Stress disrupts hippocampal integration of overlapping events and memory inference in humans.

Abstract

Integrating related events in memory is essential for building knowledge that extends beyond direct observation and enables flexible inference. Here, we show that acute stress impairs inference by both reducing the degree to which past memories are reactivated during new learning and leading to their differentiation, rather than integration, in hippocampus. Adults learned A-B associations on day 1 and underwent a stress or control manipulation before learning overlapping B-C associations on day 2, with A-C inference tested thereafter. We demonstrate that stress reduces hippocampal reactivation of A elements during B-C learning, and lower reactivation was directly correlated with impaired A-C inference. Representational similarity analysis revealed that stress increases neural dissimilarity between overlapping A and C elements in the hippocampus, indicating pattern differentiation and a representation as discrete events. Our findings demonstrate that acute stress hampers a key memory integration mechanism, with broad implications for educational, legal, and clinical settings.