Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This ... more Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n ¼ 18) and controls (CON group; n ¼ 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p ¼ 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure.
Fetal alcohol spectrum disorders constitute a major public health problem. This article presents ... more Fetal alcohol spectrum disorders constitute a major public health problem. This article presents an overview of important issues that surround these disorders and emphasizes the structural and neurobehavioral consequences associated with prenatal exposure to alcohol. Diagnostic criteria are discussed, and possible moderating factors for the range of outcomes are mentioned. In addition, the prevalence of fetal alcohol spectrum disorders is described, and estimates of the financial impact of these disorders are given. Heavy prenatal alcohol exposure can severely affect the physical and neurobehavioral development of a child. Autopsy and brain imaging studies indicate reductions and abnormalities in overall brain size and shape, specifically in structures such as the cerebellum, basal ganglia, and corpus callosum. A wide range of neuropsychological deficits have been found in children prenatally exposed to alcohol, including deficits in visuospatial functioning, verbal and nonverbal le...
Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on ... more Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on behavior. Disrupted development of the pituitary gland, which has been observed in rodent studies, may account for some of these effects. To determine if gestational exposure to alcohol produces measureable changes in the pituitary in human adolescents, we manually traced the pituitary in T1-weighted structural magnetic resonance images (MRI) from adolescents with (15 males, 11 females) and without (16 males, 11 females) heavy prenatal alcohol exposure. Pituitary gland volume and maximum signal intensity were examined for group differences. Control female adolescents presented with significantly greater pituitary volume compared to males, as has been previously reported. However, this sexual dimorphism was absent in adolescents with histories of prenatal alcohol exposure. Alcohol-exposed adolescents, regardless of sex, demonstrated reduced pituitary maximum signal intensity compared to c...
Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure co... more Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure correlates of this deficit have not been determined with sufficient detail. We examined the hypothesis that the structure of the anterior cingulate cortex (ACC) relates to inhibition performance in youth with histories of heavy prenatal alcohol exposure (AE, n=32) and non-exposed controls (CON, n=21). Adolescents (12-17y) underwent structural magnetic resonance imaging yielding measures of gray matter volume, surface area, and thickness across four ACC subregions. A subset of subjects were administered the NEPSY-II Inhibition subtest. MANCOVA was utilized to test for group differences in ACC and inhibition performance and multiple linear regression was used to probe ACC-inhibition relationships. ACC surface area was significantly smaller in AE, though this effect was primarily driven by reduced right caudal ACC (rcACC). AE also performed significantly worse on inhibition speed but not on i...
Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism, 2001
Children prenatally exposed to alcohol can suffer from serious cognitive deficits and behavioral ... more Children prenatally exposed to alcohol can suffer from serious cognitive deficits and behavioral problems as well as from alcohol-related changes in brain structure. Neuropsychological studies have identified deficits in learning and memory as well as in executive functioning both in children with fetal alcohol syndrome and in children with less severe impairments. Both groups of children also exhibit problem behaviors, such as alcohol and drug use, hyperactivity, impulsivity, and poor socialization and communication skills. Brain imaging studies have identified structural changes in various brain regions of these children--including the basal ganglia, corpus callosum, cerebellum, and hippocampus--that may account for the cognitive deficits. Functional brain imaging studies also have detected changes in alcohol-exposed children indicative of deficits in information processing and memory tasks.
This paper reviews the magnetic resonance imaging (MRI) literature on the effects of prenatal alc... more This paper reviews the magnetic resonance imaging (MRI) literature on the effects of prenatal alcohol exposure on the developing human brain. A literature search was conducted through the following databases: PubMed, PsycINFO and Google Scholar. Combinations of the following search terms and keywords were used to identify relevant studies: 'alcohol', 'fetal alcohol spectrum disorders', 'fetal alcohol syndrome', 'FAS', 'FASD', 'MRI',…
Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and fun... more Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and functional changes in brain regions involved in response inhibition such as the prefrontal cortex and striatum. The current study examined blood oxygen level-dependent (BOLD) response during a stop signal task in adolescents (ages 13-16 y) with histories of heavy prenatal alcohol exposure (AE, n = 21) and controls (CON, n = 21). Task performance was measured using percent correct inhibits during three difficulty conditions: easy, medium, and hard. Group differences in BOLD response relative to baseline motor responding were examined across all inhibition trials and for each difficulty condition separately. The contrast between hard and easy trials was analyzed to determine whether increasing task difficulty affected BOLD response. Groups had similar task performance and demographic characteristics, except for full scale IQ scores (AE < CON). The AE group demonstrated greater BOLD response in frontal, sensorimotor, striatal, and cingulate regions relative to controls, especially as task difficulty increased. When contrasting hard vs. easy inhibition trials, the AE group showed greater medial/superior frontal and cuneus BOLD response than controls. Results were unchanged after demographics and FAS diagnosis were statistically controlled. This was the first fMRI study to utilize a stop signal task, isolating fronto-striatal functioning, to assess response inhibition and the effects task difficulty in adolescents with prenatal alcohol exposure. Results suggest that heavy prenatal alcohol exposure disrupts neural function of this circuitry, resulting in immature cognitive processing and motor-association learning and neural compensation during response inhibition.
Attention deficits are often observed in children with prenatal alcohol exposure and attentiondef... more Attention deficits are often observed in children with prenatal alcohol exposure and attentiondeficit/hyperactivity disorder (ADHD) is commonly diagnosed in this population. This study used an objective assessment tool to examine differences between alcohol-exposed and non-exposed children on core symptoms of ADHD: inattention, impulsivity, and hyperactivity. Two groups of individuals, aged 7-14 years, participated in the study: alcohol-exposed children (AE, n = 43), and non-exposed children (CON, n = 54). Subjects were evaluated with the Quotient ADHD System, which provides objective data on ADHD core symptoms by combining an infrared motion tracking system and a computerized continuous performance task. Twelve separate ANCOVAs controlling for the effects of age and sex, were conducted on attention and motion variables. Results revealed that in comparison to the CON group, the AE group was significantly (p's < .05) less accurate, made an increased number of omission errors, and had longer response latencies and increased variability in response time; moreover, the AE group spent less time staying still, and made an increased number of head movements, which traveled a larger distance, covered a greater area, and demonstrated a less complex movement pattern. No significant group differences were observed on the number of commission errors and temporal scaling. Our findings provide further support for the notion that inattention is a core deficit in children prenatally exposed to alcohol. Results from this study are also consistent with parent reports of increased hyperactivity. The
Objective: To validate an automated cerebellar segmentation method based on active shape and appe... more Objective: To validate an automated cerebellar segmentation method based on active shape and appearance modeling and then segment the cerebellum on images acquired from adolescents with histories of prenatal alcohol exposure (PAE) and non-exposed controls (NC). Methods: Automated segmentations of the total cerebellum, right and left cerebellar hemispheres, and three vermal lobes (anterior, lobules I-V; superior posterior, lobules VI-VII; inferior posterior, lobules VIII-X) were compared to expert manual labelings on 20 subjects, studied twice, that were not used for model training. The method was also used to segment the cerebellum on 11 PAE and 9 NC adolescents. Results: The test-retest intraclass correlation coefficients (ICCs) of the automated method were greater than 0.94 for all cerebellar volume and mid-sagittal vermal area measures, comparable or better than the test-retest ICCs for manual measurement (all ICCs N 0.92). The ICCs computed on all four cerebellar measurements (manual and automated measures on the repeat scans) to compare comparability were above 0.97 for non-vermis parcels, and above 0.89 for vermis parcels. When applied to patients, the automated method detected smaller cerebellar volumes and mid-sagittal areas in the PAE group compared to controls (p b 0.05 for all regions except the superior posterior lobe, consistent with prior studies). Discussion: These results demonstrate excellent reliability and validity of automated cerebellar volume and midsagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.
Objective-The current study examined the relationship between mathematics and attention, working ... more Objective-The current study examined the relationship between mathematics and attention, working memory, and visual memory in children with heavy prenatal alcohol exposure and controls. Method-Fifty-six children (29 AE, 27 CON) were administered measures of global mathematics achievement (WRAT-3 Arithmetic & WISC-III Written Arithmetic), attention, (WISC-III Digit Span forward and Spatial Span forward), working memory (WISC-III Digit Span backward and Spatial Span backward), and visual memory (CANTAB Spatial Recognition Memory and Pattern Recognition Memory). The contribution of cognitive domains to mathematics achievement was analyzed using linear regression techniques. Attention, working memory and visual memory data were entered together on step 1 followed by group on step 2, and the interaction terms on step 3. Results-Model 1 accounted for a significant amount of variance in both mathematics achievement measures, however, model fit improved with the addition of group on step 2. Significant predictors of mathematics achievement were Spatial Span forward and backward and Spatial Recognition Memory. Conclusions-These findings suggest that deficits in spatial processing may be related to math impairments seen in FASD. In addition, prenatal alcohol exposure was associated with deficits in mathematics achievement, above and beyond the contribution of general cognitive abilities.
Alcohol consumption during pregnancy can lead to a variety of cognitive and other birth defects, ... more Alcohol consumption during pregnancy can lead to a variety of cognitive and other birth defects, collectively termed fetal alcohol spectrum disorders (FASD), which includes the Fetal Alcohol Syndrome (FAS). This study examined the impact of gestational alcohol exposure on the morphology of the cingulate gyrus, given this region's role in cognitive control, attention, and emotional regulation, all of which are affected in children with FASD. Thirty-one youth (ages 8-16) with histories of heavy prenatal alcohol exposure (n = 21) and demographically-matched comparison subjects (n = 10) underwent structural magnetic resonance imaging. The cingulate gyrus was manually delineated, and parcellated volumes of grey and white matter were compared across groups. Alcohol-exposed individuals had significantly smaller raw cingulate grey matter, white matter, and tissue volumes, compared to controls. After adjusting for respective cranial tissue constituents, only white matter volumes remained significantly reduced, and this held regardless of whether or not the child qualified for a diagnosis of FAS. A correlation between posterior cingulate grey matter volume and the WISC-III Freedom from Distractibility Index was also observed in alcohol-exposed children. These data suggest that cingulate white matter is compromised beyond global white matter hypoplasia in alcohol-exposed individuals, regardless of FAS diagnosis. The observed volumetric reductions in the cingulate gyrus may contribute to the disruptive and emotionally dysregulated behavioral profile commonly observed in this population.
Heavy prenatal alcohol exposure causes permanent structural alterations to the brain and can lead... more Heavy prenatal alcohol exposure causes permanent structural alterations to the brain and can lead to numerous cognitive and behavioral outcomes. Consistent with many of the neuropsychological and behavioral deficits that have been reported, neuroimaging studies reveal a pattern of structural abnormalities associated with prenatal alcohol exposure. This chapter systematically reviews structural anomalies by brain region, identifying cognitive and behavioral correlates when relevant. The consensus shows that in addition to the overall reduction of brain size, prominent brain shape abnormalities have been observed, with narrowing in the parietal region and reduced brain growth in portions of the frontal lobe. Commensurate with these anomalies, volumetric and tissue density findings cite disproportionate reductions in the parietal lobe, cerebellar vermis, corpus callosum, and the caudate nucleus, suggesting that certain areas of the brain may be especially vulnerable to prenatal alcohol exposure. In sum, neuroimaging techniques have greatly advanced our understanding of brain-behavior relationships in fetal alcohol spectrum disorders (FASD), and hopefully will lead to improved diagnosis and treatment options for those affected by prenatal exposure to alcohol.
Journal of the International Neuropsychological Society, 2007
Children with either fetal alcohol spectrum disorder (FASD) or attention-deficit/hyperactivity di... more Children with either fetal alcohol spectrum disorder (FASD) or attention-deficit/hyperactivity disorder (ADHD) display deficits in attention and executive function (EF) and differential diagnosis of these two clinical groups may be difficult, especially when information about prenatal alcohol exposure is unavailable. The current study compared EF performance of three groups: children with heavy prenatal alcohol exposure (ALC); nonexposed children with attention-deficit/hyperactivity disorder (ADHD); and typically developing controls (CON). Both clinical groups met diagnostic criteria for ADHD. The EF tasks used were the Wisconsin Card Sorting Test (WCST), the Controlled Oral Word Association Test (COWAT), and the Trail Making Test (TMT). Results indicated different patterns of deficit; both clinical groups displayed deficits on the WCST and a relative weakness on letterversuscategory fluency. Only the ALC group displayed overall deficits on letter fluency and a relative weakness on ...
Journal of the International Neuropsychological Society, 2011
An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to d... more An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to determine neurobehavioral profiles to identify affected individuals. Deficits observed when children with FASD are compared to typically developing controls may be confounded by lower IQ scores in the subjects with FASD. To determine if prenatal alcohol exposure is associated with neurobehavioral deficits after controlling for IQ differences, multivariate analyses were conducted to compare alcohol-exposed (ALC) subjects to a comparison group closely matched on IQ (IQC). The initial analysis included a broad neuropsychological battery with measures of language, executive function, visual–motor integration, motor ability, and academic achievement. Additional, in depth comparisons focused on visual sustained attention, verbal learning and memory and parent/guardian-reported behavior problems. Group differences (ALC < IQC) were found on verbal learning and parent-rated behavior problems. G...
Based on caregiver report, children with prenatal alcohol exposure have difficulty with social fu... more Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge's reformulated six-stage model. Fifty-two children (aged 7-11) with and without heavy prenatal alcohol exposure were tested using a structured interview measure of social information processing involving 18 videotaped vignettes of children in group entry and provocation situations. Alcohol-exposed children displayed maladaptive processing patterns on the goal, response generation, and response evaluation steps in group entry situations, and encoding, attribution, response evaluation, and enactment steps during provocation situations. Children with heavy prenatal alcohol exposure also had difficulty on the Test of Problem Solving, and performance correlated with social information processing measures. Such difficulties may lead to problems in social functioning and warrant early intervention.
Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive... more Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive and psychosocial functioning and alterations in brain structure that persist into adulthood. In this report, data from 99 participants collected across three sites (Los Angeles and San Diego, California, and Cape Town, South Africa) were analyzed to examine relationships between brain structure, neurocognitive function, facial morphology, and maternal reports of quantities of alcohol consumption during the first trimester. Across study sites, we found highly significant volume reductions in the FASD group for all of the brain regions evaluated. After correcting for scan location, age, and total brain volume, these differences remained significant in some regions of the basal ganglia and diencephalon. In
Alcoholism: Clinical and Experimental Research, 2007
Background: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral ... more 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 5 13) and without (n 5 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.
Alcoholism: Clinical and Experimental Research, 2011
Background-Children with fetal alcohol spectrum disorders (FASD) have deficits in verbal learning... more Background-Children with fetal alcohol spectrum disorders (FASD) have deficits in verbal learning and recall. However, the specificity of these deficits has not been adequately tested. In the current study, verbal learning and memory performance of children with heavy prenatal alcohol exposure was compared to children with attention-deficit/hyperactivity disorder (ADHD), a disorder commonly seen in alcohol-exposed children. Methods-Performance on the California Verbal Learning Test-Children's Version (CVLT-C) was examined in three groups of children (N=22/group): (1) heavy prenatal alcohol exposure and ADHD (ALC), (2) nonexposed with ADHD (ADHD), and (3) nonexposed typically developing (CON). Groups were matched on age, sex, race, ethnicity, handedness, and socioeconomic status. Results-Group differences were noted on learning trials (CON > ADHD > ALC). On the delayed recall trial, CON children performed better than both clinical groups, who did not differ from each other. Children in the ALC group demonstrated poorer recognition than children in the CON and ADHD groups, who did not differ from each other. Marginally significant group differences were noted on retention of previously learned material. Post hoc analyses indicated that ADHD children showed worse retention relative to the CON group, whereas retention in the ALC children remained intact. Conclusions-These data suggest that children with heavy prenatal alcohol exposure and nonexposed children with ADHD show differential patterns of deficit on the CVLT-C. Performance of alcohol-exposed children reflects inefficient encoding of verbal material, whereas performance of the ADHD group may be better characterized by a deficit in retrieval of learned material. Differences noted between clinical groups add to a growing neurobehavioral profile of FASD that may aid in differential diagnosis.
Alcoholism: Clinical and Experimental Research, 2009
Background-The study examined whether prenatal alcohol exposure is associated with increased moto... more Background-The study examined whether prenatal alcohol exposure is associated with increased motor timing variability when the timing response is partitioned into central clock variability, which indexes information processing at the central nervous system (CNS) level and motor delay variability, which reflects timing processes at the level of the peripheral nervous system (PNS). Methods-Eighteen children with histories of prenatal alcohol exposure and 22 control children were assigned to young (7-11 years) or older (12-17 years) groups. Children tapped a single response key with the index finger in synchrony with a series of externally generated tones (the paced phase). At the conclusion of these tones, children continued tapping (the continuation phase) while attempting to maintain the same rate of tapping imposed by the paced phase. Two blocks of tapping were completed with inter-tone-intervals set at either 400 or 900 ms. Interresponse interval, central clock variability, and motor delay variability produced during the continuation phase were the dependent variables. Results-Mean inter-response interval for the four groups did not differ for either time interval. Central clock variability produced by the young alcohol-exposed group was significantly greater than the two older groups for the 400 ms interval and all other groups for the 900 ms interval. Motor delay variability produced by the young alcohol-exposed group was significantly greater than the other three groups for both time intervals. Central and motor delay variability in children with and without alcohol exposure was directly related to the duration of the interval to be reproduced. Conclusions-Central and peripheral timing variability was significantly greater for the young alcohol-exposed children. This atypical timing may be related to the teratogenic effects of alcohol, although the negative effects are limited to younger alcohol-exposed children since there were no differences in central and peripheral timing variability between the older alcohol-exposed children and controls.
Alcoholism: Clinical and Experimental Research, 2012
Background-Children with heavy prenatal alcohol exposure often meet criteria for attentiondeficit... more Background-Children with heavy prenatal alcohol exposure often meet criteria for attentiondeficit/hyperactivity disorder (ADHD). ADHD research has examined subtype differences in symptomology, including sluggish cognitive tempo (SCT). This construct is defined by behavioral symptoms including, hypoactivity and daydreaming, and has been linked to increased internalizing behaviors. The current study examined if similar findings are displayed in children with prenatal alcohol exposure. Methods-As part of a multisite study, caregivers of 272 children (8-16y) completed the SCT scale and Child Behavior Checklist (CBCL). Four groups were included: alcohol-exposed children with ADHD (ALC+; n=75), alcohol-exposed children without ADHD (ALC−; n=35), nonexposed children with ADHD (ADHD; n=60), and non-exposed children without ADHD (CON; n=102). SCT and CBCL scores were analyzed using 2 (exposure) × 2 (ADHD) ANOVAs. Pearson
Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This ... more Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n ¼ 18) and controls (CON group; n ¼ 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p ¼ 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure.
Fetal alcohol spectrum disorders constitute a major public health problem. This article presents ... more Fetal alcohol spectrum disorders constitute a major public health problem. This article presents an overview of important issues that surround these disorders and emphasizes the structural and neurobehavioral consequences associated with prenatal exposure to alcohol. Diagnostic criteria are discussed, and possible moderating factors for the range of outcomes are mentioned. In addition, the prevalence of fetal alcohol spectrum disorders is described, and estimates of the financial impact of these disorders are given. Heavy prenatal alcohol exposure can severely affect the physical and neurobehavioral development of a child. Autopsy and brain imaging studies indicate reductions and abnormalities in overall brain size and shape, specifically in structures such as the cerebellum, basal ganglia, and corpus callosum. A wide range of neuropsychological deficits have been found in children prenatally exposed to alcohol, including deficits in visuospatial functioning, verbal and nonverbal le...
Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on ... more Prenatal alcohol exposure can interfere with endocrine function and have sex-specific effects on behavior. Disrupted development of the pituitary gland, which has been observed in rodent studies, may account for some of these effects. To determine if gestational exposure to alcohol produces measureable changes in the pituitary in human adolescents, we manually traced the pituitary in T1-weighted structural magnetic resonance images (MRI) from adolescents with (15 males, 11 females) and without (16 males, 11 females) heavy prenatal alcohol exposure. Pituitary gland volume and maximum signal intensity were examined for group differences. Control female adolescents presented with significantly greater pituitary volume compared to males, as has been previously reported. However, this sexual dimorphism was absent in adolescents with histories of prenatal alcohol exposure. Alcohol-exposed adolescents, regardless of sex, demonstrated reduced pituitary maximum signal intensity compared to c...
Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure co... more Prenatal alcohol exposure is associated with behavioral disinhibition, yet the brain structure correlates of this deficit have not been determined with sufficient detail. We examined the hypothesis that the structure of the anterior cingulate cortex (ACC) relates to inhibition performance in youth with histories of heavy prenatal alcohol exposure (AE, n=32) and non-exposed controls (CON, n=21). Adolescents (12-17y) underwent structural magnetic resonance imaging yielding measures of gray matter volume, surface area, and thickness across four ACC subregions. A subset of subjects were administered the NEPSY-II Inhibition subtest. MANCOVA was utilized to test for group differences in ACC and inhibition performance and multiple linear regression was used to probe ACC-inhibition relationships. ACC surface area was significantly smaller in AE, though this effect was primarily driven by reduced right caudal ACC (rcACC). AE also performed significantly worse on inhibition speed but not on i...
Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism, 2001
Children prenatally exposed to alcohol can suffer from serious cognitive deficits and behavioral ... more Children prenatally exposed to alcohol can suffer from serious cognitive deficits and behavioral problems as well as from alcohol-related changes in brain structure. Neuropsychological studies have identified deficits in learning and memory as well as in executive functioning both in children with fetal alcohol syndrome and in children with less severe impairments. Both groups of children also exhibit problem behaviors, such as alcohol and drug use, hyperactivity, impulsivity, and poor socialization and communication skills. Brain imaging studies have identified structural changes in various brain regions of these children--including the basal ganglia, corpus callosum, cerebellum, and hippocampus--that may account for the cognitive deficits. Functional brain imaging studies also have detected changes in alcohol-exposed children indicative of deficits in information processing and memory tasks.
This paper reviews the magnetic resonance imaging (MRI) literature on the effects of prenatal alc... more This paper reviews the magnetic resonance imaging (MRI) literature on the effects of prenatal alcohol exposure on the developing human brain. A literature search was conducted through the following databases: PubMed, PsycINFO and Google Scholar. Combinations of the following search terms and keywords were used to identify relevant studies: 'alcohol', 'fetal alcohol spectrum disorders', 'fetal alcohol syndrome', 'FAS', 'FASD', 'MRI',…
Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and fun... more Heavy prenatal alcohol exposure results in a range of deficits, including both volumetric and functional changes in brain regions involved in response inhibition such as the prefrontal cortex and striatum. The current study examined blood oxygen level-dependent (BOLD) response during a stop signal task in adolescents (ages 13-16 y) with histories of heavy prenatal alcohol exposure (AE, n = 21) and controls (CON, n = 21). Task performance was measured using percent correct inhibits during three difficulty conditions: easy, medium, and hard. Group differences in BOLD response relative to baseline motor responding were examined across all inhibition trials and for each difficulty condition separately. The contrast between hard and easy trials was analyzed to determine whether increasing task difficulty affected BOLD response. Groups had similar task performance and demographic characteristics, except for full scale IQ scores (AE < CON). The AE group demonstrated greater BOLD response in frontal, sensorimotor, striatal, and cingulate regions relative to controls, especially as task difficulty increased. When contrasting hard vs. easy inhibition trials, the AE group showed greater medial/superior frontal and cuneus BOLD response than controls. Results were unchanged after demographics and FAS diagnosis were statistically controlled. This was the first fMRI study to utilize a stop signal task, isolating fronto-striatal functioning, to assess response inhibition and the effects task difficulty in adolescents with prenatal alcohol exposure. Results suggest that heavy prenatal alcohol exposure disrupts neural function of this circuitry, resulting in immature cognitive processing and motor-association learning and neural compensation during response inhibition.
Attention deficits are often observed in children with prenatal alcohol exposure and attentiondef... more Attention deficits are often observed in children with prenatal alcohol exposure and attentiondeficit/hyperactivity disorder (ADHD) is commonly diagnosed in this population. This study used an objective assessment tool to examine differences between alcohol-exposed and non-exposed children on core symptoms of ADHD: inattention, impulsivity, and hyperactivity. Two groups of individuals, aged 7-14 years, participated in the study: alcohol-exposed children (AE, n = 43), and non-exposed children (CON, n = 54). Subjects were evaluated with the Quotient ADHD System, which provides objective data on ADHD core symptoms by combining an infrared motion tracking system and a computerized continuous performance task. Twelve separate ANCOVAs controlling for the effects of age and sex, were conducted on attention and motion variables. Results revealed that in comparison to the CON group, the AE group was significantly (p's < .05) less accurate, made an increased number of omission errors, and had longer response latencies and increased variability in response time; moreover, the AE group spent less time staying still, and made an increased number of head movements, which traveled a larger distance, covered a greater area, and demonstrated a less complex movement pattern. No significant group differences were observed on the number of commission errors and temporal scaling. Our findings provide further support for the notion that inattention is a core deficit in children prenatally exposed to alcohol. Results from this study are also consistent with parent reports of increased hyperactivity. The
Objective: To validate an automated cerebellar segmentation method based on active shape and appe... more Objective: To validate an automated cerebellar segmentation method based on active shape and appearance modeling and then segment the cerebellum on images acquired from adolescents with histories of prenatal alcohol exposure (PAE) and non-exposed controls (NC). Methods: Automated segmentations of the total cerebellum, right and left cerebellar hemispheres, and three vermal lobes (anterior, lobules I-V; superior posterior, lobules VI-VII; inferior posterior, lobules VIII-X) were compared to expert manual labelings on 20 subjects, studied twice, that were not used for model training. The method was also used to segment the cerebellum on 11 PAE and 9 NC adolescents. Results: The test-retest intraclass correlation coefficients (ICCs) of the automated method were greater than 0.94 for all cerebellar volume and mid-sagittal vermal area measures, comparable or better than the test-retest ICCs for manual measurement (all ICCs N 0.92). The ICCs computed on all four cerebellar measurements (manual and automated measures on the repeat scans) to compare comparability were above 0.97 for non-vermis parcels, and above 0.89 for vermis parcels. When applied to patients, the automated method detected smaller cerebellar volumes and mid-sagittal areas in the PAE group compared to controls (p b 0.05 for all regions except the superior posterior lobe, consistent with prior studies). Discussion: These results demonstrate excellent reliability and validity of automated cerebellar volume and midsagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.
Objective-The current study examined the relationship between mathematics and attention, working ... more Objective-The current study examined the relationship between mathematics and attention, working memory, and visual memory in children with heavy prenatal alcohol exposure and controls. Method-Fifty-six children (29 AE, 27 CON) were administered measures of global mathematics achievement (WRAT-3 Arithmetic & WISC-III Written Arithmetic), attention, (WISC-III Digit Span forward and Spatial Span forward), working memory (WISC-III Digit Span backward and Spatial Span backward), and visual memory (CANTAB Spatial Recognition Memory and Pattern Recognition Memory). The contribution of cognitive domains to mathematics achievement was analyzed using linear regression techniques. Attention, working memory and visual memory data were entered together on step 1 followed by group on step 2, and the interaction terms on step 3. Results-Model 1 accounted for a significant amount of variance in both mathematics achievement measures, however, model fit improved with the addition of group on step 2. Significant predictors of mathematics achievement were Spatial Span forward and backward and Spatial Recognition Memory. Conclusions-These findings suggest that deficits in spatial processing may be related to math impairments seen in FASD. In addition, prenatal alcohol exposure was associated with deficits in mathematics achievement, above and beyond the contribution of general cognitive abilities.
Alcohol consumption during pregnancy can lead to a variety of cognitive and other birth defects, ... more Alcohol consumption during pregnancy can lead to a variety of cognitive and other birth defects, collectively termed fetal alcohol spectrum disorders (FASD), which includes the Fetal Alcohol Syndrome (FAS). This study examined the impact of gestational alcohol exposure on the morphology of the cingulate gyrus, given this region's role in cognitive control, attention, and emotional regulation, all of which are affected in children with FASD. Thirty-one youth (ages 8-16) with histories of heavy prenatal alcohol exposure (n = 21) and demographically-matched comparison subjects (n = 10) underwent structural magnetic resonance imaging. The cingulate gyrus was manually delineated, and parcellated volumes of grey and white matter were compared across groups. Alcohol-exposed individuals had significantly smaller raw cingulate grey matter, white matter, and tissue volumes, compared to controls. After adjusting for respective cranial tissue constituents, only white matter volumes remained significantly reduced, and this held regardless of whether or not the child qualified for a diagnosis of FAS. A correlation between posterior cingulate grey matter volume and the WISC-III Freedom from Distractibility Index was also observed in alcohol-exposed children. These data suggest that cingulate white matter is compromised beyond global white matter hypoplasia in alcohol-exposed individuals, regardless of FAS diagnosis. The observed volumetric reductions in the cingulate gyrus may contribute to the disruptive and emotionally dysregulated behavioral profile commonly observed in this population.
Heavy prenatal alcohol exposure causes permanent structural alterations to the brain and can lead... more Heavy prenatal alcohol exposure causes permanent structural alterations to the brain and can lead to numerous cognitive and behavioral outcomes. Consistent with many of the neuropsychological and behavioral deficits that have been reported, neuroimaging studies reveal a pattern of structural abnormalities associated with prenatal alcohol exposure. This chapter systematically reviews structural anomalies by brain region, identifying cognitive and behavioral correlates when relevant. The consensus shows that in addition to the overall reduction of brain size, prominent brain shape abnormalities have been observed, with narrowing in the parietal region and reduced brain growth in portions of the frontal lobe. Commensurate with these anomalies, volumetric and tissue density findings cite disproportionate reductions in the parietal lobe, cerebellar vermis, corpus callosum, and the caudate nucleus, suggesting that certain areas of the brain may be especially vulnerable to prenatal alcohol exposure. In sum, neuroimaging techniques have greatly advanced our understanding of brain-behavior relationships in fetal alcohol spectrum disorders (FASD), and hopefully will lead to improved diagnosis and treatment options for those affected by prenatal exposure to alcohol.
Journal of the International Neuropsychological Society, 2007
Children with either fetal alcohol spectrum disorder (FASD) or attention-deficit/hyperactivity di... more Children with either fetal alcohol spectrum disorder (FASD) or attention-deficit/hyperactivity disorder (ADHD) display deficits in attention and executive function (EF) and differential diagnosis of these two clinical groups may be difficult, especially when information about prenatal alcohol exposure is unavailable. The current study compared EF performance of three groups: children with heavy prenatal alcohol exposure (ALC); nonexposed children with attention-deficit/hyperactivity disorder (ADHD); and typically developing controls (CON). Both clinical groups met diagnostic criteria for ADHD. The EF tasks used were the Wisconsin Card Sorting Test (WCST), the Controlled Oral Word Association Test (COWAT), and the Trail Making Test (TMT). Results indicated different patterns of deficit; both clinical groups displayed deficits on the WCST and a relative weakness on letterversuscategory fluency. Only the ALC group displayed overall deficits on letter fluency and a relative weakness on ...
Journal of the International Neuropsychological Society, 2011
An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to d... more An objective in current research on children with fetal alcohol spectrum disorders (FASD) is to determine neurobehavioral profiles to identify affected individuals. Deficits observed when children with FASD are compared to typically developing controls may be confounded by lower IQ scores in the subjects with FASD. To determine if prenatal alcohol exposure is associated with neurobehavioral deficits after controlling for IQ differences, multivariate analyses were conducted to compare alcohol-exposed (ALC) subjects to a comparison group closely matched on IQ (IQC). The initial analysis included a broad neuropsychological battery with measures of language, executive function, visual–motor integration, motor ability, and academic achievement. Additional, in depth comparisons focused on visual sustained attention, verbal learning and memory and parent/guardian-reported behavior problems. Group differences (ALC < IQC) were found on verbal learning and parent-rated behavior problems. G...
Based on caregiver report, children with prenatal alcohol exposure have difficulty with social fu... more Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge's reformulated six-stage model. Fifty-two children (aged 7-11) with and without heavy prenatal alcohol exposure were tested using a structured interview measure of social information processing involving 18 videotaped vignettes of children in group entry and provocation situations. Alcohol-exposed children displayed maladaptive processing patterns on the goal, response generation, and response evaluation steps in group entry situations, and encoding, attribution, response evaluation, and enactment steps during provocation situations. Children with heavy prenatal alcohol exposure also had difficulty on the Test of Problem Solving, and performance correlated with social information processing measures. Such difficulties may lead to problems in social functioning and warrant early intervention.
Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive... more Individuals with heavy prenatal alcohol exposure can experience significant deficits in cognitive and psychosocial functioning and alterations in brain structure that persist into adulthood. In this report, data from 99 participants collected across three sites (Los Angeles and San Diego, California, and Cape Town, South Africa) were analyzed to examine relationships between brain structure, neurocognitive function, facial morphology, and maternal reports of quantities of alcohol consumption during the first trimester. Across study sites, we found highly significant volume reductions in the FASD group for all of the brain regions evaluated. After correcting for scan location, age, and total brain volume, these differences remained significant in some regions of the basal ganglia and diencephalon. In
Alcoholism: Clinical and Experimental Research, 2007
Background: Prenatal alcohol exposure can lead to widespread cognitive impairment and behavioral ... more 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 5 13) and without (n 5 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.
Alcoholism: Clinical and Experimental Research, 2011
Background-Children with fetal alcohol spectrum disorders (FASD) have deficits in verbal learning... more Background-Children with fetal alcohol spectrum disorders (FASD) have deficits in verbal learning and recall. However, the specificity of these deficits has not been adequately tested. In the current study, verbal learning and memory performance of children with heavy prenatal alcohol exposure was compared to children with attention-deficit/hyperactivity disorder (ADHD), a disorder commonly seen in alcohol-exposed children. Methods-Performance on the California Verbal Learning Test-Children's Version (CVLT-C) was examined in three groups of children (N=22/group): (1) heavy prenatal alcohol exposure and ADHD (ALC), (2) nonexposed with ADHD (ADHD), and (3) nonexposed typically developing (CON). Groups were matched on age, sex, race, ethnicity, handedness, and socioeconomic status. Results-Group differences were noted on learning trials (CON > ADHD > ALC). On the delayed recall trial, CON children performed better than both clinical groups, who did not differ from each other. Children in the ALC group demonstrated poorer recognition than children in the CON and ADHD groups, who did not differ from each other. Marginally significant group differences were noted on retention of previously learned material. Post hoc analyses indicated that ADHD children showed worse retention relative to the CON group, whereas retention in the ALC children remained intact. Conclusions-These data suggest that children with heavy prenatal alcohol exposure and nonexposed children with ADHD show differential patterns of deficit on the CVLT-C. Performance of alcohol-exposed children reflects inefficient encoding of verbal material, whereas performance of the ADHD group may be better characterized by a deficit in retrieval of learned material. Differences noted between clinical groups add to a growing neurobehavioral profile of FASD that may aid in differential diagnosis.
Alcoholism: Clinical and Experimental Research, 2009
Background-The study examined whether prenatal alcohol exposure is associated with increased moto... more Background-The study examined whether prenatal alcohol exposure is associated with increased motor timing variability when the timing response is partitioned into central clock variability, which indexes information processing at the central nervous system (CNS) level and motor delay variability, which reflects timing processes at the level of the peripheral nervous system (PNS). Methods-Eighteen children with histories of prenatal alcohol exposure and 22 control children were assigned to young (7-11 years) or older (12-17 years) groups. Children tapped a single response key with the index finger in synchrony with a series of externally generated tones (the paced phase). At the conclusion of these tones, children continued tapping (the continuation phase) while attempting to maintain the same rate of tapping imposed by the paced phase. Two blocks of tapping were completed with inter-tone-intervals set at either 400 or 900 ms. Interresponse interval, central clock variability, and motor delay variability produced during the continuation phase were the dependent variables. Results-Mean inter-response interval for the four groups did not differ for either time interval. Central clock variability produced by the young alcohol-exposed group was significantly greater than the two older groups for the 400 ms interval and all other groups for the 900 ms interval. Motor delay variability produced by the young alcohol-exposed group was significantly greater than the other three groups for both time intervals. Central and motor delay variability in children with and without alcohol exposure was directly related to the duration of the interval to be reproduced. Conclusions-Central and peripheral timing variability was significantly greater for the young alcohol-exposed children. This atypical timing may be related to the teratogenic effects of alcohol, although the negative effects are limited to younger alcohol-exposed children since there were no differences in central and peripheral timing variability between the older alcohol-exposed children and controls.
Alcoholism: Clinical and Experimental Research, 2012
Background-Children with heavy prenatal alcohol exposure often meet criteria for attentiondeficit... more Background-Children with heavy prenatal alcohol exposure often meet criteria for attentiondeficit/hyperactivity disorder (ADHD). ADHD research has examined subtype differences in symptomology, including sluggish cognitive tempo (SCT). This construct is defined by behavioral symptoms including, hypoactivity and daydreaming, and has been linked to increased internalizing behaviors. The current study examined if similar findings are displayed in children with prenatal alcohol exposure. Methods-As part of a multisite study, caregivers of 272 children (8-16y) completed the SCT scale and Child Behavior Checklist (CBCL). Four groups were included: alcohol-exposed children with ADHD (ALC+; n=75), alcohol-exposed children without ADHD (ALC−; n=35), nonexposed children with ADHD (ADHD; n=60), and non-exposed children without ADHD (CON; n=102). SCT and CBCL scores were analyzed using 2 (exposure) × 2 (ADHD) ANOVAs. Pearson
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Papers by Edward Riley