@phdthesis{Brunhuber2021, author = {Brunhuber, Bettina Stefanie}, title = {Modifikation konditionierter Furchtreaktionen durch transkranielle Gleichstromstimulation}, doi = {10.25972/OPUS-23756}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237562}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {In dieser Arbeit wurde untersucht, ob eine anodale tDCS {\"u}ber der Elektrodenposition AF3 und der Kathode {\"u}ber dem kontralateralen Mastoid Extinktionslernen modulieren kann. Auf Basis aktueller Forschungsergebnisse wurden die Hypothesen aufgestellt, dass im Vergleich von real stimulierter zu sham stimulierter Gruppe ein Unterschied in der Hautleitf{\"a}higkeitsrekation, dem Arousalrating und dem Valenzrating der Versuchsteilnehmenden im Vergleich von CS+ und CS- und im zeitlichen Verlauf von Akquisition zu Extinktion gezeigt werden kann. Um dies zu pr{\"u}fen wurde eine randomisiert doppelt-verblindete Studie mit insgesamt 86 Probanden durchgef{\"u}hrt, von denen nach {\"U}berpr{\"u}fen einer suffizienten Furchtkonditionierungsreaktion nach der Akquisitionsphase noch 46 Teilnehmer eingeschlossen wurden. Diese wurden auf zwei tDCS Gruppen im Sinne von realer Stimulation und sham Stimulation verblindet und zuf{\"a}llig aufgeteilt. Alle Teilnehmer durchliefen ein eint{\"a}giges Furchtkonditionierungsparadigma mit drei Phasen: Habituation, Akquisition und Extinktion. W{\"a}hrend allen Phasen wurde die Hautleitf{\"a}higkeitsreaktion gemessen und die Probanden wurden gebeten die ihnen pr{\"a}sentierten Stimuli hinsichtlich deren Valenz und Arousal einzusch{\"a}tzen. Die tDCS fand in einer zehnmin{\"u}tigen Pause vor der Extinktion und w{\"a}hrend destdcs Extinktionsdurchlaufs statt. In den Ergebnissen zeigt sich kein differenzieller Effekt der tDCS. In den erhobenen Hautleitf{\"a}higkeitsdaten zeigt sich in der fr{\"u}hen Extinktionsphase eine verringerte Hautleitf{\"a}higkeit in der verum stimulierten tDCS Gruppe unabh{\"a}ngig davon, ob ein CS+ oder ein CS- zu sehen war. Dies deutet auf eine generell verminderte Aufregung bei realer tDCS hin. In den Bewertungen bez{\"u}glich Arousal und Valenz findet sich ebenfalls kein Effekt der tDCS. In den Bewertungen zeigt sich jedoch die erfolgreiche Konditionierung und deren Extinktion. Nachfolgend stellt sich die Frage, ob zuk{\"u}nftig Paradigmen mit einem zweit{\"a}gigen Design bevorzugt werden sollten, da diese realen Bedingungen n{\"a}herkommen und teilweise auch Effekte der tDCS gezeigt haben. Abschließend l{\"a}sst sich die große Rolle des vmPFC in der Verarbeitung von aversiven Reizen darstellen und betonen, welch großes Potential in einer Beeinflussung der Aktivit{\"a}t des vmPFC liegt, das zuk{\"u}nftig genauer untersucht werden muss.}, subject = {Furchtkonditionierung}, language = {de} } @article{DittertHuettnerPolaketal.2018, author = {Dittert, Natalie and H{\"u}ttner, Sandrina and Polak, Thomas and Herrmann, Martin J.}, title = {Augmentation of fear extinction by transcranial direct current stimulation (tDCS)}, series = {Frontiers in Behavioral Neuroscience}, volume = {12}, journal = {Frontiers in Behavioral Neuroscience}, number = {76}, doi = {10.3389/fnbeh.2018.00076}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176056}, year = {2018}, abstract = {Although posttraumatic stress disorder (PTSD; DSM-V 309.82) and anxiety disorders (DSM-V 300.xx) are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS) might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS) and a 95-dB female scream as unconditioned stimulus (UCS). We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC), which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR) and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84). The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS- discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS- in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be tested in a clinical context further investigation is needed to assess the reason for the reaction increase on CS-. If this negative side effect can be avoided, tDCS may be a tool to improve exposure-based anxiety therapies.}, language = {en} } @article{AsthanaBrunhuberMuehlbergeretal.2016, author = {Asthana, Manish Kumar and Brunhuber, Bettina and M{\"u}hlberger, Andreas and Reif, Andreas and Schneider, Simone and Herrmann, Martin J.}, title = {Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism}, series = {International Journal of Neuropsychopharmacology}, volume = {19}, journal = {International Journal of Neuropsychopharmacology}, number = {6}, doi = {10.1093/ijnp/pyv137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166217}, year = {2016}, abstract = {Background: Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. Methods: An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. Results: The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Conclusions: Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans.}, language = {en} } @article{SchieleReinhardReifetal.2016, author = {Schiele, Miriam A. and Reinhard, Julia and Reif, Andreas and Domschke, Katharina and Romanos, Marcel and Deckert, J{\"u}rgen and Pauli, Paul}, title = {Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults}, series = {Developmental Psychobiology}, volume = {58}, journal = {Developmental Psychobiology}, number = {4}, doi = {10.1002/dev.21393}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189488}, pages = {471-481}, year = {2016}, abstract = {Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues.}, language = {en} } @article{GuhnDreslerAndreattaetal.2014, author = {Guhn, Anne and Dresler, Thomas and Andreatta, Marta and M{\"u}ller, Laura D. and Hahn, Tim and Tupak, Sara V. and Polak, Thomas and Deckert, J{\"u}rgen and Herrmann, Martin J.}, title = {Medial prefrontal cortex stimulation modulates the processing of conditioned fear}, doi = {10.3389/fnbeh.2014.00044}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111309}, year = {2014}, abstract = {The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS-) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).}, language = {en} } @article{ManishNueckelMuehlbergeretal.2013, author = {Manish, Asthana and Nueckel, Katharina and M{\"u}hlberger, Andreas and Neueder, Dorothea and Polak, Thomas and Domschke, Katharina and Deckert, J{\"u}rgen and Herrmann, Martin J.}, title = {Effects of transcranial direct current stimulation on consolidation of fear memory}, series = {Frontiers in Neuropsychiatric Imaging and Stimulation}, journal = {Frontiers in Neuropsychiatric Imaging and Stimulation}, doi = {10.3389/fpsyt.2013.00107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97294}, year = {2013}, abstract = {It has been shown that applying transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) influences declarative memory processes. This study investigates the efficacy of tDCS on emotional memory consolidation, especially experimental fear conditioning. We applied an auditory fear-conditioning paradigm, in which two differently colored squares (blue and yellow) were presented as conditioned stimuli (CS) and an auditory stimulus as unconditioned stimulus (UCS). Sixty-nine participants were randomly assigned into three groups: anodal, cathodal, and sham stimulation. The participants of the two active groups (i.e., anodal and cathodal) received tDCS over the left DLPFC for 12 min after fear conditioning. The effect of fear conditioning and consolidation (24 h later) was measured by assessing the skin conductance response (SCR) to the CS. The results provide evidence that cathodal stimulation of the left DLPFC leads to an inhibitory effect on fear memory consolidation compared to anodal and sham stimulation, as indicated by decreased SCRs to CS+ presentation during extinction training at day 2. In conclusion, current work suggests that cathodal stimulation interferes with processes of fear memory consolidation.}, language = {en} }