Hippocampal-cortical connectivity relates to inter-individual differences and training gains in distinguishing similar memories

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 functional connectivity patterns between these regions are related to MD before and after 2-weeks of web-based cognitive training. We identified a functional connectivity signature involving MTL-PFC-visual areas during successful MD. We found that hippocampal-PFC connectivity was negatively associated with interindividual variability in MD performance across two different tasks. Hippocampal-PFC connectivity decrease was also linked to interindividual 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 which is a reliable, task-invariant, marker of MD performance. This pattern is further related to MD training gains providing causal evidence for its relevance in distinguishing similar memories. Overall, we show that hippocampal-PFC connectivity constitutes a neural resource for MD that enables training-related improvements and could be targeted in future research to enhance cognition.