Systematic investigation of the experimental boundary conditions and mechanisms contributing to reinstatement of fear in humans.

成功的心理或药物治疗后复发是治疗焦虑症患者的主要问题。复发，或者换句话说，恐惧的回归（ROF），可以由时间的流逝（自发恢复），情境变化的诱导（更新）或暴露于无信号的US（恢复）引发。几十年前，在啮齿动物中就已经描述了恢复，但人类的研究才刚刚开始。近年来，人们观察到复原的使用持续增加，例如，在再巩固文献中，恐惧条件反射研究调查长期回忆的关键结果测试。更具体地说，在迄今为止发表的20项人类恢复研究中，只有8项在2012年之前发表。这里的一个主要问题是，实验的细节，数据分析和结果差异很大，因为没有系统的研究实验的边界条件和机制，有助于恢复在人类已经进行了。因此，目前尚不清楚早期啮齿动物工作的结果是否可以转化为人类。由于这使得对研究结果的比较和解释难以确定日期，本项目旨在1）建立这些实验，特别是背景，有助于人类恢复的边界条件2）探索机制（例如介导条件反射，背景条件反射，非联想过程）和3）探索人类介导恢复的神经基础。该项目的结果可能有助于理解以前的不同发现（例如，差异与广义恢复），并为更标准化的实验方法铺平道路。建立这一点将最终使我们能够系统地研究个体和生物学差异（例如通过药物干预或遗传多态性）。最后，更好地了解实验方案中促进或减弱恢复的情况可能有助于我们理解临床复发，从而最终有助于改善认知行为治疗程序。

Relapse after successful psychological or pharmacological treatment represents a major problem in the treatment of anxiety patients. Relapse, or in other words, return of fear (ROF), can be triggered by the mere passage of time (spontaneous recovery), induction of contextual change (renewal) or by exposure to unsignaled USs (reinstatement). Reinstatement has been described in rodents decades ago, but human research has just begun. In the recent years a continuous increases in the use of reinstatement has been observed e.g as the critical outcome test in fear conditioning studies investigating long-term recall in the reconsolidation literature. More specifically, out of twenty reinstatement studies published to date in humans, only eight have been published before the year 2012. A major problem here is that experimental details, data analyses and consequently results vary widely as no systematic investigation of the experimental boundary conditions and mechanisms contributing to reinstatement in humans have been conducted to date. It thus remains unclear whether the results of the early rodent work can be translated to humans. As this renders comparisons and interpretation of the findings difficult to date, this project aims at 1) establishing these experimental, in particular contextual, boundary conditions contributing to reinstatement in humans 2) exploring the mechanisms (e.g. mediated conditioning, context conditioning, non-associative processes) and 3) exploring the neural underpinnings mediating reinstatement in humans. The results of this project might contribute to the understanding of divergent previous findings (e.g. differential vs. generalized reinstatement) and pave the way to a more standardized experimental approach. Having established this will finally allow us to systematically investigate individual and biological differences (e.g. through pharmacological interventions or genetic polymorphisms) in reinstatement. Ultimately, a better understanding of the circumstances facilitating or attenuating reinstatement in experimental protocols may aid our understanding of clinical relapse and thus might ultimately help to improve cognitive-behavioural treatment procedures.