No abstract

This study examines neural mechanisms of negative overgeneralization, the increased likelihood of generalizing negative information, in peri-puberty. Theories suggest that weak pattern separation (overlapping representations are made distinct, indexed by DG/CA3 hippocampal subfield activation) underlies negative overgeneralization. We alternatively propose that neuro-maturational changes that favor pattern completion (cues reinstate stored representations, indexed by CA1 activation) are modulated by circuitry involved in emotional responding (amygdala, medial prefrontal cortices [mPFC]) to drive negative overgeneralization. Youth (N=34, 9-14 years) recruited from community and clinic settings participated in an emotional mnemonic similarity task while undergoing MRI. At Study, participants indicated the valence of images; at Test, participants made recognition memory judgments. Critical lure stimuli, that were similar to images at Study, were presented at Test, and errors (“false alarms”) to negative relative to neutral stimuli reflected negative overgeneralization. Negative overgeneralization was related to greater and more similar patterns of activation in CA1 and both dorsal and ventral mPFC for negative relative to neutral stimuli. At Study, amygdala exhibited greater functional coupling with CA1 and dorsal mPFC during negative items that were later generalized. Negative overgeneralization is rooted in amygdala and mPFC modulation at encoding and pattern completion at retrieval.

Negative overgeneralization is a dimension of anxiety whereby responses to one aversive situation (e.g., severe weather) spread to others that share contextual features (e.g., breezy day). We aim to sharpen mechanistic understanding of negative overgeneralization. In peripuberty -a time when changes in neurodevelopment potentiate generalization of salient experiences -these mechanisms may shape behavior and contribute to emotional health. In an emotional mnemonic similarity task conducted with youth, negative, relative to neutral, scene images were generalized more frequently. Negative overgeneralization was related to both greater and more similar patterns of activation in the CA1 hippocampal subfield and medial prefrontal cortex (mPFC) for negative relative to neutral stimuli. At encoding, the amygdala increased functional coupling with CA1 and mPFC during negative items that were later generalized. Negative overgeneralization is rooted in mechanisms of modulation at encoding and pattern completion at retrieval. Targeting these mechanisms during peripuberty could positively shape emotional health. previously stored representations, is associated with behavioral generalization

Highlights Generalized Additive Models fit the nature of diffusion-weighted imaging data. High anxiety participants had greater left uncinate FA values than low anxiety. Left uncinate FA differences were positively related with memory overgeneralization.