Abstract Background Prenatal alcohol exposure (PAE) has been linked to atypical brain development and a wide range of cognitive and behavioral impairments, including poor reading performance in childhood and adolescence. However, little is known about how structural and/or functional teratogenesis in the brain mediate reading impairment in fetal alcohol spectrum disorders (FASD) and whether neural correlates of reading and phonological processing differ between FASD subtypes with different clinical presentations in facial morphology. Methods The current study utilized functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to characterize functional and structural mechanisms mediating reading deficits in 26 syndromal adolescents with PAE-related facial dysmorphology (i.e., fetal alcohol syndrome (FAS) or partial FAS (PFAS)) and 30 heavily exposed (HE) without this dysmorphology, in comparison with 19 typically developing controls. Importantly, the levels of PAE and reading ability were comparable between the FAS/PFAS and HE groups in the current study. Results Compared to the nonsyndromal HE and control groups, the syndromal adolescents showed greater activation in the right precentral gyrus during an fMRI phonological processing task and rightward lateralization in an important reading-related tract (inferior longitudinal fasciculus, ILF), suggesting an atypical reliance on the right hemisphere during reading. By contrast, in the HE group, better reading skills were associated with increased neural activation in the left angular gyrus (LAG) and higher fractional anisotropy in the white matter organization of the left ILF. However, the brain function-behavior relation was weaker in the HE than among the controls, suggesting less efficient function of the typical reading neural network that may contribute to the observed reading impairments. Conclusions Our findings provide the first evidence for the distinctive functional and structural mechanisms underlying atypical reading and phonological processing in PAE adolescents with and without FAS facial dysmorphology. Highlights Prenatal alcohol exposure is associated with altered neural reading networks FASD subtypes exhibit distinctive neural correlates of phonological processing Greater right-hemispheric reliance was observed in FASD with facial dysmorphology Non-syndromal FASD showed deficits in the typical left-hemispheric reading network
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