Systematic investigation of the experimental boundary conditions and mechanisms contributing to reinstatement of fear in humans.
Human Cognitive and Systems Neuroscience
Final Report Abstract
Relapse after successful psychological or pharmacological treatment represents a major problem in the treatment of anxiety patients. Relapse, or in other words, return of fear (ROF), can be triggered by the mere passage of time (spontaneous recovery), induction of contextual change (renewal) or by exposure to unsignaled USs (reinstatement). Reinstatement has been described in rodents decades ago, but human research has just begun. In the recent years a continuous increases in the use of reinstatement has been observed e.g as the critical outcome test in fear conditioning studies investigating long-term recall in the reconsolidation literature. More specifically, out of twenty reinstatement studies published to date in humans, only eight have been published before the year 2012. A major problem here is that experimental details, data analyses and consequently results vary widely as no systematic investigation of the experimental boundary conditions and mechanisms contributing to reinstatement in humans have been conducted to date. It thus remains unclear whether the results of the early rodent work can be translated to humans and the project aimed to fill this gap by 1) establishing thee experimental, in particular contextual, boundary conditions contributing to reinstatement in humans 2) exploring the mechanisms (e.g. mediated conditioning, context conditioning, non-associative processes) and 3) exploring the neural underpinnings mediating reinstatement in humans. Our results show that generally, the design of an experiment that specifically targets the reinstatement phenomen in humans – as we know it from rodents – is more difficult than anticipated. We do observe comparable (generalized, i.e., CS-unspecific) return of fear in both groups intended to trigger context conditioning (AAAB) and mediated (AABB) conditioning respectively. Both experimental groups also show response enhancement beyond response enhancement in the control groups in startle but not in skin conductance responding and fear ratings. Furthermore, a group exposed to a novel context during reinstatement shock administration (AABA) showed comparable response enhancement to a group in which the test context was identical to the reinstatement administration context (AABA vs. AABB). Yet, also the AABB control group showed response enhancement in fear ratings – particular the CS-, providing some evidence of context conditioning transferring to CS responding. We also illustrate a number of additional potential boundary conditions such as the number of reinstatement shocks administered as well as other findings from extensive piloting such as that triggered responses (i.e., startle probes) impact on the process under study. In addition we report on individual differences in fear acquisition which was found to be associated with trait anxiety levels – which however renders the interpretation of individual diffrences in subsequent experimental phases more complex. Lastly, we illustrate in a within-subject design with 2 CS+s and 2 CS-s, that response enhancement to the CS+ occurs specifically when the respective context associate presented during reinstatement shock administration and test was not extinguished previously. This was on a neural level mirrored in differential hippocampus activation, matching our previous work on the neural undeprinnings of reinstatement induced return of fear in humans. The results of this project might contribute to the understanding of divergent previous findings and pave the way to a more standardized and optimzed experimental approach. Having established this will finally allow us to systematically investigate individual and biological differences (e.g. through pharmacological interventions) in reinstatement. Ultimately, a better understanding of the circumstances facilitating or attenuating reinstatement in experimental protocols may aid our understanding of clinical relapse and thus might ultimately help to improve cognitive-behavioural treatment procedures.
Publications
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Experimental boundary conditions of reinstatement induced return of fear in humans: Is reinstatement in humans what we think it is?
Sjouwerman, Rachel, & Lonsdorf, Tina B.
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(2015). Contextual Change After Fear Acquisition Affects Conditioned Responding and the Time Course of Extinction Learning— Implications for Renewal Research. Frontiers in Behavioral Neuroscience, 337
Sjouwerman, Rachel, Niehaus, Johanna, & Lonsdorf, Tina B.
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(2016). Don’t startle me-Interference of startle probe presentations and intermittent ratings with fear acquisition. Psychophysiology, 53(12), 1889–1899
Sjouwerman, Rachel, Niehaus, Johanna, Kuhn, Manuel, & Lonsdorf, Tina B.
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(2018). Individual differences in fear learning: Specificity to trait-anxiety beyond other measures of negative affect, and mediation via amygdala activation
Sjouwerman, Rachel, Scharfenort, Robert, & Lonsdorf, Tina B.
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(2019). How to not get lost in the garden of forking paths: Lessons learned from human fear conditioning research regarding exclusion criteria
Lonsdorf, Lonsdorf, T. B., Klingelhöfer-Jens, M., Andreatta, M., Beckers, T., Chalkia, A., Gerlicher, A., … Merz, C. J.
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(2019). Latency of skin conductance responses across stimulus modalities. Psychophysiology, 56(4), e13307
Sjouwerman, Rachel, & Lonsdorf, Tina B.
