PT - JOURNAL ARTICLE AU - Christopher N. Wahlheim AU - Alexander P. Christensen AU - Zachariah M. Reagh AU - Brittany S. Cassidy TI - Connectome-based Modeling of Mnemonic Discrimination in Younger and Older Adults AID - 10.1101/2021.07.09.451777 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.07.09.451777 4099 - http://biorxiv.org/content/early/2021/07/10/2021.07.09.451777.short 4100 - http://biorxiv.org/content/early/2021/07/10/2021.07.09.451777.full AB - The ability to distinguish existing memories from similar perceptual experiences is a core feature of episodic memory. This ability is often examined using the Mnemonic Similarity Task in which people discriminate memories of studied objects from perceptually similar lures. Studies of the neural basis of such mnemonic discrimination have focused on hippocampal function and connectivity. However, default mode network (DMN) connectivity may also support such discrimination, given that the DMN includes the hippocampus, and its connectivity supports many aspects of episodic memory. Here, we used connectome-based modeling to identify associations between intrinsic DMN connectivity and mnemonic discrimination. We leveraged established discrimination deficits in older adults to test whether such age differences moderate network-wide relationships. Resting-state functional connectivity in the DMN predicted mnemonic discrimination ability outside the MRI scanner, especially among prefrontal and temporal regions and including several hippocampal regions. This predictive relationship was stronger for younger than older adults, with age differences primarily reflecting older adults’ weaker temporal-prefrontal connectivity. These novel associations suggest that broader cortical networks including the hippocampus support mnemonic discrimination. They also suggest that disruptions within the DMN that emerge in healthy aging undermine the extent that the DMN supports this ability. These findings provide the first indication of how intrinsic functional properties of the DMN support mnemonic discrimination.Competing Interest StatementThe authors have declared no competing interest.