Research

Altered functional brain networks in patients with Mild Cognitive Impairment

Resting state assessments of functional brain connectivity help us understand interindividual differences in brain function, such as a decline in communication between brain areas with ageing or in dementia. Classical functional brain connectivity methods struggle however, to assess connectivity which is more variable over time, which is likely the case in older or clinical populations. Here we use methods robust to these differences in variability by focusing on activations exceeding an activation threshold. In doing so, we use data acquired on 3T as well as 7T MRI scanners in patients with amnestic mild cognitive impairment (aMCI) as well as cognitively normal older adults to investigate in particular differences in functional connectivity within the noradrenergic system, which is known to be affect in the early stages of Alzheimers.

Image extracted from: Cifre et al. 2021

Role of the LC/NE system in flexible learning: An MRI investigation

Our project explores the connection between arousal systems and cognitive flexibility, focusing on the crucial role of the locus coeruleus-norepinephrine (LC/NE) system in flexible behavior. A recent computational model has suggested that latent state reset mechanisms can account for a broad range of adaptive learning behaviors as well as the context-dependence of arousal indicators and learning. The purpose of this research project is to test the key projections of this model by investigating the role of the LC/NE system in regulating such latent states and how they affect behavior. A behavioral task and simultaneous pupillometry-fMRI recording will be used to look into the relationship between arousal signals, neural latent states, and behavior. The findings hold potential for developing LC/NE-targeted interventions that may help relieve the behavioral symptoms of psychiatric illnesses characterized by inflexible as well as inconsistent behavior.

Picture references: Saper et al. & Mander et al.

Neural dynamics of sleep-wake regulation in aging

Sleep disruption is common in old age and sleep disturbances are a feature of neurodegenerative conditions, including Alzheimer`s disease. This study aims at understanding the neurobiological mechanisms underlying sleep impairments in aging. To this end, we use simultaneous EEG-fMRI to characterize patterns of brain (dys)function across the sleep stages. Furthermore, we investigate the association between functional and structural alterations of sleep-wake maintenance systems, cognitive decline, and neuropathology.

Picture references: Saper et al., 2010 & Mander et al., 2017

Changes in noradrenergic brain function in early stages of Alzheimer's

Postmortem data suggest that for reasons that are not yet known, the noradrenergic locus coeruleus is one of the brain structures earliest affected by brain pathologies in Alzheimer's disease. In this study, we investigate to what extent a functional and structural decrease in the locus coeruleus can be detected using non-invasive methods in the early stages of Alzheimer's dementia. For this we use functional magnetic resonance imaging, volumetric magnetic resonance imaging and cognitive tasks sensitive to changes in noradrenergic modulation.

Relevance of the noradrenergic system for maintaining cognitive functions in old age

Noradrenaline not only supports cognitive functions such as memory and attention, but also physiological brain functions such as regulation of blood flow or inhibition of inflammatory processes. In this project, we investigate whether the nordrenergic system in older adults who are exceptionally good at maintaining cognitive function, differs from that of typically aging older adults. We are also investigating to what extent a drug increase in noradrenaline can improve cognitive functions in old age and in patients with midl cognitive impariment.

Picture reference: Sclocco et al. 2018

Poster on links between Neuromodulation, Protein pathologies and Atrophy at the OHBM 2024

Stimulation of the noradrenergic system as a therapeutic intervention in old age

A decrease in noradrenergic modulation with age is related to a decrease in cognitive functions such as remembering things. In this project we try to find out whether an increase in noradrenergic modulation by non-invasive vagus nerve stimulation is possible in old age and whether this can be accompanied by an increase in cognitive functions. The vagus nerve projects indirectly to the noradrenergic locus coeruleus in the brain and can be reached by a stimulator placed in the ear. To better understand the mode of action of the stimulator, we are closely coordinating with a partner project investigating physiological correlates of noninvasive vagus nerve stimulation in mice.

Dopaminergic modulation of memory consolidation in old age

A decrease in dopaminergic modulation with age is associated with a decrease in the ability to consolidate memory. In this study, we investigate whether a single dose of a drug that increases dopamine levels can improve the consolidation of memories in old age. Here we also use functional and structural brain imaging to investigate whether inter-individual differences in brain health with age can explain inter-individual differences in the effects of increasing dopamine levels.

Picture reference: Sclocco et al. 2018

Dopamine release in memory encoding in old age

In this study, we investigate whether reduced dopamine release in old age is associated with poorer memory function. For this purpose, we simultaneously measure functional brain activity using magnetic resonance imaging and endogenous dopamine release using positron emission tomography while participants work on a memory task. Furthermore, we use high-resolution functional imaging to track the activation of dopaminergic and noradrenergic nuclei in memory encoding.

Autonomic markers of metacognitive monitoring

Metacognition plays a crucial role in learning and decision-making across the life span. However, the neurophysiological substrates of metacognitive processes remain poorly understood. Recent but limited evidence suggests that the locus coeruleus-noradrenaline (LC-NA) system, as indirectly measured by cognitive pupillometry, may subserve post-response monitoring processes such as error awareness. The study aims at investigating whether pupil dilation, as an indirect and non-exclusive measure of LC activation, is a robust biomarker of metacognitive monitoring across tasks and cognitive domains. Furthermore we will validating methodology to assess metacognitive changes in the aging population using ecological tasks across cognitive domains.

Cerebrovascular aging

coming soon ...

Selected publications on the role of the noradrenergic system in ageing and dementia

Chen HY, Parent JH, Ciampa CJ, Dahl MJ, Hämmerer D, Maass A, Winer JR, Yakupov R, Inglis B, Betts MJ, Berry AS (2023). Interactive effects of locus coeruleus structure and catecholamine synthesis capacity on cognitive function. Front Aging Neurosci. 2023 Sep 6. doi: 10.3389/fnagi.2023.1236335. fnagi.2023.1236335. eCollection 2023. PMID: 37744395 Free PMC article. PDF

Ludwig M, Yi YJ, Lüsebrink F, Callaghan MF, Betts MJ, Yakupov R, Weiskopf N, Dolan RJ, Düzel E, Hämmerer D. (2024) Functional locus coeruleus imaging to investigate an ageing noradrenergic system. doi: 10.1038/s42003-024-06446-5. PDF

Leiman M, Ludwig M, Krohn F, Hämmerer D, Yi YJ. (2024) Cholinergic neuromodulation in the aging brain - Implications for neuropsychiatric diseases: Commentary on "neuromodulatory systems in aging and disease" special issue. doi: 10.1016/j.neubiorev.2024.105654. PDF

Yi YJ, Lüsebrink F, Ludwig M, Maaß A, Ziegler G, Yakupov R, Kreißl MC, Betts M, Speck O, Düzel E, Hämmerer D. (2023) It is the locus coeruleus! Or… is it?: a proposition for analyses and reporting standards for structural and functional magnetic resonance imaging of the noradrenergic locus coeruleus. doi: 10.1016/j.neurobiolaging. PDF

Lancini E, Haag L, Bartl F, Rühling M, Ashton NJ, Zetterberg H, Düzel E, Hämmerer D, Betts MJ. (2023) Cerebrospinal fluid and positron-emission tomography biomarkers for noradrenergic dysfunction in neurodegenerative diseases: a systematic review and meta-analysis. doi: 10.1093/braincomms/fcad085. PDF

Ehrenberg AJ, Kelberman MA, Liu KY, Dahl MJ, Weinshenker D, Falgàs N, Dutt S, Mather M, Ludwig M, Betts MJ, Winer JR, Teipel S, Weigand AJ, Eschenko O, Hämmerer D, Leiman M, Counts SE, Shine JM, Robertson IH, Levey AI, Lancini E, Son G, Schneider C, Egroo MV, Liguori C, Wang Q, Vazey EM, Rodriguez-Porcel F, Haag L, Bondi MW, Vanneste S, Freeze WM, Yi YJ, Maldinov M, Gatchel J, Satpati A, Babiloni C, Kremen WS, Howard R, Jacobs HIL, Grinberg LT. (2023) Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART. doi: 10.1002/alz.12937. PDF

Liebe, T., Kaufmann, J., Hämmerer, D., Betts, M., Walter, M. (2022) In vivo tractography of human locus coeruleus-relation to 7T resting state fMRI, psychological measures and single subject validity. Molecular Betts, M., Ehrenberger, A. J., Hämmerer, D., Düzel, E. (2018) Commentary: Locus Coeruleus Ablation Exacerbates Cognitive Deficits, Neuropathology, and Lethality in P301S Tau Transgenic Mice. Frontiers in Neuroscience 12, 401. PDF

Hämmerer, D., Callaghan, M.F., Hopkins, A., Kosciessa, J., Betts, M.., Cardenas-Blanco, A., Kanowski, M., Weiskopf, N., Dayan, P., Dolan, R.J. and Düzel, E. (2018) Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events. Proceedings of the National Academy of Sciences, 115 (9), 2228-2233. PDF

Hämmerer, D., Hopkins, A., Betts, M., Maaß, A., Dolan, R. J., Duzel, E. (2017) Emotional arousal and recognition memory are differentially reflected in pupil diameter responses during emotional memory for negative events in younger and older adults. Neurobiology of Aging, 58, 129-139. PDF

Liu, K.Y., Marijatta F., Hämmerer, D., Düzel E., Howard R.J. (2017) Magnetic resonance imaging of the human locus coeruleus: A systematic review. Neuroscience & Biobehavioral Reviews, 83, 325-355. PDF

Düzel, E., Guitart-Masip, M., Maass, A., Hämmerer, D., Betts, M. J., Speck, O., Weiskopf, N., Kanowski, M. (2015) Midbrain fMRI: Applications, Limitations and Challenges. In: fMRI: From Nuclear Spins to Brain Functions, BIological Magnetic Resonance, 581-609. PDF

Selected publications on changes in cognitive functions across the lifespan: Cognitive control

Hämmerer, D., Müller, V., Heekeren, H. R., Lindenberger, U., & Li, S.-C. (2014) Performance monitoring across the lifespan: Still maturing post-conflict regulation in children and declining task- set monitoring in older adults.Neuroscience & Biobehavioral Reviews, 46, 105-123. PDF

Hämmerer, D., Li, S.-C., Völkle, M., Müller, V., & Lindenberger, U. (2013). The reliability of event- related potentials related to performance monitoring across the lifespan. Psychophysiology. PDF

Papenberg, G., Hämmerer, D., Müller, V., Lindenberger, U., & Li, S.-C. (2013) Lower theta inter- trial phase coherence during performance monitoring is related to higher reaction time variability: A lifespan study. NeuroImage, 83, 912-920. PDF

Hämmerer, D., Li, S.-C., Müller, V., & Lindenberger, U. (2010). An electrophysiological study of response conflict monitoring across the lifespan: Assessing the roles of conflict monitoring, cue utilization, response anticipation, and response suppression. Neuropsychologia, 48, 3305-3316.PDF

Li, S.-C., Hämmerer, D., Müller, V., Hommel, B., & Lindenberger, U. (2009). Lifespan development of stimulus-response conflict cost: Similarities and differences between maturation and senescence. Psychological Research. 73(6), 777-785. PDF

Selected publications on changes in cognitive functions across the lifespan: Reinforcement learning

Fitzgerald, T. H. B., Hämmerer, D., Friston, K. J., Li, S.-C., Dolan, R. J. (2017) Sequential inference strategies correlate with individual differences in brain structures. PLOS Computational Biology, 13(5): e1005418. PDF

Hämmerer, D., Biele, G., Müller, V., Thiele, H., Nürnberg, P., Heekeren, H. R. & Li, S.-C. (2013) Striatal Dopamine Signaling and Outcome Updating across the Lifespan: The Effect of PPP1R1B (DARPP-32) Polymorphism on Event-related Potentials. Frontiers in Decision Neuroscience. 4(89). PDF

Hämmerer, D. & Eppinger, B. (2012) Dopaminergic and prefrontal contributions to learning and outcome monitoring during childhood and old age. Developmental Psychology, 48, 862-874. PDF

Eppinger, B., Hämmerer, D. & Li, S.-C. (2011) Neuromodulation of reward-based learning and decision making in human aging. Annals of the New York Academy of Sciences, 1235, 1-17. PDF

Hämmerer, D., Li, S.-C., Müller, V., & Lindenberger, U. (2011). Life span differences in electrophysiological correlates of monitoring gains and losses during probabilistic reinforcement learning. Journal of Cognitive Neuroscience, 23(3), 1-14. PDF

Selected publications on altering cognitive functions with non-invasive brain stimulation

Ludwig M, Pereira C, Keute M, Düzel E, Betts MJ, Hämmerer D. (2024). Evaluating phasic transcutaneous vagus nerve stimulation (taVNS) with pupil dilation: the importance of stimulation intensity and sensory perception. Sci Rep. 2024 Oct 17;14(1):24391. doi: 10.1038/s41598-024-72179-4. PDF

Ludwig, M., Wienke, C., Betts, M., Zaehle, T., Hämmerer, D. (2021) Current challenges in reliably targeting the noradrenergic locus coeruleus using transcutaneous auricular vagus nerve stimulation (taVNS). Autonomic Neuroscience: Basic & Clinical, 236, 102900.PDF

Hämmerer, D., Bonaiuto, J., Klein-Flügge, M. et al. (2016) Selective alteration of human value decisions with medial frontal tDCS is predicted by changes in attractor dynamics. Sci Rep 6, 25160. PDF

Chen, J. A., Hämmerer, D., Strigaro, G., Liou, L.M., Tsai, C. H., Rothwell, J. C., Edwards, M. J. (2014) Domain-Specific Suppression of Auditory Mismatch Negativity with Transcranial Direct Current Stimulation. Clinical Neurophysiology, 125, 585-592. PDF

Chen, J. A., Hämmerer, D., Marshal, L., Strigaro, G., Liou, L.M., Tsai, C. H., Rothwell, J. C., Edwards, M. J. (2014) Bi-directional Modulation of Somatosensory Mismatch Negativity with Transcranial Direct Current Stimulation. Clinical Neurophysiology, 592, 745-757. PDF

2025-2029: EU COST Action 24118 ‘ImagingBrainstemHealth’ – Advancing human brainstem MRI and its application in clinical research and practice (Coord.) (600.000 €)

2022-2028: NIH R01MH126971 ‘Representational dynamics for flexible learning in complex environments’ (Subaward for collaborator) (223.706 USD) (personnel costs, direct costs)

2022-2026: SFB 1315 Projekt B06 ‘Connectivity dynamics related to memory consolidation in cortical layers and subcortical networks’ (PI) (508.400 €) (personnel costs, direct costs, equipment)

2021: Forschungsinfrastrukturförderung Leopold-Franzens University of Innsbruck ‘Zirkadiane Gesundheit’ (PI) (73.315 € - intramural) (equipment)

2021: Brenda Milner Award (7.500 €) (direct costs)

2020-2024: SFB 1436 Project A08 The noradrenergic system’s contribution to neural resource in aging (PI) (502.600 €) (personnel costs, direct costs)

2019-2023: CBBS ‘Neuronetwork Stimulation of the LC-NE system as a personalized therapeutic intervention’, Europäischer Fonds für regionale Entwicklung (EFRE) (205.000 € as PI of one subproject and coordinator of 4 subprojects of ‘Neuronetwork 17’, total funding 556.000 €) (personnel costs, direct costs, equipment)

2018-2025: Senior research fellowship: ‘Noradrenergic treatment for Alzheimer’s Disease’, Alzheimer Research UK (ARUK) (420.000 £) (personnel costs, direct costs)

2016-2018: MRC research grant: ‘Assessing the role of the noradrenergic locus coeruleus in healthy ageing and early Alzheimer's disease’ (Chief Investigator, Co-Applicant with Emrah Düzel, 233.555 £) (personnel costs, direct costs)

2013-2014: DAAD: Postdoctoral fellowship (40.000 €) (personnel costs)

2025: Initiated lecture series ‘Science for everyday life’ (link)
2023-2024: ‘ORF Radiokolleg’ ‘Schönheit im Alter’, Stern Magazin: ‚Geheimnis der SuperAger‘, Salzburger Nachrichten ‘Empathie im Alter’, Kleine Unbekannte im Gehirn’,
2023-2024’: Bildungspass’, Lecture series for parents of young children, Innsbruck

Warum Empathie so wichtig ist - und warum sie sogar gefährlich sein kann. Sich in andere hineinfühlen zu können ... ist eine Voraussetzung für gutes Denken und Handeln. Und Empathie hält die Gesellschaft erst zusammen. Jedoch: Sie hat auch ihre dunklen Seiten. Daniela Müller, 20. 12. 2024. https://www.sn.at/wochenende/warum-empathie-so-wichtig-ist-und-warum-sie-sogar-gefaehrlich-sein-kann-art-572873

Geistig fit bis ins Alter. Ein Super-Ager verrät seine Geheimnisse – und gibt ein Rätsel auf. Doris Schneyink aufgezeichnet, 05. November 2025.https://www.stern.de/panorama/wissen/gehirn--so-schafft-es-ein-super-ager--im-alter-geistig-fit-zu-sein-35265778.html

MEIN BILDUNGSPASS – kostenlos für jedes Kind von 0 bis 6 Jahren.

Der Bildungspass ist ein einzigartiges Programm, das Kindern die besten Chancen für eine erfolgreiche Zukunft bietet. Für Eltern ist er ein wertvolles Werkzeug, um die Entwicklung ihrer Kinder gezielt zu fördern und den Familienalltag spürbar zu entlasten – mit minimalem Aufwand, aber maximaler Wirkung. Kinder profitieren, indem sie von klein auf wertvolle Lebenserfahrungen sammeln, Entwicklungsdefizite vermeiden und wichtige Grundlagen für Schule, Beruf und das spätere Leben erlernen. https://regio3.meinbildungspass.at/

Radiokolleg: Im Namen der Schönheit (4) - Die Angst vorm Altern - ein Gegenentwurf: https://oe1.orf.at/programm/20230907/732641/Im-Namen-der-Schoenheit-4

Hirnregion als Schlüssel für Demenzprognose. ORF Tirol. Wissenschaft. 9. September 2024: https://tirol.orf.at/stories/3272323/

Anne Berry, Brandeis University: FMT PET

Dr. Bryce Mander, University of Irvine California, USA: Sleep and aging

Dr. Daniela G. Femminella, Clinical Psychopathology - AOU Federico II, Napoli, Italy: fMRI in AD

Dr. Elif Kurt, Istanbul University: fMRI in AD

Dr. Giulio Bernardi, IMT Lucca, Italy: Simultaneous EEG-fMRI and sleep

Dr. Matt Nassar, Brown University, USA: Pupillometry & cognitive modelling

Hendrik Mattern, University Magdeburg & Stefanie Schreiber, University Magdeburg: Vascular health in the brainstem

Ildiko Dunay, University Magdeburg: Immunological assessments

Jarkko Joahnsson, Umeå University: Fallypride PET

Jens Wiltfang, German Center for Neurodegenerative Diseases: Neurodegeneration markers