Temporal Interference Modulates Medial Temporal and Frontoparietal Activity During Mnemonic Discrimination: A High-Resolution Whole-Brain fMRI Investigation

Abstract

Mnemonic discrimination—the ability to distinguish between existing memories and similar new inputs—supports accurate memory in the face of interference (e.g., in a card game, recognizing that the card you are currently seeing, the King of Hearts, is distinct from the King of Diamonds you encountered earlier in the same hand). Although hippocampal pattern separation has been emphasized as a key mechanism for this process, recent theoretical frameworks and empirical findings suggest that surrounding medial temporal lobe and cortical regions also contribute by resolving interference. An important source of interference in everyday life is temporal interference: similar events may compete not only because they overlap perceptually, but also because they are separated by intervening experiences (e.g., distinguishing the King of Hearts you are currently holding in your hand from the King of Diamonds you encountered earlier in the game becomes increasingly difficult as additional cards are played and additional hands intervene between the two episodes). Here, we examined how temporal interference impacts mnemonic discrimination and its neural correlates using high-resolution fMRI and a continuous recognition task in which the lag between an item's first presentation and its subsequent target or similar lure was systematically manipulated (10, 60, or 140 intervening trials). Behaviorally, increasing lag impaired both mnemonic discrimination and target recognition. At the neural level, lag effects were not observed in hippocampal subfields. Instead, temporal interference modulated activity in extrahippocampal MTL regions including parahippocampal and perirhinal cortex, as well as distributed cortical regions including frontoparietal control areas. Importantly, lag-related modulation was process-specific, with partially dissociable patterns for successful mnemonic discrimination and target recognition. Together, these findings demonstrate that temporal interference engages a distributed MTL-cortical network that supports interference resolution during mnemonic discrimination.