Cognitive bias during associative threat and safety learning: Neurophysiological markers and possible interventions

焦虑症可以通过暴露疗法成功治疗，但从长远来看，并非所有患者都能从中获益。目前的荟萃分析表明，焦虑症患者在安全学习方面存在困难。也就是说，威胁被高估了，对与威胁无关的刺激的恐惧反应被增强了。这种损伤使暴露疗法复杂化，在暴露疗法中，患者面对安全但害怕的刺激。根据目前的考虑，暴露疗法的成功关键取决于认知过程，特别是期望违反。这个项目的目的是找出这些关键的认知过程何时发生，哪些大脑区域参与其中，以及我们如何调节它们，从而改善焦虑症的治疗效果。假设成功的安全学习依赖于对安全后果的注意加工，并且注意分配对安全学习和对其他刺激的恐惧泛化有有益的影响。为了尽可能全面地理解这些过程，我们将从多个层面（记忆、评分、神经生理学、外周生理学）对这些过程进行测量。为此，首先，随后的记忆范式将用于找出哪些电生理电位预测，一个人是否能记住某些中性刺激与威胁有关，而其他中性刺激与威胁的遗漏有关的事实。我们认为，特别是P3到忽略威胁可以预测成功的安全学习。在另一项实验中，我们将探讨恐慌障碍患者在联想威胁学习及其对其他刺激的推广过程中，这些神经生理反应是否减少，这可能是安全学习缺陷的一个解释。为了测试这种认知过程的因果影响，将进一步研究对威胁的注意分配是否有效。对威胁省略的影响，会对联想威胁学习、对其他刺激的泛化和P3产生影响。最后，借助功能磁共振成像，分析在忽略威胁时哪些脑区被激活，哪些脑区预示着安全学习的成功。这些见解将拓宽我们对成功的安全学习及其潜在神经关联的理解。此外，实验将有助于制定简单的认知策略，旨在提高安全学习。

Anxiety disorders can be treated successfully with exposure therapy, but not all patients profit on the long run. Current meta-analyses suggest that patients with anxiety disorders have difficulties in safety learning. That is, threat is overestimated and fear responding is enhanced towards stimuli which are not associated with threat. This impairment complicates exposure therapy, in which patients are confronted with safe but feared stimuli. According to current considerations, the success of exposure therapy depends crucially on cognitive processes, especially on expectancy violations. The aim of this project is to find out when these crucial cognitive processes take place, which brain regions are involved and how we can modulate them in a way that will improve therapy outcome for anxiety disorders. It is hypothesized that successful safety learning depends on the attentional processing of safe consequences, and that attentional allocation can have a beneficial influence on safety learning and on the generalization of fear to other stimuli. In order to understand these processes as comprehensively as possible, they will be measured on multiple levels (memory, ratings, neurophysiology, peripheral physiology). To this end, first, the subsequent memory paradigm will be used to find out which electrophysiological potentials predict, whether one can remember the fact that certain neutral stimuli are associated with threat, while others are associated with the omission of threat. It is assumed that especially the P3 to the omission of threat will predict successful safety learning. In another experiment, it will be investigated whether these neurophysiological responses are reduced in patients with panic disorder during associative threat learning and its generalization to other stimuli, which would be an explanation for deficient safety learning. In order to test the causal impact of such cognitive processes, it will be further examined whether the allocation of attention on threat, resp. on the omission of threat, will have an influence on associative threat learning, on its generalization to other stimuli and on the P3. Finally, with the help of functional magnetic resonance imaging, it will be analyzed, which brain regions are activated during the omission of threat and which predict successful safety learning. These insights will broaden our understanding of successful safety learning and its underlying neural correlates. Moreover, the experiments will help to develop simple cognitive strategies aiming at the improvement of safety learning.