Awake reactivation of cortical memory traces predicts subsequent memory retrieval

Brief periods of rest after learning facilitate consolidation of new memories. Memory reactivation and hippocampal-cortical dialogue have been proposed as candidate mechanisms supporting consolidation. However, the study of these mechanisms has mostly concerned sleep-based consolidation. Whether and how awake reactivation can selectively consolidate cortical memory traces to guide subsequent behavior requires more human electrophysiological evidence. This study addressed these issues by utilizing intracranial electroencephalography (iEEG) recordings from 11 patients with drug-resistant epilepsy, who learned a set of object-location associations. Using representational similarity analysis, we found that, among the multiple cortical memory traces of object-location associations for the same object generated through several rounds of learning, the association corresponding to memory traces with stronger cortical activation during wakeful rest was more likely to be retrieved later. Awake reactivation of cortical memory trace was accompanied by increased hippocampal ripple rates and enhanced theta-band hippocampal-cortical communication, with hippocampal interactions with cortical regions within the default mode network preceding cortical reactivation. Together, these results suggest that awake reactivation of cortical memory trace during post-learning rest supports memory consolidation, predicting subsequent recall.