The hippocampal formation (HF) facilitates the creation of declarative memories, with subfields providing unique contributions to the discriminability and generalizability of events. The HF itself and its connections with other structures exhibit a protracted development. Maturational differences across subfields facilitate a shift towards memory specificity, with peri-puberty sitting at the inflection point. Peri-puberty also happens to be a sensitive period in the development of anxiety disorders. Taken together, we believe HF development is critical to negative overgeneralization, a common feature of anxiety disorders. To investigate the role of the HF in behavioral discrimination and generalization we examined the relation between behavior and cross-sectional indices of HF maturity derived from subfield volume. Participants aged 9-14 years, recruited from clinical and community sources, performed a recognition task with emotionally valent (positive, negative) and neutral images. T1-weighted and diffusion-weighted structural scans were collected. Partial least squares correlations were used to derive a singular metric of maturity for both HF volume and structural connectivity. We found our volumetric HF maturity index was positively associated with discrimination for neutral images and generalization for negative images. Hippocampal-medial prefrontal cortex structural connectivity maturity metric evidenced a similar trend with behavior as the HF volumetric approach. These findings are important because they reflect a novel developmentally related balance between discrimination and generalization behavior supported by the hippocampus and its connections with other regions. Maturational shifts in this balance may contribute to negative overgeneralization, a common feature of anxiety disorders that escalates during the same developmental window.
bioRxiv Subject Collection: Neuroscience