Hippocampal Subregion Function and Its Clinical Correlations in Childhood Autism Spectrum Disorders

The hippocampus plays a crucial role in memory and social processing, both of which are impaired in autism spectrum disorder (ASD). Investigating the functional activity of hippocampal subregions can provide valuable insights into their involvement in ASD-related social and behavioral symptoms. This study analyzed hippocampal resting-state functional connectivity (rsFC) in 507 male child participants from the ABIDE dataset (225 ASD, 282 typical controls) and its relation to clinical features. The hippocampus was subdivided into rostral and caudal subregions, and rsFC patterns were compared between groups. Significant group differences were observed in the left caudal, right rostral, and right caudal hippocampus, with enhanced connectivity to widespread cortical and subcortical regions, including visual, motor, parietal, and cerebellar networks. Machine learning using hippocampal rsFC achieved modest classification performance. Clinically, rsFC correlated with core ASD symptoms: social awareness was associated with right caudal connectivity to fusiform and temporal regions, while restricted and repetitive behaviors were linked to distinct rostral-caudal patterns involving frontal, motor, and cerebellar areas. Age of onset showed positive correlations with rsFC across all subregions, with rostral hippocampus engaging socioemotional and motor control networks and caudal hippocampus connecting more strongly to visual and sensorimotor integration regions. These findings demonstrate subregional specificity of hippocampal connectivity in ASD, suggesting distinct anterior-posterior contributions to symptom expression and developmental timing.