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DOI: 10.1101/2023.05.18.23289319

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

B.Sundermann R. Feldmann C. Mathys ...+4 B. Pfleiderer
Background: Fetal Alcohol Syndrome (FAS) can result in substantial cognitive dysfunction. Many of the 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. However, previous reports varied substantially regarding which exact cognitive networks were affected, their interactions, and the directionalities of FC alterations. Despite persisting deficits, no previous studies have examined FC in older individuals. Purpose of this rs-fMRI study was to assess FC within and between cognition-related networks in young adults with FAS. Methods: Cross-sectional study in patients with FAS (n = 39, age: 20.9 +- 3.4 years) and controls 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 two-tailed t-tests 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 (compared with controls) in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks, and finally to individual connections. The overall and network-level tests are based on the Higher Criticism (HC) approach for the detection of rare and week effects in high dimensional data. In an additional exploratory time-resolved FC analysis, potential group differences of dynamic FC states were assessed. Results: Comparing FAS subjects 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 the dorsal attention A sub-network, followed by the salience / ventral attention A subnetwork. Findings also spanned subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the final high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences in the temporal behavior of FC states. Conclusions: FC in cognition-related brain networks was altered in adults with FAS. Effects were widely distributed across these networks, potentially reflecting the diversity of cognitive deficits in these individuals. Findings were pronounced in attention-related networks in line with attentional deficits previously reported. An additional exploratory time-resolved FC analysis did not reveal altered dynamic FC patterns.