Understanding fundamental threat responses is crucial for improving therapeutic applications for various psychopathologies. Exploring their neural correlates offers a unique perspective on adaptive threat responses and their dysfunctions. This symposium examines fear learning, generalization, and extinction processes, highlighting their underlying neural mechanisms as well as the influence of contextual factors and psychopathologies. Specifically, Bierwirth et al. will present data on the neurophysiological correlates of prediction errors during the acquisition and extinction of fear memories. Stegmann et al. will address how aversive contexts impact visuocortical correlates of sustained attention during generalized threat, showing that competing attentional demands related to cue- and context-responses are segregated into different neural harmonics. Prantner et al. will explore the magnetoencephalographic correlates of a conditioning paradigm in patients with spider phobia compared to healthy controls, focusing on differential behavioral and neural processing in relation to the phobia relevance of the conditioned stimulus and fear generalization. Espino-Payá et al. will investigate the role of classical conditioning in tinnitus distress, demonstrating that tinnitus patients exhibit maladaptive aversive learning across both auditory and visual domains, along with evidence for an impaired auditory threat inhibition in prefrontal regions. Together, this symposium provides valuable insights into the neural mechanisms underlying defense behaviors and how they are influenced by contextual factors and individual differences. Additionally, it highlights the impact of dysfunctional threat processing on fear and anxiety, offering a deeper understanding of the mechanisms contributing to psychopathology and potential avenues for therapeutic intervention.

Recent evidence highlights the role of dopamine in fear extinction learning. More specifically, studies in rodents have shown that the unexpected omission of a threat during early extinction elicits a dopaminergic reward prediction error that drives fear extinction. Early human fMRI studies have also revealed a prominent role of prediction errors in dopamine-related brain regions during extinction learning. In the present study, we aimed to further elucidate the role of prediction errors in human fear extinction by leveraging the high temporal resolution of electroencephalography (EEG). We were primarily interested in the reward positivity (RewP) as a presumed proxy for dopaminergic prediction errors in humans.
To this end, we used a differential fear conditioning paradigm involving three conditioned stimuli (CS). To systematically manipulate threat expectancy, one CS+ was paired with the unconditioned stimulus (US) in 66% of fear acquisition trials (CS+66%; high expectancy), another CS+ was paired in 33% of trials (CS+33%; low expectancy), and one CS– was never paired with the US (CS–0%; no expectancy). All CSs were subsequently subjected to extinction learning. EEG was recorded throughout both phases, and single-trial expectancy ratings were collected.
As expected, preliminary analyses (n = 11/20) revealed strong prediction error signals at the behavioral level (i.e., expectancy ratings), particularly during early extinction learning. Importantly, this was accompanied by a significant enhancement of the RewP for both CS+ stimuli compared to the CS–. The final results of this ongoing study will be presented.

Adapting behavior to environmental demands is a fundamental aspect of survival. In the face of unfamiliar potential dangers, organisms display a wide range of defensive mechanisms, such as using contextual information to prepare for upcoming threats and extrapolating from previous experiences with similar encounters (threat generalization). However, detecting an imminent threat cue within an aversive context presents competing attentional demands: on one hand, vigilance is required to monitor the environment, while on the other, attention must be selectively focused on the threatening stimulus once detected. How these mechanisms interact remains poorly understood. Therefore, the current study aimed to orthogonally combine threat generalization with contextual information and measure correlates of defensive behavior on a subjective, autonomic, and electrocortical level. Fifty-two human participants completed a threat generalization paradigm followed by a context phase in which the conditioned cues were presented against aversive or neutral contexts, respectively. Results revealed successful threat generalization for subjective and pupillary responses, with overall heightened responses for cues presented in aversive compared to neutral contexts. For visuocortical activity, as measured by steady-state visually evoked potentials (ssVEPs), this response pattern was separated into different frequencies. While the fundamental frequency showed the general main effect of aversive contexts, the second harmonic followed a generalization gradient, suggesting a segregation of competing attentional demands via neural harmonics. Together, these findings provide new insights into adaptive defensive behavior in complex situations, characterized by an additive model of different defensive processes.

Specific phobias are among the most common anxiety disorders. As overgeneralization of fear is a pathogenic marker of anxiety disorders, we investigated its neurocognitive basis in patients with spider phobia and matched healthy controls. Using magnetoencephalography (MEG), we employed a differential conditioning paradigm utilizing phobia-relevant (images of a spider) and non-phobia-relevant (images of a screaming face) audiovisual unconditioned stimuli. Source reconstructions of event-related magnetic fields, as well as behavioral UCS-expectancy and fear ratings in response to CS+, CS-, and generalization stimuli (GS), were obtained. Behavioral results from a preliminary subsample (n = 50 persons per group) indicate equivalent discrimination performance for GS. However, patients rated all stimuli (CS+, GS1-7, CS-) within the phobia-relevant UCS-condition as more fear-evoking compared to healthy controls and the phobia-irrelevant UCS-condition. Additionally, there was some evidence for group-dependent generalization gradients; however, evidence regarding the influence of UCS-condition on this effect was inconclusive. Group-dependent generalization gradients were also found in parieto-occipital and fronto-temporal brain regions. Interestingly, influences of the UCS-condition on these gradients were revealed in similar regions. These preliminary results suggest that the effects of phobia-related unconditioned stimuli on fear generalization may be more pronounced at a neural level. A multimodal approach to studying the fear pathogenic mechanisms of generalization in specific phobias might be fruitful in future studies.

Tinnitus-related distress can be explained through classical conditioning, where the tinnitus sound becomes linked to an aversive emotional state, reinforcing a distress-perception loop. However, no previous research has investigated whether maladaptive aversive learning in tinnitus patients extends beyond auditory stimuli to involve other sensory modalities. We hypothesized that tinnitus patients would show increased aversive and diminished safety learning and overgeneralization to aversive conditioned stimuli in both the tinnitus-related auditory and the tinnitus-unrelated visual domain. We also expected a dysfunctional prefrontal activation. Tinnitus patients and healthy controls underwent an auditory and visual conditioning paradigm. In the auditory domain, low- and high-frequency tones (CS+) were paired with an aversive sound (US), while the other served as a safety signal (CS-). In the visual domain, high- and low-spatial frequency gratings followed the same conditioning procedure. Generalization stimuli (GS) spanning both modalities were presented before and after conditioning while neural responses were recorded via magnetoencephalography (MEG), alongside subjective threat ratings. Both groups exhibited generalization effects in their threat ratings, but MEG data revealed tinnitus-specific alterations. While early sensory activations aligned with expected generalization gradients, prefrontal regions (vmPFC, dlPFC) showed typical inhibitory patterns in controls but reversed activation in tinnitus patients, indicating dysfunctional threat regulation. These findings suggest that tinnitus patients experience maladaptive aversive learning across modalities, with dysregulated prefrontal activity contributing to heightened distress, further advancing our understanding of tinnitus-related neurophysiological mechanisms.