Negative overgeneralization is associated with anxiety and mechanisms of pattern completion in peripubertal youth

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 dentate gyrus/ cornu ammonis (CA)3 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 magnetic resonance imaging. At study, participants indicated the valence of images; at test, participants made recognition memory judgments. Critical lure stimuli, which 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 mPFC (dmPFC)and ventral mPFC (vmPFC) for negative relative to neutral stimuli. At study, amygdala exhibited greater functional coupling with CA1 and dmPFC during negative items that were later generalized. Negative overgeneralization is rooted in amygdala and mPFC modulation at encoding and pattern completion at retrieval.