Abstract
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-individ…
Abstract
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.
Data availability
The data employed in this study are not publicly available. The source data for the figures and tables are provided as Supplementary Data 1, 2, respectively.
Code availability
No custom code or algorithms were used in this study. All analyses were performed using publicly available software tools as described in detail in the Methods section.
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Acknowledgements
This work was supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 425899996—SFB 1436. We are grateful to Aditya Nemali for his help in setting up the training website. We thank all participants who volunteered to participate in the training. We also want to thank the staff at the IKND and the university clinic for neurology, Medical Faculty, Otto-von-Guericke University, for assistance in testing and scanning the participants.
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Author notes
These authors contributed equally: Panagiotis Iliopoulos, Jeremie Güsten.
Authors and Affiliations
Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany
Panagiotis Iliopoulos, Jeremie Güsten, Friedrich Krohn & Emrah Düzel 1.
German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Panagiotis Iliopoulos, Eóin Molloy, Friedrich Krohn, Anne Maass & Emrah Düzel 1.
Division of Nuclear Medicine, Department of Radiology & Nuclear Medicine, Faculty of Medicine, Otto von Guericke University Magdeburg, Magdeburg, Germany
Eóin Molloy 1.
AICURA medical GmbH, Colditzstraße 34/36, 16A, Berlin, Germany
Eóin Molloy 1.
Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany
Radoslaw Martin Cichy
Authors
- Panagiotis Iliopoulos
- Jeremie Güsten
- Eóin Molloy
- Radoslaw Martin Cichy
- Friedrich Krohn
- Anne Maass
- Emrah Düzel
Contributions
Conceptualization: P.I. and E.D. Methodology: J.G., E.D., and P.I. Investigation: J.G. (performed the experiment). Data curation: J.G. Formal analysis: P.I. Writing—original draft: P.I. Writing—review & editing: P.I., E.D., E.M., J.G., A.M., R.C., and F.K. Supervision: E.D. and A.M. Funding acquisition: E.D. Project administration: P.I. (managed manuscript revisions and correspondence during peer review).
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Correspondence to Panagiotis Iliopoulos.
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Iliopoulos, P., Güsten, J., Molloy, E. et al. Hippocampal-prefrontal connectivity relates to inter-individual differences and training gains in distinguishing similar memories. Commun Biol (2025). https://doi.org/10.1038/s42003-025-09408-7
Received: 07 February 2025
Accepted: 10 December 2025
Published: 28 December 2025
DOI: https://doi.org/10.1038/s42003-025-09408-7