Amygdala and hippocampal contributions to broad autism phenotype: Project Ice Storm

Prenatal maternal stress (PNMS) increases the risk for autism, and individuals with autism inconsistently exhibit increased or decreased volumes and functional connectivity of the whole amygdala and the whole hippocampus. Given heterogeneous structures of the amygdala and hippocampus and the heterogeneity of autism symptoms, it is worth examining how their subregions contribute to different autism phenotypes. T1-weighted and resting-state functional MRI data were acquired from 32 young adults of mothers who were pregnant during, or within 3 months of, the 1998 Quebec ice storm. Their broad autism phenotype (BAP) was self-reported, including aloof personality, pragmatic language impairment and rigid personality. This sample has a wide range of scores on the BAP Questionnaire. Volumes of the amygdala nuclei and hippocampal subfields were calculated. Seed-to-voxel analysis was applied to examine functional connectivity of the amygdala nuclei and hippocampal subfields with the rest of the brain, and linear regressions were implemented to examine associations of volume and functional connectivity with the three autism phenotypes. Primarily, we found that 1) rigid personality was associated with decreased left hippocampal cornu ammonis (CA)1 volume; 2) pragmatic language impairment was associated with decreased left hippocampal CA1 connectivity with the supplementary motor area, and increased right hippocampal CA4 connectivity with the left putamen; and 3) rigid personality was associated with increased right central amygdala connectivity with the left inferior lateral occipital cortex (LOC); and increased left hippocampal CA3 connectivity with the right superior parietal lobule, increased right hippocampal CA4 connectivity with the left superior LOC, and increased right hippocampal dentate gyrus connectivity with the left superior LOC. In contrast, we found no associations with aloof personality. Our results suggest that, within a sample exposed to PNMS, amygdala and hippocampal structure and function contribute differently to two different autistic-like characteristics, with hippocampus-motor connectivity explaining variance in communication impairment, and with hippocampal volume, amygdala- and hippocampus- sensory connectivity sharing the common mechanism in rigid behaviors. Given these links between brain and autistic-like traits, future research should examine whether brain volumes and connectivity mediate associations between PNMS and autistic-like traits in young adulthood.