Neurobiology of context-dependent extinction learning: modulation by multiple extinction contexts and cortisol

虽然认知行为疗法构成了治疗焦虑症的一种很有前途的可能性，但经常可以观察到复发和恐惧的复发。在将已取得的成功推广到治疗背景之外的情况方面遇到困难，在这一框架内发挥着重要作用。类似于恐惧的回归，许多动物和人类在恐惧条件反射的背景下进行的实验表明，与灭绝背景相比，使用新的、不熟悉的空间背景会导致在灭绝回忆过程中增强条件恐惧的回归。这种所谓的条件性恐惧的更新是在神经元水平上进行的，特别是在海马体介导的过程中。为了在临床环境中减少恐惧的回归，开发减少上下文依赖更新的干预措施具有重大意义。以前的研究发现，在学习灭绝的过程中使用多个语境提供了一种很有希望的可能性。进一步的研究指出皮质醇对于减少上下文依赖(海马体介导的)学习的重要性。但到目前为止，人们对这些干预措施背后的神经机制知之甚少，甚至一无所知，这些干预措施调节了上下文相关的消亡学习。这个联合研究项目的目的是研究多种环境和皮质醇对皮肤和神经元水平上的更新过程的调节。在两个功能磁共振断层扫描研究中，将探索使用多个背景与只使用一个消退背景(研究1)以及使用皮质醇(30毫克氢化可的松)与安慰剂(研究2)相比，对灭绝回忆过程中条件性电皮肤和神经元反应更新的影响。我们假设，由于海马体介导的神经过程的调节，多个消亡背景以及皮质醇将导致在新的和不熟悉的背景下更新的减少。此外，我们的目标是确定与更新的个体差异和更新的调节相关的潜在因素(例如，海马体体积)。这些研究的结果可能会对更好地理解新环境下治疗成功的神经生物学基础做出重大贡献。从长远来看，更好地了解相关的影响因素和潜在的(神经元)过程将有助于优化现有的干预措施，并制定新的关于灭绝泛化的干预措施。

Although cognitive behavioral therapy constitutes a prosperous possibility to treat anxiety disorders, relapses with a return of fear are often observed. Difficulties in the generalization of achieved successes to situations outside of the therapy context play an important role within this framework. Analogous to this return of fear, numerous animal and human experiments in the context of fear conditioning have shown that the use of a new, unfamiliar spatial context compared to the extinction context leads to an enhanced return of conditioned fear during extinction recall. This so-called renewal of conditioned fear is on the neuronal level particularly represented in hippocampus mediated processes. To the end that the return of fear should be reduced in clinical settings, the development of interventions that decrease context-dependent renewal carries great weight. Previous studies found that the use of multiple contexts during extinction learning provides a promising possibility. Further studies point to the importance of cortisol for the reduction of context-dependent (hippocampus mediated) learning. But to date, only little to nothing is known about the neuronal mechanisms underlying these interventions that modulate context-dependent extinction learning. The aim of this combined research project is to investigate the modulation of renewal processes by multiple contexts and cortisol on the electrodermal and the neuronal level. In two functional magnetic resonance tomography studies, the influence of the use of multiple contexts compared to only one extinction context (study 1) as well as the administration of cortisol (30mg hydrocortisone) compared to placebo (study 2) on the renewal of conditioned electrodermal and neuronal reactions during extinction recall will be explored. We hypothesize that multiple extinction contexts as well as cortisol will lead to a reduction of renewal in a new and unfamiliar context due to the modulation of hippocampus mediated neuronal processes. Besides, we are aiming at identifying potential factors (e.g. hippocampal volume) related to individual differences in renewal and the modulation of renewal. The results of these studies could make a major contribution to a better understanding of the neurobiological basis underlying the generalization of therapy success to new contexts. In the long run, a better knowledge of relevant influential factors and of underlying (neuronal) processes will contribute to the optimization of existing and the development of new interventions concerning the generalization of extinction.