Our Projects

(Project of the 2nd Cohort)

Adverse childhood experiences (ACEs) increase the risk for later mental health problems, including anxiety disorders. We propose that altered fear and reward learning - particularly blunted responses to threat cues - contribute to this vulnerability. We aim to inquire whether ACEs may be associated with reduced neural precision of threat encoding, leading to less stable representations of threat. We further hypothesize decreased neural coupling between the CS+ and US during acquisition, reflecting reduced transfer of US-based arousal. We suggest that such an impaired emotional tagging of the CS+ may ultimately result in diminished physiological and arousal-related responses to the CS+.

Associations between childhood maltreatment and responding to signals of threat and safety in a fear conditioning paradigm

(Project of the 1st Cohort)

In project A1, we aim to investigate how childhood adversity gets ‚under the skin‘ by investigating the neuro-physiological mechanisms underlying response differences to signals of threat and safety in individuals exposed and not exposed to early life adversity. To this end, we use state of the art functional and structural imaging in combination with defensive startle responding and measures of physiological arousal and endocrine stress responding (cortisol in hair and saliva) in a fear conditionig and generalization paradigm. Together with projects C1 and C2, we also follow a long-term perspective and assess symptom scores recurrently for a 72 month period to explore data driven subgroups and their link to responding in a fear conditioning paradigm in a large pooled sample.

(Project of the 2nd Cohort)

We commonly learn about dangers in our environment by interacting with it. Yet, it is unclear how instrumental learning shapes our memory of threats and what neurotransmitter systems regulate such emotional learning and memory. We aim to reveal how actions to avoid or escape threats influence emotional memories and if opioidergic receptors not only regulate passive, but also action-driven learning about threats.

Opioid regulation of the consolidation of conditioned fear

(Project of the 1st Cohort)

Emotional memories induce a complex neurotransmitter response that transforms labile learning experience into persistent memories. Project A2 aims to illuminate the underlying neuropsychopharmacological mechanisms how emotional memories become less persistent.
To this end, this project will conduct psychopharmacological, as well as neuropsychopharmacological fMRI experiments to examine the impact of the opioid and noradrenaline system on conditioned fear in humans.
This project is closely linked to other project that investigate noradrenergic arousal (B1, B2), stress (B2, B3), and the opioid system (A3), as well as fear conditioning in healthy and clinical populations (A1, C1, C2).

(Project of the 2nd Cohort)

Currently, two (contradictory) mechanisms have been proposed to explain how emotional learning and fear influence pain. Both agree that pain predictive cues induce fear and lead to generalization, but the first suggests that pain-predictive cues increase pain perception, while the second posits that these cues can activate a pain modulatory system, potentially reducing pain. We hypothesize that these mechanisms rely on different neural systems that can be disentangled using pharmacological fMRI, because the latter system relies on endogenous opioids. This is clinically highly relevant as it has been suggested that the opioid-based modulatory system is particularly compromised in chronic pain.

Representation of aversive cues predicting appetitive outcomes

(Project of the 1st Cohort)

In everyday life, there are many instances in which an aversive event predicts a positive outcome. Yet, how the prospect of a reward linked to a negatively valenced stimulus can change the responding to and representation of the aversive stimulus is unknown. This project aims to establish a classical conditioning paradigm in which a negatively valenced conditioned stimulus (CS) differentially predicts a positively valenced US. This paradigm in combination with computational modelling will allow us to investigate learning related effects at the autonomic (EDA) and neurobiological level (fMRI). With respect to model based fMRI, we will focus on multivariate methods such as representational similarity analysis5 to characterize dynamically changing representations of the CS as a function of learning.

We expect that the pairing with a reward will lead to a decrease of the unpleasantness rating and EDA response to the paired CS. With respect to multivariate neural representation of each CS, we expect them to differ initially in the insula and mPFC, but over time the representations of the aversive CSs in these regions should get more similar to the pattern evoked by the rewarding US. As previous studies have suggested a role of endogenous opioids in signaling hedonic aspects of reward, we expect that the pattern changes described above can be blocked by Naloxone.

(Project of the 2nd Cohort)

Fear extinction and safety learning form the foundation of exposure therapy, but their ability to predict exposure success remains insufficiently understood, and most studies focus primarily on symptom reduction rather than the underlying mechanisms. The aim of this project is to systematically assess behavioral, neural, and computational mechanisms of extinction and safety learning in the lab and test whether these predict similar processes measured during exposure therapy in real life. This approach has the potential to improve mechanistic insights, may identify predictive markers, and, may ultimately, pave the way for optimized treatment approaches.

Fear conditioning in obsessive-compulsive disorder, participants at risk and healthy controls

(Poject of the 1stCohort)

Project A4/C1 examines the role of fear and safety learning in the etiology of obsessive-compulsive disorder (OCD), a debilitating mental disorder characterized by intrusive thoughts and repetitive compulsions. We address the following questions: Are altered fear and safety learning the cause or the consequence of symptoms? Can we predict symptom development and disorder course from altered learning processes? What cognitive and neural mechanisms underlie observed changes in fear and safety learning?
To this end, we use EEG and peripheral physiological markers to examine fear learning and extinction in patients with OCD, participants at increased risk of developing OCD (unaffected relatives), and healthy participants. The predictive value of fear conditioning for symptom development is examined with recurrent follow-up measures of symptoms.

(Project of 2nd Cohort)

Resistance to contradicting evidence is a core feature of many fear-related pathological beliefs and is most striking in persecutory delusions. However, we lack a mechanistic learning-based account of why pathological beliefs are not updated even when a person is explicitly confronted with disconfirming evidence. The project addresses this gap by investigating the interaction of two potential mechanisms derived from Bayesian frameworks of belief updating: the formation of auxiliary hypotheses and the consistency of a newly learnt association with pre-existing beliefs.

Fear acquisition and extinction learning and transition to psychosis

(Poject of 1stCohort)

In project A5/C2 we aim to identify aberrancies in fear acquisition and extinction associated with psychotic liability. We will focus on participants with clinical high risk of psychosis and use an established differential fear conditioning paradigm in close collaboration with projects A1 and C1 and a novel fear conditioning paradigm, in which the unconditioned stimulus is aversive imagery. We will also test whether altered psychophysiological and neural (EEG) indicators of fear learning can be accounted for by baseline-differences in neurocognition, arousal and psycho-social vulnerability and whether they predict transition to DSM-5 psychotic disorder by a 72-month follow-up.

(Project of 2nd Cohort)

The brainstem systems controlling arousal state are transiently (“phasically”) activated by events that violate prior expectations. Arousal is clearly implicated in memory, but the current understanding of the impact of such phasic arousal boosts on memory mechanisms operating in the cerebral cortex is rudimentary. Here, we will test the causal effect of phasic arousal on the reactivation of cortical memory representations that is thought to be instrumental for both, memory consolidation and retrieval during memory-based decisions.

Control of memory formation and memory-based decision-making by brainstem arousal systems

(Project of 1st Cohort)

Mounting evidence points to a strong impact of brainstem arousal systems on memory mechanisms (encoding and recall) operating in the cerebral cortex. Unraveling this brainstem-cortical interplay is critical for advancing our understanding of healthy memory and of psychiatric disorders. In this project, we plan to uncover the causal effect of arousal signals from the brainstem on memory formation and memory-based decisions. This will be afforded by an integrated application of pupillometry, behavioral modeling, brainstem fMRI, and magnetoencephalography (MEG) in healthy human participants. We will use novel experimental designs to manipulate the responses of brainstem arousal systems, precisely in time, and quantify the effect on memory processes at a high level of mechanistic detail.

(Project of the 2nd Cohort)

Emerging research suggests that enhanced memory for emotionally-relevant events may be driven by prediction errors (PEs). However, the mechanisms underlying such PE-related memory enhancements—and their relevance for psychopathology—remain poorly understood. This project combines fMRI, EEG, and cognitive modeling with a sophisticated behavioral task to investigate how neural reactivation and replay processes contribute to PE-driven memory enhancement, with a particular focus on their role in obsessive-compulsive disorder (OCD). 

How stressful encounters bias memory for surrounding events

(Project of the 1st Cohort)

In project B2, we aim to elucidate the cognitive and neural mechanisms underlying stress-induced biases in the memory for events surrounding the stressful episode. To this end, we will combine, in healthy participants, a novel memory paradigm probing predictive coding-related changes in memory formation with an experimental stress manipulation, fMRI and state-of-the art multivariate analyses of human brain imaging data (e.g. representational similarity analysis). Further, this project will include pupillometry as well as autonomic and endocrine stress response measurements.

(Project of 2nd Cohort)

Beyond its established role in memory consolidation and retrieval of single events, acute stress may also influence memory flexibility, as reflected in the mnemonic integration of initially distinct events. While the clinical relevance of stress effects on memory flexibility is generally assumed, direct evidence supporting this remains scarce, and the underlying mechanisms are poorly understood. Using a multidisciplinary approach including fMRI, EEG, pharmacological manipulations, chemogenetics and optogenetics alongside sophisticated behavioral tasks, project B3 investigates the neural and cognitive mechanisms by which stress impacts memory flexibility in humans and rodents and explores the clinical relevance of these effects within a population at high-risk for schizophrenia.    

Linking memories under stress

(Project of the 1st Cohort)

Project B3 will examine how and through which mechanisms acute stress may affect the linking of overlapping events. For this purpose, we will employ an associative inference task, in combination with an established experimental stress induction, fMRI and multivarite pattern classification. This project will be conducted in close collaboration with colleagues from the Donders Insitute of Brain, Cognition and Behaviour (Nijmegen, The Netherlands) and the University of Texas at Austin.

(Project of 2nd Cohort)

PTSD is a major psychiatric disorder possibly emerging after traumatic events with a substantial risk for chronicity. A preventive intervention just after a traumatic experience which could dampen symptom development would be a game changer in the treatment of mental disorders. Animal experiments and clinical studies in healthy subjects indicate a possible benefit of sleep deprivation in symptom prevention after experimental traumatization. Within the scientific framework of the RTG, a controlled study with healthy subjects undergoing an experimental trauma was developed to investigate the effect of repeated retrieval of the emotional traumatic memory just after the trauma and sleep deprivation in the night after the trauma onto MRI assessed neuronal signatures and symptoms of PTSD (e.g. intrusions) in the subsequent week. The results of this study will be used to design an intervention for subjects who experienced a real-world trauma to prevent the subsequent development of symptoms of PTSD. Knowledge about the biological mechanisms of the emergence of PTSD would foster the understanding of normal and abnormal memory formation and emotion regulation in the RTG and inspire future therapeutic strategies.

Systematic Training of Cognitive Processes in Patients with Posttraumatic Stress Disorder (PTSD)

(Project of 1st Cohort)

In project B4/C3, we aim to study cognitive processes in patients with PTSD. We will develop and systematically test a video-game based training intervention in a clinical sample by use of a pre-post-test design. Behavioural and structural as well as functional magnetic resonance imaging assessments will be done before and after a six-week training period. Two clinical follow-ups will be conducted after six and twelve months to investigate the training effects in comparison to a control group.

(Project of 2ndCohort)

Stress, sleep, and environmental factors are key modulators of cognitive performance. However, their combined effects on episodic memory in real-world settings remain underexplored. While most research relies on single measurements conducted in laboratory settings, this project uses an ecological momentary assessment approach to capture memory performance, perceived stress, sleep quality, and environmental exposure (e.g., air quality, noise, light) in daily life. In a day-to-day design, participants complete 15-20 repeated sessions over 2-3 months. This allows us to assess intraindividual variability in brain structure and function alongside fluctuations in memory, stress, sleep, and environmental exposure.

Effects of stress on event memory in everyday life in healthy and (sub)clinical populations

(Project of the 1st Cohort)

Within the scope of B5/C4 we aim to understand how stress can alter memory processes and whether exposure to nature can buffer these effects. We plan to conduct a laboratory functional MRI study using a scene encoding task where we vary the content of nature depicted in the stimulus material and the timepoint of the administration of the stressor. Moreover an ecological momentary assessment (EMA) study will be conducted where stressors will be applied via a smartphone and photos will be taken in the daily life of participants to test, whether the effects observed in the laboratory study extend into real life.