Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome.

BACKGROUND: Fetal alcohol syndrome (FAS) can result in cognitive dysfunction. Cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting-state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. Previous reports varied substantially regarding the exact nature of findings. The purpose of this study was to assess FC of cognition-related networks in young adults with FAS. METHODS: Cross-sectional rs-fMRI study in participants with FAS (n = 39, age: 20.9 ± 3.4 years) and healthy participants without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on linear models comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks based on the Higher Criticism (HC) approach for detecting rare and weak effects in high-dimensional data. Finally, group differences in single connections were assessed using conventional multiple-comparison correction. In an additional exploratory analysis, dynamic FC states were assessed. RESULTS: Comparing FAS participants with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in attention-related network components. Findings also spanned across subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the conventional high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences of dynamic FC states. CONCLUSIONS: FC in cognition-related networks was altered in adults with FAS. Effects were widely distributed across networks, potentially reflecting the diversity of cognitive deficits in FAS. However, no altered single connections could be determined in the most detailed analysis level. Findings were pronounced in networks in line with attentional deficits previously reported.

Approaching altered inhibitory control in phenylketonuria: A functional MRI study with a Go-NoGo task in young female adults.

Subtle executive function deficits, particularly regarding inhibitory control, have been reported in patients with phenylketonuria (PKU) despite early dietary treatment. Purpose of this study was to assess whether young female adults with PKU exhibit altered neural activity underlying such deficits, particularly in a fronto-parietal cognitive control network (CCN). Behavioural data and functional magnetic resonance imaging (fMRI) data were acquired during a Go-NoGo task in 16 young adult patients with PKU and 17 control subjects. Hypothesis-driven analyses of behavioural and fMRI data in the CCN were supplemented by exploratory whole brain activation analyses. PKU patients exhibited a trend towards higher errors of commission. Patients exhibited marginally increased activation associated with inhibitory control in only one CCN core region (right middle frontal gyrus, p = .043). Whole brain analyses revealed widespread relatively increased activation in adults with PKU in the main task contrast (NoGo > Go). This increased activation was mainly observed outside the CCN and largely overlapped with the default mode network (DMN). In conclusion, only subtle inhibitory control deficits and associated brain activity differences were observed in young adults with PKU. Thus, this work adds to the notion that this particular population seems to be only slightly affected by such cognitive deficits. While there were also only minimal increases when compared to healthy subjects in brain activity in a cognitive control network, we observed more widespread activation increases outside this network. These results support the assumption of DMN dysfunction in PKU.

Inhibitory control in young adult women with fetal alcohol syndrome: Findings from a pilot functional magnetic resonance imaging study.

BACKGROUND: Executive dysfunction, especially impaired inhibitory control, is a common finding in individuals with fetal alcohol syndrome (FAS). Previous research has mostly focused on neural correlates of inhibitory deficits in children and adolescents. We investigated inhibitory functions and underlying cerebral activation patterns in young adult women with FAS. METHODS: Task performance and functional magnetic resonance imaging (fMRI) data were acquired during a Go/NoGo (GNG) inhibition task in 19 young adult women with FAS and 19 healthy female control subjects. Whole-brain activation and task performance analyses were supplemented by region of interest (ROI) analyses of fMRI data within a predefined cognitive control network (CCN). RESULTS: Task performance did not differ significantly between groups on errors of commission, associated with inhibitory control. Similarly, overall activation within the preselected ROIs did not differ significantly between groups for the main inhibitory contrast NoGo > Go. However, whole-brain analyses revealed activation differences in the FAS group when compared to controls under inhibitory conditions. This included hyperactivations in the left inferior frontal, superior temporal, and supramarginal gyri in the FAS group. Likewise, lateralization tendencies toward right-hemispheric ROIs were weaker in FAS subjects. In contrast to comparable inhibitory performance, attention-related errors of omission were significantly higher in the FAS group. Correspondingly, FAS subjects had lower activity in attention-related temporal and parietal areas. CONCLUSIONS: The known alterations of inhibitory functions associated with prenatal alcohol exposure in children and adolescents were not seen in this adult sample. However, differential brain activity was observed, reflecting potential compensatory mechanisms. Secondary results suggest that there is impaired attentional control in young adult women with FAS.