Biology subjects

Elsenbruch, S.

Publications and source records attributed to Elsenbruch, S..

3 recordsLinked to original sources

bioRxiv2025

The impact of contingency awareness on the neurocircuitry underlying pain-related fear and safety learning

Visceral pain-related fear, shaped by associative learning, drives maladaptive emotional reactions and may contribute to the chronicity of pain in disorders of gut-brain interaction. However, the role of contingency awareness remains unclear. In a translational model of pain-related conditioning, we investigated the brain-behavior relationships underlying contingency awareness in shaping the neural circuitry involved in visceral pain-related fear and safety learning. Data from 75 healthy individuals undergoing differential conditioning were acquired in two functional magnetic resonance imaging studies. Visceral pain as unconditioned stimulus (US) was paired with a visual cue as conditioned stimulus (CS+) while another cue (CS-) remained unpaired. Differential neural responses to predictive cues were analyzed using a full factorial model and regression analyses to evaluate the predictive value of neural activation patterns based on contingency awareness. Analyses revealed a significant interaction between CS-type and contingency awareness involving dorsolateral prefrontal cortex (dlPFC) and parahippocampus, driven by an enhanced CS+>CS- differentiation in highly aware participants. The reverse contrast revealed widespread activation in fronto-parietal and limbic networks, more pronounced in the highly aware group. Regression analyses showed that enhanced CS--related were associated with increased contingency awareness and CS- valence change, while no activation clusters predictive of behavioral responses were found for CS+. The recruitment of emotional arousal and executive control networks as a function of contingency awareness highlights its relevance in shaping pain- and, particularly, safety-predictive cue properties. These results suggest distinct processes for fear acquisition and inhibition, with significant implications for exposure-based treatments of disorders of gut-brain interaction.

neuroscience↗

bioRxiv2025

Deceptive safety? The impact of costly pain avoidance on the modulation and extinction of visceral pain-related fear

Along the gut-brain axis, visceral pain demonstrably evokes emotional learning and memory processes shaping behavior in clinically relevant ways. Avoidance motivated by learned fear may constitute a major obstacle to treatment success in extinction-based interventions. However, the effects of avoidance on visceral pain-related fear extinction remain poorly understood. By implementing an ecologically valid experimental protocol, we investigated how costly avoidance affects the modulation and extinction of visceral pain-related fear. Thirty-three healthy volunteers underwent conditioning with visual cues (conditioned stimuli; CS+,CS-) consistently followed by visceral pain or remaining unpaired. During avoidance, participants decided to avoid or receive pain upon confronting CS+. Avoidance decisions resulted in pain omission in some trials, while in others, participants experienced unpredictable pain. During extinction, CS were presented unpaired. CS valence, fear, and trial-by-trial decisions were analyzed. Avoidance decisions depended on prior experiences, with the highest probability of avoidance following successful pain omission. Negative CS+ valence and fear remained elevated across avoidance and extinction. Learned fear and more avoidance decisions explained 57% variance in sustained CS+ fear. Our findings indicate that avoidance, which provides short-term absence of pain even when followed by unpredictable pain, motivates its maintenance. However, it perpetuates pain-related fear and may impede extinction, with implications for persisting symptoms and therapeutic outcomes in chronic visceral pain.

neuroscience↗

bioRxiv2025

Predicting individual differences of fear and cognitive learning and extinction

The abilities to acquire new information and to modify previously learned knowledge are critical in an ever-changing world. However, the efficacy of learning is notably variable among individuals, with extinction learning being the epitome of such variability. Abundant studies have identified a core network of brain regions including amygdala, hippocampus, dorsal anterior cingulate cortex (ACC), ventromedial prefrontal cortex (PFC) and, more recently, the cerebellum, as key players in learning and extinction. Yet, the precise interactions within this network and their relationship to individual learning abilities and extinction have remained largely unexplored. In the present study, we examined how functional (FC), effective (EC), and structural (SC) connectivity patterns in the core learning network allow predicting individual differences in the efficacy of learning, extinction, and renewal. Analysing a large dataset of over 500 participants across a multitude of paradigms, our results revealed that FC predicted better acquisition, with a central role of ACC and hippocampus, whereas SC, involving ACC and amygdala, predicted higher levels of extinction learning. EC results suggested a predominantly inhibitory coupling among core learning network nodes, with paradigm-specific EC connectivity patterns predicting learning. Our predictions not only generalised between fear and cognitive predictive learning paradigms but were also successful in predicting learning from task-related FC and simulated data. Together, these results describe the multimodal neural determinants of learning, extinction, and renewal, and may inform individualised interventions for affective disorders based on neural connectivity patterns.

neuroscience↗