Time-dependent consolidation mechanisms of durable memory in spaced learning

Emerging studies suggest that time-dependent consolidation enables memory stabilization by promoting memory integration and hippocampal-cortical transfer. Compared to massed learning, how time-dependent consolidation contributes to forming durable memory and what neural signatures predict durable memory in spaced learning remain unclear. We recruited 48 participants who underwent either 3-day spaced learning or 1-day massed learning, and both resting-state and task-based fMRI data were collected in multiple delayed tests (i.e., immediate, 1-week, and 1-month). We use representational similarity analysis to assess neural integration and replay in the hippocampus and default mode network (DMN) subsystems. In contrast with massed learning, spaced learning induces higher neural pattern similarity during immediate retrieval only in DMN subsystems. Particularly, the neural pattern similarity in the dorsal-medial DMN (DMN_dm) and medial-temporal DMN subsystems predicts the durable memory defined by 1-month delay. Moreover, we find increased neural replay of durable memory in the DMN_dm for spaced learning and in the hippocampus for both spaced and massed learning. Our findings suggest that time-dependent consolidation promotes neural integration and replay in the cortex rather than in the hippocampus, which may underlie the formation of durable memory after spaced learning.