormalities using diffusion tensor imaging (DTI) in children with fetal alcohol spectrum disorders (FASD) in comparison with nonexposed controls. The data suggest that posterior regions of the callosum may be disproportionately affected. The current study builds on previous efforts, including our own work, and moves beyond midline corpus callosum to probe major inter-hemispheric white matter pathways with an improved DTI tractographic method. This study also expands on our prior work by evaluating a larger sample and by incorporating children with a broader range of clinical effects including full-criteria fetal alcohol syndrome (FAS). Methods: Participants included 33 children with FASD (8 FAS, 23 partial FAS, 2 static encephalopathy) and 19 nonexposed controls between the ages of 10 and 17 years. Participants underwent DTI scans and intelligence testing. Groups (FASD vs. controls) were compared on fractional anisotropy (FA) and mean diffusivity (MD) in 6 white matter tracts projected through the corpus callosum. Exploratory analyses were also conducted examining the relationships between DTI measures in the corpus callosum and measures of intellectual functioning and facial dysmorphology. Results: In comparison with the control group, the FASD group had significantly lower FA in 3 posterior tracts of the corpus callosum: the posterior mid-body, the isthmus, and the splenium. A trend-level finding also suggested lower FA in the genu. Measures of white matter integrity and cognition were correlated and suggest some regional specificity, in that only posterior regions of the corpus callosum were associated with visual-perceptual skills. Correlations between measures of facial dysmorphology and posterior regions of the corpus callosum were nonsignificant. Conclusions: Consistent with previous DTI studies, these results suggest that microstructural posterior corpus callosum abnormalities are present in children with prenatal alcohol exposure and cognitive impairment. These abnormalities are clinically relevant because they are associated with cognitive deficits and appear to provide evidence of abnormalities associated with prenatal alcohol exposure independent of dysmorphic features. As such, they may yield important diagnostic and prognostic information not provided by the traditional facial characteristics. [ABSTRACT FROM AUTHOR]

Aim: Adolescents with psychotic disorders show deficits in IQ, attention, learning and memory, executive functioning, and processing speed that are related to important clinical variables including negative symptoms, adaptive functioning and academics. Previous studies have reported relatively consistent deficits with varying relationships to illness status and symptoms. The goals of this study were to examine these relationships in a larger sample at baseline, and also to examine the longitudinal course of these deficits in a smaller subset of adolescents. Method: Thirty-six subjects, aged 10 to 17 years, were included at baseline. All had Diagnostic and Statistical Manual-Fourth Edition diagnoses of schizophrenia, schizoaffective disorder, schizophreniform disorder and psychosis – not otherwise specified, as determined by Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children structured interviews. Patients were administered a neuropsychological battery, and Positive and Negative Syndrome Scale ratings were completed at baseline and again at 1 year ( n = 14). Most participants were inpatients at baseline, and 13 of 14 were on atypical antipsychotic medication during both sessions. Results: At baseline, the patients demonstrated impairments in working memory, processing speed, executive function and verbal learning. No significant cognitive change was detected at 1-year follow-up. In contrast, clinical symptoms were variable across 1 year, with an improvement in positive symptoms at 1 year. No relationships between clinical and cognitive symptoms were observed, with the exception of baseline IQ predicting negative symptoms at 1 year. Conclusions: Young patients with schizophrenia-spectrum disorders displayed neurocognitive impairments at baseline. Despite measurable fluctuations in clinical symptoms over the year, no significant changes were measured in cognition. Lower IQ at baseline was predictive of more negative symptoms at 1 year. [ABSTRACT FROM AUTHOR]

Abstract: Rationale: Two previous studies have utilized diffusion tensor imaging (DTI) to examine microstructural integrity in cocaine abuse and found evidence of brain abnormalities in white matter. Objective: Using anatomical magnetic resonance imaging (MRI), DTI, and clinical evaluation, the macrostructural and microstructural correlates of cocaine abuse were investigated. Methods: Twenty-one men and women (mean age 42.5 and mean 18.9 years of cocaine use) and 21 age/gender-matched controls were included. Fractional anisotropy (FA) was measured in frontal white matter ROIs. Gray and white matter volumes in superior and inferior frontal regions were compared. Results: DTI data revealed that cocaine users had lower FA than controls, specifically in inferior frontal white matter. FA differences were not seen in other areas. Significant volumetric differences were not seen, but both gray and white matter inferior frontal volumes trended toward smaller in the cocaine group. The data suggested that duration of use was associated with decreased gray and white matter volumes. FA and gray matter volume were correlated in cocaine users. Conclusions: Both macrostructural and microstructural abnormalities were seen in a group of cocaine abusers. Length of cocaine use was associated with severity of the brain abnormalities. Future studies of white matter tissue integrity are warranted including examination of the relationship between DTI measures and traditional volumetric measures. [Copyright &y& Elsevier]

Abstract: This study examined the sensitivity of diffusion tensor imaging (DTI) to microstructural white matter (WM) damage in mild and moderate pediatric traumatic brain injury (TBI). Fourteen children with TBI and 14 controls ages 10–18 had DTI scans and neurocognitive evaluations at 6–12 months post-injury. Groups did not differ in intelligence, but children with TBI showed slower processing speed, working memory and executive deficits, and greater behavioral dysregulation. The TBI group had lower fractional anisotropy (FA) in three WM regions: inferior frontal, superior frontal, and supracallosal. There were no group differences in corpus callosum. FA in the frontal and supracallosal regions was correlated with executive functioning. Supracallosal FA was also correlated with motor speed. Behavior ratings showed correlations with supracallosal FA. Parent-reported executive deficits were inversely correlated with FA. Results suggest that DTI measures are sensitive to long-term WM changes and associated with cognitive functioning following pediatric TBI. [Copyright &y& Elsevier]

Background: Prenatal alcohol exposure, which is associated with macrostructural brain abnormalities, neurocognitive deficits, and behavioral disturbances, is characterized as fetal alcohol syndrome (FAS) in severe cases. The only published study thus far using diffusion tensor imaging (DTI) showed microstructural abnormalities in patients with FAS. The current study investigated whether similar abnormalities are present in less severely affected, prenatally exposed patients who did not display all of the typical FAS physical stigmata. Methods: Subjects included 14 children, ages 10 to 13, with fetal alcohol spectrum disorders (FASD) and 13 matched controls. Cases with full-criteria FAS, mental retardation, or microcephaly were excluded. Subjects underwent MRI scans including DTI. Results: Although cases with microcephaly were excluded, there was a trend toward smaller total cerebral volume in the FASD group ( p=0.057, Cohen's d effect size =0.73). Subjects with FASD had greater mean diffusivity (MD) in the isthmus of the corpus callosum than controls ( p=0.013, effect size =1.05), suggesting microstructural abnormalities in this region. There were no group differences in 5 other regions of the corpus callosum. Correlations between MD in the isthmus and facial dysmorphology were nonsignificant. Conclusions: These results suggest that even relatively mild forms of fetal alcohol exposure may be associated with microstructural abnormalities in the posterior corpus callosum that are detectable with DTI. [ABSTRACT FROM AUTHOR]

Abstract: Several newer magnetic resonance imaging (MRI) techniques are increasingly being applied to the study of white matter development and pathology across the lifespan. These techniques go beyond traditional macrostructural volumetric methods and provide valuable information about underlying tissue integrity and organization at the microstructural and biochemical levels. We first provide an overview of white matter development and discuss the role of white matter and myelin in cognitive function. We also review available studies of development that have employed traditional volumetric measures. Then, we discuss the contributions of four newer imaging paradigms to our understanding of brain development and aging. These paradigms are Diffusion Tensor Imaging (DTI), Magnetization Transfer Imaging (MTI), T2-Relaxography, and Magnetic Resonance Spectroscopy (MRS). Studies examining brain development during childhood and adulthood as well as studies of the effects of aging are discussed. [Copyright &y& Elsevier]

This study compared the Behavior Assessment System for Children-Third Edition (BASC-3) to the Child Behavior Checklist (CBCL) and the Vineland Adaptive Behavior Scales-Third Edition (VABS-3) in children with and without histories of prenatal alcohol exposure. Data were collected from Collaborative Initiative on Fetal Alcohol Spectrum Disorders Phase 4 sites. Caregivers rated their child's behavior using three questionnaires: BASC-3, CBCL, and VABS-3. BASC-3 Adaptive Skills, Externalizing Problems, and Internalizing Problems scores were correlated with comparable scores from the CBCL (Externalizing and Internalizing Problems) and VABS-3 (Adaptive Skills) both within and across groups. Sensitivity, specificity, and positive and negative predictive values were calculated for the BASC-3. BASC-3 sensitivity rates were 78.1%, 80.5%, and 47.0% and specificity rates were 79.4%, 80.4%, and 81.5% for Adaptive Skills, Externalizing Problems, and Internalizing Problems, respectively. Positive predictive values were 87.1%, 88.0%, and 81.9% and negative predictive values were 67.0%, 69.8%, and 46.3% for Adaptive Skills, Externalizing Problems, and Internalizing Problems, respectively. Results replicated previous reports of behavioral and adaptive difficulties in children with prenatal alcohol exposure. These findings provide support for using the BASC-3 in this population. [ABSTRACT FROM AUTHOR]

Background: We have recently shown that binge or heavy levels of alcohol drinking increase deoxyribonucleic acid (DNA) methylation and reduce gene expression of proopiomelanocortin (POMC) and period 2 (PER2) in adult human subjects (Gangisetty et al., Alcohol Clin Exp Res, 43, 2019, 212). One hypothesis would be that methylation of these 2 genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of prenatal alcohol exposure (PAE). Results of the present study provided some support for this hypothesis. Methods: We conducted a series of studies to determine DNA methylation changes in stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) using biological samples from 3 separate cohorts of patients: (i) pregnant women who consumed moderate‐to‐high levels of alcohol or low/unexposed controls, (ii) children with PAE and non–alcohol‐exposed controls, and (iii) children with PAE treated with or without choline. Results: We found pregnant women who consumed moderate‐to‐high levels of alcohol and gave birth to PAE children had higher DNA methylation of POMC and PER2. PAE children also had increased methylation of POMC and PER2. The differences in the gene methylation of PER2 and POMC between PAE and controls did not differ by maternal smoking status. PAE children had increased levels of stress hormone cortisol and adrenocorticotropic hormone. Choline supplementation reduced DNA hypermethylation and increased expression of POMC and PER2 in children with PAE. Conclusions: These data suggest that PAE significantly elevates DNA methylation of POMC and PER2 and increases levels of stress hormones. Furthermore, these results suggest the possibility that measuring DNA methylation levels of PER2 and POMC in biological samples from pregnant women or from children may be useful for identification of a woman or a child with PAE. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed whether the outcome of a screening tool for fetal alcohol spectrum disorders (FASD), the FASD‐Tree, was associated with neuropsychological and behavioral outcomes. Methods: Data for this study were collected as part of the fourth phase of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD‐4). Participants (N = 175, 5 to 16 years) with or without histories of prenatal alcohol exposure were recruited from San Diego and Minneapolis. Each participant was screened using the FASD‐Tree and administered a neuropsychological test battery; parents or guardians completed behavioral questionnaires. The FASD‐Tree incorporates physical and behavioral measures and provides an outcome regarding the presence of FASD (FASD‐Positive or FASD‐Negative). Logistic regression was used to test whether the FASD‐Tree outcome was associated with general cognitive ability, executive function, academic achievement, and behavior. Associations were tested in two groups: the whole sample and only correctly classified participants. Results: Results of the FASD‐Tree were associated with neuropsychological and behavioral measures. Participants classified as FASD‐Positive were more likely than those classified as FASD‐Negative to have a lower IQ score and exhibit poorer performance on measures of executive and academic functions. Behaviorally, participants classified as FASD‐Positive were rated as having more behavior problems and adaptive difficulties. Similar relationships were found for all measures when including only participants correctly classified by the FASD‐Tree screening tool. Conclusion: Results from the FASD‐Tree screening tool were associated with neuropsychological and behavioral measures. Participants classified as FASD‐Positive were more likely to have impairment in all domains tested. The results support the effectiveness of the FASD‐Tree as a screening tool for use in clinical settings, providing an efficient and accurate way to identify patients in need of additional evaluation. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) is associated with abnormalities in cortical structure and maturation, including cortical thickness (CT), cortical volume, and surface area. This study provides a longitudinal context for the developmental trajectory and timing of abnormal cortical maturation in PAE. Methods: We studied 35 children with PAE and 30 nonexposed typically developing children (Comparisons), aged 8–17 at enrollment, who were recruited from the University of Minnesota FASD Program. Participants were matched on age and sex. They underwent a formal evaluation of growth and dysmorphic facial features associated with PAE and completed cognitive testing. MRI data were collected on a Siemens Prisma 3T scanner. Two sessions, each including MRI scans and cognitive testing, were spaced approximately 15 months apart on average. Change in CT and performance on tests of executive function (EF) were examined. Results: Significant age‐by‐group (PAE vs. Comparison) linear interaction effects in CT were observed in the parietal, temporal, occipital, and insular cortices suggesting altered developmental trajectories in the PAE vs. Comparison groups. Results suggest a pattern of delayed cortical thinning in PAE, with the Comparison group showing more rapid thinning at younger ages and those with PAE showing accelerated thinning at older ages. Overall, children in the PAE group showed reduced cortical thinning across time relative to the Comparison participants. Symmetrized percent change (SPC) in CT in several regions was significantly correlated with EF performance at 15‐month follow‐up for the Comparison group but not the group with PAE. Conclusions: Regional differences were seen longitudinally in the trajectory and timing of CT change in children with PAE, suggesting delayed cortical maturation and an atypical pattern of development compared with typically developing individuals. In addition, exploratory correlation analyses of SPC and EF performance suggest the presence of atypical brain–behavior relationships in PAE. The findings highlight the potential role of altered developmental timing of cortical maturation in contributing to long‐term functional impairment in PAE. [ABSTRACT FROM AUTHOR]

Background: As many as 80% of individuals with fetal alcohol spectrum disorders (FASD) are misdiagnosed or not diagnosed. This study tests the accuracy and validity of a web‐based screening tool (the FASD‐Tree) for identifying children and adolescents with FASD. Methods: Children with histories of prenatal alcohol exposure (PAE) and controls (N = 302, including 224 with PAE and 78 controls) were examined for physical signs of fetal alcohol syndrome (FAS), and parents completed behavioral questionnaires. Data were entered into the FASD‐Tree, a web‐based decision tree application. The FASD‐Tree provided two outcomes: a dichotomous indicator (yes/no) and a numeric risk score (0 to 5), which have been shown separately to identify children with PAE and neurobehavioral impairment and to correlate with neurobehavioral outcomes. Overall accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the decision tree, risk score, and their combination. Misclassified cases were examined for systematic bias. Results: The FASD‐Tree was successful in accurately identifying youth with histories of PAE and the subgroup of individuals with FASD, indicating its validity as an FASD screening tool. Overall accuracy rates for FASD‐Tree components ranged from 75.0% to 84.1%, and both the decision tree outcome and risk score, and their combination, resulted in fair to good discrimination (area under the curve = 0.722 to 0.862) of youth with histories of PAE or FASD. While most participants were correctly classified, those who were misclassified differed in IQ and attention. Race, ethnicity, and sex did not affect the results. Conclusion: The FASD‐Tree is not a biomarker of PAE and does not provide definitive evidence of prenatal alcohol exposure. Rather it is an accurate and valid screening tool for FASD and can be used by clinicians who suspect that a patient has a history of PAE, even if the exposure is unknown. [ABSTRACT FROM AUTHOR]

The 2015 Fetal Alcohol Spectrum Disorders Study Group (FASDSG) meeting was titled "Basic Mechanisms and Translational Implications." Despite decades of basic science and clinical research, our understanding of the mechanisms by which ethanol affects fetal development is still in its infancy. The first keynote presentation focused on the role of heat shock protein pathways in the actions of ethanol in the developing brain. The second keynote presentation addressed the use of magnetoencephalography to characterize brain function in children with FASD. The conference also included talks by representatives from several government agencies, short presentations by junior and senior investigators that showcased the latest in FASD research, and award presentations. An important part of the meeting was the presentation of the 2015 Henry Rosett award to Dr. Michael Charness in honor of his achievements in research on FASD. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to evaluate the relationship between parent-report and objective measures of executive function in children diagnosed with Fetal Alcohol Spectrum Disorder (FASD). The participants were a clinical sample of 551 children who completed 597 evaluations, including initial and re-evaluations. Participants were 6–16 years old, with a mean age of 10. Pearson correlations were used to determine the relationship between performance-based measures and parent-report measures of executive functioning. Relationships among the same types of measures, that is, performance based or parent report, were also evaluated. The data largely demonstrate low nonsignificant correlations between performance-based measures and parental report of executive function. Parent-report measures were internally consistent as were objective measures. It is possible that a third variable, for example, parental frustration, significantly influences parent reports. It is also likely that objective measures, which are administered in a controlled environment, do not fully capture children’s day-to-day functioning. That is, a child may have the executive function abilities (i.e., good performance on objective measures) but may be unable to deploy the appropriate skills in their daily lives, as evidenced by parental report. Children with FASD who have executive function abilities but not implementation skills likely require different interventions than children who lack abilities and skills. [ABSTRACT FROM AUTHOR]

This study evaluated criteria for neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). Kable et al. (Child Psychiatry Hum Dev 55:426, 2022) assessed the validity of this diagnosis in a sample with low exposure to alcohol. The current study expanded this assessment to a sample with a wider age range and heavier alcohol exposure. Data were collected from participants (5–17 years) with prenatal alcohol exposure (PAE) and typically developing controls at six Collaborative Initiative on Fetal Alcohol Spectrum Disorders sites using neuropsychological assessment and caregiver reports. Impairment was tested at 1SD, 1.5SD, and 2SD below the normative average and a modification of the adaptive functioning requirement was tested. Testing impairment at 1SD resulted in the highest endorsement rates in both groups. Our findings replicated the study by Kable et al. and show that current criteria captured a high rate of those with PAE and that requiring fewer adaptive functioning criteria resulted in higher sensitivity to PAE. [ABSTRACT FROM AUTHOR]

Abstract: Kleptomania is characterized by the failure to resist impulses to steal objects not needed for personal use or their monetary value. The objective of this study was to examine cognitive and executive functioning in subjects with kleptomania. Fifteen women with a primary DSM-IV diagnosis of kleptomania underwent a detailed psychiatric examination, including measures of kleptomania severity, and a battery of neuropsychological tests that emphasized executive functions. Correlational analyses were computed between measures of kleptomania severity and tests of executive functioning. Kleptomania subjects reported a mean duration of illness of 17.9 years and shoplifting a mean of 1.7 times per week. All subjects reported an inability to resist urges to shoplift. Neuropsychological testing revealed group mean test scores within 0.5 standard deviations of normative standards for age. Five subjects (33.3%), however, had below-average performance on at least one measure of executive functioning, and 4 (26.7%) had below-average scores on two executive measures. Correlational analyses revealed a statistically significant correlation between kleptomania severity and Wisconsin Card Sorting Test performance (, ). As a group, subjects with kleptomania did not demonstrate deficits on neuropsychological testing. Greater kleptomania symptom severity, however, was correlated with impairment in executive functioning. [Copyright &y& Elsevier]

To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4–25 years, enrolled under the study protocol NCT01870375 , were compared to 98 healthy controls. Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4–5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration. • Quantitively measured brain macrostructure distinguished MPS I and healthy subjects. • Brain MRI volumes differed in participants with severe and attenuated MPS I forms. • In addition to white matter, other brain regions showed morphometric changes. • Cortical and subcortical gray matter, ventricles, and choroid plexus were altered. • IQ-related associations to ventricular volume and cortical thickness were present. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop an efficient and easily calculable risk score that can be used to identify an individual's risk of having been exposed to alcohol prenatally. Methods: Data for this study were collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, Phases 2 and 3. Two cohorts (ages 5 to 17 years) completed a comprehensive neurobehavioral battery and a standard dysmorphology exam: a development cohort (DC; n = 325) and a comparative cohort (CC; n = 523). Both cohorts included two groups: those with histories of heavy prenatal alcohol exposure (AE‐DC, n = 121; AE‐CC, n = 177) and a control group that included subjects with minimal or no prenatal alcohol exposure (CON‐DC, n = 204; CON‐CC, n = 346). Behavioral assessments and physical exam data were combined using regression techniques to derive a risk score indicating the likelihood of prenatal alcohol exposure. Subjects were then divided into two subgroups: (1) low risk and (2) high risk. Chi‐square (χ2) determined classification accuracy and ROC curves were produced to assess the predictive accuracy. Correlations between risk scores and intelligence quotient and executive function scores were calculated. Results: Subjects were accurately classified in the DC (χ2 = 78.61, p < 0.001) and CC (χ2 = 86.63, p < 0.001). The classification model also performed well in the DC (ROC = 0.835 [SE = 0.024, p < 0.001]) and CC (ROC = 0.786 [SE = 0.021, p < 0.001]). In the AE‐CC and CON‐CC, there were modest but significant associations between the risk score and executive function (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001) and intelligence quotient (AE‐CC: r = −0.20, p = 0.034; CON‐CC: r = −0.28, p < 0.001). Conclusion(s): The risk score significantly distinguished alcohol‐exposed from control subjects and correlated with important cognitive outcomes. It has significant clinical potential and could be easily deployed in clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model. Participants and Methods: The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI). Results: Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading). Conclusions: These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions. [ABSTRACT FROM AUTHOR]

Objective: Fetal alcohol spectrum disorder (FASD) is a common neurodevelopmental condition associated with deficits in cognitive functioning (executive functioning [EF], attention, working memory, etc.), behavioral impairments, and abnormalities in brain structure including cortical and subcortical volumes. Rates of comorbid attention-deficit/hyperactivity disorder (ADHD) are high in children with FASD and contribute to significant functional impairments. Sluggish cognitive tempo (SCT) includes a cluster of symptoms (e.g. underactive/slow-moving, confusion, fogginess, daydreaming) found to be related to but distinct from ADHD, and previous research suggests that it may be common in FASD. We explored SCT by examining the relationship between SCT and both brain volumes (corpus callosum, caudate, and hippocampus) and objective EF measures in children with FASD vs. typically developing controls. Participants and Methods: This is a secondary analysis of a larger longitudinal CIFASD study that consisted of 35 children with prenatal alcohol exposure (PAE) and 30 controls between the ages of 9 to 18 at follow-up. Children completed a set of cognitive assessments (WISC-IV, DKEFS, & NIH Toolbox) and an MRI scan, while parents completed the Child Behavior Checklist (CBCL), which includes a SCT scale. We examined group differences between PAE and controls in relation to SCT symptoms, EF scores, and subcortical volumes. Then, we performed within-and between-group comparisons with and without controlling for total intracranial volume, age, attention problems, and ADHD problems between SCT and subcortical brain volumes. Finally, we performed correlations between SCT and EF measures for both groups. Results: Compared to controls, participants with PAE showed significantly more SCT symptoms on the CBCL (t [57] = 3.66, p = 0.0006), more parent-rated attention problems and ADHD symptoms, lower scores across several EF measures (DKEFS Trail-Making and Verbal Fluency; WISC-IV Digit Span, Symbol Search, and Coding; effect sizes ranging from 0.44 to 1.16), and smaller regional volumes in the caudate, hippocampus, and posterior areas of the corpus callosum. In the PAE group, a smaller hippocampus was associated with more SCT symptoms (controlling for parent-rated attention problems and ADHD problems, age, and intracranial volume). However, in the control group, a larger mid posterior and posterior corpus callosum were significantly associated with more SCT symptoms (controlling for parent-rated attention problems, intracranial volume, and age; r [24] = 0.499, p = 0.009; r [24] = 0.517, p = 0.007). In terms of executive functioning, children in the PAE group with more SCT symptoms performed worse on letter sequencing of the Trail-Making subtest (controlling attention problems & ADHD symptoms). In comparison, those in the control group with more SCT symptoms performed better on letter sequencing and combined number letter sequencing of the Trail-Making subtest (controlling attention problems). Conclusions: Findings suggest that children with FASD experience elevated SCT symptoms compared to typically developing controls, which may be associated with worse performance on EF tasks and smaller subcortical volumes (hippocampus) when taking attention difficulties and ADHD symptoms into account. Additional research into the underlying causes and correlates of SCT in FASD could result in improved tailoring of interventions for this population. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) is linked to a variety of neurodevelopmental challenges, including social functioning (SF) and executive functioning (EF) deficits. These deficits present differently across developmental stages from preschool age to adolescence. Methods: The post hoc analyses described here were conducted on data from 83 preschool‐age children with PAE (early childhood group; ages 2.5 to 5.0) and 95 adolescents (49 with PAE, 46 controls; ages 8 to 16). Each child completed EF tasks as part of several prior studies. Parents completed social and communication inventories about their child's abilities. Thirty‐three participants from the early childhood group returned for a 4‐year follow‐up and completed both SF and EF measures. Results: Both the early childhood and adolescent groups with PAE showed deficits in SF and EF. There was a relationship between SF and EF within the adolescent PAE group that was not present in the adolescent control group or the early childhood PAE group. However, at the 4‐year follow‐up (Mage = 8.45), participants originally in the early childhood PAE group also demonstrated this relationship. Conclusions: These findings support previous research on EF/SF deficits in adolescents with PAE while also addressing a gap in the literature concerning early childhood research on this topic. Additionally, these findings suggest that the relationship between EF and SF deficits may strengthen throughout development. This line of research highlights potential sensitive periods for SF and EF training in children with PAE and suggests that fetal alcohol spectrum disorders programs consider targeting EF training as a component of social skill interventions. [ABSTRACT FROM AUTHOR]

Fetal alcohol spectrum disorder (FASD) affects 2–5% of the children in the United States. In the preschool age-range, inhibitory deficits frequently manifest as impaired ability to delay gratification, which is associated with deficits in cognitive flexibility in these children. The goal of this longitudinal study was to determine whether the ability to delay gratification in preschool children with FASD is (1) associated with broader manifestations in temperament and behavior; (2) predictive of later inhibitory control, cognitive flexibility and working memory in middle childhood; and (3) predictive of later parent-reported behavioral problems and school functioning in middle childhood. Forty-seven children with FASD, ages 2.5–5 years were administered a delay of gratification task in which they chose between receiving 2 snacks immediately or 10 snacks after waiting for 10 min. Two groups were defined based on a median split of waiting time. Four years later, 29 children completed measures of inhibitory control (Flanker task), cognitive flexibility (Dimensional Change Card Sort Test), and working memory (Stanford–Binet Intelligence Scales), and their parents completed the Child Behavior Checklist as a measure of the child's behavioral problems and school functioning. Children with longer wait times on the delay of gratification task in preschool showed better inhibitory control on the Flanker task in middle childhood and better parent-reported school functioning in English. These findings indicate that early inhibitory capacity persists into middle childhood in those with FASD, and may be a promising target for early intervention to improve later cognitive outcomes in these children. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) is associated with a variety of structural abnormalities in the brain, including several within the para‐limbic system. Children with PAE have higher rates of internalizing disorders, including depression and anxiety, which may be related to underlying limbic system anomalies. Methods: Children aged 8 to 16 with PAE (n = 41) or without PAE (n = 36) underwent an magnetic resonance imaging of the brain and parents completed behavioral questionnaires about their children. Semi‐automated procedures (FreeSurfer) were used to derive para‐limbic volumes from T1‐weighted anatomical images. Results: There were significant group differences (PAE vs. nonexposed controls) in the caudate, hippocampus, and the putamen; children with PAE had smaller volumes in these regions even after controlling for total intracranial volume. A trend‐level association was seen between caudate volume and internalizing symptoms in children with PAE; smaller caudate volumes (presumably reflecting less optimal neurodevelopment) were associated with higher levels of anxiety and depression symptoms in these children. Conclusions: Caudate structure may be disproportionately affected by PAE and may be associated with the later development of internalizing symptoms in those affected by PAE. [ABSTRACT FROM AUTHOR]

Background: Youth with heavy prenatal alcohol exposure have high rates of behavioral concerns and psychopathology, including increased oppositional and conduct behaviors. The relation between those concerns and executive function (EF) deficits is unknown. We investigated the association of oppositional and conduct behavior and EF in adolescents to inform targeted intervention. Methods: Subjects (N = 267) ages 10 to 17 years comprised 3 groups: alcohol‐exposed with oppositional/conduct behaviors (AE+), alcohol‐exposed without oppositional/conduct behaviors (AE−), and controls (CON). Group differences on direct neuropsychological (Delis‐Kaplan Executive Function System [D‐KEFS]) and indirect parent‐report (Behavior Rating Inventory of Executive Function [BRIEF]) EF measures were tested with multivariate analysis of covariances, followed by univariate analysis of variances and pairwise comparisons. The contribution of attention‐deficit/hyperactivity disorder (ADHD) within the AE groups was assessed in secondary analyses. Results: On the D‐KEFS, there was an omnibus main effect of group, with significant main effects on 3 of 6 variables (CON>AE+, AE−). Within the AE groups, ADHD did not alter the results. On the BRIEF, there was an omnibus significant main effect of group, with significant main effects on all scales (CON

Objectives: Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure. Methods: Subjects (ages 10–16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales – Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models. Results: Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory. Conclusions: Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS , 2018, 24 , 1026–1037) [ABSTRACT FROM AUTHOR]

Background Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form. Methods All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced. Results (i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism. Conclusions Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation. [ABSTRACT FROM AUTHOR]

Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure ( n = 192) and controls ( n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. Results No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Conclusions Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. [ABSTRACT FROM AUTHOR]

Executive function (EF) deficit is a hallmark of Fetal Alcohol Spectrum Disorders (FASD), but the vast majority of available evidence comes from school-age children and adolescents. Very little is known about EF during the critical developmental period prior to 6 years of age in FASD. We evaluated EF in 39 children with FASD (3.0–5.5 years) and a comparison group of 50 age-matched, nonexposed controls. Measures included the EF Scale for Early Childhood and a Delay of Gratification task. Compared to age-matched controls, preschool children with FASD had impairments on the EF Scale and showed more impulsivity on the Delay of Gratification task. To confirm the EF Scale finding, FASD group performance was compared to a separate normative dataset (N = 1,400). Those with FASD performed below normal (M = –0.57,SD = 0.92). Within the FASD group, IQ was correlated with the EF Scale (partialr = .60,p = .001) and Delay of Gratification (partialr = .58,p = .005). EF Scale performance did not differ significantly across levels of FASD severity (fetal alcohol syndrome [FAS], partial FAS, or alcohol-related neurobehavioral disorder [ARND]). However, compared to normative data, those with FAS had the largest deficits (M = –0.91SDfrom the mean,SE = 0.23), followed by partial FAS (M = –0.66SDfrom the mean,SE = 0.26), then ARND (M = –0.36SDfrom the mean,SE = 0.20). These novel data show that EF deficits manifest well before the age of 6 years in children with FASD, that they occur across the spectrum, and that EF may be most impaired in children with more severe forms of FASD and/or lower IQs. [ABSTRACT FROM AUTHOR]

The phenotype of attenuated mucopolysaccharidosis type II (MPS II), also called Hunter syndrome, has not been previously studied in systematic manner. In contrast to the “severe” phenotype, the “attenuated” phenotype does not present with behavioral or cognitive impairment; however, the presence of mild behavior and cognitive impairment that might impact long-term functional outcomes is unknown. Previously, significant MRI abnormalities have been found in MPS II. Recent evidence suggests white matter abnormalities in many MPS disorders. Methods As the initial cross-sectional analysis of a longitudinal study, we studied the association of brain volumes and somatic disease burden with neuropsychological outcomes, including measures of intelligence, memory, and attention in 20 patients with attenuated MPS II with a mean age of 15.8. MRI volumes were compared to 55 normal controls. Results While IQ and memory were average, measures of attention were one standard deviation below the average range. Corpus callosum volumes were significantly different from age-matched controls, differing by 22%. Normal age-related volume increases in white matter were not seen in MPS II patients as they were in controls. Somatic disease burden and white matter and corpus callosum volumes were significantly associated with attention deficits. Neither age at evaluation nor age at starting treatment predicted attention outcomes. Conclusions Despite average intelligence, attention is compromised in attenuated MPS II. Results confirm an important role of corpus callosum and cortical white matter abnormality in MPS II as well as the somatic disease burden in contributing to attention difficulties. Awareness by the patient and caregivers with appropriate management and symptomatic support will benefit the attenuated MPS II patient. [ABSTRACT FROM AUTHOR]

Background Because prenatal alcohol exposure is associated with growth deficiency, little attention has been paid to the potential for overweight and obesity in children with fetal alcohol spectrum disorders ( FASD). This study examined the prevalence of overweight/obesity (body mass index [ BMI]) in a large clinical sample of children with FASD. Methods Children, aged 2 to 19 years, who were evaluated for FASD at University Clinics, included 445 with an FASD diagnosis and 171 with No- FASD diagnosis. Prevalence of overweight/obesity ( BMI ≥85 percentile) was compared to national and state prevalence. BMI was examined in relation to FASD diagnosis, gender, and age. Dietary intake data were examined for a young subsample ( n = 42). Results Thirty-four percent with any FASD diagnosis were overweight or obese, which did not differ from the No- FASD group or U.S. prevalence. Underweight was prevalent in those with fetal alcohol syndrome ( FAS) (17%). However, increased rates of overweight/obesity were seen in those with partial FAS (40%). Among adolescents, those with any FASD diagnosis had increased overweight/obesity (42%), particularly among females (50%). The rate in adolescent females with FASD (50%) was nearly 3 times higher than state prevalence for adolescent females (17 to 18%), p < 0.001. In the young subsample, those who were overweight/obese consumed more calories, protein, and total fat per day than those who were not overweight or obese. Conclusions Rates of overweight/obesity are increased in children with partial FAS. In adolescents, rates are increased for any FASD diagnosis (particularly in females). Results are suggestive of possible metabolic/endocrine disruption in FASD-a hypothesis for which there is evidence from animal models. These data suggest that clinicians may consider prenatal alcohol exposure as a risk factor for metabolic/endocrine disruption, should evaluate diet as a risk in this population, and may need to target interventions to females prior to puberty to effect changes in overweight-related outcomes. [ABSTRACT FROM AUTHOR]

Abstract: This study evaluated dietary intake in children with fetal alcohol spectrum disorders (FASD). Pre-clinical research suggests that nutrient supplementation may attenuate cognitive and behavioral deficits in FASD. Currently, the dietary adequacy of essential nutrients in children with FASD is unknown. Dietary data were collected as part of a randomized, double-blind controlled trial of choline supplementation in FASD. Participants included 31 children with FASD, ages 2.5–4.9years at enrollment. Dietary intake data was collected three times during the nine-month study via interview-administered 24-hour recalls with the Automated Self-Administered 24-hour Recall. Dietary intake of macronutrients and 17 vitamins/minerals from food was averaged across three data collection points. Observed nutrient intakes were compared to national dietary intake data of children ages 2–5years (What we Eat in America, NHANES 2007–2008) and to the Dietary Reference Intakes. Compared to the dietary intakes of children in the NHANES sample, children with FASD had lower intakes of saturated fat, vitamin D, and calcium. The majority (>50%) of children with FASD did not meet the Recommended Dietary Allowance (RDA) or Adequate Intake (AI) for fiber, n−3 fatty acids, vitamin D, vitamin E, vitamin K, choline, and calcium. This pattern of dietary intake in children with FASD suggests that there may be opportunities to benefit from nutritional intervention. Supplementation with several nutrients, including choline, vitamin D, and n−3 fatty acids, has been shown in animal models to attenuate the cognitive deficits of FASD. These results highlight the potential of nutritional clinical trials in FASD. [Copyright &y& Elsevier]

Abstract: Pathophysiological mechanisms underlying the clinically devastating CNS features of myotonic dystrophy (DM) remain more enigmatic and controversial than do the muscle abnormalities of this common form of muscular dystrophy. To better define CNS and cranial muscle changes in DM, we used quantitative volumetric and diffusion tensor MRI methods to measure cerebral and masticatory muscle differences between controls (n =5) and adults with either congenital (n =5) or adult onset (n =5) myotonic dystrophy type 1 and myotonic dystrophy type 2 (n =5). Muscle volumes were diminished in DM1 and strongly correlated with reduced white matter integrity and gray matter volume. Moreover, correlation of reduced fractional anisotropy (white matter integrity) and gray matter volume in both DM1 and DM2 suggests that these abnormalities may share a common underlying pathophysiological mechanism. Further quantitative temporal and spatial characterization of these features will help delineate developmental and progressive neurological components of DM, and help determine the causative molecular and cellular mechanisms. [Copyright &y& Elsevier]

• Children (ages 8-16) with prenatal alcohol exposure showed poor social functioning. • They had smaller volumes of the precuneus and lateral orbitofrontal cortex than controls. • Smaller social brain volumes may contribute to their social difficulties. The goal of this study was to examine: 1) differences in parent-reported prosocial and antisocial behaviors between children and adolescents with and without prenatal alcohol exposure (PAE); 2) differences in gray matter volumes of brain areas supporting social cognition between children and adolescents with and without PAE; 3) correlations between gray matter volumes of brain areas supporting social cognition and parent-reported prosocial and antisocial behaviors. Parents of children and adolescents ages 8–16 years completed measures on their prosocial and antisocial behaviors (i.e., Behavior Assessment Scale for Children, Vineland Adaptive Behaviors Scales, and Child Behavior Checklist) (n = 84; 41 with PAE, 43 without PAE). Seventy-nine participants (40 with PAE, 39 without PAE) also completed a structural Magnetic Resonance Imaging (MRI) scan with quality data. Gray matter volumes of seven brain areas supporting social cognitive processes were computed using automated procedures (FreeSurfer 6.0): bilateral fusiform gyrus, superior temporal gyrus, medial orbitofrontal cortex, lateral orbitofrontal cortex, posterior cingulate cortex, precuneus, and temporal pole. Children and adolescents with PAE showed decreased prosocial behaviors and increased antisocial behaviors as well as smaller volumes of the precuneus and lateral orbitofrontal cortex, even when controlling for total intracranial volume. Social brain volumes were not significantly correlated with prosocial or antisocial behaviors. These findings suggest that children and adolescents with PAE show worse social functioning and smaller volumes of brain areas supporting self-awareness, perspective-taking and emotion-regulation than their same-age peers without PAE. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure (PAE) affects early brain development and has been associated with hippocampal damage. Animal models of PAE have suggested that some subfields of the hippocampus may be more susceptible to damage than others. Recent advances in structural MRI processing now allow us to examine the morphology of hippocampal subfields in humans with PAE. Structural MRI scans were collected from 40 children with PAE and 39 typically developing children (ages 8–16). The images were processed using the Human Connectome Project Minimal Preprocessing Pipeline (v4.0.1) and the Hippocampal Subfields package (v21) from FreeSurfer. Using a large dataset of typically developing children enrolled in the Human Connectome Project in Development (HCP-D) for normative standards, we computed age-specific volumetric z-scores for our two samples. Using these norm-adjusted hippocampal subfield volumes, comparisons were performed between children with PAE and typically developing children, controlling for total intracranial volume. Lastly, we investigated whether subfield volumes correlated with episodic memory (i.e., Picture Sequence Memory test of the NIH toolbox). Five subfields had significantly smaller adjusted volumes in children with PAE than in typically developing controls: CA1, CA4, subiculum, presubiculum, and the hippocampal tail. Subfield volumes were not significantly correlated with episodic memory. The results suggest that several regions of the hippocampus may be particularly affected by PAE. The finding of smaller CA1 volumes parallels previous reports in rodent models. The novel findings of decreased volume in the subicular cortex, CA4 and the hippocampal tail suggest avenues for future research. • Children with FASD have abnormally small hippocampal volume compared to controls. • Small volumes were seen in CA1, CA4, subiculum, presubiculum, and hippocampal tail. • Correlations between subfield volumes and visual episodic memory were not observed. [ABSTRACT FROM AUTHOR]