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

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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.