Carmen Rasmussen

Executive Function Deficits in Children with Fetal Alcohol Spectrum Disorders (FASD) Measured Using the Cambridge Neuropsychological Tests Automated Battery (CANTAB).

BACKGROUND Chronic prenatal alcohol exposure causes a spectrum of deleterious effects in offspring, collectively termed fetal alcohol spectrum disorders (FASD), and deficits in executive function are prevalent in FASD. The goal of this research was to test the hypothesis that children with FASD exhibit performance deficits in tasks that assess attention, planning and spatial working memory. METHODS Subjects (8-15 years male and female children) with a diagnosis of fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol-related neurodevelopmental disorder (ARND), and age- and sex-matched controls, completed four tasks selected from the Cambridge Neuropsychological Tests Automated Battery (CANTAB). RESULTS Compared with age-matched control children (n = 92), subjects with FASD (n = 89) exhibited longer reaction and decision times (effect size range; Cohens d = .51 to .73), suggesting deficits in attention. Children with FASD demonstrated deficits in planning and spatial working memory that became more pronounced when task difficulty increased. The largest effect size in this study population (Cohens d = 1.1) occurred in the spatial working memory task. Only one outcome measure revealed differences across the diagnostic subgroups, although all groups were different from control. CONCLUSION This study demonstrates that deficits in multiple executive function domains, including set shifting, planning and strategy use, attention and spatial working memory, can be assessed in children with FASD using an easy to administer, brief battery of computer-based neuropsychological tasks. The tasks appear to be equally sensitive for brain injury resulting from prenatal exposure to alcohol, regardless of the presence of facial dysmorphology.

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.

Neurobehavioral Functioning in Children with Fetal Alcohol Spectrum Disorder

Neurobehavioral functioning of 50 Canadian children diagnosed with Fetal Alcohol Spectrum Disorder (FASD) was evaluated. The aims of this study were to identify specific areas of weakness in neurobehavioral functioning, to examine whether neurobehavioral functioning was related to various predictor variables, and to determine which measures differentiated between children given a brain score of 2 (possible dysfunction) and 3 (probable dysfunction). Participants displayed difficulties with many aspects of intelligence, memory, executive functioning, and attention. Measures of Full scale and Verbal IQ, as well as memory for faces and numbers differentiated between children with a brain 2 and 3 ranking. An interesting pattern of strengths and weaknesses emerged as well as significant differences related to ethnic background, gender, and age. Aboriginal children and Caucasian children with FASD do not appear to show the same pattern of strengths and weaknesses in neurobehavioral functioning.

Executive Functioning in Children with Fetal Alcohol Spectrum Disorders: Profiles and Age-Related Differences

The goal of this project was to examine the profile of executive function (EF) deficits and age-related differences among children with FASD. Twenty-nine children with FASD (8 to 16 years of age) completed 8 tests from the Delis-Kaplan Executive Function System (D-KEFS). They had difficulty on many components of EF including cognitive flexibility, inhibition, some measures of verbal fluency, abstract thinking, deductive reasoning, hypothesis testing, problem solving, and concept formation. A distinctive profile emerged with performance being poorest on the card sorting test and relatively high on category fluency, design fluency, and the tower test, indicating relative strengths on some visual-spatial EF tasks. Older children with FASD showed more difficulty (relative to the norm) on some verbal tests of EF than younger children with FASD, suggesting that difficulty on some verbal EF tasks appears to become more pronounced with increasing age.

Brain Microstructure Is Related to Math Ability in Children With Fetal Alcohol Spectrum Disorder

BACKGROUND Children with fetal alcohol spectrum disorder (FASD) often demonstrate a variety of cognitive deficits, but mathematical ability seems to be particularly affected by prenatal alcohol exposure. Parietal brain regions have been implicated in both functional and structural studies of mathematical ability in healthy individuals, but little is known about the brain structure underlying mathematical deficits in children with FASD. The goal of this study was to use diffusion tensor imaging (DTI) to investigate the relationship between mathematical skill and brain white matter structure in children with FASD. METHODS Twenty-one children aged 5 to 13 years diagnosed with FASD underwent DTI on a 1.5-T MRI scanner and cognitive assessments including the Woodcock-Johnson Quantitative Concepts test. Voxel-based analysis was conducted by normalizing subject images to a template and correlating fractional anisotropy (FA) values across the brain white matter with age-standardized math scores. RESULTS Voxel-based analysis revealed 4 clusters with significant correlations between FA and math scores: 2 positively-correlated clusters in the left parietal region, 1 positively-correlated cluster in the left cerebellum, and 1 negatively-correlated cluster in the bilateral brainstem. Diffusion tractography identified the specific white matter tracts passing through these clusters, namely the left superior longitudinal fasciculus, left corticospinal tract and body of the corpus callosum, middle cerebellar peduncle, and bilateral projection fibers including the anterior and posterior limbs of the internal capsule. CONCLUSIONS These results identify 4 key regions related to mathematical ability and provide a link between brain microstructure and cognitive skills in children with FASD. Given previous findings in typically developing children and those with other abnormal conditions, our results highlight the consistent importance of the left parietal area for mathematical tasks across various populations, and also demonstrate other regions that may be specific to mathematical processing in children with FASD.

Developmental cortical thinning in fetal alcohol spectrum disorders.

Regional cortical thickness was evaluated using CIVET processing of 3D T1-weighted images (i) to compare the variation in cortical thickness between 33 participants with fetal alcohol spectrum disorders (FASD) aged 6-30 years (mean age 12.3 years) versus 33 age/sex/hand-matched controls, and (ii) to examine developmental changes in cortical thickness with age from children to young adults in both groups. Significant cortical thinning was found in the participants with FASD in large areas of the bilateral middle frontal lobe, pre- and post- central areas, lateral and inferior temporal and occipital lobes compared to controls. No significant cortical thickness increases were observed for the FASD group. Cortical thinning with age in a linear model was observed in both groups, but the locations were different for each group. FASD participants showed thinning with age in the left middle frontal, bilateral precentral, bilateral precuneus and paracingulate, left inferior occipital and bilateral fusiform gyri; while controls showed decreases with age in the bilateral middle frontal gyrus, right inferior frontal gyrus, bilateral precuneus gyrus, and bilateral occipital gyrus. A battery of cognitive assessments of memory, attention, motor, and verbal abilities was conducted with many of the FASD participants, but no significant correlations were found between these cognitive scores and regional cortical thickness. Non-invasive measurements of cortical thickness in children to young adults with FASD have identified both key regions of cortex that may be more deleteriously affected by prenatal alcohol exposure as well as cortical changes with age that differ from normal developmental thinning.

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.

Use of the Mathematical Principle of Inversion in Young Children.

An important issue in the development of mathematical cognition is the extent to which children use and understand fundamental mathematical concepts. We examined whether young children successfully use the principle of inversion and, if so, whether they do so based on qualitative identity, length, or quantity. Twenty-four preschool children and 24 children in Grade 1 were presented with three-term inversion problems (e.g., 3+2-2) and standard problems of similar magnitude (e.g., 2+4-3). Problems were presented in three conditions to determine whether children used inversion at all and, if so, whether their decisions were based on quantitative or nonquantitative features of the problems. Both preschool and Grade 1 children showed evidence of using inversion in a fully quantitative manner, indicating that this principle is available in some form prior to extensive formal instruction in arithmetic.

The remarkably high prevalence of epilepsy and seizure history in fetal alcohol spectrum disorders.

BACKGROUND Fetal alcohol spectrum disorder (FASD) is the umbrella term that describes the range of adverse developmental outcomes that may occur in the offspring of mothers who drink alcohol during pregnancy. FASD is associated with several comorbidities including epilepsy. The objective of the study was to evaluate the prevalence of epilepsy or a history of seizures in subjects with FASD and the contribution of relevant risk factors. METHODS A retrospective chart review was conducted on all active charts (N = 1063) at two FASD clinics. After exclusion of subjects without a confirmed diagnosis, a total of 425 subjects between the ages of 2-49 were included in the analysis. The relationships between FASD diagnosis and other risk factors for co-occurrence of epilepsy or a seizure disorder (e.g., extent of exposure to alcohol and other drugs, type of birth, and trauma) were examined using chi-square and multivariate multinomial logistic regression. RESULTS Twenty-five (5.9%) individuals in the study population had a confirmed diagnosis of epilepsy, and 50 (11.8%) had at least one documented seizure episode, yielding an overall prevalence of 17.7% in this population. Importantly, a history of epilepsy or seizures was not different across the three diagnostic subgroups. In those subjects with available maternal drinking histories, first trimester exposure or drinking throughout all three trimesters were the predominant forms of fetal exposure. None of the other risk factors were associated with a greater prevalence of epilepsy or seizures. CONCLUSIONS There is a remarkably high prevalence of epilepsy/seizures in the FASD population.

Longitudinal MRI reveals altered trajectory of brain development during childhood and adolescence in fetal alcohol spectrum disorders.

Diffusion tensor imaging (DTI) of brain development in fetal alcohol spectrum disorders (FASD) has revealed structural abnormalities, but studies have been limited by the use of cross-sectional designs. Longitudinal scans can provide key insights into trajectories of neurodevelopment within individuals with this common developmental disorder. Here we evaluate serial DTI and T1-weighted volumetric MRI in a human sample of 17 participants with FASD and 27 controls aged 5–15 years who underwent 2–3 scans each, ∼2–4 years apart (92 scans total). Increases of fractional anisotropy and decreases of mean diffusivity (MD) were observed between scans for both groups, in keeping with changes expected of typical development, but mixed-models analysis revealed significant age-by-group interactions for three major white matter tracts: superior longitudinal fasciculus and superior and inferior fronto-occipital fasciculus. These findings indicate altered developmental progression in these frontal-association tracts, with the FASD group notably showing greater reduction of MD between scans. ΔMD is shown to correlate with reading and receptive vocabulary in the FASD group, with steeper decreases of MD in the superior fronto-occipital fasciculus and superior longitudinal fasciculus between scans correlating with greater improvement in language scores. Volumetric analysis revealed reduced total brain, white, cortical gray, and deep gray matter volumes and fewer significant age-related volume increases in the FASD group, although age-by-group interactions were not significant. Longitudinal DTI indicates delayed white matter development during childhood and adolescence in FASD, which may underlie persistent or worsening behavioral and cognitive deficits during this critical period.