An Analysis Of Virtual Place Learning/navigation In Children And Young Adults Prenatally Exposed To Alcohol

Fetal alcohol spectrum disorder refers to the spectrum of disorders resulting from prenatal alcohol exposure and is the leading cause of preventable mental retardation. Rodent studies have found that prenatal alcohol exposure impairs performance on the Morris water maze. This task requires the rodent to use distal room cues to locate a hidden platform in a pool of opaque water. Successful performance on this task is dependent upon hippocampal function. Rodents prenatally exposed to alcohol are impaired on the Morris water maze and show damage to hippocampal neurons. A human analogue of the Morris water maze, the virtual water maze has been created using computer-generated 3D virtual environments. Only one study has been conducted examining performance on the virtual water maze and FASD. This dissertation examined performance on the virtual water in three cohorts of individuals prenatally exposed to alcohol from Detroit and Cape Town, South Africa. Hypotheses were that children with a diagnosis of fetal alcohol syndrome or partial fetal alcohol syndrome, and those with a known history of prenatal alcohol exposure, but lacking the characteristic facial features will be impaired on the virtual water maze. Second, the amount of prenatal alcohol exposure will be negatively correlated with virtual water maze performance. Third, fetal alcohol-related reductions in hippocampal volume will mediate the relationship between FASD and virtual water maze performance. Lastly, prenatal alcohol related changes in testosterone will also mediate the relation between FASD and virtual water maze performance. Results indicated that both those with an FASD diagnosis were impaired on the virtual water maze. Degree of prenatal alcohol exposure was also correlated with poorer performance on the virtual water maze. These results were detected in the cohort with the heaviest levels of prenatal alcohol exposure. Right hippocampal volume was shown to be a mediator of the relation between FASD/prenatal alcohol exposure and virtual water maze performance. Testosterone was not related to virtual water maze performance. These data demonstrate that virtual water maze performance is sensitive to the effects of heavy prenatal alcohol exposure. Furthermore, impairments on this task may be due to fetal alcohol-related damage in the hippocampus

Parietal dysfunction in children with prenatal alcohol exposure

The parietal lobe has been shown to be one of the regions most affected by prenatal alcohol exposure. Functional domains dependent on intact parietal functioning, including mathematical and visuospatial ability, have been consistently implicated in fetal alcohol spectrum disorders. This thesis examines, in children, using blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging, the effect of prenatal alcohol exposure on brain activation during symbolic and nonsymbolic number processing, and place learning in a virtual environment. These functional domains were investigated using tasks of proximity judgment and exact addition to assess neural correlates of symbolic number processing in 65 children (mean age ± SD = 9.45 ± 0.42 years), nonsymbolic number comparison at varying difficulties in 34 children (11.55 ± 1.15 years), and place learning in a virtual reality computer generated (CG) arena in 57 children (9.44 ± 0.42 years; 29 boys). In the symbolic number processing tasks greater prenatal alcohol exposure was related to less activation in the right horizontal intraparietal sulcus known to mediate mental representation and manipulation of quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome appeared to compensate for this deficit by increased activation of the left angular gyrus during the proximity judgment task. Syndromal children with fetal alcohol syndrome or partial fetal alcohol syndrome also demonstrated poor recruitment of the right horizontal intraparietal sulcus during nonsymbolic number comparison, indicating that mental representation and manipulation of quantity are impaired in children with heavy prenatal alcohol exposure, irrespective of the representation format used. This impairment was compensated for by the left angular gyrus, with only exposed children needing to recruit the left angular gyrus to a greater extent as number comparison task difficulty increased. Further, reduced activation of the right posterior superior parietal lobule in children with increasing prenatal alcohol exposure suggests that exposed children may be less able to employ the attentional systems associated with number processing. Notably, activation of nonsyndromal heavily exposed children was impaired in the right posterior superior parietal lobule, but spared in the right horizontal intraparietal sulcus. In boys only, prenatal alcohol exposure was associated with poorer place learning and reduced activation during place learning in the precuneus and posterior cingulate, as well as parahippocampal gyrus, frontal and temporal lobes, caudate, insula, claustrum, lentiform nucleus and thalamus. In girls, prenatal alcohol exposure was not associated with place learning performance or activation during place learning in any regions. These results confirm that boys and girls use different navigation strategies that rely on different brain regions and suggest that the regions used by boys are more susceptible to alcohol damage, while the regions used by girls are relatively spared. In conclusion, all the tasks investigated showed prenatal alcohol exposure related alterations in parietal function, with the impairments being widespread throughout the parietal lobe bilaterally. Notably, activation of the bilateral precuneus was affected by prenatal alcohol exposure in both the spatial navigation and nonsymbolic number comparison tasks. It is possible that this is a key region linking the deficits in number processing and visuospatial skills in children with prenatal alcohol exposure

Facial Curvature Detects and Explicates Ethnic Differences in Effects of Prenatal Alcohol Exposure

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

Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse

BACKGROUND: The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J). RESULTS: Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age. CONCLUSION: Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models

Preterm birth and small for gestational age in relation to alcohol consumption during pregnancy: stronger associations among vulnerable women? Results from two large Western-European studies

Pfinder M, Kunst AE, Feldmann R, van Eijsden M, Vrijkotte TGM. Preterm birth and small for gestational age in relation to alcohol consumption during pregnancy: stronger associations among vulnerable women? Results from two large Western-European studies. BMC Pregnancy and Childbirth. 2013;13(1): 49.BACKGROUND: Inconsistent data on the association between prenatal alcohol exposure and a range of pregnancy outcomes, such as preterm birth (PTB) and small for gestational age (SGA) raise new questions. This study aimed to assess whether the association between low-moderate prenatal alcohol exposure and PTB and SGA differs according to maternal education, maternal mental distress or maternal smoking. METHODS: The Amsterdam Born Children and their Development (ABCD) Study (N=5,238) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (N=16,301) are both large studies. Women provide information on alcohol intake in early pregnancy, 3 months postpartum and up to 17 years retrospectively. Multivariate logistic regression analyses and stratified regression analyses were performed to examine the association between prenatal alcohol exposure and PTB and SGA, respectively. RESULTS: No association was found between any level of prenatal alcohol exposure (non-daily, daily, non-abstaining) and SGA. The offspring of daily drinkers and non-abstainers had a lower risk of PTB [ABCD: odds ratio (OR) 0.31, 95% confidence interval (CI) 0.13, 0.77; KiGGS: OR 0.75, 95% CI 0.57, 0.99]. Interactions with maternal education, maternal distress or maternal smoking were not significant. CONCLUSIONS: Although these results should be interpreted with caution, both studies showed no adverse effects of low-moderate prenatal alcohol exposure on PTB and SGA, not even in the offspring of women who were disadvantaged in terms of low education, high levels of distress, or smoking during pregnancy

Reduced expression of brain cannabinoid receptor 1 (Cnr1) is coupled with an increased complementary micro-RNA (miR-26b) in a mouse model of fetal alcohol spectrum disorders

BACKGROUND: Prenatal alcohol exposure is known to result in fetal alcohol spectrum disorders, a continuum of physiological, behavioural, and cognitive phenotypes that include increased risk for anxiety and learning-associated disorders. Prenatal alcohol exposure results in life-long disorders that may manifest in part through the induction of long-term gene expression changes, potentially maintained through epigenetic mechanisms. FINDINGS: Here we report a decrease in the expression of Canabinoid receptor 1 (Cnr1) and an increase in the expression of the regulatory microRNA miR-26b in the brains of adult mice exposed to ethanol during neurodevelopment. Furthermore, we show that miR-26b has significant complementarity to the 3’-UTR of the Cnr1 transcript, giving it the potential to bind and reduce the level of Cnr1 expression. CONCLUSIONS: These findings elucidate a mechanism through which some genes show long-term altered expression following prenatal alcohol exposure, leading to persistent alterations to cognitive function and behavioural phenotypes observed in fetal alcohol spectrum disorders

Fetal alcohol spectrum disorders: current issues in awareness, prevention and intervention

This paper reviews the research and current policy surrounding prenatal alcohol exposure and fetal alcohol spectrum disorders (FASD). Alcohol use during pregnancy is linked to a spectrum of adverse fetal outcomes. This spectrum of abnormalities is collectively termed fetal alcohol spectrum disorders and may include physical, cognitive and/or developmental symptoms. The aim of this paper is to inform practitioners and other professionals working in a range of fields about the implications of FASD for children and their families. Current research on interventions or programs to work with families affected by FASD is also explored. Key messages Prenatal alcohol exposure can cause a range of cognitive and physical abnormalities in embryos that can lead to impairments in a range of functions: sensory systems, language and communication, processing pace, learning and memory, abstract thinking, and executive functioning. Misunderstanding and labelling of those with FASD can lead to a poor self-concept, disrupted peer relationships, fractured educational and placement experiences and contact with youth justice services. The prevalence of FASD is likely to be underestimated by current measures. Certain populations, including children in out-of-home care and children in contact with youth justice services are thought to include an over-representation of individuals living with an undetected FASD. Tackling FASD requires focused and coordinated multidisciplinary and cross sector approaches. More information about the prevalence and nature of FASD will allow for improved service planning and implementation. Policy directions are needed that prioritise the screening and prevention of FASD in the community. Current and future professionals, including those in traditionally adult-focused services, need awareness and knowledge about the significance of FASD and prenatal alcohol exposure on children\u27s lives

Fetal alcohol spectrum disorder: development of concensus referral criteria for specialist diagnostic assessment in Australia

Background: Fetal alcohol spectrum disorder (FASD) is known to be under-recognised in Australia. The use of standard methods to identify when to refer individuals who may have FASD for specialist assessment could help improve the identification of this disorder. The purpose of this study was to develop referral criteria for use in Australia. Method: An online survey about FASD screening and diagnosis in Australia, which included 23 statements describing criteria for referral for fetal alcohol syndrome (FAS) and FASD based on published recommendations for referral in North America, was sent to 139 health professionals who had expertise or involvement in FASD screening or diagnosis. Survey findings and published criteria for referral were subsequently reviewed by a panel of 14 investigators at a consensus development workshop where criteria for referral were developed.Results: Among the 139 health professionals who were sent the survey, 103 (74%) responded, and 90 (65%) responded to the statements on criteria for referral. Over 80% of respondents agreed that referral for specialist evaluation should occur when there is evidence of significant prenatal alcohol exposure, defined as 7 or more standard drinks per week and at least 3 standard drinks on any one day, and more than 70% agreed with 13 of the16 statements that described criteria for referral other than prenatal alcohol exposure. Workshop participants recommended five independent criteria for referral: confirmed significant prenatal alcohol exposure; microcephaly and confirmed prenatal alcohol exposure; 2 or more significant central nervous system (CNS) abnormalities and confirmed prenatal alcohol exposure; 3 characteristic FAS facial anomalies; and 1 characteristic FAS facial anomaly, growth deficit and 1 or more CNS abnormalities .Conclusion: Referral criteria recommended for use in Australia are similar to those recommended in North America. There is a need to develop resources to raise awareness of these criteria among health professionals and evaluate their feasibility, acceptability and capacity to improve the identification of FASD in Australia