Sex-specific Differences in Resting Oscillatory Dynamics in Children with Prenatal Alcohol Exposure.

At rest children with prenatal alcohol exposure (PAE) exhibit impaired static and dynamic functional connectivity, along with decreased alpha oscillations. Sex-specific information regarding the impact of PAE on whole-brain resting-state gamma spectral power remains unknown. Eyes-closed and eyes-open MEG resting-state data were examined in 83 children, ages 6-13 years of age. Using a matched design, the sample consisted of 42 typically developing children (TDC) (22 males/20 females) and 41 children with PAE and/or a fetal alcohol spectrum disorders (FASD) diagnosis (21 males/20 females). Whole-brain source resting-state spectral power was examined to determine group and sex specific relationships. Within gamma, we found sex and group specific changes such that female participants with PAE/FASD had increased gamma power when compared to female TDC and male participants with PAE/FASD. These differences were detected in most source regions analyzed during both resting-states, and were observed across the age spectrum examined. Within delta, we found sex and group specific changes such that female participants with PAE/FASD had decreased delta power when compared to female TDC and male participants with PAE/FASD. The reduced delta oscillations in female participants with PAE/FASD were detected in several source regions during eyes-closed rest and were evident at younger ages. These results indicate PAE alters neural oscillations during rest in a sex-specific manner, with females with PAE/FASD showing the largest perturbations. These results further demonstrate PAE has global effects on resting-state spectral power and connectivity, creating long-term consequences by potentially disrupting the excitation/inhibition balance in the brain, interrupting normative neurodevelopment.

Brain structural differences in children with fetal alcohol spectrum disorder and its subtypes.

Introduction: The teratogenic effects of prenatal alcohol exposure (PAE) have been examined in animal models and humans. The current study extends the prior literature by quantifying differences in brain structure for individuals with a fetal alcohol spectrum disorder (FASD) compared to typically developing controls, as well as examining FASD subtypes. We hypothesized the FASD group would reveal smaller brain volume, reduced cortical thickness, and reduced surface area compared to controls, with the partial fetal alcohol syndrome (pFAS)/fetal alcohol syndrome (FAS) subtypes showing the largest effects and the PAE/alcohol-related neurodevelopmental disorder (ARND) subtype revealing intermediate effects. Methods: The sample consisted of 123 children and adolescents recruited from a single site including children with a diagnosis of FASD/PAE (26 males, 29 females) and controls (34 males, 34 females). Structural T1-weighted MRI scans were obtained on a 3T Trio TIM scanner and FreeSurfer v7.2 was used to quantify brain volume, cortical thickness, and surface area. Analyses examined effects by subgroup: pFAS/FAS (N = 32, Mage = 10.7 years, SEage = 0.79), PAE/ARND (N = 23, Mage = 10.8, SEage = 0.94), and controls (N = 68, Mage = 11.1, SEage = 0.54). Results: Total brain volume in children with an FASD was smaller relative to controls, but subtype analysis revealed only the pFAS/FAS group differed significantly from controls. Regional analyses similarly revealed reduced brain volume in frontal and temporal regions for children with pFAS/FAS, yet children diagnosed with PAE/ARND generally had similar volumes as controls. Notable differences to this pattern occurred in the cerebellum, caudate, and pallidum where children with pFAS/FAS and PAE/ARND revealed lower volume relative to controls. In the subset of participants who had neuropsychological testing, correlations between volume and IQ scores were observed. Goodness-of-Fit analysis by age revealed differences in developmental patterns (linear vs. quadratic) between groups in some cases. Discussion: This study confirmed prior results indicating decreased brain volume in children with an FASD and extended the results by demonstrating differential effects by structure for FASD subtypes. It provides further evidence for a complex role of PAE in structural brain development that is likely related to the cognitive and behavioral effects experienced by children with an FASD.

Disrupted dynamic functional network connectivity in fetal alcohol spectrum disorders.

BACKGROUND: Prenatal alcohol exposure (PAE) can result in harmful and long-lasting neurodevelopmental changes. Children with PAE or a fetal alcohol spectrum disorder (FASD) have decreased white matter volume and resting-state spectral power compared to typically developing controls (TDC) and impaired resting-state static functional connectivity. The impact of PAE on resting-state dynamic functional network connectivity (dFNC) is unknown. METHODS: Using eyes-closed and eyes-open magnetoencephalography (MEG) resting-state data, global dFNC statistics and meta-states were examined in 89 children aged 6-16 years (51 TDC, 38 with FASD). Source analyzed MEG data were used as input to group spatial independent component analysis to derive functional networks from which the dFNC was calculated. RESULTS: During eyes-closed, relative to TDC, participants with FASD spent a significantly longer time in state 2, typified by anticorrelation (i.e., decreased connectivity) within and between default mode network (DMN) and visual network (VN), and state 4, typified by stronger internetwork correlation. The FASD group exhibited greater dynamic fluidity and dynamic range (i.e., entered more states, changed from one meta-state to another more often, and traveled greater distances) than TDC. During eyes-open, TDC spent significantly more time in state 1, typified by positive intra- and interdomain connectivity with modest correlation within the frontal network (FN), while participants with FASD spent a larger fraction of time in state 2, typified by anticorrelation within and between DMN and VN and strong correlation within and between FN, attention network, and sensorimotor network. CONCLUSIONS: There are important resting-state dFNC differences between children with FASD and TDC. Participants with FASD exhibited greater dynamic fluidity and dynamic range and spent more time in states typified by anticorrelation within and between DMN and VN, and more time in a state typified by high internetwork connectivity. Taken together, these network aberrations indicate that prenatal alcohol exposure has a global effect on resting-state connectivity.

Decreased resting-state alpha peak frequency in children and adolescents with fetal alcohol spectrum disorders or prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can result in long-lasting changes to physical, behavioral, and cognitive functioning in children. PAE might result in decreased white matter integrity, corticothalamic tract integrity, and alpha cortical oscillations. Previous investigations of alpha oscillations in PAE/fetal alcohol spectrum disorder (FASD) have focused on average spectral power at specific ages; therefore, little is known about alpha peak frequency (APF) or its developmental trajectory making this research novel. Using resting-state MEG data, APF was determined from parietal/occipital regions in participants with PAE/FASD or typically developing controls (TDC). In total, MEG data from 157 infants, children, and adolescents ranging in age from 6 months to 17 years were used, including 17 individuals with PAE, 61 individuals with an FASD and 84 TDC. In line with our hypothesis, we found that individuals with PAE/FASD had significantly reduced APF relative to TDC. Both age and group were significantly related to APF with differences between TDC and PAE/FASD persisting throughout development. We did not find evidence that sex or socioeconomic status had additional impact on APF. Reduced APF in individuals with an FASD/PAE may represent a long-term deficit and demonstrates the detrimental impact prenatal alcohol exposure can have on neurophysiological processes.

School-aged children diagnosed with an FASD exhibit visuo-cortical network disturbance: A magnetoencephalography (MEG) study.

Children with prenatal alcohol exposure (PAE) often suffer from cognitive and neurobehavioral dysfunction throughout their lives, which may rise to a level of concern such that children receive a diagnosis under the fetal alcohol spectrum disorders (FASD) umbrella. Magnetoencephalography (MEG) contributes direct insight into neural processing and functional connectivity measures with temporal precision to understand cortical processing disorders that manifest during development. The impairment of perception may become more consequential among school-aged children with an FASD in the process of intellectual functioning and behavioral maturation. Fifty participants with the age range of 8-13 years participated in our study following parental informed consent and child assent. For each participant, visual responses were recorded using magnetoencephalography (MEG) while performing a prosaccade task with central stimuli (fovea centralis) and peripheral stimuli (left and right of central) presented on a screen, requiring participants to shift their gaze to the stimuli. After source analysis using minimum norm estimation (MNE), we investigated visual responses from each participant by measuring the latency and amplitude of visual evoked fields. Delayed peak latency of the visual response was identified in the primary visual area (calcarine fissure) and visual association areas (v2, v3) in young children with an FASD for both stimulus types (central and peripheral). But the difference in visual response latency was only statistically significant (p ≤ 0.01) for the peripheral (right) stimulus. We also observed reduced amplitude (p ≤ 0.006) of visual evoked response in children with an FASD for the central stimulus type in both primary and visual association areas. Multiple visual areas show impairment in children with an FASD, with visual delay and conduction disturbance more prominent in response to peripheral stimuli. Children with an FASD also exhibit significantly reduced amplitude of neural activation to central stimuli. These sensory deficits may lead to slow cognitive processing speed through continued intra-cortical network disturbance in children with an FASD.