Neuroimaging study of prenatal alcohol exposure effects on structural and functional connectivity in children

Doctoral Thesis


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University of Cape Town

Fetal alcohol spectrum disorders (FASD) describe the spectrum of cognitive, behavioural and neurological impairments associated with prenatal alcohol exposure (PAE). Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were used to assess effects of PAE on microstructural integrities of cerebellar and cerebral white matters (WM) and on resting-state functional connectivity (RSFC) in gray matter (GM) in children with varying degrees of FASD severity (fetal alcohol syndrome (FAS) and partial FAS (PFAS)), as well as nonsyndromal heavily exposed (HE) children. Children with FAS revealed lower fractional anisotropy (FA) bilaterally in the superior peduncles. Mean diffusivity (MD) was higher in the left middle peduncle in children with FAS or PFAS (FAS/PFAS). Mediation of effects of PAE on eyeblink conditioning (EBC) provided statistical evidence that poorer microstructural integrity in these regions may play an important role in the EBC deficit observed in children with FASD. The FAS/PFAS children also revealed lower FA and/or higher MD in 7 cortical WM regions and lower RSFC in 5 GM regions within 5 networks. Four of the 7 WM and 3 of the 5 GM regions also showed alterations in HE children, providing evidence that alterations in nonsyndromal children are less extensive and that some regions appear to be relatively spared. Alterations in DTI parameters (FA and MD) were dose dependent in many, but not all, of the regions where group differences were detected, specifically in the left (L) and right (R) superior peduncles, L middle peduncle, L inferior longitudinal fasciculus, medial (M) splenium of the corpus callosum (CC), and M isthmus of the CC. The WM deficits were attributable to increased radial diffusivity (RD) rather than decreased axial diffusivity (AD), suggesting poorer axon packing density and/or myelination. Increasing alcohol exposure was associated with reduced fractional amplitude of low frequency fluctuations (fALFF), indicating changes in functional connectivity in the default mode, salience, and dorsal attention networks. The locations of the WM alterations found with DTI suggest that the compromised RSFC found in 3 of the 5 networks could be attributable to WM deficits in tracts providing intra-network connections.

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