Some of the earliest age-related changes in brain activity and functional connectivity occur within the hippocampus and posteromedial cortex. These regions are strongly interconnected and both are involved in a variety of cognitive tasks that are compromised during ageing, including episodic memory. Our aim is to better understand the spatio-temporal dynamics and implications of these age- and memory-related functional changes.

Functional magnetic resonance imaging (fMRI) studies in cognitively normal older adults have found increased fMRI task-related activity in the hippocampus as well as posterior-midline regions relative to younger adults [1–3]. While this „hyperactivation” has been related to poorer memory performance in older adults [4,5] evidence also suggest that it may represent functional compensation [6,7]. However, the picture is complex, with studies reporting both poorer memory performance associated with higher [8] and lower [9,10] intrinsic functional connectivity. Furthermore, the relationship between changes in activity and functional connectivity and how this relates to memory performance may be further moderated by early tau pathology in ageing [11,12]. Thus, future studies in the cognitively normal elderly should also account for hidden Alzheimer’s pathology.

A systematic investigation into the task-related changes in activity and network connectivity in relation to this aberrant fMRI activity across hippocampal-posterior cortical regions during critical stages of healthy ageing (age ranges 60-80 years) has not been undertaken in humans. In addition, our aim is to elucidate the relationship between alterations in activity and functional connectivity in these regions with episodic memory performance in normal ageing.

We use multimodal neuroimaging methods including fMRI and positron emission tomography (PET) as well as cognitive testing and demographic data to address those open questions.

Project D1. Anne Maass, Larissa Fischer

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[1] Diersch, N., Valdes-Herrera, J. P., Tempelmann, C., & Wolbers, T. (2021). Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging. Journal of Neuroscience, 41(14), 3204–3221.

[2] Lustig, C., Snyder, A. Z., Bhakta, M., O’Brien, K. C., McAvoy, M., Raichle, M. E., Morris, J. C., & Buckner, R. L. (2003). Functional deactivations: Change with age and dementia of the Alzheimer type. Proceedings of the National Academy of Sciences, 100(24), 14504–14509.

[3] Richter, A., Soch, J., Kizilirmak, J. M., Fischer, L., Schütze, H., Assmann, A., Behnisch, G., Feldhoff, H., Knopf, L., Raschick, M., Schult, A., Seidenbecher, C. I., Yakupov, R., Düzel, E., & Schott, B. H. (2023). Single-value scores of memory-related brain activity reflect dissociable neuropsychological and anatomical signatures of neurocognitive aging. Human Brain Mapping, 44(8), 3283–3301.

[4] Adams, J. N., Maass, A., Berron, D., Harrison, T. M., Baker, S. L., Thomas, W. P., Stanfill, M., & Jagust, W. J. (2021). Reduced Repetition Suppression in Aging is Driven by Tau–Related Hyperactivity in Medial Temporal Lobe. The Journal of Neuroscience, 41(17), 3917–3931.

[5] Billette, O. V., Ziegler, G., Aruci, M., Schütze, H., Kizilirmak, J. M., Richter, A., Altenstein, S., Bartels, C., Brosseron, F., Cardenas-Blanco, A., Dahmen, P., Dechent, P., Dobisch, L., Fliessbach, K., Freiesleben, S. D., Glanz, W., Göerß, D., Haynes, J. D., Heneka, M. T., … on behalf of the DELCODE Study Group. (2022). Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease. Neurology, 99(8), e775–e788.

[6] Cabeza, R., Albert, M., Belleville, S., Craik, F. I. M., Duarte, A., Grady, C. L., Lindenberger, U., Nyberg, L., Park, D. C., Reuter-Lorenz, P. A., Rugg, M. D., Steffener, J., & Rajah, M. N. (2018). Maintenance, reserve and compensation: The cognitive neuroscience of healthy ageing. Nature Reviews Neuroscience, 19(11), 701–710.

[7] Reuter-Lorenz, P. A., & Cappell, K. A. (2008). Neurocognitive Aging and the Compensation Hypothesis. Current Directions in Psychological Science, 17(3), 177–182.

[8] Berron, D., van Westen, D., Ossenkoppele, R., Strandberg, O., & Hansson, O. (2020). Medial temporal lobe connectivity and its associations with cognition in early Alzheimer’s disease. Brain: A Journal of Neurology, 143(4), 1233–1248.

[9] Kaboodvand, N., Bäckman, L., Nyberg, L., & Salami, A. (2018). The retrosplenial cortex: A memory gateway between the cortical default mode network and the medial temporal lobe. Human Brain Mapping, 39(5), 2020–2034.

[10] Wang, L., LaViolette, P., O’Keefe, K., Putcha, D., Bakkour, A., Van Dijk, K. R. A., Pihlajamäki, M., Dickerson, B. C., & Sperling, R. A. (2010). Intrinsic connectivity between the hippocampus and posteromedial cortex predicts memory performance in cognitively intact older individuals. NeuroImage, 51(2), 910–917.

[11] Maass, A., Berron, D., Harrison, T. M., Adams, J. N., La Joie, R., Baker, S., Mellinger, T., Bell, R. K., Swinnerton, K., Inglis, B., Rabinovici, G. D., Düzel, E., & Jagust, W. J. (2019). Alzheimer’s pathology targets distinct memory networks in the ageing brain. Brain, 142(8), 2492–2509.

[12] Ziontz, J., Adams, J. N., Harrison, T. M., Baker, S. L., & Jagust, W. J. (2021). Hippocampal Connectivity with Retrosplenial Cortex is Linked to Neocortical Tau Accumulation and Memory Function. The Journal of Neuroscience, 41(42), 8839–8847.