Mnemonic discrimination (MD) is the ability to distinguish current experiences from similar memories. Research on the brain correlates of MD has focused on how regional neural responses are linked to MD. Here we go beyond this approach to investigate inter-regional functional connectivity patterns related to MD, its inter-individual variability and training-related improvement. Based on prior work we focused on medial temporal lobe (MTL), prefrontal cortex (PFC) and visual regions. We used fMRI to determine how connectivity patterns between these regions are related to MD before and after 2-weeks of web-based cognitive training. We found MD-related connectivity involving MTL-PFC-visual areas. Hippocampal-PFC connectivity was negatively associated with inter-individual variability in MD performance across two tasks. Hippocampal-PFC connectivity decrease was also linked to inter-individual variability in post-training MD improvement. Additionally, training led to increased connectivity from the lateral occipital cortex to the occipital pole area. Our results point to a hippocampal-PFC connectivity pattern that is a reliable marker of MD performance. This pattern is further related to MD training gains providing strong evidence for its role in distinguishing similar memories. Overall, we show that hippocampal-PFC connectivity constitutes a neural resource for MD that enables training-related improvement and may be targeted to enhance cognition.
