Neuropsychological characteristics of Italian children with fetal alcohol spectrum disorders

Background: Children with fetal alcohol spectrum disorders (FASD) display many problems ranging from deficits in intelligence to behavioral difficulties. Thus, many studies have aimed at defining the neuropsychological characteristics of children with FASD. The current article describes the neuropsychological characteristics of Italian children with severe diagnosis within FASD and compares them with controls. It was expected that intellectual functioning, language comprehension, academic skills, and inattention/hyperactivity would discriminate children with FASD from randomly selected peers without FASD. Methods: This article presents data from a second cohort of children examined in 2005 as part of an in‐school epidemiological study of FASD in Italy. Of 80 children, 23 diagnosed with a FASD, and 57 randomly selected control children from the same first‐grade classes, participated. After screening for FASD via growth and dysmorphology, the children were administered a test of general intelligence (WISC‐R) as well as tests of nonverbal reasoning (Raven Colored Progressive Matrices), language comprehension (Rustioni), academic achievement (IPDA), and problem behavior (Disruptive Behavior Disorder Rating Scale). Results: Children diagnosed with a FASD achieved lower scores than control children on Verbal, Performance, and Full Scale IQ. Profile analysis of the WISC‐R indicates overall differences between the groups. However, some intact functioning within the FASD group was found, as the Similarities and Vocabulary subtests were similar to the controls. After an alpha adjustment to 0.004, the Block Design, Object Assembly, and Mazes subtests were significantly different from controls. On tests of nonverbal reasoning, language comprehension, and academic achievement, the children with a FASD scored significantly lower. Moreover, teachers rated children with a severe diagnosis within FASD as showing more inattentive symptoms than controls, while hyperactive/impulsive characteristics among children with a FASD were comparable with the control children. Significant correlations between head circumference, child dysmorphology, WISC‐R, and Raven CPM scores are also reported. Conclusions: This study indicates that a sample of Italian children with a FASD, when compared with control children, display poorer functioning on measures of general intelligence, nonverbal reasoning, academic achievement, and teacher‐rated problem behaviors. The findings also contribute to the formulation of a neuropsychological profile of children diagnosed with a FASD.     

Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders

Background: Structural abnormalities of the corpus callosum (CC), such as reduced size and increased shape variability, have been documented in individuals with fetal alcohol spectrum disorders (FASD). However, the regional specificity of altered CC structure, which may point to the timing of neurodevelopmental disturbances and/or relate to specific functional impairments, remains unclear. Furthermore, associations between facial dysmorphology and callosal structure remain undetermined. Methods: One hundred and fifty‐three participants (age range 8 to 16) including 82 subjects with FASD and 71 nonexposed controls were included in this study. The structural magnetic resonance imaging data of these subjects was collected at 3 sites (Los Angeles and San Diego, California, and Cape Town, South Africa) and analyzed using classical parcellation schemes, as well as more refined surface‐based geometrical modeling methods, to identify callosal morphological alterations in FASD at high spatial resolution. Results: Reductions in callosal thickness and area, specifically in the anterior third and the splenium, were observed in FASD compared with nonexposed controls. In addition, reduced CC thickness and area significantly correlated with reduced palpebral fissure length. Conclusions: Consistent with previous reports, findings suggest an adverse effect of prenatal alcohol exposure on callosal growth and further indicate that fiber pathways connecting frontal and parieto‐occipital regions in each hemisphere may be particularly affected. Significant associations between callosal and facial dysmorphology provide evidence for a concurrent insult to midline facial and brain structural development in FASD.     

Neurobehavioral characteristics of children with fetal alcohol spectrum disorders in communities from Italy: Preliminary results

BACKGROUND: There has been considerable effort expended on defining neurobehavioral characteristics of children with fetal alcohol spectrum disorders (FASD). Children with FASD display a range of cognitive deficits and behavioral problems. In this article, we report on the neurobehavioral characteristics of children with FASD in selected communities in Italy. It was expected that both inattentive and hyperactive/impulsive characteristics would discriminate children with FASD from controls and that the groups would also differ on intellectual functioning, language comprehension, and academic skills. METHODS: Eighty-two children, 22 diagnosed with FASD and 60 control children, participated in this study. The children were administered tests of nonverbal reasoning, language comprehension, academic achievement, and behavior. RESULTS: On tests of nonverbal reasoning and language comprehension, the FASD group earned lower scores than did controls. Moreover, on a test of academic achievement the FASD group scored lower. When comparing these 2 groups on disruptive behavioral symptomatology, similar results were obtained, the FASD group showing greater attentional difficulties and hyperactivity/impulsivity behaviors and more overall behavioral problems. Stepwise logistic regression analysis showed that a model containing inattention and error scores on the language comprehension task correctly classified 85% of the participants. Compared with the control group, a significantly greater proportion of children with FASD met the Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) criteria of ADD, inattentive type, as reported by teachers. In contrast, hyperactive symptoms among children with FASD were comparable with the control group. Teachers rated children with FASD as having more inattentive behaviors and as performing lower in academic skills than controls. The association between reported hyperactivity symptoms and achievement scores was nonsignificant for both language and math scores, suggesting that it is not the hyperactivity causing problems, but the child's inattention. CONCLUSIONS: This research indicates that a nonclinic-referred sample of Italian children with FASD display a profile of neurobehavioral functioning consistent with that reported by other researchers. Furthermore, the neurobehavioral characteristic most identified with children diagnosed with FASD was inattention followed by hyperactivity.     

Extensive deep gray matter volume reductions in children and adolescents with fetal alcohol spectrum disorders

Background: The link between the numerous cognitive, motor, and behavioral difficulties of individuals with fetal alcohol spectrum disorders (FASD) and underlying specific structural brain injuries can be investigated using high‐resolution imaging. Differential sensitivity of the brain’s “relay” stations, namely the deep gray matter structures, may play a key factor given their multifaceted role in brain function. The purpose of our study was to analyze differences in deep gray matter volumes of children and adolescents with FASD relative to age/sex‐matched controls and to examine whether any volume differences were consistent across the age range of neurodevelopment. Methods: Children and adolescents (N = 28, 6 to 17 years) diagnosed with FASD and 56 age‐ and sex‐matched healthy controls (i.e., 2 matched controls per FASD subject) underwent 3‐dimensional T1‐weighted MRI scans that were used for the automated volume measurement (FreeSurfer) of the intracranial space, total white matter, cortical gray matter, and 6 deep gray matter structures, namely the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus, with left and right measured separately. Volumes were compared between FASD and controls, as well as changes with age. Results: Significant reductions of volume in FASD were observed for the intracranial vault (7.6%), total white matter (8.6%), total cortical gray matter (7.8%), and total deep gray matter (13.1%). All 6 deep gray matter structures showed significant volume reductions bilaterally with the caudate (approximately 16%) and globus pallidus (approximately 18%) being most affected. The hippocampus, thalamus, and globus pallidus showed reductions in all 3 age subgroups (6 to 9, 10 to 13, and 14 to 17 years) but the caudate and putamen had smaller volumes for FASD only within the 2 youngest subgroups; the amygdala was only smaller for FASD in the 2 oldest subgroups. Conclusions: Significant, but variable, volume reductions throughout the deep gray matter are observed over a wide age range of 6 to 17 years in FASD.     

Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure

BACKGROUND: Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. METHODS: The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. RESULTS: Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. CONCLUSIONS: These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor delays in children with FAS may be related to specific neurobehavioral deficits that affect fine motor skills. The findings support the concept of an FASD continuum in some areas of motor development.     

Fetal alcohol spectrum disorders in children residing in Russian orphanages: a phenotypic survey

BACKGROUND: Alcohol use in Russia is among the highest in the world. Over 600,000 children reside in institutional care in Russia, most of them in baby homes and orphanages. The actual prevalence of fetal alcohol spectrum disorders (FASD) among these children is unknown. Therefore, we performed a systematic survey of phenotypic features associated with prenatal alcohol exposure among institutionalized Russian children and related these findings to their growth, development, medical, and social histories. METHODS: Phenotypic screening was conducted of all 234 baby home residents in the Murmansk region of Russia (mean age 21+12.6 months). Phenotypic expression scores were devised based on facial dysmorphology and other readily observable physical findings. Growth measurements from birth, time of placement in the baby home, and at present were analyzed. In addition, the charts of 64% of the children were randomly selected for retrospective review. Information collected included maternal, medical, developmental, and social histories. RESULTS: Thirteen percent of children had facial phenotype scores highly compatible with prenatal alcohol exposure and 45% had intermediate facial phenotype scores. These scores correlated with maternal gravidity and age. At least 40% of mothers in whom history was available ingested alcohol during pregnancy; some also used illicit drugs and tobacco. Z scores for growth measurements corresponded to phenotypic score, as did the degree of developmental delay. Children with no or mild delay had significantly lower phenotypic scores than those with moderate or severe delay (p = 0.04); more than 70% of children with high phenotypic scores were moderately or severely delayed. CONCLUSIONS: More than half of residents of the baby homes in Murmansk, Russia, have intermediate (45%) or high (13%) phenotypic expression scores suggesting prenatal exposure to alcohol. Despite good physical care, stable daily routine, availability of well-trained specialists, and access to medical care, these vulnerable children show significant growth and developmental delays compared with their institutionalized peers.     

A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: profiles, mechanisms, and interventions

Background: Individuals gestationally exposed to alcohol experience a multitude of sociobehavioral impairments, including deficits in adaptive behaviors such as social skills. Methods: The goal of this report is to critically review research on social skills deficits in individuals with prenatal alcohol exposure, including individuals with and without fetal alcohol spectrum disorders (FASD). Results: Social deficits are found in alcohol‐exposed children, adults, and adolescents with and without a clinical presentation. These deficits tend to persist across the lifespan and may even worsen with age. Social deficits in this population appear to be independent of facial dysmorphology and IQ and are worse than can be predicted based on atypical behaviors alone. Abnormalities in neurobiology, executive function, sensory processing, and communication likely interact with contextual influences to produce the range of social deficits observed in FASD. Conclusions: Future investigations should strive to reconcile the relationship between social skills deficits in FASD and variables such as gender, age, cognitive profile, and structural and functional brain impairments to enable better characterization of the deficits observed in this population, which will enhance diagnosis and improve remediation.     

Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol syndrome in South Africa: a third study

Objectives: This is a third exploration of risk factors for the two most severe forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS) and Partial FAS (PFAS), in a South African community with the highest reported prevalence of FAS in the world. Methods: In a case control design, interview and collateral data concerning mothers of 72 first grade children with FAS or PFAS are compared with 134 randomly selected maternal controls of children from the same schools. Results: Significant differences were found between the mothers of FASD children and controls in socio‐economic status, educational attainment, and a higher prevalence of FASD among rural residents. The birth order of the index children, gravidity, and still birth were significantly higher among mothers of FASD children. Mothers of children with a FASD are less likely to be married and more likely to have a male partner who drank during the index pregnancy. Current and gestational alcohol use by mothers of FASD children is bingeing on weekends, with no reduction in drinking reported in any trimester in 75 to 90% of the pregnancies that resulted in an FAS child or during 50 to 87% of PFAS‐producing pregnancies. There was significantly less drinking among the controls in the second and third trimesters (11 to 14%). Estimated peak blood alcohol concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the first trimester to 0.102 in the third, and for mothers of FAS children the range is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking percentage during pregnancy was significantly higher for mothers of FASD children (82 to 84%) than controls (35%); but average quantity smoked is low in the 3 groups at 30 to 41 cigarettes per week. A relatively young average age of the mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of age). But the mean years of alcohol consumption is different between groups, 16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking controls. Mothers of FAS and PFAS children were significantly smaller in height and weight than controls at time of interview. The child’s total dysmorphology score correlates significantly with mother’s weight (?0.46) and BMI (?0.39). Bivariate correlations are significant between the child’s dysmorphology and known independent demographic and behavioral maternal risk factors for FASD: higher gravidity and parity; lower education and income; rural residence; drinks consumed daily, weekly, and bingeing during pregnancy; drinking in all trimesters; partner's alcohol consumption during pregnancy; and use of tobacco during pregnancy. Similar significant correlations were also found for most of the above independent maternal risk variables and the child’s verbal IQ, non‐verbal IQ and behavioral problems. Conclusions: Maternal data in this population are generally consistent with a spectrum of effects exhibited in the children. Variation within the spectrum links greater alcohol doses with a greater severity of effects among children of older and smaller mothers of lower socio economic status in their later pregnancies. Prevention is needed to address known maternal risk factors for FASD in this population.     

Diffusion tensor imaging in children with fetal alcohol spectrum disorders

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

Magnetic Resonance Microscopy Defines Ethanol-Induced Brain Abnormalities in Prenatal Mice: Effects of Acute Insult on Gestational Day 8

Background: Magnetic resonance microscopy (MRM), magnetic resonance imaging (MRI) at microscopic levels, provides unprecedented opportunities to aid in defining the full spectrum of ethanol’s insult to the developing brain. This is the first in a series of reports that, collectively, will provide an MRM‐based atlas of developmental stage‐dependent structural brain abnormalities in a Fetal Alcohol Spectrum Disorders (FASD) mouse model. The ethanol exposure time and developmental stage examined for this report is gestational day (GD) 8 in mice, when the embryos are at early neurulation stages; stages present in humans early in the fourth week postfertilization. Methods: For this study, pregnant C57Bl/6J mice were administered an ethanol dosage of 2.8 g/kg intraperitoneally at 8 days, 0 hour and again at 8 days, 4 hours postfertilization. On GD 17, fetuses that were selected for MRM analyses were immersion fixed in a Bouin’s/Prohance^® solution. Control fetuses from vehicle‐treated dams were stage‐matched to those that were ethanol‐exposed. The fetal mice were scanned ex vivo at 7.0 T and 512 × 512 × 1024 image arrays were acquired using 3‐D spin warp encoding. The resulting 29 μm (isotropic) resolution images were processed using ITK‐SNAP, a 3‐D segmentation/visualization tool. Linear and volume measurements were determined for selected brain, head, and body regions of each specimen. Comparisons were made between control and treated fetuses, with an emphasis on determining (dis)proportionate changes in specific brain regions. Results: As compared with controls, the crown‐rump lengths of stage‐matched ethanol‐exposed GD 17 fetuses were significantly reduced, as were brain and whole body volumes. Volume reductions were notable in every brain region examined, with the exception of the pituitary and septal region, and were accompanied by increased ventricular volumes. Disproportionate regional brain volume reductions were most marked on the right side and were significant for the olfactory bulb, hippocampus, and cerebellum; the latter being the most severely affected. Additionally, the septal region and the pituitary were disproportionately large. Linear measures were consistent with those of volume. Other dysmorphologic features noted in the MR scans were choanal stenosis and optic nerve coloboma. Conclusions: This study demonstrates that exposure to ethanol occurring in mice at stages corresponding to the human fourth week postfertilization results in structural brain abnormalities that are readily identifiable at fetal stages of development. In addition to illustrating the utility of MR microscopy for analysis of an FASD mouse model, this work provides new information that confirms and extends human clinical observations. It also provides a framework for comparison of structural brain abnormalities resulting from ethanol exposure at other developmental stages and dosages.     

Maternal oral intake mouse model for fetal alcohol spectrum disorders: ocular defects as a measure of effect

BACKGROUND: This work was conducted in an effort to establish an oral intake model system in which the effects of ethanol insult that occur during early stages of embryogenesis can be easily examined and in which agents that may modulate ethanol's teratogenicity can be readily tested in vivo. The model system described utilizes the alcohol deprivation effect to obtain teratogenic levels of maternal ethanol intake on days 7 and 8 of pregnancy in C57Bl/6J mice. Ocular defects including microphthalmia and uveal coloboma, which have previously been shown to result from ethanol administered by gavage or via intraperitoneal injection on these days, served as the developmental end point for this study. The ocular defects are readily identifiable and their degree of severity is expected to correlate with concurrently developing defects of the central nervous system (CNS). METHODS: Female C57Bl/6J mice were maintained on an ethanol-containing (4.8% v/v) liquid diet for 14 days and then mated during a subsequent abstinence period. Mice were then reexposed to ethanol on days 7 and 8 of pregnancy only. Control as well as ethanol-exposed dams were killed on their 14th day of pregnancy. Fetuses were then weighed, measured for crown rump length, photographed, and analyzed for ocular abnormalities. Globe size, palpebral fissure length, and pupil size and shape were noted for both the right and left eyes of all fetuses and informative comparisons were made. RESULTS: This exposure paradigm resulted in peak maternal blood alcohol concentrations that ranged from 170 to 220 mg/dL on gestational day (GD) 8. Compared with the GD 14 fetuses from the normal control group, the pair-fed, acquisition controls, as well as the ethanol-exposed fetuses, were developmentally delayed and had reduced weights. Confirming previous studies, comparison of similarly staged control and treated GD 8 embryos illustrated reductions in the size of the forebrain in the latter. Subsequent ocular malformations were noted in 33% of the right eyes and 25% of the left eyes of the 103 GD 14 ethanol-exposed fetuses examined. This incidence of defects is twice that observed in the control groups. Additionally, it was found that the palpebral fissure length is directly correlated with globe size. CONCLUSIONS: The high incidence of readily identifiable ocular malformations produced by oral ethanol intake in this model and their relevance to human fetal alcohol spectrum disorders (FASD) makes this an excellent system for utilization in experiments involving factors administered to the embryo that might alter ethanol's teratogenic effects. Additionally, the fact that early ethanol insult yields ocular and forebrain abnormalities that are developmentally associated allows efficient specimen selection for subsequent detailed analyses of CNS effects in this in vivo mammalian FASD model.     

Brain diffusion abnormalities in children with fetal alcohol spectrum disorder

Background: Children with fetal alcohol spectrum disorder (FASD) have a variety of cognitive, behavioral, and neurological impairments, including structural brain damage. Despite the importance of white matter connections for proper brain function, little is known about how these connections, and the deep gray matter structures that act as relay stations, are affected in children with FASD. The purpose of this study was to use diffusion tensor imaging, an advanced magnetic resonance imaging technique, to examine microstructural differences of white and deep gray matter in children with FASD. Methods: Subjects were 24 children aged 5–13 years previously diagnosed with FASD and 95 healthy children over the same age range. Diffusion tractography was used to delineate 10 major white matter tracts in each individual, and region‐of‐interest analysis was used to assess 4 deep gray matter structures. Fractional anisotropy, an indicator of white matter integrity, and mean diffusivity, a measure of the average water diffusion, were assessed in all 14 brain structures. Results: Diffusion tensor imaging revealed significant differences of diffusion parameters in several areas of the brain, including the genu and splenium of the corpus callosum, cingulum, corticospinal tracts, inferior fronto‐occipital fasciculus, inferior and superior longitudinal fasciculi, globus pallidus, putamen, and thalamus. Reduced white and gray matter volumes, as well as total brain volume, were observed in the FASD group. Conclusions: These results demonstrate diffusion abnormalities in FASD beyond the corpus callosum and suggest that several specific white matter regions, particularly commissural and temporal connections, and deep gray matter areas of the brain are sensitive to prenatal alcohol exposure.     

Diffusion tensor imaging of the cerebellum and eyeblink conditioning in fetal alcohol spectrum disorder

Background: Prenatal alcohol exposure is related to a wide range of neurocognitive effects. Eyeblink conditioning (EBC), which involves temporal pairing of a conditioned with an unconditioned stimulus, has been shown to be a potential biomarker of fetal alcohol exposure. A growing body of evidence suggests that white matter may be a specific target of alcohol teratogenesis, and the neural circuitry underlying EBC is known to involve the cerebellar peduncles. Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that has proven useful for assessing central nervous system white matter integrity. This study used DTI to examine the degree to which the fetal alcohol‐related deficit in EBC may be mediated by structural impairment in the cerebellar peduncles. Methods: Thirteen children with fetal alcohol spectrum disorder (FASD) and 12 matched controls were scanned using DTI and structural MRI sequences. The DTI data were processed using a voxelwise technique, and the structural data were used for volumetric analyses. Prenatal alcohol exposure group and EBC performance were examined in relation to brain volumes and outputs from the DTI analysis. Results: Fractional anisotropy (FA) and perpendicular diffusivity group differences between alcohol‐exposed and nonexposed children were identified in the left middle cerebellar peduncle. Alcohol exposure correlated with lower FA and greater perpendicular diffusivity in this region, and these correlations remained significant even after controlling for total brain and cerebellar volumes. Conversely, trace conditioning performance was related to higher FA and lower perpendicular diffusivity in the left middle peduncle. The effect of prenatal alcohol exposure on trace conditioning was partially mediated by lower FA in this region. Conclusions: This study extends recent findings that have used DTI to reveal microstructural deficits in white matter in children with FASD. This is the first DTI study to demonstrate mediation of a fetal alcohol‐related effect on neuropsychological function by deficits in white matter integrity.     

Prenatal alcohol exposure affects frontal-striatal BOLD response during inhibitory control

BACKGROUND: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral dysregulation, including deficits in attention and response inhibition. This study characterized the neural substrates underlying the disinhibited behavioral profile of individuals with fetal alcohol spectrum disorders (FASD). METHODS: Children and adolescents (ages 8-18) with (n=13) and without (n=9) histories of heavy prenatal alcohol exposure underwent functional magnetic resonance imaging while performing a response inhibition (go/no-go) task. RESULTS: Despite similar task performance (mean response latency, performance accuracy, and signal detection), blood oxygen level-dependent (BOLD) response patterns differed by group. Region-of-interest analyses revealed that during portions of the behavioral task that required response inhibition, alcohol-exposed participants showed greater BOLD response across prefrontal cortical regions (including the left medial and right middle frontal gyri), while they showed less right caudate nucleus activation, compared with control participants. CONCLUSIONS: These data provide an account of response inhibition-related brain functioning in youth with FASD. Furthermore, results suggest that the frontal-striatal circuitry thought to mediate inhibitory control is sensitive to alcohol teratogenesis.     

Impaired eyeblink conditioning in children with fetal alcohol syndrome

Background: Eyeblink conditioning (EBC) is a Pavlovian paradigm that involves contingent temporal pairing of a conditioned stimulus (e.g., tone) with an unconditioned stimulus (e.g., air puff). Animal studies have shown that binge consumption of alcohol during pregnancy impairs EBC and that this impairment is likely mediated by a loss of neurons in the inferior olive and the cerebellar cortex and deep nuclei, as well as by a reduction in neural plasticity in the cerebellar deep nuclei. Methods: Short delay EBC was examined in 98 5‐year‐old children born to women from the Coloured (mixed ancestry) community in Cape Town, South Africa, who were recruited prenatally and are participating in the first prospective longitudinal study of children with fetal alcohol syndrome (FAS). FAS status was assessed at 5 years by expert dysmorphologists. Two sessions of 50 trials each were administered to the children; a third session was administered the following day to those children who did not meet criterion of 40% conditioned responses in session 2. Results: Not a single child with FAS met criterion for conditioning as contrasted with 75.0% of the controls. Whereas 86.7% of the controls who were conditioned met criterion by the end of Session 2, a large proportion of the relatively few alcohol‐exposed nonsyndromal children who conditioned did not do so until Session 3. These alcohol effects on EBC persisted after controlling for IQ. Three of 4 microcephalic children who were not exposed to alcohol were successfully conditioned. Conclusions: This is the first prospective study to demonstrate impaired EBC in children diagnosed with FAS. Successful EBC in a microcephalic group supports the inference that the EBC deficit is specific to prenatal alcohol exposure and a potential biomarker for diagnosis of exposed children lacking the distinctive FAS dysmorphology. Delay EBC has a high sensitivity for identifying individuals with a diagnosis of probable FAS.     

Implicit strategy affects learning in children with heavy prenatal alcohol exposure

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.