Project
Modulation of memory consolidation in humans
The consolidation of hippocampus-dependent memory benefits from slow-wave sleep (SWS). A mechanism was proposed for this consolidation process, where the depolarizing ‘up’ phase of cortical slow oscillations (SO) drives the replay of newly encoded memories in the hippocampus (accompanied by sharp wave ripples and thalamocortical spindles) and mediates their long-term storage in the neocortical networks. Probing the mechanisms of sleep−dependent memory consolidation in humans, in order to understand causal relationships and to ultimately restore normal function in patients with consolidation impairments, requires manipulations of the consolidation process. We therefore propose a study that combines perturbation experiments in humans using transcranial current stimulation (tCS) applied during SWS, with a theoretical approach that mechanistically describes the interaction between the external stimulation and the global brain dynamics and which ultimately may allow for optimizing therapeutic interventions in patients. We start with the hypothesis that the interplay between SO, spindle and ripple activity sets the “operating point’’ for successful memory consolidation, and we will eventually validate elements of this hypothesis by correlating brain activity patterns recorded with EEG during SWS with the behavioral assessment of consolidation success. We will first apply and empirically optimize tCS protocols, which have been used previously to enhance SO and spindle activity, and we will search for, and validate electrophysiological features that are predictive for improved behavioral performance. This search will be guided by whole-brain computational models, initially constructed to understand the patterns of SO during SWS and later extended to study SO−spindle interactions. Computational models will be tuned to reproduce SO and spindle activity recorded with EEG during SWS, and will be used to formulate and evaluate mechanistic hypotheses about the state dependent impact of tCS. tCS protocols optimized in silico for enhancing SO and spindle activity − will then be empirically validated against EEG responses and tested on SWS-dependent memory consolidation in humans, using a previously validated object recognition learning paradigm. According to our hypothesis − that a proper adjustment of the brain’s “operating point” is beneficial for memory consolidation − we expect that enhancing electrophysiological markers that have been shown to correlate with memory consolidation is already sufficient to improve behavioral performance. If so, the model-based approach will not only convey novel insights into causal relations between electrophysiological features and successful memory consolidation, but also help us to design efficient stimulation protocols which are personalized and adapted to various patient groups. Given that the amount of SWS per night significantly declines with aging (a trend accelerated in patients with Alzheimers Disease) and that the disturbed sleeping patterns contribute to deficits in memory consolidation, the results of this project may be of high clinical relevance.
Image Time frequency representation (TFR) in the frequency range of 5 to 20 Hz for SO (left) and delta (right) events. Courtesy of B03 members
Team
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Prof Dr Klaus Obermayer
Technische Universität Berlin & BCCN
Head Neural Information Processing Group
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Prof Dr Agnes Flöel
Universitätsmedizin Greifswald
Chair, Department of Neurology
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Caglar Cakan
Technische Universität Berlin
PhD B03
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Robert Malinowski
Universitätsmedizin Greifswald
PhD B03
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Cristiana Dimulescu
Technische Universität Berlin
Associated PhD B03
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Dr Nikola Jajcay
Technische Universität Berlin
Associated Postdoc B03
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Dr Jeffrey Scott Hanna
Universitätsmedizin Greifswald
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Liliia Khakimova
Universitätsmedizin Greifswald
Associated PhD B03
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Dr Daniela Obst
Universitätsmedizin Greifswald
Associated Postdoc B03
Publications
Spatiotemporal patterns of adaptation-induced slow oscillations in a whole-brain model of slow-wave sleep
Caglar Cakan, Cristiana Dimulescu, Liliia Khakimova, Daniela Obst, Agnes Flöel, Klaus Obermayer
Front Comput Neurosci. 15:800101 (2022)
Memory-relevant nap sleep physiology in healthy and pathological aging
Julia Ladenbauer, Josef Ladenbauer, Nadine Külzow, Agnes Flöel
Sleep. 44(7):zsab002 (2021)
Towards optimization of oscillatory stimulation during sleep
Julia Ladenbauer, Liliia Khakimova, Robert Malinowski, Daniela Obst, Eric Tönnies, Daria Antonenko, Klaus Obermayer, Jeff Hanna, Agnes Flöel
bioRxiv (2021)
Interrelations between delta waves, spindles and slow oscillations in human NREM sleep and their functional role in memory
Larissa N. Wüst, Daria Antonenko, Robert Malinowski, Liliia Khakimova, Ulrike Grittner, Klaus Obermayer, Julia Ladenbauer, Agnes Flöel
bioRxiv
Applications of optimal nonlinear control to a whole-brain network of FitzHugh-Nagumo oscillators
Teresa Chouzouris, Nicolas Roth, Caglar Cakan, Klaus Obermayer
Phys Rev E. 104(2-1):024213 (2021)
Cross-frequency slow oscillation–spindle coupling in a biophysically realistic thalamocortical neural mass model
Nikola Jajcay, Caglar Cakan, Klaus Obermayer
Front. Comput. Neurosci. 16:769860 (2022)
Brain Modelling as a Service: The Virtual Brain on EBRAINS
Michael Schirner, Lia Domide, Dionysios Perdikis, Paul Triebkorn,...., Agnes Flöel, ...Jochen Mersmann, Viktor Jirsa, Petra Ritter
arXiv
Virtual deep brain stimulation: Multiscale co-simulation of a spiking basal ganglia model and a whole-brain mean field model with The Virtual Brain
Jil M. Meier, Dionysios Perdikis, André Blickensdörfer, Leon Stefanovski, Qin Liu, Oliver Maith, Helge Ü. Dinkelbach, Javier Baladron, Fred H. Hamker, Petra Ritter
bioRxiv (2021)
Inter-individual and age-dependent variability in simulated electric fields induced by conventional transcranial electrical stimulation
Daria Antonenko, Ulrike Grittner, Guilherme Saturnino, Till Nierhaus, Axel Thielscher, Agnes Flöel
NeuroImage. 224: 117413 (2021)
Neurolib: A simulation framework for whole-brain neural mass modeling
Caglar Cakan, Nikola Jajcay, Klaus Obermayer
Cogn Comput. 1158(31) (2021)
Cognitive training and brain stimulation in prodromal Alzheimer’s disease (AD-Stim)—study protocol for a doubleblind randomized controlled phase IIb (monocenter) trial
Friederike Thams, Anna Kuzmina, Malte Backhaus, Shu-Chen Li, Ulrike Grittner, Daria Antonenko and Agnes Flöel
Alzheimer’s Res Ther. 12(1):142 (2020)
Biophysically grounded mean-field models of neural populations under electrical stimulation
Caglar Cakan and Klaus Obermayer
PLoS Comput Biol. 16(4):e1007822 (2020)
Weight loss reduces head motion: re-visiting a major confound in neuroimaging
Frauke Beyer, Kristin Prehn, Katharina A Wüsten, Arno Villringer, Jürgen Ordemann, Agnes Flöel, A Veronica Witte
Hum Brain Mapping. 41(9):2490-2494 (2020)
Cross-reactivity as a mechanism linking infections in stroke
Guglielmo Lucchese, Agnes Flöel, Benjamin Stahl
Front Neurol. 10:469 (2019)