Moderate Prenatal Alcohol Exposure Alters Functional Connectivity in the Adult Rat Brain

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Abstract

Background:

Past studies of moderate prenatal alcohol exposure (PAE) have focused on specific brain regions, neurotransmitter systems, and behaviors. However, the effects of PAE on brain function and behavior are complex and not limited to discrete brain regions. Thus, there is a critical need to understand the global effects of moderate PAE on neural function. A primary aim of this research was to explore the functional relationships in neural activity of spatially distinct areas by applying a widely used computational algorithm—group-independent component analysis (gICA)—to resting-state functional magnetic resonance imaging data from rats exposed to either an alcohol or saccharin control solution via maternal consumption during pregnancy.

Methods:

Long–Evans rat dams consumed either 5% (v/v) alcohol or a saccharin control solution throughout gestation. Adult offspring from each prenatal treatment group were anesthetized for functional, structural, and perfusion magnetic resonance-based image acquisition sequences. gICA was applied to the functional data to extract components. To determine connectivity, component time-course correlations were computed and compared. Additionally, spectral power analyses were utilized as an additional measure of functional connectivity. Finally, blood perfusion—assessed by arterial spin labeling—and whole-brain volumetric analyses were evaluated.

Results:

Analyses revealed 17 components in several brain regions such as the cortex, hippocampus, and thalamus. PAE was associated with reductions in coordinated activity between components, especially in males. PAE was also associated with reductions in low-frequency spectral power, an effect that was more robust in females. Brain volumetric analyses revealed sex-dependent reductions in females while blood flow analyses revealed sex-dependent reductions in males.

Conclusions:

Moderate PAE leads to persistent changes in functional connectivity in the absence of whole-brain volume or blood flow measures. Future studies will investigate the relationships between alterations in functional network connectivity and behavior.

The effects of moderate prenatal alcohol exposure (PAE) on specific brain regions, neurotransmitters, and behaviors have received considerable attention. In contrast, the effects of moderate PAE on whole-brain functional network connectivity (FNC) remain under-represented in the animal literature. Here, we report that moderate PAE contributes to persistent brain region- and sex-dependent changes in FNC in anesthetized rats. Understanding FNC changes may contribute to the development of novel approaches for understanding fetal alcohol spectrum disorders and evaluating potential treatment strategies.

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