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Stress Blocks Hippocampal Memory Integration and Inference

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Researchers used fMRI to test how acute stress reshapes the brain’s handling of overlapping memories. Participants learned A‑B pairs on day 1, then faced either the Trier Social Stress Test or a control before learning B‑C pairs on day 2. One hour later they were probed on A‑C inference, revealing stress‑induced deficits. The design controlled for emotional valence of stimuli, mixing neutral and threat‑related images.

fMRI data showed that stressed participants reactivated the original A elements far less during B‑C encoding. The reduction correlated tightly with poorer A‑C inference scores. Representational similarity analysis further indicated that stress increased hippocampus pattern dissimilarity between A and C items, turning what should be integrated traces into distinct, separated representations. These neural shifts occurred regardless of whether A items were emotionally charged, suggesting a general stress effect.

The findings pinpoint a neural mechanism by which acute stress impairs memory inference: it suppresses hippocampal replay of prior elements and drives pattern differentiation rather than integration. This mechanism explains why stressful environments can hinder learning, legal testimony, and therapeutic reconsolidation, underscoring the need to manage stress during critical encoding phases. Interventions that lower cortisol or norepinephrine spikes could preserve replay and maintain integrative memory networks.