Poster No:
732
Submission Type:
Abstract Submission
Authors:
Isabelle Ridderbusch1, Adrian Wroblewski1, Yunbo Yang2, Hans-Ulrich Wittchen3, Andre Pittig4, Andreas Ströhle5, Jennifer Mumm6, Alfons Hamm7, Jan Richter2, Maike Hollandt7, Christoph Szeska8, Martin Lotze7, Volker Arolt9, Udo Dannlowski9, Katja Koelkebeck10, Dirk Adolph11, Jürgen Margraf11, Silvia Schneider11, Jan Cwik12, Jürgen Deckert13, Katharina Domschke14, Martin Herrmann13, Ulrike Lueken15, Ricarda Evens15, Constantin Rothkopf16, Winfried Rief1, Tilo Kircher1, Benjamin Straube1
Institutions:
1University of Marburg, Marburg, Germany, 2University of Hildesheim, Hildesheim, Germany, 3University of Dresden, Dresden, Germany, 4University of Goettingen, Goettingen, Germany, 5Charité Berlin, Berlin, Germany, 6Freie Universität Berlin, Berlin, Germany, 7University of Greifswald, Greifswald, Germany, 8University of Potsdam, Potsdam, Germany, 9University of Münster, Münster, Germany, 10University of Duisburg-Essen, Essen, Germany, 11University of Bochum, Bochum, Germany, 12University of Cologne, Cologne, Germany, 13University of Würzburg, Würzburg, Germany, 14University of Freiburg, Freiburg, Germany, 15Humboldt Universität zu Berlin, Berlin, Germany, 16University of Darmstadt, Darmstadt, Germany
First Author:
Co-Author(s):
Yunbo Yang
University of Hildesheim
Hildesheim, Germany
Alfons Hamm
University of Greifswald
Greifswald, Germany
Jan Richter
University of Hildesheim
Hildesheim, Germany
Jan Cwik
University of Cologne
Cologne, Germany
Introduction:
Fear extinction is learning that a prior threat signal no longer indicates danger. An essential aspect of extinction learning is the violation of an expected outcome, in the context of fear specifically the expectation of an upcoming aversive event. This is experimentally operationalized via extinction training: a CS+ (conditioned stimulus, previously paired with an aversive stimulus) is repeatedly presented without an US (unconditioned aversive stimulus). A meta-analysis on neural correlates of fear extinction showed consistent brain activation in the cingulate cortex and insula in the overall CS+>CS- comparison in healthy subjects (HS) [1]. However, fMRI studies typically do not distinguish between expectation (EXP) and its violation (VIO) during CS-presentations. To close this knowledge gap, here we analyzed the beginning of CS-presentation (where the EXP of US/no US is set), separate from the timepoint at which the US would be present during conditioning (VIO) to investigate the following questions:
1) How does neural activation differ between the EXP of a potential aversive event and the VIO of this expectation? 2) Is there an interaction between CS-type and EXP vs. VIO?
Methods:
We used an optimized protocol of delayed extinction training [2]: For fear conditioning, one of two neutral visual stimuli (CS+) was followed (5 seconds after stimulus start) by an aversive electric US (electric stimulus, 60% reinforcement rate) while the other stimulus (CS˗) was never paired with the US. The US was applied by an MRI compatible electrodermal electrode attached to the inside of the non-dominant forearm. 24h later, uninstructed extinction over 20 trials was tested during functional magnetic resonance imaging (fMRI). Time courses of subjects' brain activity were acquired using 3-Tesla MR scanners equipped with a 12-channel head matrix receive coils. Functional images were obtained using a T2-weighted gradient-echo echo-planar imaging (EPI) sequence sensitive for the BOLD contrast (TE=30ms, TR=2s, flip angle 90°, matrix size 64×64 voxels, voxel size 3.6×3.6×4.0mm, slice thickness 4mm, inter-slice gap 0.4mm, field of view (FOV)=230mm, 33 slices, ascending phase encoding direction) [3]. A Family-wise error (FWE) correction was used. Quality controlled data-sets of n=103 HS from five sites in Germany were included.
Results:
1) Differential activation between the overall EXP and VIO during the full course of the experiment was found: activation in the MCC and anterior insula was higher during EXP, in the basal ganglia (nucleus caudate, putamen, pallidum), thalamus, middle frontal and temporal cortices activation was higher during VIO.
2) An Interaction between stimulus type (CS+ vs. CS-) and the EXP vs. VIO phase of the stimulus presentations was found in the inferior frontal gyrus, supramarginal gyrus and cerebellum, suggesting that EXP and VIO provide complementary information about neural processing of fear and safety signals. Separate post-hoc analyses for EXP and VIO respectively on CS-type associated differences revealed higher activation in the middle cingulate cortex, nucleus caudate and in the anterior insula towards CS+ than towards CS- during EXP, whereas in the paracentral lobule it was higher towards CS . During VIO, activation in the basal ganglia, the anterior cingulate cortex, the inferior frontal cortex including the anterior insula and in temporal areas and the cerebellum was higher towards CS+ than towards CS-, whereas in the medial orbitofrontal cortex and gyrus rectus it was higher towards CS-.
Conclusions:
Our findings suggest that the differentiation between EXP an VIO phase of CS-presentation provides useful additional information about extinction learning processes on the neural level. This finer strategy of analysis holds the potential to possibly better detect and understand altered processes in patients with anxiety disorders compared to HS in future analyses.
Emotion, Motivation and Social Neuroscience:
Emotional Learning 1
Learning and Memory:
Learning and Memory Other
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Keywords:
ADULTS
Anxiety
Basal Ganglia
Design and Analysis
FUNCTIONAL MRI
Learning
Memory
NORMAL HUMAN
Other - Extinction Learning; Expectation and Violation
1|2Indicates the priority used for review
Provide references using author date format
[1] Fullana, M.A., Albajes, A. et al. (2018), ‘Fear extinction in the human brain: a meta-analysis of fMRI studies in healthy participants’, Neurosci. Biobehav. Rev., vol. 88, pp. 16-25.
[2] Hollandt, M., Wroblewski, A., et al. (2020), ‘Facilitating translational science in anxiety disorders by adjusting extinction training in the laboratory to exposure-based therapy procedures’, Transl. Psychiatry, vol. 10, p. 110.
[3] Ridderbusch, I. C., Wroblewski, A., et al. (2021), ‘Neural adaptation of cingulate and insular activity during delayed fear extinction: A replicable pattern across assessment sites and repeated measurements’, NeuroImage, vol. 237, pp. 118157.