High‐resolution diffusion tensor imaging identifies hippocampal volume loss without diffusion changes in individuals with prenatal alcohol exposure

Abstract

Background Magnetic resonance imaging (MRI) studies of prenatal alcohol exposure (PAE) commonly report reduced hippocampal volumes, which animal models suggest may result from microstructural changes that include cell loss and altered myelination. Diffusion tensor imaging (DTI) is sensitive to microstructural changes but has not yet been used to study the hippocampus in PAE. Methods Thirty‐six healthy controls (19 females; 8 to 24 years) and 19 participants with PAE (8 females; 8 to 23 years) underwent high‐resolution (1 mm isotropic) DTI, anatomical T1‐weighted imaging, and cognitive testing. Whole‐hippocampus, head, body, and tail subregions were manually segmented to yield DTI metrics (mean, axial, and radial diffusivities—MD, AD, and RD; fractional anisotropy—FA), volumes, and qualitative assessments of hippocampal morphology and digitations. Automated segmentation of T1‐weighted images was used to corroborate manual whole‐hippocampus volumes. Results Gross morphology and digitation counts were similar in both groups. Whole‐hippocampus volumes were 18% smaller in the PAE than the control group on manually traced diffusion images, but automated T1‐weighted image segmentations were not significantly different. Subregion segmentation on DTI revealed reduced volumes of the body and tail, but not the head. There were no significant differences in diffusion metrics between groups for any hippocampal region. Correlations between age and volume were not significant in either group, whereas negative correlations between age and whole‐hippocampus MD/AD/RD, and head/body (but not tail) MD/AD/RD were significant in both groups. There were no significant effects of sex, group by age, or group by sex for any hippocampal metric. In controls, seven positive linear correlations were found between hippocampal volume and cognition; five of these were left lateralized and included episodic and working memory, and two were right lateralized and included working memory and processing speed. In PAE, left tail MD positively correlated with executive functioning, and right head MD negatively correlated with episodic memory. Conclusions Reductions of hippocampal volumes and altered relationships with memory suggest disrupted hippocampal development in PAE.

Limbic brain subregions associated with mental health symptoms in youth with and without prenatal alcohol exposure

“…Our results show numerous hippocampal subfields were smaller in the PAE group compared to the unexposed group. This is aligned with previous research on youth and young adults with PAE which noted smaller volumes in some hippocampal subfields and regions (Roediger et al, 2021; Solar et al, 2022). The hippocampus is primarily involved in learning and memory.…”

“…Less is known, however, about subfield volumes in people with PAE. Two studies showed smaller hippocampal subfield volumes in the CA1, CA4, subiculum, presubiculum, body, and tail region in youth and young adults with PAE compared to unexposed controls (Roediger et al, 2021; Solar et al, 2022). Animal models of PAE provide further evidence of limbic effects, showing decreased volume in the anterior nuclei group, fewer neurons in the medial nuclei group, and fewer lateral geniculate nucleus (LGN) magnocellular neurons of the thalamus (Gursky & Klintsova, 2021; Papia et al, 2010; Savage et al, 2021).…”

Prenatal alcohol exposure alters expression of genes involved in cell adhesion, immune response, and toxin metabolism in adolescent rat hippocampus

“…Functional magnetic resonance imaging (fMRI) studies have reported altered neuronal activation during working memory and executive function tasks, but the data from neuroimaging studies has been inconsistent [7]. A recent study by Solar et al (2022) used magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to show that although the volume of the hippocampus was smaller in individuals with PAE, there were no significant group differences in mean diffusivity, axial diffusivity, or fractional anisotropy, suggesting that alcohol-related cognitive dysfunction is a result of changes at the cellular level [8]. Rodent models have been critical in evaluating the short-and long-term effects of PAE at the neuronal level.…”

Prenatal alcohol exposure alters expression of genes involved in cell adhesion, immune response, and toxin metabolism in adolescent rat hippocampus

“…Functional MRI studies have reported altered neuronal activation during working memory and executive function tasks, but the data from neuroimaging studies has been inconsistent (Coles & Li, 2011). A recent study by Solar et al (2022) used MRI and DTI to show that although the volume of the hippocampus was smaller in individuals with PAE, there were no significant group differences in mean diffusivity, axial diffusivity, or fractional anisotropy, suggesting that alcohol-related cognitive dysfunction is a result of changes at the cellular level (Solar, Treit, & Beaulieu, 2022). Rodent models have been critical in evaluating the short-and long-term effects of prenatal alcohol exposure at the neuronal level.…”