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Distributed fear learning systems in the human brain

Applicant Bach Dominik
Number 149586
Funding scheme Project funding (Div. I-III)
Research institution Psychiatrische Universitätsklinik Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurophysiology and Brain Research
Start/End 01.09.2014 - 31.10.2017
Approved amount 337'000.00
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All Disciplines (2)

Discipline
Neurophysiology and Brain Research
Neurology, Psychiatry

Keywords (5)

Functional magnetic resonance imaging; Transcranial magnetic stimulation; Multivariate ; Fear conditioning; Fear memory

Lay Summary (German)

Lead
Die Vorhersage von drohender Gefahr ist eine fundamentale Überlebensstrategie für viele Organismen. In diesem Projekt wird untersucht, wie der Zusammenhang zwischen komplexen Prädiktoren und Gefahr im Gehirn verankert wird.
Lay summary

Alle Säugetiere und viele einfachere Organismen können lernen, Gefahr aus bestimmten Prädiktoren vorherzusagen und sie zu vermeiden. Beim Menschen vermutet man, dass fehlgeleitetes Lernen zu überschiessender Furcht führt - zum Beispiel bei spezifischen Phobien. Das Pavlovsche Furchtkonditionieren ist eine typische Anordnung, um solche Lernvorgänge zu untersuchen. Gängige Theorien gehen davon aus, dass der Zusammenhang zwischen Prädiktor und droheneder Gefahr in einem einzigen Gehirnbereich abgespeichert wird - dem Mandelkern (Amygdala). Die dem zugrunde liegenden Untersuchungen benutzen jedoch grösstenteils sehr simple Prädiktoren. Neuere Tieruntersuchungen legen nahe, dass sich bei komplexere Prädiktoren das Lernen über mehrere Hirnareale verteilt. In diesem Projekt wird am Menschen untersucht, in welchem Mass Lernvorgänge von der Komplexität der Prädiktoren abhängig sind. Dabei benutzen wir funktionelle Kernspintomographie und transcranielle Magnetstimulation. Dieses Projekt kann dabei helfen, Lernvorgänge unter realistischen Bedingungen zu untersuchen, und leistet damit einen Beitrag zum besseren Verständnis von Furchterkrankungen.

Direct link to Lay Summary Last update: 21.03.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
High‐precision magnetoencephalography for reconstructing amygdalar and hippocampal oscillations during prediction of safety and threat
Tzovara Athina, Meyer Sofie S., Bonaiuto James J., Abivardi Aslan, Dolan Raymond J., Barnes Gareth R., Bach Dominik R. (2019), High‐precision magnetoencephalography for reconstructing amygdalar and hippocampal oscillations during prediction of safety and threat, in Human Brain Mapping, 40(14), 4114-4129.
Human Pavlovian fear conditioning conforms to probabilistic learning
Tzovara Athina, Korn Christoph W., Bach Dominik R. (2018), Human Pavlovian fear conditioning conforms to probabilistic learning, in PLOS Computational Biology, 14(8), e1006243-e1006243.
Stimulus-invariant auditory cortex threat encoding during fear conditioning with simple and complex sounds.
Staib Matthias, Bach Dominik R (2017), Stimulus-invariant auditory cortex threat encoding during fear conditioning with simple and complex sounds., in NeuroImage, 166, 276-284.
Testing a linear time invariant model for skin conductance responses by intraneural recording and stimulation.
Gerster Samuel, Namer Barbara, Elam Mikael, Bach Dominik R (2017), Testing a linear time invariant model for skin conductance responses by intraneural recording and stimulation., in Psychophysiology.
Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline.
Bach D R, Tzovara A, Vunder J (2017), Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline., in Molecular psychiatry.
A pupil size response model to assess fear learning.
Korn Christoph W, Staib Matthias, Tzovara Athina, Castegnetti Giuseppe, Bach Dominik R (2017), A pupil size response model to assess fear learning., in Psychophysiology, 54(3), 330-343.
Assessing fear learning via conditioned respiratory amplitude responses.
Castegnetti Giuseppe, Tzovara Athina, Staib Matthias, Gerster Samuel, Bach Dominik R (2017), Assessing fear learning via conditioned respiratory amplitude responses., in Psychophysiology, 54(2), 215-223.
Modeling startle eyeblink electromyogram to assess fear learning.
Khemka Saurabh, Tzovara Athina, Gerster Samuel, Quednow Boris B, Bach Dominik R (2017), Modeling startle eyeblink electromyogram to assess fear learning., in Psychophysiology, 54(2), 204-214.
A solid frame for the window on cognition: Modeling event-related pupil responses.
Korn Christoph W, Bach Dominik R (2016), A solid frame for the window on cognition: Modeling event-related pupil responses., in Journal of vision, 16(3), 28-28.
A linear model for event-related respiration responses.
Bach Dominik R, Gerster Samuel, Tzovara Athina, Castegnetti Giuseppe (2016), A linear model for event-related respiration responses., in Journal of neuroscience methods, 270, 147-55.
Modeling event-related heart period responses.
Paulus Philipp C, Castegnetti Giuseppe, Bach Dominik R (2016), Modeling event-related heart period responses., in Psychophysiology, 53(6), 837-46.
Modeling fear-conditioned bradycardia in humans.
Castegnetti Giuseppe, Tzovara Athina, Staib Matthias, Paulus Philipp C, Hofer Nicolas, Bach Dominik R (2016), Modeling fear-conditioned bradycardia in humans., in Psychophysiology, 53(6), 930-9.
Optimising a model-based approach to inferring fear learning from skin conductance responses.
Staib Matthias, Castegnetti Giuseppe, Bach Dominik R (2015), Optimising a model-based approach to inferring fear learning from skin conductance responses., in Journal of neuroscience methods, 255, 131-8.
A matching pursuit algorithm for inferring tonic sympathetic arousal from spontaneous skin conductance fluctuations.
Bach Dominik R, Staib Matthias (2015), A matching pursuit algorithm for inferring tonic sympathetic arousal from spontaneous skin conductance fluctuations., in Psychophysiology, 52(8), 1106-12.

Collaboration

Group / person Country
Types of collaboration
Prof. Christian Ruff, SNSlab, Department of Economics, University of Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Wellcome Trust Centre for Neuroimaging, University College London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Awards

Title Year
Robert-Bing-Preis der Schweizerischen Akademie für Medizinische Wissenschaften 2018
Advanced PostDoc Mobility Fellowship 2017
Pfizer Forschungspreis Klinische Neurowissenschaften 2018 2017
International Short Visits Award (2017) 2016

Associated projects

Number Title Start Funding scheme
168980 Neural oscillations during perception of threat in humans 01.06.2016 International short research visits

Abstract

Learning to predict danger is a fundamental adaptive strategy for most animal organisms. Missing a source of danger might imply death. On the other hand, false alarms - predicting danger when there is none - wastes valuable resources necessary for survival, and is often thought to underlie human psychiatric conditions such as phobias, generalized anxiety, posttraumatic stress disorder, and even depression. Hence, research into this area is of interest both for a basic understanding of the brain and for clinical application. Pavlovian delay fear conditioning (DFC) is a translational paradigm for the comparative study of aversive learning. Most research suggests that during DFC, the association between a simple predictive cue - conditioned stimulus, CS - and an aversive event - unconditioned stimulus, US - is formed in the amygdala. However, in the last decade, cortical plasticity in this model has received renewed interest and might account for some features of DFC that have not yet been explained. Crucially, these data suggest that learning mechanisms might be different for the very simple paradigms commonly used in animal assays, and more complex tasks, which are probably more relevant to psychiatric disorder. As yet, this has only been assessed in rodents, and replication in primate species is lacking. Importantly, recent research has suggested possible species differences in the representation of fear memory between rodents and primates; at present this claim has neither been refuted nor substantiated, warranting further cross-species research. In the current project, I propose to revisit the question of cortical plasticity, long-term fear memory storage, and CS/US-interval (trace fear conditioning) in humans, using a combination of high-resolution functional magnetic resonance imaging with multivariate pattern analysis, as well as transcranial magnetic stimulation. The project will investigate to which extent CS complexity determines whether cortical pre-processing and/or plasticity are necessary for DFC, whether amygdala-based fear memories are reconfigured after training, and at which time point during training the amygdala and hippocampus are required for fear memory. The project is based on animal work, but capitalises on state-of-the art research methods in humans in order to assess how animal concepts can be generalised across species boundaries, and to furnish possible application to psychiatric disorder.
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