Temporal Interference Modulates Medial Temporal and Frontoparietal Activity During Mnemonic Discrimination: A high-resolution whole-brain fMRI investigation

Mnemonic discrimination--the ability to distinguish between existing memories and similar new inputs--supports accurate memory in the face of interference (e.g., remembering where you parked today versus yesterday in the same parking deck). Although hippocampal pattern separation has been emphasized as a key mechanism, 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., having to remember your morning parking spot after a full day of work). Here, we investigated 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 items 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. Rather, 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.