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Differences in cortico-striatal-cerebellar activation during working memory in syndromal and nonsyndromal children with prenatal alcohol exposure.

ABSTRACT: Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with FAS/PFAS, 13 HE, and 17 controls) during fMRI. Intra-group one-sample t-tests were used to identify activity regions of interest central to verbal working memory including the dorsal prefrontal cortex (dPFC), inferior frontal gyrus, caudate/putamen, parietal cortex, and cerebellar Crus I/lobule VI and lobule VIIB-IX. Whereas groups did not differ in task sensitivity, fMRI analyses suggested different patterns of sub-network recruitment across groups. Controls primarily recruited left inferior frontal gyrus (Broca's area). By contrast, HE primarily recruited an extensive set of fronto-striatal regions, including left dPFC and left caudate, and the FAS/PFAS group relied primarily on two cerebellar subregions and parietal cortex. This study is, to our knowledge, the first to demonstrate differential recruitment of critical brain regions that subserve basic function in children with different fetal alcohol spectrum disorders compared to controls. The distinct activation patterns seen in the two exposed groups may be related to substantial differences in alcohol dose/occasion to which these groups were exposed in utero.

SUBMITTER: Diwadkar VA

PROVIDER: S-EPMC6870023 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Differences in cortico-striatal-cerebellar activation during working memory in syndromal and nonsyndromal children with prenatal alcohol exposure.

Diwadkar Vaibhav A VA Meintjes Ernesta M EM Goradia Dhruman D Dodge Neil C NC Warton Christopher C Molteno Christopher D CD Jacobson Sandra W SW Jacobson Joseph L JL

Human brain mapping 20120325 8

Although children with heavy prenatal alcohol exposure may exhibit the distinctive facial dysmorphology seen in full or partial fetal alcohol syndrome (FAS/PFAS), many lack that dysmorphology. This study examined the functional organization of working memory in the brain in three groups of children-those meeting diagnostic criteria for FAS or PFAS, heavily exposed (HE) nonsyndromal children, and healthy controls. A verbal n-back task (1-back and 0-back) was administered to 47 children (17 with F ...[more]

PMID: 22451272

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Project description:Working memory is the ability to keep information in one's mind and mentally manipulate it. Decrements in working memory play a key role in many behavioral and psychiatric disorders, therefore identifying modifiable environmental risk factors for such decrements is important for mitigating these disorders. There is some evidence that prenatal exposure to individual chemicals may adversely impact working memory among children, but few studies have explored the association of co-exposure to multiple chemicals with this outcome in adolescence, a time when working memory skills undergo substantial development. We investigated the association of organochlorines (DDE, HCB, PCBs) and metals (lead, manganese) measured in cord serum and cord blood, respectively, with working memory measured with the Wide Range Assessment of Memory and Learning, 2nd Edition among 373 adolescents living near a Superfund site in New Bedford, Massachusetts. We used Bayesian Kernel Machine Regression (BKMR) and linear regression analyses and assessed effect modification by sex and prenatal social disadvantage. In BKMR models, we observed an adverse joint association of the chemical mixture with Verbal, but not Symbolic, Working Memory. In co-exposure and covariate-adjusted linear regression models, a twofold increase in cord blood manganese was associated with lower working memory scaled scores, with a stronger association with Verbal Working Memory (difference = -0.75; 95% CI: -1.29, -0.20 points) compared to Symbolic Working Memory (difference = -0.44; 95% CI: -1.00, 0.12 points). There was little evidence of effect modification by sex and some evidence associating organochlorine pesticides with poorer working memory scores among those with greater prenatal social disadvantage. This study provided evidence of an adverse joint association of a chemical mixture with a verbal working memory task among adolescents, as well as an adverse association of prenatal manganese exposure with working memory.

Project description:BackgroundOur objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form.MethodsAll 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.ConclusionsFacial 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.

Project description:BackgroundPrenatal and childhood exposure to polybrominated diphenyl ether (PBDE) flame retardants has been inversely associated with cognitive performance, however, few studies have measured PBDE concentrations in samples collected during both prenatal and postnatal periods.MethodsWe examined prenatal (cord) and childhood (ages 2, 3, 5, 7 and 9 years) plasma PBDE concentrations in relation to memory outcomes assessed between the ages of 9 and 14 years. The study sample includes a subset (n = 212) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used multivariable linear regression to examine associations between continuous log10-transformed PBDE concentrations and performance on tests of visual, verbal and working memory in age-stratified models. We additionally used latent class growth analysis to estimate trajectories of exposure across early life, which we analyzed as a categorical variable in relation to memory outcomes. We examined interactions between PBDE exposure and sex using cross-product terms.ResultsAssociations between prenatal exposure and working memory significantly varied by sex (p-interaction = 0.02), with inverse relations observed only among girls (i.e. βBDE-47 = -7.55, 95% CI: -13.84, -1.24). Children with sustained high concentrations of BDEs-47, 99 or 100 across childhood scored approximately 5-8 standard score points lower on tests of visual memory. Children with PBDE plasma concentrations that peaked during toddler years performed better on verbal domains, however, these associations were not statistically significant.ConclusionsExposure to PBDEs during both prenatal and postnatal periods may disrupt memory domains in early adolescence. These findings contribute to a substantial body of evidence supporting the developmental neurotoxicity of PBDEs and underscore the need to reduce exposure among pregnant women and children.

Project description:Verbal working memory is one of the most studied non-motor functions with robust cerebellar involvement. While the superior cerebellum (lobule VI) has been associated with articulatory control, the inferior cerebellum (lobule VIIIa) has been linked to phonological storage. The present study was aimed to elucidate the differential roles of these regions by investigating whether the cerebellum might contribute to verbal working memory via predictions based on sequence learning/detection. 19 healthy adult subjects completed an fMRI-based Sternberg task which included repeating and novel letter sequences that were phonologically similar or dissimilar. It was hypothesized that learning a repeating sequence of study letters would reduce phonological storage demand and associated right inferior cerebellar activations and that this effect would be modulated by phonological similarity of the study letters. Specifically, while increased phonological storage demand due to high phonological similarity was expected to be reflected in increased right inferior cerebellar activations for similar relative to dissimilar study letters, the reduction in activation for repeating relative to novel sequences was expected to be more profound for phonologically similar than for dissimilar study letters, especially at higher memory load. Results confirmed the typical effects of cognitive load (5 vs. 2 study letters) and phonological similarity in several cerebellar and neocortical brain regions as well as in behavioral data (accuracy and response time). Importantly, activations in superior and inferior cerebellar regions were differentially modulated as a function of similarity and sequence novelty, indicating that particularly lobule VIIIa may contribute to verbal working memory by generating predictions of letter sequences that reduce the likelihood of phonological loop failure before stored items need to be retrieved. The present study is consistent with other investigations that support prediction, which can be based on sequence learning or detection, as an overarching cerebellar function.

Dataset Information

Differences in cortico-striatal-cerebellar activation during working memory in syndromal and nonsyndromal children with prenatal alcohol exposure.

Publications

Differences in cortico-striatal-cerebellar activation during working memory in syndromal and nonsyndromal children with prenatal alcohol exposure.

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