Sarah Treit

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.

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.

White matter correlates of cognitive inhibition during development: A diffusion tensor imaging study

Inhibitory control and cognitive flexibility are two key executive functions that develop in childhood and adolescence, increasing ones capacity to respond dynamically to changing external demands and refrain from impulsive behaviors. These gains evolve in concert with significant brain development. Magnetic resonance imaging studies have identified numerous frontal and cingulate cortical areas associated with performance on inhibition tasks, but less is known about the involvement of the underlying anatomical connectivity, namely white matter. Here we used diffusion tensor imaging (DTI) to examine correlations between a DTI-derived parameter, fractional anisotropy (FA) of white matter, and performance on the NEPSY-II Inhibition test (Naming, Inhibition and Switching conditions) in 49 healthy children aged 5-16years (20 females; 29 males). First, whole brain voxel-based analysis revealed several clusters in the frontal projections of the corpus callosum, where higher FA was associated with worse inhibitory performance, as well as several clusters in posterior brain regions and one in the brainstem where higher FA was associated with better cognitive flexibility (in the Switching task), suggesting a dichotomous relationship between FA and these two aspects of cognitive control. Tractography through these clusters identified several white matter tracts, which were then manual traced in native space. Pearsons correlations confirmed associations between higher FA of frontal projections of the corpus callosum with poorer inhibitory performance (independent of age), though associations with Switching were not significant. Post-hoc evaluation suggested that FA of orbital and anterior frontal projections of the corpus callosum also mediated performance differences across conditions, which may reflect differences in self-monitoring or strategy use. These findings suggest a link between the development of inhibition and cognitive control with that of the underlying white matter, and may help to identify deviations of neurobiology in adolescent psychopathology.

Accelerated longitudinal cortical thinning in adolescence

It remains unclear if changes of the cerebral cortex occur gradually from childhood to adulthood, or if adolescence marks a differential period of cortical development. In the current study of 90 healthy volunteers aged 5-32years (48 females, 85 right handed) with 180 scans (2 scans for each participant with ~4year gaps), thinning of overall mean thickness and across the four major cortical lobes bilaterally was observed across this full age span. However, the thinning rate, calculated as Δcortical thickness/Δage (mm/year) between scans of each participant, revealed an accelerated cortical thinning during adolescence, which was preceded by less thinning in childhood and followed by decelerated thinning in young adulthood. Males and females showed similarly faster thinning rates during adolescence relative to young adults. The underlying basis and role of accelerated cortical thinning during adolescence for cognition, behaviour and disorders that appear at such a stage of development remains to be determined in future work.

Longitudinal MRI Reveals Impaired Cortical Thinning in Children and Adolescents Prenatally Exposed to Alcohol

Brain imaging studies suggest that cortical thickness decreases during childhood and adolescence, in concert with underlying structural and synaptic changes required for cognitive maturation and regional specialization of function. Abnormalities of this protracted developmental process may provide key insights into the cognitive and behavioral deficits that emerge in individuals with fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cortical thickness differences in children and adolescents who were prenatally exposed to alcohol, though all have been cross sectional, limiting conclusions about cortical development with age. In this study, we analyze serially collected T1‐weighted MRI from 11 children with FASD and 21 controls, scanned twice each ∼2 to 4 years apart. Mixed‐models analysis of cortical thickness measurements revealed age‐by‐group interactions in cortical thinning, with FASD participants undergoing less developmental thinning than controls across many regions of the cortex, particularly in medial frontal and parietal areas. These results provide further longitudinal evidence in humans that prenatal alcohol exposure is associated with altered patterns of brain development that persist during childhood and adolescence. Hum Brain Mapp 35:4892–4903, 2014.

Affective Decision-Making on the Iowa Gambling Task in Children and Adolescents with Fetal Alcohol Spectrum Disorders

Individuals with fetal alcohol spectrum disorders (FASD) have difficulties with cognitive-based executive function (EF) tasks. The goal of the present study was to determine if children with FASD have impairments on the Iowa Gambling Task (IGT), which measures affective EF (i.e., decision-making and risk-taking). Individuals with FASD (n = 31) and healthy controls (n = 31), aged 8-17 completed the IGT. Children with FASD were significantly impaired on the IGT compared to controls. Over the course of the task, control scores improved, whereas children with FASD exhibited an overall decrease in scores. Scores increased significantly with age in the control group but did not differ significantly with age for FASD participants. Children with FASD exhibited decision-making and risk-taking impairments on a hot EF task. Children with FASD did not appear to learn from negative experiences and shift to making more positive decisions over time and their performance did not improve with age. The implications of poor task performance and a lack of age-related findings in children with FASD are discussed.

Response inhibition deficits in children with Fetal Alcohol Spectrum Disorder: relationship between diffusion tensor imaging of the corpus callosum and eye movement control.

Response inhibition is the ability to suppress irrelevant impulses to enable goal-directed behavior. The underlying neural mechanisms of inhibition deficits are not clearly understood, but may be related to white matter connectivity, which can be assessed using diffusion tensor imaging (DTI). The goal of this study was to investigate the relationship between response inhibition during the performance of saccadic eye movement tasks and DTI measures of the corpus callosum in children with or without Fetal Alcohol Spectrum Disorder (FASD). Participants included 43 children with an FASD diagnosis (12.3 ± 3.1 years old) and 35 typically developing children (12.5 ± 3.0 years old) both aged 7–18, assessed at three sites across Canada. Response inhibition was measured by direction errors in an antisaccade task and timing errors in a delayed memory-guided saccade task. Manual deterministic tractography was used to delineate six regions of the corpus callosum and calculate fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity, and perpendicular diffusivity. Group differences in saccade measures were assessed using t-tests, followed by partial correlations between eye movement inhibition scores and corpus callosum FA and MD, controlling for age. Children with FASD made more saccade direction errors and more timing errors, which indicates a deficit in response inhibition. The only group difference in DTI metrics was significantly higher MD of the splenium in FASD compared to controls. Notably, direction errors in the antisaccade task were correlated negatively to FA and positively to MD of the splenium in the control, but not the FASD group, which suggests that alterations in connectivity between the two hemispheres of the brain may contribute to inhibition deficits in children with FASD.

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.

A review of diffusion MRI of typical white matter development from early childhood to young adulthood

Understanding typical, healthy brain development provides a baseline from which to detect and characterize brain anomalies associated with various neurological or psychiatric disorders and diseases. Diffusion MRI is well suited to study white matter development, as it can virtually extract individual tracts and yield parameters that may reflect alterations in the underlying neural micro‐structure (e.g. myelination, axon density, fiber coherence), though it is limited by its lack of specificity and other methodological concerns. This review summarizes the last decade of diffusion imaging studies of healthy white matter development spanning childhood to early adulthood (4–35 years). Conclusions about anatomical location, rates, and timing of white matter development with age are discussed, as well as the influence of image acquisition, analysis, age range/sample size, and statistical model. Despite methodological variability between studies, some consistent findings have emerged from the literature. Specifically, diffusion studies of neurodevelopment overwhelmingly demonstrate regionally varying increases of fractional anisotropy and decreases of mean diffusivity during childhood and adolescence, some of which continue into adulthood. While most studies use linear fits to model age‐related changes, studies with sufficient sample sizes and age range provide clear evidence that white matter development (as indicated by diffusion) is non‐linear. Several studies further suggest that maturation in association tracts with frontal‐temporal connections continues later than commissural and projection tracts. The emerging contributions of more advanced diffusion methods are also discussed, as they may reveal new aspects of white matter development. Although non‐specific, diffusion changes may reflect increases of myelination, axonal packing, and/or coherence with age that may be associated with changes in cognition.

Evolution of deep gray matter volume across the human lifespan

Magnetic resonance imaging of subcortical gray matter structures, which mediate behavior, cognition and the pathophysiology of several diseases, is crucial for establishing typical maturation patterns across the human lifespan. This single site study examines T1‐weighted MPRAGE images of 3 healthy cohorts: (i) a cross‐sectional cohort of 406 subjects aged 5–83 years; (ii) a longitudinal neurodevelopment cohort of 84 subjects scanned twice approximately 4 years apart, aged 5–27 years at first scan; and (iii) a longitudinal aging cohort of 55 subjects scanned twice approximately 3 years apart, aged 46–83 years at first scan. First scans from longitudinal subjects were included in the cross‐sectional analysis. Age‐dependent changes in thalamus, caudate, putamen, globus pallidus, nucleus accumbens, hippocampus, and amygdala volumes were tested with Poisson, quadratic, and linear models in the cross‐sectional cohort, and quadratic and linear models in the longitudinal cohorts. Most deep gray matter structures best fit to Poisson regressions in the cross‐sectional cohort and quadratic curves in the young longitudinal cohort, whereas the volume of all structures except the caudate and globus pallidus decreased linearly in the longitudinal aging cohort. Males had larger volumes than females for all subcortical structures, but sex differences in trajectories of change with age were not significant. Within subject analysis showed that 65%–80% of 13–17 year olds underwent a longitudinal decrease in volume between scans (∼4 years apart) for the putamen, globus pallidus, and hippocampus, suggesting unique developmental processes during adolescence. This lifespan study of healthy participants will form a basis for comparison to neurological and psychiatric disorders. Hum Brain Mapp 38:3771–3790, 2017.