Predicting Dropouts of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Joint Modelling of Survival and Longitudinal Data.

Organisms form associations between environmental stimuli and outcomes, a process critical for adaptive behaviour and survival. Aversive conditioning—where a neutral stimulus acquires negative valence through pairing with an aversive event, and its subsequent suppression via extinction learning—form the cornerstone of emotional memory regulation. These processes support not only fundamental to learning but also central to understanding maladaptive responses in psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD). The conditioning-extinction paradigm, rooted in Pavlovian learning principles, provides a widely used framework to investigate these associative processes across species. In animal models, aversive conditioning is typically induced using unconditioned stimuli (US) such as foot shocks or loud auditory stimuli, while human studies often employ painful shocks, airpuffs, or visual/auditory stimuli. However, the salience of aversive US can confound interpretations of learning effects, as the observed responses may reflect general arousal rather than specific associative learning. Moreover, extinction is often interpreted as the weakening of conditioned responses, but it may instead involve the formation of new inhibitory memories that compete with the original association, complicating the distinction between unlearning and response suppression. These challenges are further compounded in real-world scenarios, where fear memories are often embedded in complex networks involving multiple stimuli and contextual cues. Nevertheless, the conditioning-extinction paradigm has revealed a distributed network supporting aversive learning and extinction, prominently involving the amygdala, hippocampus, insula, anterior cingulate cortex (ACC), and prefrontal cortex. Within this network, the amygdala and hippocampus are central to the neural circuits governing aversive learning and extinction. The amygdala encodes emotional salience and drives fear responses, while the hippocampus supports contextual memory and the flexible regulation of conditioned associations. Although these regions interact dynamically, the neural mechanisms underlying their coordination during aversive learning and extinction remain incompletely understood in humans, particularly at the level of fast-timescale neuronal oscillations.