Lifespan Neuromodulation of Cognition (LINE)

In this project, we use imaging to examine how neuronal changes in older adulthood are associated with  neurodegenerative diseases involving cognitive decline. Our particular focus is on certain neurotransmitters, so-called neuromodulators.

We live in an aging society. While life expectancy is rising in Germany and other developed countries, the birth rate is falling. Older age, however, is associated with declining attention and memory, and constitutes a risk factor for neurodegenerative diseases such as Alzheimer’s dementia.

In our research at the MPIB and in collaboration with the University of Southern California, we investigate brain changes across the lifespan that explain why our cognition deteriorates as we age. In particular, we investigate a small cluster of cells, barely the size of a fingernail, that is literally called the blue spot (locus coeruleus). Despite its small size, the blue spot is our brain’s main supply of noradrenaline – a neurotransmitter involved in attention and memory-related processes throughout the brain.

We focus on the blue spot because it has been identified as one of the first sites to show signs of Alzheimer’s pathology, decades before the symptoms of dementia surface. While its size and location at the base of the brain have long hampered research in living humans, novel imaging techniques promise to shed light on this little-studied brain region.

We combine multiple dedicated brain imaging methods with repeated neuropsychological assessments to track how changes in the blue spot are linked to cognitive changes in aging and disease. This research holds promise to provide insights into the brain mechanisms of senescent cognitive decline and the development of Alzheimer’s.


Selected Publications

Dahl, M. J., Bachman, S. L., Dutt, S., Düzel, S., Bodammer, N. C., Lindenberger, U., Kühn, S., Werkle-Bergner, M., & Mather, M. (2023). The integrity of dopaminergic and noradrenergic brain regions is associated with different aspects of late-life memory performance. Nature Aging, 3(9), 1128–1143. https://doi.org/10.1038/s43587-023-00469-z
Dahl, M. J., Kulesza, A., Werkle-Bergner, M., & Mather, M. (2023). Declining locus coeruleus-dopaminergic and noradrenergic modulation of long-term memory in aging and Alzheimer’s disease. Neuroscience & Biobehavioral Reviews, 153, Article 105358. https://doi.org/10.1016/j.neubiorev.2023.105358
Dahl, M. J., Mather, M., Werkle-Bergner, M., Kennedy, B. L., Guzman, S., Hurth, K., Miller, C. A., Qiao, Y., Shi, Y., Chui, H. C., & Ringman, J. M. (2022). Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer’s disease. Neurobiology of Aging, 112, 39–54. https://doi.org/10.1016/j.neurobiolaging.2021.11.006
Dahl, M. J., Mather, M., & Werkle-Bergner, M. (2022). Noradrenergic modulation of rhythmic neural activity shapes selective attention. Trends in Cognitive Sciences, 26(1), 38–52. https://doi.org/10.1016/j.tics.2021.10.009
Dahl, M. J., Mather, M., Sander, M. C., & Werkle-Bergner, M. (2020). Noradrenergic responsiveness supports selective attention across the adult lifespan. The Journal of Neuroscience, 40(22), 4372–4390. https://doi.org/10.1523/JNEUROSCI.0398-19.2020
Dahl, M. J., Mather, M., Düzel, S., Bodammer, N. C., Lindenberger, U., Kühn, S., & Werkle-Bergner, M. (2019). Rostral locus coeruleus integrity is associated with better memory performance in older adults. Nature Human Behaviour, 3, 1203–1214. https://doi.org/10.1038/s41562-019-0715-2
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