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Cortical Thickness in Fetal Alcohol Syndrome and Attention Deficit Disorder
Abstract
Fetal alcohol syndrome represents the classic and most severe manifestation of epigenetic changes induced by exposure to alcohol during pregnancy. Often these patients develop attention deficit hyperactivity disorder. We analyzed cortical thickness in 20 children and adolescents with fetal alcohol syndrome and attention deficit hyperactivity disorder (group 1), in 20 patients without fetal alcohol syndrome (group 2), and in 20 control cases. The first group revealed total cortical thickness significantly superior to those of the other two groups. In per-lobe analyses of cortical thickness, group 1 demonstrated greater cortical thickness in the frontal, occipital, and right temporal and left frontal lobes compared with the second group, and in both temporal lobes and the right frontal lobe compared with the control group. This study demonstrated greater cortical thickness in patients with attention deficit hyperactivity disorder and heavy prenatal exposure to alcohol, probably as an expression of immature or abnormal brain development.
... However, these reductions were not evident after correcting for total brain volume and no alterations were seen in cortical thickness. Prior work is mixed regarding the relationship between prenatal alcohol exposure and cortical thickness, reporting both increases [13][14][15] and decreases [16]. Other studies have found disproportionate volumetric reductions in specific brain areas [17,18,11]; however, those reports included individuals with heavy prenatal alcohol exposure who fell along the entire continuum of diagnoses, including those with facial dysmorphology. ...
... • Fernández-Jaén 1 et al. [14]; Yang 2 et al. [15] • ↓ Cortical thickness in the middle frontal lobe, precentral gyrus, ...
... • Zhou et al. [16] • ↓ • Fernández-Jaén 1 et al. [14]; Yang 2 et al. [15] • ↓ Cortical thickness in the L lateral and inferior temporal regions ...
Since the identification of Fetal Alcohol Syndrome over 40 years ago, much has been learned about the detrimental effects of prenatal alcohol exposure on the developing brain. This review highlights recent neuroimaging studies within the context of previous work. Structural magnetic resonance imaging has described morphological differences in the brain and their relationships to cognitive deficits and measures of facial dysmorphology. Diffusion tensor imaging has elaborated on the relationship between white matter microstructure and behavior. Atypical neuromaturation across childhood and adolescence has been observed in longitudinal neuroimaging studies. Functional imaging has revealed differences in neural activation patterns underlying sensory processing, cognition, and behavioral deficits. A recent functional connectivity analysis demonstrates reductions in global network efficiency. Despite this progress, much remains unknown about the impact of prenatal alcohol exposure on the brain, and continued research efforts are essential.
... Four published cross-sectional studies have investigated cortical thickness in children with prenatal alcohol exposure, with three finding increased cortical thickness [Fernandez-Jaen et al., 2011;Sowell et al., 2008;Yang et al., 2012] and one finding reduced cortical thickness [Zhou et al., 2011] relative to typically developing controls. One of these studies found both increased thickness and positive correlations with cognitive scores in the FASD group (whereby thinner cortex related to poorer performance on verbal recall and memory scores) [Sowell et al., 2008], further complicating interpretation of these contrasting results. ...
... These findings highlight the impact of quantity and timing of gestational exposure on subsequent development in childhood, which may contribute to contrasting results in previous crosssectional studies that have included varied clinical severities under the FASD umbrella. Although mean age has been similar across previous cross-sectional cortical thickness studies [Fernandez-Jaen et al., 2011;Sowell et al., 2008;Yang et al., 2012;Zhou et al., 2011], other differences, Examples of significant regional age-by-group interactions (A-C) and a contrasting example showing significant thinning in both groups with no significant interaction (D). Age-effects are shown in the first column for controls (solid lines) and second column for FASD participants (dotted lines), followed by age-by-group interactions in the third column. ...
... such as the proportion of participants with full FAS (ranging from 10% [Zhou et al., 2011] to 100% [Fernandez-Jaen et al., 2011]), presence of co-morbid ADHD (ranging from 30% [Yang et al., 2012;Zhou et al., 2011] to 100% [Fernandez-Jaen et al., 2011]) and mean IQ, (65 in [Yang et al., 2012], not reported in others) may also contribute to inconsistent findings. Age-by-group interactions emphasize the value of longitudinal data in uncovering trajectories that may have been masked in previous cross-sectional studies. ...
Brain imaging studies suggest that cortical thickness decreases during childhood and adolescence, in concert with underlying structural and synaptic changes required for cognitive maturation and regional specialization of function. Abnormalities of this protracted developmental process may provide key insights into the cognitive and behavioral deficits that emerge in individuals with fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cortical thickness differences in children and adolescents who were prenatally exposed to alcohol, though all have been cross sectional, limiting conclusions about cortical development with age. In this study, we analyze serially collected T1-weighted MRI from 11 children with FASD and 21 controls, scanned twice each ∼2 to 4 years apart. Mixed-models analysis of cortical thickness measurements revealed age-by-group interactions in cortical thinning, with FASD participants undergoing less developmental thinning than controls across many regions of the cortex, particularly in medial frontal and parietal areas. These results provide further longitudinal evidence in humans that prenatal alcohol exposure is associated with altered patterns of brain development that persist during childhood and adolescence. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
... Overall brain volume is commonly reduced in PAE and is widespread including gray matter (cortical and subcortical) and white matter [Gautam et al., 2015a; for a review, see Lebel et al., 2011]. Alterations of regional cortical thickness in PAE relative to controls has been more variable with reductions [Robertson et al., 2015;Treit et al., 2014;Zhou et al., 2011], increases [Fern andez-Ja en et al., 2011;Sowell et al., 2008;Yang et al., 2012], or no differences [Rajaprakash et al., 2014;Wozniak et al., 2013]. Previous studies showed that lower regional cortical thickness was associated with higher degrees of PAE [Gautam et al., 2015b;Robertson et al., 2015]. ...
... The thinner cortex in PAE replicates our previous study on 33 PAE participants [Zhou et al., 2011], with similar patterns that cover bilateral paracentral, inferior frontal, temporal, and occipital regions ( Fig. 1d and Fig. 2d in Zhou et al. [2011]). Three previous studies have reported increased regional cortical thickness for PAE participants in a variety of brain regions including in bilateral temporal lobes and the right frontal lobe [Fern andez-Ja en et al., 2011], in bilateral temporal and inferior parietal and right inferior frontal regions [Sowell et al., 2008], and in frontal, temporal, and parietal regions [Yang et al., 2012]. The two latter studies were from the same research group and had partly overlapping participants. ...
Prenatal alcohol exposure (PAE) is associated with reduced overall brain volume. Although this has been reported consistently across studies, the status of cortical thickness after PAE is more variable. The cortex is asymmetric in typical controls, but it is unclear whether the left and right counter parts of the cortical gray matter are unevenly influenced in postpartum brain development after PAE. Brain MRI was acquired in a newly recruited sample of 157 participants (PAE: N = 78, 5.5–18.9 years, 40 females and controls: N = 79, 5.8–18.5 years, 44 females) across four Canadian sites in the NeuroDevNet project. The PAE group had other confounds such as psychiatric co-morbidity, different living environment, and so on, not present in the control group. In agreement with previous studies, the volumes of all brain structures were reduced in PAE compared to controls, including gray and white matter of cerebrum and cerebellum, and all deep gray matter including the hippocampus, amygdala, thalamus, caudate, putamen, and pallidum. The PAE group showed reductions in global and regional cortical thickness, while the pattern and degree of cortical thickness asymmetry were preserved in PAE participants with the greatest rightward asymmetry in the lateral parietal lobe and the greatest leftward asymmetry in the lateral frontal cortex. This persistent asymmetry reflects that the homologous left and right cortical regions followed typical relative developmental patterns in the PAE group despite being thinner bilaterally than controls. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
... Verbal learning and memory requires input from a number of brain regions that are affected in children with FASD. For example, individuals with prenatal alcohol exposure have smaller volumes (Chen et al. 2012;Coles et al. 2011;Rajaprakash et al. 2014) and surface areas (Rajaprakash et al. 2014) in the frontal cortex compared to controls, although research on cortical thickness has produced mixed results (Fernandez-Jaen et al. 2011;Rajaprakash et al. 2014;Robertson et al. 2016;Yang et al. 2012;Zhou et al. 2011). As cortical thickness and surface area have distinct developmental trajectories in typically developing populations (Giedd et al. 2015;Lenroot and Giedd 2008), and at least some aspects of neurodevelopment appear to be altered in subjects with prenatal alcohol exposure (Gautam et al. 2015;Lebel et al. 2012), some of these discrepancies may be result of variance being masked or enhanced due to the age range of the sample (e.g. ...
... To our knowledge, only two other studies have examined surface area in this population, and both have reported smaller surface area in AE (Migliorini et al. 2015;Rajaprakash et al. 2014). Several studies have examined cortical thickness in this population but findings have varied widely, reporting greater thickness (Fernandez-Jaen et al. 2011;Sowell et al. 2008;Yang et al. 2012), thinning (Zhou et al. 2011), or no significant differences compared to controls (Rajaprakash et al. 2014). Further investigation into these thickness discrepancies is warranted, but two methodological factors-how thickness is measured and in-scanner motion-likely account for some of the variability in reports (Walhovd et al. 2016). ...
Prenatal alcohol exposure can impact both brain development and neurobehavioral function, including verbal learning and recall, although the relation between verbal recall and brain structure in this population has not been examined fully. We aimed to determine the structural neural correlates of verbal learning and recall in youth with histories of heavy prenatal alcohol exposure using a region of interest (ROI) approach. As part of an ongoing multisite project, subjects (age 10-16 years) with prenatal alcohol exposure (AE, n = 81) and controls (CON, n = 81) were tested using the CVLT-C and measures of cortical volume, surface area, and thickness as well as hippocampal volume were derived from MRI. Group differences in brain and memory indices were tested with ANOVA. Multiple regression analyses tested whether brain ROIs significantly predicted memory performance. The AE group had lower scores than the CON group on all CVLT-C variables (ps ≤ .001) and volume and surface area (ps < .025), although results varied by ROI. No group differences in cortical thickness were found. The relations between cortical structure and memory performance differed between group among some ROIs, particularly those in the frontal cortex, generally with smaller surface area and/or thinner cortex predicting better performance in CON but worse performance in AE. Cortical surface area appears to be the most sensitive index to the effects of prenatal alcohol exposure, while cortical thickness appears to be the least sensitive. These findings also indicate that the neural correlates of verbal memory are altered in youth with heavy prenatal alcohol exposure compared to controls.
... In children and youth with FASD, studies have reported both thicker (Fernandez-Jaen et al., 2011;Sowell et al., 2008b;Yang et al., 2011b) and thinner cortex (Robertson et al., 2016;Zhou et al., 2011). Software packages vary in how they calculate cortical thickness and may lead to slight differences in findings; however, processing differences should not produce completely opposite results. ...
Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by prenatal exposure to alcohol. FASD is characterized by life-long cognitive, behavioural, and neurological deficits. This includes structural and functional brain alterations that are apparent, dynamically, across the lifespan. The initial understanding of brain alterations in FASD came from post-mortem autopsy studies. However, advances in neuroimaging over the past quarter century have permitted greater understanding of the common effects that prenatal alcohol exposure can have on the brain. This chapter provides an in-depth summary of the major findings from magnetic resonance imaging (MRI) research in children and adults with histories of prenatal alcohol exposure. Global brain alterations are reviewed, including those from structural and functional MRI techniques. The implications of more subtle brain abnormalities are then discussed, in relation to both their functional (clinical) relevance and impact on neurodevelopmental trajectories across the lifespan. Necessary next steps and acknowledged gaps in clinical and scientific understanding also are discussed.
... Neuroimaging has helped highlight the neurodevelopmental effects, reliably demonstrating both macrostructural and microstructural brain abnormalities (Archibald et al., 2001;Nardelli et al., 2011;Roussotte et al., 2012;Sowell et al., 2008Sowell et al., , 2002Swayze et al., 1997;Wozniak et al., 2009) for reviews, see Moore et al., 2014). More subtle disruptions in functional connectivity have also been observed Santhanam et al., 2011;Wozniak et al., 2013Wozniak et al., , 2011) and a few studies have begun to show atypical cortical development including abnormal gyrification (De Guio et al., 2014;Hendrickson et al., 2017;Infante et al., 2015), cortical thickness (Fernández-Jaén et al., 2011;Robertson et al., 2016;Sowell et al., 2008;Treit et al., 2014;Yang et al., 2012;Zhou et al., 2011), and cortical surface area and volume (Lebel et al., 2012;Leigland et al., 2013;Migliorini et al., 2015;Rajaprakash et al., 2014;Roussotte et al., 2012;Treit et al., 2013). ...
Objectives:
Cortical abnormalities in prenatal alcohol exposure (PAE) are known, including in gyrification (LGI), thickness (CT), volume (CV), and surface area (CS). This study provides longitudinal and developmental context to the PAE cortical development literature.
Experimental design:
Included: 58 children with PAE and 52 controls, ages 6-17 at enrollment, from four Collaborative Initiative on FASD (CIFASD) sites. Participants underwent a formal evaluation of physical anomalies and dysmorphic facial features associated with PAE. MRI data were collected on three platforms (Siemens, GE, and Philips) at four sites. Scans were spaced two years apart. Change in LGI, CT, CS, and CV were examined.
Principal observations:
Several significant regional age-by-diagnosis linear and quadratic interaction effects in LGI, CT, and CV were found, indicating atypical developmental trajectories in PAE. No significant correlations were observed between cortical measures and IQ.
Conclusions:
Regional differences were seen longitudinally in CT, CV, and LGI in those with PAE. The findings represent important insights into developmental trajectories and may have implications for the timing of assessments and interventions in this population. It is noteworthy that cortical metrics did not correlate with IQ, suggesting that more specific aspects of cognitive development may need to be explored to provide further context.
... As it is known, the weight of the brain cortex in the offspring of rats exposed to alcohol during pregnancy is reduced, it becomes thinner and contains fewer neurons and glia (at G13 and G21) [9]. These findings contradict the results of MRI showing thickening of the brain cortex in children and adolescents with fetal alcohol syndrome [10]. Our study revealed an increased (on the 2 nd and 5 th postnatal days) and decrease (on the 90 th postnatal day) parietal cortex thickness. ...
... El consumo de alcohol aumenta el riesgo de restricción del crecimiento intrauterino, de aborto espontáneo u óbito fetal. La manifestación característica y más grave de la exposición fetal al alcohol es el síndrome de alcohol fetal, que incluye distintos grados de microcefalia, retraso del crecimiento, lesiones cardíacas, alteraciones faciales y en el desarrollo neurológico (6,7) . Si bien el nivel de evidencia no es tan fuerte, también se han observado efectos negativos en la salud del niño a largo plazo por la exposición a tabaco y alcohol durante la gestación, como aumento del riesgo de obesidad, trastornos en el comportamiento y peor rendimiento escolar (8) . ...
Introducción: la prevalencia del consumo de drogas entre las mujeres que quedan embarazadas es probable que sea similar al de la población general, lo que puede resultar en una alta exposición fetal durante el primer trimestre, etapa más vulnerable con respecto al neurodesarrollo y organogénesis(1).
Objetivo: conocer la prevalencia de consumo de tabaco, alcohol, marihuana y derivados de cocaína durante el embarazo, según el autorreporte en mujeres que tuvieron su parto en el Centro Hospitalario Pereira Rossell.
Material y método: se realizó un estudio descriptivo de tipo transversal, analítico, durante el período de un año. Los datos fueron recabados a partir de una encuesta protocolizada realizada a mujeres durante el puerperio inmediato y se recolectaron datos de la historia clínica.
Resultados: se entrevistaron 319 mujeres. La mayoría eran mayores de 18 años (83,65%) con una media de 24,67 años; el embarazo no había sido planificado en 182 casos (57%). Declararon haber fumado tabaco alguna vez durante el embarazo 136 mujeres (42,63%), la mayor parte de las que abandonaron el hábito lo hicieron en el primer trimestre. Declararon consumo de alcohol en el embarazo 76 mujeres (23,82%), 5 (1,5%) reportaron consumo de marihuana durante el embarazo. Declararon consumir cocaína y pasta base de cocaína 3 (0,94%) y 3 (0,94%), respectivamente.
Conclusiones: la sustancia que se consume con mayor frecuencia en el embarazo es el tabaco seguido en frecuencia por el alcohol. Un elevado porcentaje de embarazos no planificados puede determinar una mayor exposición a hábitos previos durante el primer trimestre de gestación, período de máxima vulnerabilidad para el desarrollo fetal.
... 18 yielded inconsistent group differences, with some studies finding reductions (Gautam et al., 2015b;Robertson et al., 2016;Zhou et al., 2011), increases (Fernandez-Jaen et al., 2011;Sowell et al., 2008;Yang et al., 2012) or no difference in cortical thickness in the FASD group relative to controls (Rajaprakash et al., 2014;Wozniak et al., 2013). others (Gautam et al., 2015b;Robertson et al., 2016), as well as less age-related change of cortical thickness in the FASD group in keeping with our previous longitudinal study (Treit et al., 2014), albeit in a cross-sectional cohort here. ...
Quantitative magnetic resonance imaging (MRI) has revealed abnormalities in brain volumes, cortical thickness and white matter microstructure in fetal alcohol spectrum disorders (FASD); however, no study has reported all three measures within the same cohort to assess the relative magnitude of deficits, and few studies have examined sex differences. Participants with FASD (n = 70; 30 females; 5–32 years) and healthy controls (n = 74; 35 females; 5–32 years) underwent cognitive testing and MRI to assess cortical thickness, regional brain volumes and fractional anisotropy (FA)/mean diffusivity (MD) of white matter tracts. A significant effect of group, age-by-group, or sex-by-group was found for 9/9 volumes, 7/39 cortical thickness regions, 3/9 white matter tracts, and 9/10 cognitive tests, indicating group differences that in some cases differ by age or sex. Volume reductions for several structures were larger in males than females, despite similar deficits of cognition in both sexes. Correlations between brain structure and cognitive scores were found in females of both groups, but were notably absent in males. Correlations within a given MRI modality (e.g. total brain volume and caudate volume) were prevalent in both the control and FASD groups, and were more numerous than correlations between measurement types (e.g. volumes and diffusion tensor imaging) in either cohort. This multi-modal MRI study finds widespread differences of brain structure in participants with prenatal alcohol exposure, and to a greater extent in males than females which may suggest attenuation of the expected process of sexual dimorphism of brain structure during typical development.
... Significant reductions in overall brain volumes and in specific brain regions in children with FASDs were reported in several studies (Archibald et al., 2001;Autti-Ramo et al., 2002;Gautam et al., 2015;Johnson, Swayze, Sato, & Andreasen, 1996;Sowell et al., 2002;Willoughby, Sheard, Nash, & Rovet, 2008). Cortical thickness, white matter, and subcortical gray matter in children with prenatal alcohol exposure are also subjects of change; however, the changes in these parameters are not unidirectional: greater cortical thickness was observed in parietal and posterior temporal regions (Fernandez-Jaen et al., 2011;Sowell et al., 2008Sowell et al., , 2001Sowell et al., , 2002Yang et al., 2012). In contrast, reduced cortical thickness was reported by other groups (Treit et al., 2014;Zhou et al., 2011), especially at ages when cortical thickness is expected to be at its maximum (Robertson et al., 2016). ...
Fetal alcohol spectrum disorders (FASDs) are a result of the teratogenic effects of alcohol on the developing fetus. Decades of research examining both individuals with FASDs and animal models of developmental alcohol exposure have revealed the devastating effects of alcohol on brain structure, function, behavior, and cognition. Neurotrophic factors have an important role in guiding normal brain development and cellular plasticity in the adult brain. This chapter reviews the current literature showing that alcohol exposure during the developmental period impacts neurotrophin production and proposes avenues through which alcohol exposure and neurotrophin action might interact. These areas of overlap include formation of long-term potentiation, oxidative stress processes, neuroinflammation, apoptosis and cell loss, hippocampal adult neurogenesis, dendritic morphology and spine density, vasculogenesis and angiogenesis, and behaviors related to spatial memory, anxiety, and depression. Finally, we discuss how neurotrophins have the potential to act in a compensatory manner as neuroprotective molecules that can combat the deleterious effects of in utero alcohol exposure.
... In contrast, FASD presented with cortical thinning in several lobes. Meanwhile, another group assessed a greater cortical thickness in 20 individuals (mean age 10.9 years) with FAS and diagnosed with attention deficit hyperactivity disorder in comparison to individuals with attention deficit hyperactivity disorder but without FAS or in comparison to a control group (Fernandez-Jaen et al., 2011). Similarly, Yang et al. found a thicker cortex in 69 children and adolescents with FASD from three different sites and mixed diagnosis (mean age 13.4 years, range 8-16) versus 58 nonexposed controls (Figure 4) (Yang et al., 2012). ...
Various magnetic resonance imaging (MRI) markers have emerged to describe the in vivo teratogenic effects of prenatal alcohol exposure on the structure of the brain. As for other brain structures, disturbance of the cortex has been implicated in fetal alcohol spectrum disorders (FASD). This chapter focuses on MRI-based cortical morphology in FASD and aims to (1) explain the principles of cortical morphology, (2) describe the various cortical parameters that can be measured from high-resolution anatomical MRI, (3) review the results obtained so far in subjects with FASD, and (4) discuss the possible applications to the development of biomarkers for the diagnosis and study of the pathophysiology of FASD.
... CT, the most commonly studied parameter, refers to the distance between the brain's inner white-matter (WM) and outer gray-matter (GM) (i.e., pial) surfaces measured across the entire cortex (34). A number of neurodevelopmental conditions, such as autism spectrum disorder, attention-deficit hyperactive disorder, human X monosomy, fetal alcohol spectrum disorder, and William's syndrome show a wide variety of CT abnormalities (35)(36)(37)(38)(39)(40)(41)(42), which are typically attributed to defects in neuronal migration or cortical layering (43,44). Recently, we reported that children with congenital hypothyroidism (CH), who are TH-deficient in the period from late gestation until the first month or two of life, show cortical thinning and thickening in diverse regions with specific effects reflecting initial disease severity and predicting current neuropsychological functioning (45). ...
In rodents, insufficient thyroid hormone (TH) gestationally has adverse effects on cerebral cortex development. Comparable studies of humans examining how TH insufficiency affects cortical morphology are limited to children with congenital hypothyroidism or offspring of hypothyroxinemic women; effects on cortex of children born to women with clinically diagnosed hypothyroidism are not known. We studied archived MRI scans from 22 children aged 10 to 12 years born to women treated for preexisting or de novo hypothyroidism within pregnancy (HYPO) and 24 similar age and sex controls from euthyroid women. FreeSurfer Image Analysis Suite software was used to measure cortical thickness (CT) and a vertex-based approach served to compare HYPO versus control groups and Severe versus Mild HYPO subgroups as well as to perform regression analyses examining effects of trimester-specific maternal TSH on CT. Results showed that relative to controls, HYPO had multiple regions of both cortical thinning and thickening, which differed for left and right hemispheres. In HYPO, thinning was confined to medial and mid-lateral regions of each hemisphere and thickening to superior regions (primarily frontal) of the left hemisphere and inferior regions (particularly occipital and temporal) of the right. The Severe HYPO subgroup showed more thinning than Mild in frontal and temporal regions and more thickening in bilateral posterior and frontal regions. Maternal TSH values predicted degree of thinning and thickening within multiple brain regions, with the pattern and direction of correlations differing by trimester. Notably, some correlations remained when cases born to women with severe hypothyroidism were removed from the analyses suggesting mild variations of maternal TH may permanently affect offspring cortex. We conclude that maternal hypothyroidism during pregnancy has long-lasting manifestations on the cortical morphology of their offspring with specific effects reflecting both severity and timing of maternal TH insufficiency.
... The observation of reduced developmental cortical thinning was related to changes seen in individuals with FASD, as revealed by imaging studies (Sowell et al., 2004;Treit et al, 2014), which suggested critical alterations of the developmental trajectory. Importantly, their findings are also consistent with work demonstrating inhibited frontal cortex thinning in children with both attention deficit/hyperactivity disorder and FASD, compared to those with FASD alone, (Fernández-Jaén et al., 2011), which supports the suggestion of delayed or immature brain development. ...
... The failure to prune these aberrant connections may be involved in delayed cortical thinning, with these alterations potentially underlying the impaired coordination and increased anxiety we observed in P50 PrEE mice. Further evidence demonstrating the dysfunctional impact of inhibited FC thinning can be found in human studies which have demonstrated that FC thickness during development is increased in individuals with both attention-deficit/ hyperactivity disorder and FASD when compared to those suffering from FASD alone, a finding they attribute to immature brain development (Fernández-Jaén et al., 2011). ...
Background:
In utero alcohol, or ethanol (EtOH), exposure produces developmental abnormalities in the brain of the fetus, which can result in lifelong behavioral abnormalities. Fetal alcohol spectrum disorders (FASD) is a term used to describe a range of adverse developmental conditions caused by EtOH exposure during gestation. Children diagnosed with FASD potentially exhibit a host of phenotypes including growth retardation, facial dysmorphology, central nervous system anomalies, abnormal behavior, and cognitive deficits. Previous research suggests that abnormal gene expression and circuitry in the neocortex may underlie reported disabilities of learning, memory, and behavior resulting from early exposure to alcohol (J Neurosci, 33, 2013, 18893).
Methods:
Here, we utilize a mouse model of FASD to examine effects of prenatal EtOH exposure (PrEE), on brain anatomy in newborn (postnatal day [P]0), weanling (P20), and early adult (P50) mice. We correlate abnormal cortical and subcortical anatomy with atypical behavior in adult P50 PrEE mice. In this model, experimental dams self-administered a 25% EtOH solution throughout gestation (gestational days 0 to 19, day of birth), generating the exposure to the offspring.
Results:
Results from these experiments reveal long-term alterations to cortical anatomy, including atypical developmental cortical thinning, and abnormal subcortical development as a result of in utero EtOH exposure. Furthermore, offspring exposed to EtOH during the prenatal period performed poorly on behavioral tasks measuring sensorimotor integration and anxiety.
Conclusions:
Insight from this study will help provide new information on developmental trajectories of PrEE and the biological etiologies of abnormal behavior in people diagnosed with FASD.
... A limited number of investigations have examined cortical thickness in children with FASD. Findings suggest that alcohol-exposed individuals have thicker cortices in the frontal, parietal, and temporal lobes compared to controls (Sowell et al., 2008b;Fernandez-Jaen et al., 2011). Similar findings occur in dysmorphic and non-dysmorphic children, particularly in the left inferior frontal and right superior and middle temporal cortices (Yang et al., 2012b), and results correlated with facial dysmorphology (Yang et al., 2012b) and cognitive outcomes (Sowell et al., 2008b). ...
... A number of studies have found differences in cortical thickness in individuals prenatally exposed to alcohol compared to non-exposed peers, but these findings have not been consistent. Some studies have reported increased thickness primarily in frontal, parietal, and temporal regions (Fernandez-Jaen et al., 2011;Sowell et al., 2008;Yang et al., 2012), whereas others have found decreased cortical thickness across multiple regions (Robertson et al., 2015;Treit et al., 2014;Zhou et al., 2011). In addition, one study found no differences in cortical thickness between children with alcohol-related neurodevelopmental disorder and typically developing control children (Rajaprakash, Chakravarty, Lerch, & Rovet, 2014). ...
Prenatal alcohol exposure can adversely affect brain development, although little is known about the effects of prenatal alcohol exposure on gyrification. Gyrification reflects cortical folding complexity and is a process by which the surface of the brain creates sulci and gyri. Prior studies have shown that prenatal alcohol exposure is associated with reduced gyrification in childhood, but no studies have examined adolescents. Subjects (12-16y) comprised two age-equivalent groups: 30 adolescents with histories of heavy prenatal alcohol exposure (AE) and 19 non-exposed controls (CON). A T1-weighted image was obtained for all participants. Local gyrification index (LGI) was estimated using FreeSurfer. General linear models were used to determine between group differences in LGI controlling for age and sex. Age-by-group interactions were also investigated while controlling for sex. The AE group displayed reduced LGI relative to CON in the bilateral superior parietal region, right postcentral region, and left precentral and lateral occipital regions (ps <.001). Significant age-by-group interactions were observed in the right precentral and lateral occipital regions, and in the left pars opercularis and inferior parietal regions (ps <.01). The AE group showed age-related reductions in gyrification in all regions whereas the CON group showed increased gyrification with age in the lateral occipital region only. While cross-sectional, the age-related reduction in gyrification observed in the AE group suggests alterations in cortical development throughout adolescence and provides further insight into the pathophysiology and brain maturation of adolescents prenatally exposed to alcohol.
Copyright © 2015. Published by Elsevier B.V.
... In rats, ethanol applied throughout gestation caused slightly thinner cortex at P11, but cortical thickness was nearly normal by P60, even though reduced volume and surface area persisted (Leigland et al., 2013). In adolescent and adult FASD subjects, cerebral cortex was found to be thicker than controls, perhaps reflecting compensatory development after ethanol-induced damage (Fernández-Jaén et al., 2011;Sowell et al., 2008;Yang et al., 2012). However, there is also a finding of thinner cortex in FASD subjects (Zhou et al., 2011). ...
... La fetopatía alcohólica puede cursar con malformaciones congénitas variadas, anomalías faciales, retraso de crecimiento y del perímetro craneal (a expensas de la sustancia blanca), y otras anomalías estructurales (la más frecuente es un mayor grosor cortical de predominio frontal), que pueden a veces ocasionar epilepsia [5,7]). El diagnóstico diferencial con síndromes malformativos de origen genético puede ser complicado, por lo que la historia y la exploración clínica deben ser minuciosas. ...
Introduction:
The term adoption or adoptive filiation is understood as referring to the legal act by which family ties are created between two persons such that a relationship of fatherhood or motherhood is established between them. AIMS. The purpose of this study is to outline the problems derived from prenatal exposure to alcohol and other risk factors, from hypostimulation during the 'critical period' in institutionalised patients (especially those adopted from eastern European countries) and their relation with attention deficit hyperactivity disorder (ADHD). This work also seeks to take a deeper look into the diagnosis, prevention and treatment of these problems.
Development:
These children have problems in terms of psychosocial relationships, behavioural problems, delayed language or reading development and, above all, ADHD. In practice it is extremely difficult to separate the two factors during the assessment of children adopted from eastern European countries in neuropaediatric consultations. Exactly how all these factors are interrelated is not well understood.
Conclusions:
There is a close relationship between prenatal exposure to alcohol and the consequences of adoption. There is a need for placebo-controlled randomised studies, with larger population samples, that test the benefits and profile of side effects, both with psychostimulants and with atomoxetine in this group of patients.
... A limited number of investigations have examined cortical thickness in children with FASD. Findings suggest that alcohol-exposed individuals have thicker cortices in the frontal, parietal, and temporal lobes compared to controls (Sowell et al., 2008b;Fernandez-Jaen et al., 2011). Similar findings occur in dysmorphic and non-dysmorphic children, particularly in the left inferior frontal and right superior and middle temporal cortices (Yang et al., 2012b), and results correlated with facial dysmorphology (Yang et al., 2012b) and cognitive outcomes (Sowell et al., 2008b). ...
Alcohol consumption during pregnancy can have deleterious consequences for the fetus, including changes in central nervous system development leading to permanent neurologic alterations and cognitive and behavioral deficits. Individuals affected by prenatal alcohol exposure, including those with and without fetal alcohol syndrome, are identified under the umbrella of fetal alcohol spectrum disorders (FASD). While studies of humans and animal models confirm that even low to moderate levels of exposure can have detrimental effects, critical doses of such exposure have yet to be specified and the most clinically significant and consistent consequences occur following heavy exposure. These consequences are pervasive, devastating, and can result in long-term dysfunction. This chapter summarizes the neurobehavioral, neurologic, and neuroimaging characteristics of FASD, focusing primarily on clinical research of individuals with histories of heavy prenatal alcohol exposure, although studies of lower levels of exposure, particularly prospective, longitudinal studies, will be discussed where relevant.
... Although the mechanism by which ethanol exposure leads to increased activity levels is unknown, however children with FASD often develop Attention Deficit Hyperactivity Disorder (ADHD) comorbidity [77][78][79]. This phenotype may be associated with neuronal reduction within the basal ganglia, cerebellum, and the prefrontal cortex [80,81] or abnormal cortical thickness [82]. These abnormalities have been observed in both FASD and ADHD, and are implicated in executive functioning and motor activity [83,84]. ...
Maternal drinking during pregnancy can result in a wide spectrum of cognitive and behavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The heterogeneity observed in FASD-related phenotypes can be attributed to a number of environmental and genetic factors; however, ethanol dose and timing of exposure may have significant influences. Here, we report the behavioral effects of acute, binge-like ethanol exposure at three neurodevelopmental times corresponding to the first, second, and third trimester of human development in C57BL/6J mice. Results show that developmental ethanol exposure consistently delays the development of basic motor skill reflexes and coordination as well as impairs spatial learning and memory. Observed changes in activity and anxiety-related behaviors, however, appear to be dependent on timing of alcohol exposure. The variability in behaviors between different treatment models suggests that these may be useful in evaluating the mechanisms disrupted by ethanol at specific neurodevelopmental times. The results provide further evidence that, regardless of developmental stage, the developing brain is acutely sen-sitive to alcohol exposure.
... Preprocessing and cortical thickness measurement was performed by two experienced technicians who were blinded to the subjects' group assignments. A detailed description of the sequential, semi-automated approach used in the present study to measure cortical thickness can be found elsewhere (Fernández-Jaén et al., 2011). Briefly, it comprises three successive steps: 1) automated removal of non-brain tissue using FSL's brain extraction tool (BET), 2) automatic segmentation of selected brain tissue into tissue types including gray matter, white matter or cerebrospinal fluid using the FSL's FAST tool, and 3) measurement of cortical thickness for each subject using the Laplace method as implemented in BrainVoyager (Goebel et al., 2006). ...
... Surprisingly, our CT results failed to differentiate individuals with ARND from controls, thus providing no support for previous studies showing either cortical thinning (Zhou et al. 2011) or cortical thickening (Sowell et al. 2008;Fern andez-Ja en et al. 2011;Yang et al. 2012) in areas of the frontal, temporal, and parietal cortices. This lack of difference may reflect methodological differences in the various image processing pipelines used and the methods for correcting for multiple comparisons, as well as the different sample compositions across studies that varied in diagnoses, age ranges, and levels and timing of prenatal alcohol exposure. ...
It is well established that individuals exposed to alcohol in utero have reduced cortical grey matter volumes. However, the candidate determinants of these reductions, cortical thickness (CT) and surface area (SA), have not been investigated exclusively in alcohol-related neurodevelopmental disorder (ARND), the most prevalent fetal alcohol spectrum disorder subgroup that lacks the characteristic facial dysmorphology.
T1-weighted magnetic resonance imaging scans were obtained from 88 participants (8-16 years), 36 diagnosed with ARND and 52 typically developing controls. Scans were submitted to the CIVET pipeline (version 1.1.10). Deformable models were used to construct the inner white matter surfaces and pial surfaces from which CT and SA measures were derived. Group differences in cortical volume, CT, and SA were computed using a general linear model covaried for age, sex, and handedness.
Global cortical volume reductions in ARND did not reflect CT, which did not differ between groups. Instead, volume decreases were consistent with global SA reductions in bilateral frontal and temporal as well as right occipital regions. Local reductions in SA were observed in the right superior temporal gyrus and the right occipital-temporal region.
Results suggest that in ARND, prenatal alcohol exposure perturbs global SA to a greater degree than CT, particularly in the right temporal lobe.
... The sequential method for analysing CTh was previously described by our group. 24 Three steps were performed successively: 1) automated removal of non-brain tissue using the Bet extraction tool, 25 2) automatic segmentation of the selected brain tissue into tissue types, including grey matter, white matter and cerebrospinal fluid, using the FSL's FAST tool, and 3) CTh measurement for each subject using the Laplace method, as implemented in BrainVoyager. 26 Prior to this analysis, anatomical data from each subject was resampled and transformed into ACPC space and Talairach standard space. ...
Background
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with a low incidence in the paediatric population; cortical atrophy is often striking, even in the early stages of the disease. Evidence of cortical thinning in childhood MS is scant.
Aims
This study aimed to assess cortical thickness in paediatric patients during the initial attack of remitting-relapsing MS.
Methods
We report two cases of remitting-relapsing MS, with initial attacks at 12 and 16 years of age. We analysed brain cortical thickness (CTh) in these patients and compared these data to the CTh of a control group comprised of six 12-year-old females and six 16-year-old males.
Results
Both cases exhibited a total brain CTh significantly below that of the control group. This difference was also observed when analysing the CTh of all lobes except the left parietal lobe in one of the cases.
Conclusions
Cortical atrophy is already present at the time of onset of MS. Studies with larger patient populations that have a more homogenous clinical presentation could identify the time of onset of cortical atrophy and use this parameter as a prognostic and/or treatment marker of MS.
Fetal alcohol spectrum disorder (FASD) is a neurodevelopmental disorder caused by prenatal exposure to alcohol. FASD is characterized by life-long cognitive, behavioural, and neurological deficits. These include structural and functional brain alterations that are apparent, dynamically, across the lifespan. The initial understanding of brain alterations in FASD came from post-mortem autopsy studies. However, advances in neuroimaging over the past quarter century have permitted a greater understanding of the common effects that prenatal alcohol exposure can have on the brain. This chapter provides an in-depth summary of the major findings from magnetic resonance imaging (MRI) research in children and adults with histories of prenatal alcohol exposure. Global brain alterations are reviewed, including those from structural and functional MRI techniques. The implications of more subtle brain abnormalities are then discussed, in relation to both their functional (clinical) relevance and impact on neurodevelopmental trajectories across the lifespan. Necessary next steps and acknowledged gaps in clinical and scientific understanding also are discussed.
Foetal alcohol spectrum disorders (FASDs) are a spectrum of neurological disorders whose neurological symptoms, besides the neuronal damage caused by alcohol, may also be associated with neuroglial damage. Tubulin-binding cofactor B (TBCB) may be involved in the pathogenesis of FASD. To understand the mechanism and provide new insights into the pathogenesis of FASD, acute foetal alcohol exposure model on astrocytes was established and the interference experiments were carried out. First, after alcohol exposure, the nascent astrocyte processes were reduced or lost, accompanied by the absence of TBCB expression and the disruption of microtubules (MTs) in processes. Subsequently, TBCB was silenced with siRNA. It was severely reduced or lost in nascent astrocyte processes, with a dramatic reduction in astrocyte processes, indicating that TBCB plays a vital role in astrocyte process formation. Finally, the regulating mechanism was studied and it was found that the extracellular signal-regulated protease 1/2 (ERK1/2) signalling pathway was one of the main pathways regulating TBCB expression in astrocytes after alcohol injury. In summary, after acute foetal alcohol exposure, the decreased TBCB in nascent astrocyte processes, regulated by the ERK1/2 signalling pathway, was the main factor leading to the disorder of astrocyte process formation, which could contribute to the neurological symptoms of FASD.
Fetal alcohol spectrum disorders (FASD) are neurodevelopmental/neurobehavioral conditions caused by prenatal alcohol exposure (PAE). Impairments caused by PAE contribute to the over‐representation of individuals with FASD in the United States juvenile and adult criminal justice systems. These same impairments can equally impact on individuals with FASD who are witnesses to or victims of crime who also have to navigate the complexities of the criminal justice system. Difficulties include increased susceptibility to confabulation throughout the legal process that, in turn, can contribute to increased rates of poor outcomes including false confessions and wrongful convictions. Individuals with FASD are particularity at risk of confabulation when they are subjected to tactics, such as stressful and anxiety‐provoking situations, threats, and leading, suggestive, or coercive questioning. Many professionals in the forensic context are unfamiliar with FASD or related confabulation risk and may unintentionally utilize tactics that intensify impacts of pre‐existing impairment. This article serves as a beginner’s guide for professionals working in criminal justice settings by (a) providing research‐based overviews of FASD and confabulation, (b) describing how FASD may lead to confabulation, and (c) suggesting ways that professionals can modify protocols when interacting with individuals with FASD. Suggestions in this article hold the potential to decrease the risk of confabulation in the criminal justice system and decrease problematic outcomes, such as false confessions and wrongful convictions among individuals with FASD.
With nearly 10% of women consuming alcohol during pregnancy, fetal alcohol spectrum disorders (FASDs) are becoming an increasing concern for clinicians and policymakers interested in the field of healthcare. Known as the range of mental and/or physical disabilities that occur among individuals with prenatal alcohol exposure, FASDs can result in dysmorphic features, problems with physical growth, neurobehavioral and cognitive problems that not only increase risk of various diseases, but also premature mortality. We investigated whether the diagnosis of FASDs result in increased risk of hospitalizations and mortality, with respect to FASD domains and relative diseases, when age effects are controlled for. The data for this study was taken from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) between 2003 and 2013. The population attributable risk (PAR) statistic was used to estimate the percentage of hospitalizations and mortality attributable to FASDs and other factors. A time-dependent Cox proportional hazards model with age of diagnosis as the timescale was employed to calculate adjusted hazard ratios and 95% CIs for hospitalizations and mortality among FASD populations compared to their general population peers. Among the 3,103 FASD cases, 27.5% experienced hospitalizations and 12.5% died. Overall, FASDs accounted for 853 FASD-attributable hospitalizations (51.0% of all hospitalizations in the study population) and 387 mortality events (34.5% of all deaths in the study population). 20.52% of hospitalizations and 21.35% of mortalities were attributable to FASDs in this population. Compared to the control group, FASD patients had a 1.25-fold (HR: 1.25, 95% CI: 1.05-1.49, p = 0.0114) increased risk of hospitalizations and a 1.33-fold (HR: 1.33, 95% CI: 1.07-1.67, p = 0.0118) increased risk of all-cause mortality. The most common cause for hospitalization was diseases of the nervous system, which accounted for 450 FASD-attributable hospitalizations (96.2% of all nervous system hospitalizations in the study population). In fact, FASD patients were 52 times more likely to be hospitalized for nervous system diseases than their peers (HR: 51.78, 95% CI: 29.09-92.17, p < .0001). The most common cause for mortality was neoplasms, which accounted for 94 FASD-attributable deaths (28.7% of all neoplasm deaths in the study population). However, FASD patients did not have increased risk of neoplasm mortality than the general population (HR: 0.88, 95% CI: 0.59-1.32, p < .0001). Overall, this study found that individuals diagnosed with FASDs have increased risk of both hospitalizations and mortality, compared to their general population peers. This is particularly so for diseases of the nervous system, which showed a 52-fold increase in hospitalizations and four-fold increase in mortality for FASD patients in our study. Likewise, while the association between FASDs and neoplasm mortality was not significant in our investigation, more attention by neurologists and related healthcare providers regarding the link between these two factors is necessary.
Although FASD is characterized by physical, behavioral and cognitive deficits that provide compelling evidence of brain damage, routine clinical brain imaging (e.g. magnetic resonance imaging; MRI) often yields non-significant findings that add little insight into the diagnostic process. Nonetheless, research studies using advanced methods have identified numerous abnormalities of brain structure when comparing groups of individuals with FASD to groups of typically developing individuals, including brain volume reductions and abnormalities of cortical thickness and white matter microstructure. In addition, several studies have identified group-level associations between abnormal brain structure and cognitive performance, degree of prenatal alcohol exposure, or other key clinical metrics. This chapter summarizes some of these key findings, highlighting how MRI has advanced our understanding of FASD while also discussing its current limitations as a biomarker of prenatal alcohol exposure.
Blueberries are a soft and small fruit native to North America with an attractive blue color. In addition, blueberries are very popular because they have low calories, high nutritional value and important antioxidant properties. Blueberries have an interesting content of phenolic compounds with high antioxidant capacity against free radicals and reactive species, such that blueberry consumption may have a potential beneficial effect on human health. Innovative technologies in the food industry are new technologies based to develop more efficient process or products, reduction of energy and water. Innovative technologies, such as freeze concentration, osmotic dehydration and vacuum impregnation at mild temperatures, are considered minimal processing techniques because they preserve the fresh characteristics of fruits such as blueberries. Freeze concentration is an innovative technology for producing a blueberry concentrate juice in a process at low temperatures where no vapor/liquid interface exists. On the other hand, osmotic dehydration and vacuum impregnation of blueberries preserves different valuable attributes of the fruit, providing products with an extended shelf-life.
Several lines of evidence suggest that the dopamine transporter gene (DAT1) plays a crucial role in attention deficit hyperactivity disorder (ADHD). Concretely, recent data indicate that the 10-repeat (10R) DAT1 allele may mediate neuropsychological functioning, response to methylphenidate, and even brain function and structure in children with ADHD. This study aimed to investigate the influence of 10R DAT1 on thickness of the prefrontal cortex in children and adolescents with ADHD. To this end, brain magnetic resonance images were acquired from 33 patients with homozygosity for the 10R allele and 30 patients with a single copy or no copy of the allele. The prefrontal cortex of each MRI scan was automatically parceled into regions of interest (ROIs) based on Brodmann areas (BA). The two groups were matched for age, gender, IQ, ADHD subtype, symptom severity, comorbidity and medication status. However, patients with two copies of the 10R allele exhibited significantly decreased cortical thickness in right BA 46 relative to patients with one or fewer copies of the allele. No other prefrontal ROI differed significantly between the two groups. Present findings suggest that cortical thickness of right lateral prefrontal cortex (BA 46) is influenced by the presence of the DAT1 10 repeat allele in children and adolescents with ADHD.
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Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neurobehavioral deficits, and reduced brain volume. Studies of cortical thickness in FASD have yielded contradictory findings, with 3 reporting thicker cerebral cortex in frontal and temporal brain regions and 2 showing thinner cortex across multiple regions. All 5 studies included subjects spanning a broad age range, and none have examined continuous measures of prenatal alcohol exposure. We investigated the relation of extent of in utero alcohol exposure to cortical thickness in 78 preadolescent children with FASD and controls within a narrow age range. A whole-brain analysis using FreeSurfer revealed no significant clusters where cortical thickness differed by FASD diagnostic group. However, alcohol dose/occasion during pregnancy was inversely related to cortical thickness in 3 regions-right cuneus/pericalcarine/superior parietal lobe, fusiform/lingual gyrus, and supramarginal/postcentral gyrus. The effect of prenatal alcohol exposure on IQ was mediated by cortical thickness in the right occipitotemporal region. It is noteworthy that a continuous measure of maternal alcohol consumption during pregnancy was more sensitive than FASD diagnosis and that the effect on cortical thickness was most evident in relation to a measure of maternal binge drinking.
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Magnetic resonance imaging of the human fetal brain has been a clinical tool for many years and provides valuable additional information to compliment more common ultrasound studies. Advances in both MRI acquisition and post processing over the last 10 years have enabled full 3D imaging and the accurate combination of data acquired in different head positions to create improved geometric integrity, tissue contrast, and resolution. This research is now motivating the development of new quantitative MRI-based techniques for clinical imaging that can more accurately characterize brain development and detect abnormalities. In this article, we will review some of the key areas that are driving changes in our understanding of fetal brain growth using quantitative measures derived from in utero MRI and the possible directions for its increased use in improving the evaluation of pregnancies and the accurate characterization of abnormal brain growth.
Copyright © 2015 Elsevier Inc. All rights reserved.
En nuestro medio, el alcoholismo materno-fetal es un hecho casi ignorado como importante factor en la génesis de un amplio espectro de enfermedades neuropsiquiátricas del niño, el adolescente y el adulto. Los hijos de madres alcohólicas pueden presentar desde un retraso mental profundo hasta una normalidad aparente, pasando por cuadros de epilepsia, déficit de atención con/sin hiperactividad, autismo y trastorno generalizado del desarrollo, y varios tipos de trastornos del aprendizaje. En la adolescencia pueden desarrollar varios tipos de trastornos de la personalidad y adicciones a drogas. Finalmente, en la adultez, pueden presentar diferentes tipos de psicosis y trastornos afectivos, entre otros. Un gran número de estos hijos de madres alcohólicas no logran desarrollar completamente su potencialidad mental y social como individuos plenamente libres. Con frecuencia, padecen diferentes déficit cognitivos, atencionales, mnésicos y afectivos. No raramente se ven involucrados en conductas antisociales o tienen problemas escolares y laborales. En este trabajo se revisan las clasificaciones clínicas y los criterios diagnósticos en uso sobre los trastornos que surgen de la exposición prenatal al etanol; su finalidad es llamar la atención a la comunidad médica pediátrica y neuropsiquiátrica acerca de la frecuencia creciente de estos trastornos, subdiagnosticados en nuestro país.
Previous studies have shown smaller brain volume and less gray matter in children with attention-deficit/hyperactivity disorder (ADHD). Relatively few morphological studies have examined structures thought to subserve inhibitory control, one of the diagnostic features of ADHD. We examined one such region, the pars opercularis, predicting a thinner cortex of the inferior frontal gyrus (IFG) in children with ADHD.
Structural images were obtained from 49 children (24 control; 25 ADHD combined subtype) aged 9 though 15 years. Images were processed using a volumetric pipeline to provide a fully automated estimate of regional volumes of gray and white matter. A further analysis using FreeSurfer provided measures of cortical thickness for each lobe, and for 13 regions in the frontal lobe.
Relative to controls, children with ADHD had smaller whole brain volume and lower gray matter, but not white matter, volumes in all lobes. An analysis of frontal regions showed a significant interaction of group by region. Planned contrasts showed bilateral thinner cortex in the pars opercularis in children with ADHD.
Children with ADHD showed both diffuse and regional gray matter abnormalities. Consistent with its putative role in response inhibition, the cortex of the pars opercularis was thinner in children with ADHD who, as expected, had significantly poorer inhibitory performance on a Go/No-go task. These differences held for both hemispheres raising the possibility that a developmental abnormality of IFG might drive development of inhibition difficulties.
Prenatal ethanol exposure, in our professional practice, is an almost neglected condition as an important etiological factor for the induction of a wide spectrum of neuropsychiatric diseases that may appear during childhood, adolescence or adulthood. Children born to alcoholic mothers may show a profound mental retardation ranging to an apparent normality, and extending through epilepsy, attention deficit disorders with or without hyperactivity, autism and pervasive developmental disorders, and different types of learning disorders. When adolescents, they may develop different kinds of personality disorders and substance abuse disorders. Finally, in adulthood, they may suffer from different types of affective and psychotic disorders, among others. A great number of those children may not develop their full mental and social potentiality as free individuals. They usually have diverse types of cognitive, attentional, mnemonic and affective impairments. Not infrequently, they engage in antisocial behaviors or have school or work troubles. In this work, the present clinical classifications and diagnostic criteria for the disorders emerging from a prenatal ethanol exposure are reviewed in order to call attention to the medical pediatric and neuropsychiatric community about the increasingly, although underdiagnosed, frequency of these disorders in our country.
Introduction:
Advances in neuroimaging in the last decade have allowed a number of new findings about attention deficit hyperactivity disorder (ADHD) to be obtained. Quickly developing technology, together with the progress being made in genetics and neurochemical research, suggests a dysfunction of the fronto striatal circuit that involves the prefrontal cortex and its relationship with the basal, thalamic and cerebellar nuclei as the pathophysiological foundation of this disorder. On the other hand, neuroimaging in the future may complement clinical evaluation, which will favour more accurate diagnoses and allow the subtypes and even the mode of treatment and its monitoring to be identified.
Aims and development:
The aim of this study was to review the more significant literature on neuroimaging and ADHD and to discuss the usefulness and drawbacks of the different modes of neuroimaging techniques that can be applied with a view to gaining an improved and deeper knowledge of ADHD in the future.
Conclusions:
Although the development of neuroimaging in ADHD is a promising area, at the present time its diagnostic value is very restricted. One of the greatest difficulties in this respect concerns the clinical, genetic and pathophysiological heterogeneity of the disorder. Hence, given the inexistence of a specific marker, future studies will have to search for several markers that have a suitable value in the diagnosis, prognosis and/or treatment of the different subtypes of ADHD.
Alcohol exposure during development can cause variable neurofacial deficit and growth retardation known as fetal alcohol spectrum disorders (FASD). The mechanism underlying FASD is not fully understood. However, alcohol, which is known to affect methyl donor metabolism, may induce aberrant epigenetic changes contributing to FASD. Using a tightly controlled whole-embryo culture, we investigated the effect of alcohol exposure (88mM) at early embryonic neurulation on genome-wide DNA methylation and gene expression in the C57BL/6 mouse. The DNA methylation landscape around promoter CpG islands at early mouse development was analyzed using MeDIP (methylated DNA immunoprecipitation) coupled with microarray (MeDIP-chip). At early neurulation, genes associated with high CpG promoters (HCP) had a lower ratio of methylation but a greater ratio of expression. Alcohol-induced alterations in DNA methylation were observed, particularly in genes on chromosomes 7, 10, and X; remarkably, a >10 fold increase in the number of genes with increased methylation on chromosomes 10 and X was observed in alcohol-exposed embryos with a neural tube defect phenotype compared to embryos without a neural tube defect. Significant changes in methylation were seen in imprinted genes, genes known to play roles in cell cycle, growth, apoptosis, cancer, and in a large number of genes associated with olfaction. Altered methylation was associated with significant (p
Just as typical development of anatomical asymmetries in the human brain has been linked with normal lateralization of motor and cognitive functions, disruption of asymmetry has been implicated in the pathogenesis of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). No study has examined the development of cortical asymmetry using longitudinal neuroanatomical data.
To delineate the development of cortical asymmetry in children with and without ADHD.
Longitudinal study.
Government Clinical Research Institute.
A total of 218 children with ADHD and 358 typically developing children, from whom 1133 neuroanatomical magnetic resonance images were acquired prospectively.
Cortical thickness was estimated at 40 962 homologous points in the left and right hemispheres, and the trajectory of change in asymmetry was defined using mixed-model regression.
In right-handed typically developing individuals, a mean (SE) increase in the relative thickness of the right orbitofrontal and inferior frontal cortex with age of 0.011 (0.0018) mm per year (t(337) = 6.2, P < .001) was balanced against a relative left-hemispheric increase in the occipital cortical regions of 0.013 (0.0015) mm per year (t(337) = 8.1, P < .001). Age-related change in asymmetry in non-right-handed typically developing individuals was less extensive and was localized to different cortical regions. In ADHD, the posterior component of this evolving asymmetry was intact, but the prefrontal component was lost.
These findings explain the way that, in typical development, the increased dimensions of the right frontal and left occipital cortical regions emerge in adulthood from the reversed pattern of childhood cortical asymmetries. Loss of the prefrontal component of this evolving asymmetry in ADHD is compatible with disruption of prefrontal function in the disorder and demonstrates the way that disruption of typical processes of asymmetry can inform our understanding of neurodevelopmental disorders.
Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of approximately 0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.
The adverse effects of alcohol on the developing human represent a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). The first descriptions in the modern medical literature of a distinctly recognizable pattern of malformations associated with maternal alcohol abuse were reported in 1968 and 1973. Since that time, substantial progress has been made in developing specific criteria for defining and diagnosing this condition. Two sets of diagnostic criteria are now used most widely for evaluation of children with potential diagnoses in the FASD continuum, ie, the 1996 Institute of Medicine (IOM) criteria and the Washington criteria. Although both approaches have improved the clinical delineation of FASD, both suffer from significant drawbacks in their practical application in pediatric practice.
The purpose of this report is to present specific clarifications of the 1996 IOM criteria for the diagnosis of FASD, to facilitate their practical application in clinical pediatric practice.
A large cohort of children who were prenatally exposed to alcohol were identified, through active case-ascertainment methods, in 6 Native American communities in the United States and 1 community in the Western Cape Province of South Africa. The children and their families underwent standardized multidisciplinary evaluations, including a dysmorphology examination, developmental and neuropsychologic testing, and a structured maternal interview, which gathered data about prenatal drinking practices and other demographic and family information. Data for these subjects were analyzed, and revisions and clarifications of the existing IOM FASD diagnostic categories were formulated on the basis of the results.
The revised IOM method defined accurately and completely the spectrum of disabilities among the children in our study. On the basis of this experience, we propose specific diagnostic criteria for fetal alcohol syndrome and partial fetal alcohol syndrome. We also define alcohol-related birth defects and alcohol-related neurodevelopmental disorder from a practical standpoint.
The 1996 IOM criteria remain the most appropriate diagnostic approach for children prenatally exposed to alcohol. The proposed revisions presented here make these criteria applicable in clinical pediatric practice.
Data from a previous prospective study of lobar volumes in children with attention-deficit/hyperactivity disorder (ADHD) are reexamined using a measure of cortical thickness.
To determine whether regional differences in cortical thickness or cortical changes across time characterize ADHD and predict or reflect its clinical outcome.
Longitudinal study of 163 children with ADHD (mean age at entry, 8.9 years) and 166 controls recruited mainly from a local community in Maryland. Participants were assessed with magnetic resonance imaging. Ninety-seven patients with ADHD (60%) had 2 or more images and baseline and follow-up clinical evaluations (mean follow-up, 5.7 years).
Cortical thickness across the cerebrum. Patients with ADHD were divided into better and worse outcome groups on the basis of a mean split in scores on the Children's Global Assessment Scale and persistence/remission of DSM-IV-defined ADHD.
Children with ADHD had global thinning of the cortex (mean reduction, -0.09 mm; P=.02), most prominently in the medial and superior prefrontal and precentral regions. Children with worse clinical outcome had a thinner left medial prefrontal cortex at baseline than the better outcome group (-0.38 mm; P=.003) and controls (-0.25 mm; P=.002). Cortical thickness developmental trajectories did not differ significantly between the ADHD and control groups throughout except in the right parietal cortex, where trajectories converged. This normalization of cortical thickness occurred only in the better outcome group.
Children with ADHD show relative cortical thinning in regions important for attentional control. Children with a worse outcome have "fixed" thinning of the left medial prefrontal cortex, which may compromise the anterior attentional network and encumber clinical improvement. Right parietal cortex thickness normalization in patients with a better outcome may represent compensatory cortical change.
Peer relationship problems are a significant part of the clinical presentation of children with Fetal Alcohol Spectrum Disorders (FASD). Many of these children have been prescribed psychotropic medications by community practitioners. The present study reports on the interaction between medication status and parent and teacher-reported outcomes for parent-assisted Children's Friendship Training (CFT).
Seventy seven children (40 boys and 37 girls, age range was 71-139 months) diagnosed with FASD were given 12 sessions of CFT. Parent- and teacher-reported social outcomes were compared across four subgroups of children who were prescribed either stimulant or neuroleptic medication, neither or both types of medications.
According to parent and teacher reports, children prescribed neuroleptic medication showed greater improvement on all outcome measures when compared to children not prescribed neuroleptics. In contrast, children prescribed stimulant medication either failed to show improvement or showed poorer outcomes when compared to children not prescribed stimulants.
Children with FASD frequently present with symptoms of inattention and hyperactivity. The present results suggest physicians routinely ask about prenatal alcohol exposure as part of history taking to treat children more effectively who appear to be displaying attention-deficit/hyperactivity disorder symptomatology but who may have FASD.
Quantitative magnetic resonance imaging (MRI) studies in children with fetal alcohol spectrum disorders (FASDs) have shown regional patterns of dysmorphology, most prominent in parietal and posterior temporal cortices. Various methods of image analysis have been employed in these studies, but abnormalities in cortical thickness have not yet been mapped over the entire cortical surface in individuals with FASD. Further, relationships between cognitive dysfunction and cortical thickness measures have not yet been explored. We applied cortical pattern matching algorithms and techniques for measuring cortical thickness in millimeters to the structural brain MRI images of 21 subjects with heavy prenatal alcohol exposure (8-22 years, mean age 12.6 years), and 21 normally developing control subjects (8-25 years, mean age 13.5 years). Dissociable cognitive measures, of verbal recall and visuospatial functioning, were correlated with cortical thickness, and group by test score interactions were evaluated for predicting cortical thickness. Significant cortical thickness excesses of up to 1.2 mm were observed in the FASD subjects in large areas of bilateral temporal, bilateral inferior parietal, and right frontal regions. Significant group by test score interactions were found in right dorsal frontal regions for the verbal recall measure and in left occipital regions for the visuospatial measure. These results are consistent with earlier analyses from our own and other research groups, but for the first time, we show that cortical thickness is also increased in right lateral frontal regions in children with prenatal alcohol exposure. Further, the significant interactions show for the first time that brain-behavior relationships are altered as a function of heavy prenatal alcohol exposure.
There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test χ(1)² = 5,609, P < 1.0 × 10⁻²⁰). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.
• cortical development
• structural neuroimaging
We assessed regional brain shape abnormalities and spatial relationships between brain shape and abnormalities observed in the underlying tissue in children and adolescents prenatally exposed to large quantities of alcohol. We used high resolution, 3-D, structural magnetic resonance imaging data and novel, whole-brain, surfacebased image analysis procedures to study 21 subjects with heavy prenatal alcohol exposure (8–22 years, mean age 12.6 years) and 21 normally developing control subjects (8–25 years, mean age 13.5 years). Significant brain size and shape abnormalities were observed in the alcohol-exposed subjects in inferior parietal/ perisylvian regions bilaterally, where their brains appeared to be narrower than those of the controls in the same general location where they also had increased gray matter density. Highly significant decreased brain surface extent or reduced brain growth was also observed in the ventral aspects of the frontal lobes most prominent in the left hemisphere. For the first time in this report we have mapped brain morphologic abnormalities to the cortical surface in subjects with prenatal alcohol exposure and have shown that the size and shape of the brain is altered in these individuals. The results imply that brain growth continues to be adversely affected long after the prenatal insult of alcohol exposure to the developing brain and the brain regions most implicated, frontal and inferior parietal/ perisylvian, may be consistent with behavioral deficits characteristic of individuals prenatally exposed to alcohol.
Background and objective
The fetal alcohol syndrome (FAS) is considered as the main preventablecause of congenital defects and mental deficiency. We analyzed whether the consumptionof alcohol during gestation has changed in Spain.
Subjects and method
We analyzed the evolution over the last 24 years, as well as the geographicaldistribution according to Spanish regions, of maternal alcohol consumption during pregnancy.We used data from the ECEMC, a registry which includes 1,820,862 liveborns, of whom30,836 were malformed. A similar number of healthy controls was collected. We established 5increasing levels of alcohol consumption, for sporadic and diary intakes, and 3 levels of maternalscholarship.
Results
Except for the lowest and highest intakes, alcohol consumption levels showed a decreasingtrend over the time. These tendencies were similar in almost all Spanish regions.When comparing the intake between regions, the differences were statistically significant. Therewas a correlation between the maternal scholarship and the alcohol intake, showing that thehigher the education the lower the amount of alcohol consumption.
Conclusions
The awareness of the alcohol effects is related to the maternal cultural level. Maternalconsumption of alcohol varies across Spanish regions, though its trends are similar.
Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia.
Exposure to ethanol during prenatal development can have devastating consequences on developing fetuses, the so-called fetal alcohol spectrum disordres (FASD). Among FASD, cases that exhibit all of three criterion; 1) central nervous system dysfunction, 2) prenatal and postnatal growth deficiency, and 3) characteristic cranial/facial abnormalities, referred as fetal alcohol syndrome (FAS). Children born to drinking mothers may suffer from severe brain damage that is expressed by a variety of behavioral alterations. We examined the effects of ethanol exposure during brain development on brain morphogenesis and circadian rhythm using a rat model. Pregnant Sprague-Dawley (SD) rats were fed a liquid diet containing 2.5-5.0% (w/v) ethanol during gestational days 10 to 21. Mean daily ethanol consumption by these dams was 11.53 +/- 2.54 g/kg/day. In rats prenatally exposed to ethanol, ectopias on the cerebral cortex, aberrant distribution of hippocampal mossy fibers, and fusion of cerebellar folia were found. Rats exposed to ethanol during the prenatal or postnatal period suffered from a fragile synchronizing system of circadian rhythms in adulthood. Although the prevalence of FAS in Japan is lower than in the United States, the increasing number of Japanese women with the drinking habit are cause for great concern. However, the preventive action of FAS/FASD has been advanced recently, and now alcoholic beverages carry labels warning of the risk of drinking during pregnancy and breastfeeding of babies. Although little is still known about how ethanol affects brain development, the only and most certain way to prevent FAS/FASD is total abstinence from alcohol during pregnancy and breastfeeding.
The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.
Ectopic neurons are often found in the brains of fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) patients, suggesting that alcohol exposure impairs neuronal cell migration. Although it has been reported that alcohol decreases the speed of neuronal cell migration, little is known about whether alcohol also affects the turning of neurons. Here we show that ethanol exposure inhibits the turning of cerebellar granule cells in vivo and in vitro. First, in vivo studies using P10 mice demonstrated that a single intraperitoneal injection of ethanol not only reduces the number of turning granule cells but also alters the mode of turning at the EGL-ML border of the cerebellum. Second, in vitro analysis using microexplant cultures of P0-P3 mouse cerebella revealed that ethanol directly reduces the frequency of spontaneous granule cell turning in a dose-dependent manner. Third, the action of ethanol on the frequency of granule cell turning was significantly ameliorated by stimulating Ca(2+) and cGMP signaling or by inhibiting cAMP signaling. Taken together, these results indicate that ethanol affects the frequency and mode of cerebellar granule cell turning through alteration of the Ca(2+) and cyclic nucleotide signaling pathways, suggesting that the abnormal allocation of neurons found in the brains of FASD and FSA patients results, at least in part, from impaired turning of immature neurons by alcohol.
Much attention has been paid in recent years to the role of prenatal exposure to alcohol. Fetal alcohol syndrome is one of the most severe afflictions resulting from such exposure. The present report documents the cases of adopted children diagnosed with fetal alcohol syndrome who developed both Tourette syndrome and attention deficit-hyperactivity disorder. Out of a population of 138 adopted children with behavior issues whose clinical histories were reviewed retrospectively, 9 children (6.5%) presented this constellation. Epidemiologic data, clinical data, neurologic examination findings, complementary testing, and developmental data were recorded. All nine patients studied had initial psychomotor retardation, despite the frequent case of subsequent intelligence quotient normalization. From a behavioral perspective, half of the cases presented obsessive-compulsive disorder and problems with social relations. Aggressive behavior was common. These cases also presented a high degree of severity of both tics and hyperactivity. The most common drug treatment was methylphenidate. This constellation of fetal alcohol syndrome, Tourette syndrome, and attention deficit-hyperactivity disorder is scantly reported in the literature and is likely underdiagnosed. This particular constellation poses its own prognosis and requires its own treatment.
A primary goal of recent research is the development of neurobehavioral profiles that specifically define fetal alcohol spectrum disorders (FASD), which may assist differential diagnosis or improve treatment. In the current study, we define a preliminary profile using neuropsychological data from a multisite study.
Data were collected using a broad neurobehavioral protocol from 2 sites of a multisite study of FASD. Subjects were children with heavy prenatal alcohol exposure and unexposed controls. The alcohol-exposed group included children with and without fetal alcohol syndrome (FAS). From 547 neuropsychological variables, 22 variables were selected for analysis based on their ability to distinguish children with heavy prenatal alcohol exposure from nonexposed controls. These data were analyzed using latent profile analysis (LPA).
The results indicated that a 2-class model best fit the data. The resulting profile was successful at distinguishing subjects with FAS from nonexposed controls without FAS with 92% overall accuracy; 87.8% of FAS cases and 95.7% of controls were correctly classified. The same analysis was repeated with children with heavy prenatal alcohol exposure but without FAS and nonexposed controls with similar results. The overall accuracy was 84.7%; 68.4% of alcohol-exposed cases and 95% of controls were correctly classified. In both analyses, the profile based on neuropsychological variables was more successful at distinguishing the groups than was IQ alone.
We used data from 2 sites of a multisite study and a broad neuropsychological test battery to determine a profile that could be used to accurately identify children affected by prenatal alcohol exposure. Results indicated that measures of executive function and spatial processing are especially sensitive to prenatal alcohol exposure.
To study the long-term changes of dendritic spine and synapse taking place in a mouse model of fetal alcohol spectrum disorders (FASDs).
Pregnant mice were intubated daily with ethanol (EtOH) from E5 to parturition. A DiI diolistic method was used to label dendritic spines of pyramidal cells in the visual cortex of EtOH-exposed and control pups over the period from postnatal (P) day P0 to P30; synaptic ultrastructure was also analyzed using transmission electron microscopy.
Prenatal alcohol exposure was associated with a significant decrease in the number of dendritic spines of pyramidal neurons in the visual cortex and an increase in their mean length. The changes were dose dependent and persisted to P30. Ultrastructural changes were also observed, with decreased numbers of synaptic vesicles, narrowing of the synaptic cleft and thickening of the postsynaptic density compared to controls; ultrastructural changes also persisted to P30.
Prenatal alcohol exposure is associated with long-term changes in dendritic spines and synaptic ultrastructure; these alterations probably reflect the developmental retardation of dendritic spines and synapses in visual cortex. These long-term changes are likely to contribute to lifelong mental retardation associated with childhood FASDs.
Some longitudinal magnetic resonance imaging (MRI) studies have shown reduced volume or cortical thickness (CT) in the frontal cortices of individuals with attention-deficit/hyperactivity disorder (ADHD). These studies indicated that the aforementioned anatomical abnormalities disappear during adolescence. In contrast, cross-sectional studies on adults with ADHD have shown anatomical abnormalities in the frontal lobe region. It is not known whether the anatomical abnormalities in ADHD are a delay or a deviation in the encephalic maturation. The aim of this study was to compare CT in the frontal lobe of children, adolescents and adults of both genders presenting ADHD with that in corresponding healthy controls and to explore its relationship with the severity of the illness.
An MRI scan study was performed on never-medicated ADHD patients. Twenty-one children (6-10 year-olds), twenty adolescents (14-17 year-olds) and twenty adults (25-35 year-olds) were matched with healthy controls according to age and sex. CT measurements were performed using the Freesurfer image analysis suite.
The data showed regions in the right superior frontal gyrus where CT was reduced in children, adolescents and adults with ADHD in contrast to their respective healthy controls. The CT of these regions correlated with the severity of the illness.
In subjects with ADHD, there is a thinning of the cortical surface in the right frontal lobe, which is present in the children, adolescents and in adults.
The purposes of this investigation were to determine the frequencies of and associations between different neurodevelopmental disorders and to study the potential lasting effects of alcohol on children adopted from eastern Europe.
In a population-based, prospective, observational, multidisciplinary, cross-sectional, cohort study of 71 children adopted from eastern Europe, children were assessed 5 years after adoption, from pediatric, neuropsychological, and ophthalmologic perspectives.
Fetal alcohol spectrum disorders, that is, fetal alcohol syndrome (FAS), partial FAS, and alcohol-related neurodevelopmental disorders, were identified for 52% of children; FAS was found for 30%, partial FAS for 14%, and alcohol-related neurodevelopmental disorders for 9%. Alcohol-related birth defects were found for 11% of children, all of whom also were diagnosed as having FAS. Mental retardation or significant cognitive impairment was found for 23% of children, autism for 9%, attention-deficit/hyperactivity disorder for 51%, and developmental coordination disorder for 34%.
Fetal alcohol spectrum disorders and neurodevelopmental disorders were common in this long-term follow-up study of children adopted from orphanages in eastern Europe. Maternal alcohol consumption during pregnancy has long-lasting adverse effects, causing structural, behavioral, and cognitive damage despite a radically improved environment.
The purpose of this article is to compare the neurodevelopmental profiles of 78 foster and adopted children with fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND).
Seventy-eight foster and adopted children underwent a comprehensive diagnostic evaluation. By using criteria more stringent than those required by current guidelines, the children were placed in 1 of 3 diagnostic categories: FAS, pFAS, or ARND. Each child was evaluated across the domains of neuropsychological functioning most frequently affected by prenatal exposure to alcohol. Multivariate analyses of variance were conducted to examine differences in neuropsychological functioning between the 3 diagnostic groups. Descriptive discriminant analyses were performed in follow-up to the multivariate analyses of variance.
The children in the 3 diagnostic categories were similar for descriptive and child welfare variables. Children with FAS had significantly decreased mean weight, height, and head circumference. Children with FAS exhibited the most impaired level of general intelligence, significantly worse language-based memory compared with children with ARND, and significantly poorer functional communication skills than children with pFAS. On executive functioning, the FAS group of children performed significantly worse on sequencing and shift than either the pFAS or ARND groups. Children with pFAS and ARND were similar in all neurodevelopmental domains that were tested.
The children who met tightly defined physical criteria for a diagnosis of FAS demonstrated significantly poorer neurodevelopmental functioning than children with pFAS and ARND. Children in these latter 2 groups were similar in all neurodevelopmental domains that were tested.
Fetal alcohol spectrum disorder (FASD) is the umbrella term that describes the range of adverse developmental outcomes that may occur in the offspring of mothers who drink alcohol during pregnancy. FASD is associated with several comorbidities including epilepsy. The objective of the study was to evaluate the prevalence of epilepsy or a history of seizures in subjects with FASD and the contribution of relevant risk factors.
A retrospective chart review was conducted on all active charts (N = 1063) at two FASD clinics. After exclusion of subjects without a confirmed diagnosis, a total of 425 subjects between the ages of 2-49 were included in the analysis. The relationships between FASD diagnosis and other risk factors for co-occurrence of epilepsy or a seizure disorder (e.g., extent of exposure to alcohol and other drugs, type of birth, and trauma) were examined using chi-square and multivariate multinomial logistic regression.
Twenty-five (5.9%) individuals in the study population had a confirmed diagnosis of epilepsy, and 50 (11.8%) had at least one documented seizure episode, yielding an overall prevalence of 17.7% in this population. Importantly, a history of epilepsy or seizures was not different across the three diagnostic subgroups. In those subjects with available maternal drinking histories, first trimester exposure or drinking throughout all three trimesters were the predominant forms of fetal exposure. None of the other risk factors were associated with a greater prevalence of epilepsy or seizures.
There is a remarkably high prevalence of epilepsy/seizures in the FASD population.
The number of neurons in the ventrobasal thalamus (VB) in the adolescent rat is unaffected by prenatal exposure to ethanol. This is in sharp contrast to other parts of the trigeminal-somatosensory system, which exhibit 30-35% fewer neurons after prenatal ethanol exposure. The present study tested the hypothesis that prenatal ethanol exposure affects dynamic changes in the numbers of VB neurons; such changes reflect the sum of cell proliferation and death. Neuronal number in the VB was determined during the first postnatal month in the offspring of pregnant Long-Evans rats fed an ethanol-containing diet or pair-fed an isocaloric non-alcoholic liquid diet. Offspring were examined between postnatal day (P) 1 and P30. The size of the VB and neuronal number were determined stereologically. Prenatal exposure to ethanol did not significantly alter neuronal number on any individual day, nor was the prenatal generation of VB neurons affected. Interestingly, prenatal ethanol exposure did affect the pattern of the change in neuronal number over time; total neuronal number was stable in the ethanol-treated pups after P12, but it continued to rise in the controls until P21. In addition, the rate of cell proliferation during the postnatal period was greater in ethanol-treated animals. Thus, the rate of neuronal acquisition is altered by ethanol, and by deduction, there appears to be less ethanol-induced neuronal loss in the VB. A contributor to these changes is a latent effect of ethanol on postnatal neurogenesis in the VB and the apparent survival of new neurons.
This article reviews recent advances in structural neuroimaging in attention-deficit/hyperactivity disorder (ADHD). Observational studies have found treatment with psychostimulants to be associated more closely with dimensions of some brain structures in typically developing children than in those found in treatment-naïve children with ADHD. Novel analytic approaches allow for greater precision in the definition of brain regions that are most compromised in ADHD, with meta-analyses highlighting compromise of the basal ganglia. Cortical changes, particularly in the lateral prefrontal and parietal cortex, are also commonly reported, but with less consensus on the exact location of structural change. Anomalies in the shape of subcortical structures, specifically of the basal ganglia, hippocampus, and amygdala, implicate frontostriatal loops and the limbic system in the disorder. Finally, longitudinal data suggest that ADHD in childhood may be characterized by a delay in cortical maturation and that different clinical outcomes may be associated with different developmental trajectories in adolescence and beyond.
The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and central nervous system (CNS) disorganization, with specific structural abnormalities of the corpus callosum, cerebellum, caudate, and hippocampus. Advances in neuroimaging techniques have allowed detection of regional increases in cortical thickness and gray matter volume along with decreased volume and disorganization of white matter in individuals with FASD. In addition, functional imaging studies have found functional and neurochemical differences in those prenatally exposed to alcohol. Behavioral alterations noted in individuals with FASD are consistent with the findings noted in the brain imaging studies. Continued neuroimaging studies are needed to further advance understanding of the neuroteratogenic effects of alcohol.
Since the identification of fetal alcohol syndrome (FAS) over 35 years ago, mounting evidence about the impact of maternal alcohol consumption during pregnancy has prompted increased attention to the link between prenatal alcohol exposure (PAE) and a constellation of developmental disabilities that are characterized by physical, cognitive, and behavioral impairments. These disabilities include a continuum of developmental disorders known as fetal alcohol spectrum disorders (FASDs). Longitudinal studies suggest that individuals with FASDs are at a greatly increased risk for adverse long-term outcomes, including mental health problems and poor social adjustment. This review summarizes the existing literature on mental health outcomes for individuals with PAE across the lifespan, including findings in infancy and early childhood, middle childhood, and adolescence and early adulthood. Research on the psychiatric disabilities suffered by individuals with FASDs throughout development highlights the need for training of mental health professionals in the identification and the provision of specific treatments to address the unique features of this developmental disability since early identification and treatment have been demonstrated to be protective against more serious secondary disabilities. It is hoped that with greater awareness of the mental health problems experienced by individuals with FASDs, these individuals can receive appropriate and early treatment resulting in more adaptive and rewarding lives.
The question of whether children with fetal alcohol spectrum disorders (FASD) exhibit a unique neurocognitive profile has received considerable attention over the past three decades. The identification of a syndrome-specific neurocognitive profile would aid in diagnosing prenatally exposed children with cognitive deficits who do not exhibit clinically discernable physical anomalies. The current review of the literature, therefore, focuses on the studies of higher-order cognitive skills in children with FASDs with a view towards delineating a pattern of cognitive functioning. Researchers have documented that children with FASDs show diminished intellectual functioning, with average IQ scores falling within the borderline to low average ranges. Slow information processing and disturbances of attention have been observed from infancy through adulthood in individuals with FASDs. Clinical and experimental reports on individuals with FASD have documented marked deficits in executive functioning, particularly in tasks that involve holding and manipulating information in working memory. Studies examining specific domains of cognitive functioning such as language, visual perception, memory and learning, social functioning, and number processing in individuals with FASDs have revealed performance decrements associated with increased task complexity. The above findings converge on the conclusion that children with FASDs have a generalized deficit in the processing and integration of information. We recommend the study of developmental trajectories of both elementary and higher-order functions in future research on FASD to elucidate the development of this cognitive profile.
This cross-sectional study sought to confirm the presence and regional profile of previously reported changes in laminar cortical thickness in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) compared with typically developing control subjects.
High-resolution magnetic resonance images were obtained from 22 (19 male and 3 female subjects; mean age 11.7 years) children and adolescents with ADHD and 22 age- and sex-matched control subjects (mean age 11.7 years). Brain tissue volumes were estimated for each subject. Cortical pattern matching methods were used to sample measures of laminar thickness at high spatial frequency across homologous regions of the cortex. Volume and thickness measures were compared across diagnostic groups with and without controlling for general intelligence. False discovery rate correction confirmed regional results.
The subjects with ADHD exhibited significant reductions in overall brain volume, gray matter volume, and mean cortical thickness compared with the controls, whereas white matter volumes were significantly increased in ADHD. Highly significant cortical thinning (false discovery rate-corrected p < .0006) was observed over large areas of the frontal, temporal, parietal, and occipital association cortices and aspects of motor cortex but not within the primary sensory regions.
Cortical thickness reductions present a robust neuroanatomical marker for child and adolescent ADHD. Observations of widespread cortical thinning expand on earlier cross-sectional findings and provide further evidence to support that the neurobiological underpinnings of ADHD extend beyond prefrontal and subcortical circuits.
Chronic prenatal alcohol exposure causes a spectrum of deleterious effects in offspring, collectively termed fetal alcohol spectrum disorders (FASD), and deficits in executive function are prevalent in FASD. The goal of this research was to test the hypothesis that children with FASD exhibit performance deficits in tasks that assess attention, planning and spatial working memory.
Subjects (8-15 years male and female children) with a diagnosis of fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND), and age- and sex-matched controls, completed four tasks selected from the Cambridge Neuropsychological Tests Automated Battery (CANTAB).
Compared with age-matched control children (n = 92), subjects with FASD (n = 89) exhibited longer reaction and decision times (effect size range; Cohen's d = .51 to .73), suggesting deficits in attention. Children with FASD demonstrated deficits in planning and spatial working memory that became more pronounced when task difficulty increased. The largest effect size in this study population (Cohen's d = 1.1) occurred in the spatial working memory task. Only one outcome measure revealed differences across the diagnostic subgroups, although all groups were different from control.
This study demonstrates that deficits in multiple executive function domains, including set shifting, planning and strategy use, attention and spatial working memory, can be assessed in children with FASD using an easy to administer, brief battery of computer-based neuropsychological tasks. The tasks appear to be equally sensitive for brain injury resulting from prenatal exposure to alcohol, regardless of the presence of facial dysmorphology.
Working with children who have developmental disorders is challenging. Besides having physical deficits, or intellectual deficits, or both, these children are at high risk for developing psychiatric disorders. This article describes three developmental disorders-autistic spectrum disorders, fragile X syndrome, and fetal alcohol syndrome-and their associated mental health issues, and provides recommendations for pharmacologic interventions.
Magnetic resonance imaging (MRI) is undertaken on fetal alcohol syndrome (FAS) subjects to document central nervous system (CNS) anomalies. The abnormalities found include agenesis and hypoplasia of the corpus callosum, cavum septi pellucidi, cavum vergae, ventriculomegaly, hypoplasia of inferior olivary eminences, small brain stem, and micrencephaly. Craniofacial anomalies range from the well-recognized FAS physiognomy to the more severe frontonasal "dysplasia" (median cleft face). CNS and craniofacial abnormalities are predominantly symmetric and central or midline. The association of these anomalies becomes self-evident with recognition of the concept of the midline as a special developmental field, vulnerable to adverse factors during embryogenesis and fetal growth and development.
Postmortem studies of fetuses, infants, and young children with fetal alcohol syndrome (FAS) have demonstrated a variety of severe central nervous system (CNS) anomalies. We undertook this magnetic resonance study (1) to assess the spectrum of CNS anomalies that occur in a clinical sample of typical patients with FAS who are medically stable; and (2) to examine the relationship between CNS and facial anomalies.
Magnetic resonance imaging was performed on a series of 10 patients (4 children, 3 adolescents, and 3 adults) who met criteria for FAS. We systematically evaluated each scan for brain anomalies and compared total brain tissue volume with that of healthy child, adolescent, and adult control subjects.
Six patients had some type of midline anomaly, ranging from partial to complete callosal agenesis (three patients) to hypoplastic corpus callosum (one patient), cavum septi pellucidi (three patients), and cavum vergae (two patients). These midline anomalies were associated with a greater number of facial anomalies. Other brain anomalies identified included micrencephaly, ventriculomegaly, and hypoplasia of the inferior olivary eminences.
Patients with classic FAS have a high incidence of midline brain anomalies. This finding is consistent with the concept that the midline CNS is a developmental field that is particularly susceptible to the teratogenic effects of alcohol. Furthermore, patients with more severe facial dysmorphologic characteristics are more likely to have midline brain anomalies. In addition, we observed a high incidence of micrencephaly with a wide range of severity.
Children of mothers who abuse alcohol during pregnancy can suffer varying degrees of neurological abnormality, cognitive impairment, and behavioral problems, and in the worst case, are diagnosed with fetal alcohol syndrome (FAS). The purpose of the present study was to localize brain abnormalities in a group of children and adolescents prenatally exposed to alcohol using high resolution, 3D structural MRI data and whole-brain voxel-based morphometry (VBM). Data were collected for 21 children and adolescents with histories of prenatal alcohol exposure (ALC) and 21 normally developing individuals. Statistical parametric maps revealed abnormalities most prominent in the left hemisphere perisylvian cortices of the temporal and parietal lobes where the ALC patients tended to have too much gray matter and not enough white matter. These results provide further support for dysmorphology in temporo-parietal cortices above and beyond the overall microcephaly that results from severe prenatal alcohol exposure.
Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia.
The finite mixture (FM) model is the most commonly used model for statistical segmentation of brain magnetic resonance (MR) images because of its simple mathematical form and the piecewise constant nature of ideal brain MR images. However, being a histogram-based model, the FM has an intrinsic limitation--no spatial information is taken into account. This causes the FM model to work only on well-defined images with low levels of noise; unfortunately, this is often not the the case due to artifacts such as partial volume effect and bias field distortion. Under these conditions, FM model-based methods produce unreliable results. In this paper, we propose a novel hidden Markov random field (HMRF) model, which is a stochastic process generated by a MRF whose state sequence cannot be observed directly but which can be indirectly estimated through observations. Mathematically, it can be shown that the FM model is a degenerate version of the HMRF model. The advantage of the HMRF model derives from the way in which the spatial information is encoded through the mutual influences of neighboring sites. Although MRF modeling has been employed in MR image segmentation by other researchers, most reported methods are limited to using MRF as a general prior in an FM model-based approach. To fit the HMRF model, an EM algorithm is used. We show that by incorporating both the HMRF model and the EM algorithm into a HMRF-EM framework, an accurate and robust segmentation can be achieved. More importantly, the HMRF-EM framework can easily be combined with other techniques. As an example, we show how the bias field correction algorithm of Guillemaud and Brady (1997) can be incorporated into this framework to achieve a three-dimensional fully automated approach for brain MR image segmentation.
We assessed regional brain shape abnormalities and spatial relationships between brain shape and abnormalities observed in the underlying tissue in children and adolescents prenatally exposed to large quantities of alcohol. We used high resolution, 3-D, structural magnetic resonance imaging data and novel, whole-brain, surface-based image analysis procedures to study 21 subjects with heavy prenatal alcohol exposure (8-22 years, mean age 12.6 years) and 21 normally developing control subjects (8-25 years, mean age 13.5 years). Significant brain size and shape abnormalities were observed in the alcohol-exposed subjects in inferior parietal/ perisylvian regions bilaterally, where their brains appeared to be narrower than those of the controls in the same general location where they also had increased gray matter density. Highly significant decreased brain surface extent or reduced brain growth was also observed in the ventral aspects of the frontal lobes most prominent in the left hemisphere. For the first time in this report we have mapped brain morphologic abnormalities to the cortical surface in subjects with prenatal alcohol exposure and have shown that the size and shape of the brain is altered in these individuals. The results imply that brain growth continues to be adversely affected long after the prenatal insult of alcohol exposure to the developing brain and the brain regions most implicated, frontal and inferior parietal/ perisylvian, may be consistent with behavioral deficits characteristic of individuals prenatally exposed to alcohol.
An automated method for segmenting magnetic resonance head images into brain and non-brain has been developed. It is very robust and accurate and has been tested on thousands of data sets from a wide variety of scanners and taken with a wide variety of MR sequences. The method, Brain Extraction Tool (BET), uses a deformable model that evolves to fit the brain's surface by the application of a set of locally adaptive model forces. The method is very fast and requires no preregistration or other pre-processing before being applied. We describe the new method and give examples of results and the results of extensive quantitative testing against "gold-standard" hand segmentations, and two other popular automated methods.
Here we report on detailed three-dimensional quantitative maps of brain surface and gray matter density asymmetry patterns during normal adolescent development and show how these anatomical features of the brain are disrupted as a result of prenatal exposure to large quantities of alcohol. We studied two independent samples of normally developing children, adolescents, and young adults, totaling 83 subjects from two different research groups, and compared them to 21 individuals with heavy prenatal alcohol exposure. Surface-based image analysis techniques allowed us to match cortical anatomy across subjects and between hemispheres based on manually delineated sulcal landmarks. Quantitative maps of brain surface asymmetry reveal prominent peri-Sylvian hemispheric differences in which the superior temporal and inferior parietal cortices are shifted backward in the left relative to the right hemisphere in both normal and alcohol-exposed subjects. Cortical surface gray matter asymmetry, mapped here in adolescent populations, is most prominent in the posterior inferior temporal lobes (right greater than left), and this effect does not differ between groups of normally developing children, adolescents, or young adults. Alcohol-exposed individuals show a significant reduction in this asymmetry, whether studied with surface-based or more traditional volumetric region of interest analyses. This region of cortex, near the junction of Brodmann's areas 21, 22, and 37, primarily subserves language functions that are known to be impaired on average in the alcohol-exposed subjects. Our findings elucidate regional patterns of brain surface and gray matter asymmetry during normal development and may contribute to a more comprehensive understanding of the neural substrates of cognitive dysfunction after heavy prenatal alcohol exposure.
Fetal alcohol syndrome (FAS) is a common developmental disorder with impairments in multiple neuropsychiatric spheres of varying severity. Few population-derived studies of the behavioral phenotype are available. The purpose of this study was to estimate the prevalence of neuropsychiatric disorders in three groups: subjects who met criteria for FAS (n=152); subjects who met criteria for partial FAS/ARND (n=150); and referred subjects who did not meet criteria for either FAS or partial FAS/ARND (n=86). Each subject had a standardized evaluation by a medical geneticist. All subjects were from North Dakota. We found increases in the prevalence rates of neuropsychiatric disorders in subjects with FAS compared to subjects with partial FAS/ARND and the lowest rates in the group that did not meet criteria for either FAS or partial FAS/ARND. Comorbid attention deficit hyperactivity disorder occurred in 73% of cases with FAS, in 72% cases with partial FAS/ARND, and in 36% subjects who did not meet criteria for either. For other neuropsychiatric disorders, a similar distribution of comorbidity was found. This study supports the concept of a continuum of impairment resulting from prenatal alcohol exposure. The presence of complex cognitive, behavioral, and physical symptomatology in the affected subjects with prenatal alcohol exposure would seem to fit well under the diagnostic rubric of fetal alcohol spectrum disorder (FASD). Diagnosis and long-term management will require increasing access to multidisciplinary child development teams including mental health professionals who treat children and adolescents. Adults will require care primarily from teams with expertise in mental health and developmental disabilities.
Deficits in attention are a hallmark of the effects of heavy prenatal alcohol exposure but although such deficits have been described in the literature, no attempt to use measures of attention to classify children with such exposure has been described. Thus, the current study attempted to classify children with heavy prenatal alcohol exposure (ALC) and non-exposed controls (CON), using four measures of attentional functioning: the Freedom from Distractibility index from the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), the Attention Problems scale from the Child Behavior Checklist (CBCL), and omission and commission error scores from the Test of Variables of Attention (TOVA). Data from two groups of children were analyzed: children with heavy prenatal alcohol exposure and non-exposed controls. Children in the alcohol-exposed group included both children with or without fetal alcohol syndrome. Groups were matched on age, sex, ethnicity, and social class. Data were analyzed using backward logistic regression. The final model included the Freedom from Distractibility index from the WISC-III and the Attention Problems scale from the CBCL. The TOVA variables were not retained in the final model. Classification accuracy was 91.7% overall. Specifically, 93.3% of the alcohol-exposed children and 90% of the control children were accurately classified. These data indicate that children with heavy prenatal alcohol exposure can be distinguished from non-exposed controls with a high degree of accuracy using 2 commonly used measures of attention.
The Functional Image Analysis Contest (FIAC) 2005 dataset was analyzed using BrainVoyager QX. First, we performed a standard analysis of the functional and anatomical data that includes preprocessing, spatial normalization into Talairach space, hypothesis-driven statistics (one- and two-factorial, single-subject and group-level random effects, General Linear Model [GLM]) of the block- and event-related paradigms. Strong sentence and weak speaker group-level effects were detected in temporal and frontal regions. Following this standard analysis, we performed single-subject and group-level (Talairach-based) Independent Component Analysis (ICA) that highlights the presence of functionally connected clusters in temporal and frontal regions for sentence processing, besides revealing other networks related to auditory stimulation or to the default state of the brain. Finally, we applied a high-resolution cortical alignment method to improve the spatial correspondence across brains and re-run the random effects group GLM as well as the group-level ICA in this space. Using spatially and temporally unsmoothed data, this cortex-based analysis revealed comparable results but with a set of spatially more confined group clusters and more differential group region of interest time courses.