@phdthesis{Klinke2022,
  author    = {Klinke, Christopher Matthias},
  title     = {Experimental investigation of the effect of distal stress induction on threat conditioning in humans},
  doi       = {10.25972/OPUS-22556},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225562},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Stress constitutes a major risk factor for the development of psychiatric disorders, such as PTSD and anxiety disorders, by shifting the brain into a state of sensitization and makes it more vulnerable when being exposed to further aversive events. This was experimentally in-vestigated in rodents by examining the effect of a distal stress induction on threat conditioning, where stress impaired extinction learning and caused spontaneous recovery. However, this effect has never been experimentally investigated in humans, so far. Thus, the aim of this dissertation was to investigate the effect of distal stress on threat conditioning in humans. Therefore, two subsequent studies were conducted. For both studies, the threat conditioning paradigm comprised threat acquisition, extinction learning, and re-extinction. In the threat acquisition phase, two geometrical shapes were used as conditioned stimulus (CS), from which one (CS+) was paired with a painful electric stimulus (unconditioned stimulus, US), but not the other one (CS-). During extinction learning 24 h later and re-extinction seventeen days later, CSs were again presented but without any US delivery. In Study 1, 69 participants underwent either a stress (socially evaluated cold pressor test; SECPT) or sham protocol 10 days prior to threat conditioning. Furthermore, context effects were examined by placing the stress protocol in the same context (context-A stress, and sham group) or a different context (context-B stress group) than conditioning. Results revealed that the context-A, but not context-B, stress group displayed impaired safety learning (i.e. potenti-ation towards CS-) for startle response during threat acquisition. Moreover, the same stress group showed impaired threat extinction, evident in sustained CS discrimination in valence and arousal ratings during extinction learning, and memory recall. In sum, distal stress on the one hand impaired safety learning during threat conditioning on a level of startle response. On the other hand, stress impaired threat extinction on a level of ratings. Noteworthy, the effect of distal stress was only found when the stressor was placed in the same context as later threat learning. Hence, suggesting that the combination of stressor and stressor-associated context exerted the effect on threat extinction. In Study 2, it was examined if distal stress induction could also have an impact on threat and extinction processes without the necessity of context association. Therefore, the same stress (n = 45) or sham protocol (n = 44) as in Study 1 was conducted in a different context than and 24 h prior to a threat conditioning paradigm. Similar to Study 1, weakened extinction learning was found in fear ratings for the stress (vs. sham) group, which was indicated by persistent CS+/CS- differentiation after the first block of extinction trials. Alterations in safety learning towards the CS- during threat acquisition were only supported by significant correlations between stress measures on the stress day and conditioned startle response of the CS- during acquisition. Taken together, in two subsequent studies this dissertation provided first evidence of impaired threat extinction after distal stress induction in humans. Furthermore, impairments in safety learning, as can be observed in PTSD, were additionally demonstrated. Interestingly, the effects were boosted and more profound when associating the stressor to the later learning context. These results have clinical implications as they can be translated to the notion that prior stress exposure makes an individual more vulnerable for later aversive events.},
  subject      = {Stress},
  language  = {en}
}
@phdthesis{Asthana2013,
  author    = {Asthana, Manish},
  title     = {Associative learning - Genetic modulation of extinction and reconsolidation and the effects of transcranial Direct Current Stimulation (tDCS)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-84158},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Scientific surveys provide sufficient evidence that anxiety disorders are one of the most common psy-chiatric disorders in the world. The lifetime prevalence rate of anxiety disorder is 28.8\% (Kessler, et al., 2005). The most widely studied anxiety disorders are as follows panic disorder (PD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social phobia (or social anxiety disorder), specific phobias, and generalized anxiety disorder (GAD). (NIMH Article, 2009). Classical conditioning is the stable paradigm used from the last one century to understand the neurobi-ology of fear learning. Neurobiological mechanism of fear learning is well documented with the condi-tioning studies. In the therapy of anxiety disorders, exposure based therapies are known to be the most effective approaches. Flooding is a form of exposure therapy in which a participant is exposed to the fear situation and kept in that situation until their fear dissipates. The exposure therapy is based on the phenomena of extinction; this means that a conditioned response diminishes if the conditioned stimulus (CS) is repeatedly presented without an unconditioned stimulus (UCS). One problem with extinction as well as with exposure-based therapy is the problem of fear return (for e.g. renewal, spontaneous recov-ery and reinstatement) after successful extinction. Therefore, extinction does not delete the fear memory trace. It has been well documented that memory processes can be modulated or disrupted using several sci-entific paradigms such as behavioral (for e.g. exposure therapy), pharmacological (for e.g. drug manipu-lation), non-invasive stimulation (for e.g. non-invasive stimulation such as electroconvulsive shock (ECS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), etc. However, modulation of memory processes after reactivation or via non-invasive stimulation is still not clear, which is the focus of the current study. In addition, study of genetic variant suggests that genetic differences play a vital role in the psychiatric disorder especially in fear learning. Hence, it is also one of the concerns of the current dissertation to investigate the interaction between gene and reconsolidation of memory. With respect to fear-conditioning, there are three findings in the current dissertation, which are as fol-lows: (i) In the first study we investigated that non-invasive weak electrical stimulation interferes with the consolidation process and disrupts the fear consolidation to attain stable form. This might offer an effective treatment in the pathological memories, for e.g. PTSD, PD, etc. (ii) In the second study we demonstrated whether a brief single presentation of the CS will inhibit the fear recovery. Like earlier studies we also found that reactivation followed by reconsolidation douses fear return. Attenuation of fear recovery was observed in the reminder group compared to the no-reminder group. (iii) Finally, in our third study we found a statistically significant role of brain derived neurotrophic factor (BDNF) polymorphism in reconsolidation. Results of the third study affirm the involvement of BDNF variants (Met vs. Val) in the modulation of conditioned fear memory after its reactivation. In summary, we were able to show in the current thesis modulation of associative learning and recon-solidation via transcranial direct current stimulation and genetic polymorphism.},
  subject      = {Konditionierung},
  language  = {en}
}