@phdthesis{Stegmann2021, author = {Stegmann, Yannik}, title = {Electrocortical mechanisms of sustained attention during the acquisition and interaction of conditioned fear and anxiety}, doi = {10.25972/OPUS-23770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237700}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Adapting defensive behavior to the characteristics of a threatening situation is a fundamental function of the brain. Particularly, threat imminence plays a major role for the organization of defensive responses. Acute threat prompts phasic physiological responses, which are usually associated with an intense feeling of fear. In contrast, diffuse and potentially threatening situations elicit a sustained state of anxious apprehension. Detection of the threatening stimulus defines the key event in this framework, initiating the transition from potential to acute threat. Consequently, attention to threat is crucial for supporting defensive behavior. The functions of attention are finely tuned to the characteristics of a threatening situation. Potential threat is associated with hypervigilance, in order to facilitate threat detection. Once a threatening stimulus has been identified, attention is selectively focused on the source of danger. Even though the concepts of selective attention and hypervigilance to threat are well established, evidence for their neural correlates remain scarce. Therefore, a major goal of this thesis is to elucidate the neural correlates of selective attention to acute threat and hypervigilance during potential threat. A second aim of this thesis is to provide a mechanistic account for the interaction of fear and anxiety. While contemporary models view fear and anxiety as mutually exclusive, recent findings for the neural networks of fear and anxiety suggest potential interactions. In four studies, aversive cue conditioning was used to induce acute threat, while context conditioning served as a laboratory model of potential threat. To quantify neural correlates of selective attention and hypervigilance, steady-state visual evoked potentials (ssVEPs) were measured as an index of visuocortical responding. Study 1 compared visuocortical responses to acute and potential threat for high versus low trait-anxious individuals. All individuals demonstrated enhanced electrocortical responses to the central cue in the acute threat condition, suggesting evidence for the neural correlate of selective attention. However, only low anxious individuals revealed facilitated processing of the contexts in the potential threat condition, reflecting a neural correlate of hypervigilance. High anxious individuals did not discriminate among contexts. These findings contribute to the notion of aberrational processing of potential threat for high anxious individuals. Study 2 and 3 realized orthogonal combinations of cue and context conditioning to investigate potential interactions of fear and anxiety. In contrast to Study 1 and 2, Study 3 used verbal instructions to induce potentially threatening contexts. Besides ssVEPs, threat ratings and skin conductance responses (SCRs) were recorded as efferent indices of defensive responding. None of these studies found further evidence for the neural correlates of hypervigilance and selective attention. However, results for ratings and SCRs revealed additive effects of fear and anxiety, suggesting that fear and anxiety are not mutually exclusive, but interact linearly to organize and facilitate defensive behavior. Study 4 tested ssVEPs to more ecologically valid forms of context conditioning, using flickering video stimuli of virtual offices to establish context representations. Contrary to expectations, results revealed decreased visuocortical responses during sustained presentations of anxiety compared to neutral contexts. A disruption of ssVEP signals eventually suggests interferences by continuously changing video streams which are enhanced as a function of motivational relevance. In summary, this thesis provided evidence for the neural correlates of attention only for isolated forms of fear and anxiety, but not for their interaction. In contrast, an additive interaction model of fear and anxiety for measures of defensive responding offers a new perspective on the topography of defensive behavior.}, subject = {Furcht}, language = {en} } @phdthesis{Simons2020, author = {Simons, Bibiane Stephanie Elisabeth}, title = {Modulation von emotionaler Anspannung mittels transkranieller Gleichstromstimulation (tDCS) des rechten inferioren pr{\"a}frontalen Kortex}, doi = {10.25972/OPUS-19928}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199289}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Emotionale Kontrolle ist f{\"u}r unsere Zusammenleben unerl{\"a}sslich. Zum neuronalen Netzwerk der Emotionsverarbeitung und Emotionskontrolle geh{\"o}rt auch der rechte inferiore pr{\"a}frontale Kortex, wobei seine Funktion h{\"a}ufig mit der einer Bremse verglichen wird. Die Antizipationsangst, die bei manchen Angstst{\"o}rungen eine Rolle spielt und das daraus resultierende Vermeidungsverhalten, bieten einen relevanten Zusammenhang, den man in der Therapie von Angsterkrankungen beeinflussen k{\"o}nnte. Hierbei bieten nichtinvasive Hirnstimulationsverfahren einen m{\"o}glichen Ansatzpunkt und der rechte IFG ein m{\"o}gliches Ziel. In dieser Studie stimulierten wir den rechten inferioren frontalen Gyrus (rIFG) mittels anodaler transkranieller Gleichstromstimulation (tDCS) um zu pr{\"u}fen, ob dadurch die emotionale Anspannung moduliert werden kann. Zu diesem Zwecke wurde der rIFG bei gesunden Probanden (N = 80), aufgeteilt in eine tDCS Gruppe und eine Sham Gruppe, {\"u}ber einen Zeitraum von 20 Minuten mit einer Stromst{\"a}rke von 2 mA und einer Elektrodengr{\"o}ße von 35 cm² elektrisch stimuliert. W{\"a}hrenddessen wurde die Hautleitf{\"a}higkeiten (SCL) als psychophysiologischer Parameter in Antizipation eines akustischen neutralen bzw. aversiven Reizes gemessen. Die Art des akustischen Reizes war dabei f{\"u}r die Probanden durch einen visuellen Hinweisstimulus vorhersehbar, jedoch war der Zeitpunkt der Pr{\"a}sentation des akustischen Reizes nicht vorhersehbar. Dadurch konnte emotionale Anspannung in Antizipation des aversiven Stimulus induziert werden, was wir durch ein insgesamt h{\"o}heres SCL w{\"a}hrend der aversiven Bedingung nachweisen konnten. Wir konnten einen signifikanten Effekt der tDCS des rIFG auf die psychophysiologischen Parameter der Antizipationsangst nachweisen. Der Effekt beruhte dabei auf einem geringeren Anstieg des Hautleitf{\"a}higkeitslevels der tDCS Gruppe von neutraler zu aversiver Bedingung im Vergleich zu Sham Gruppe. Wir k{\"o}nnen daher best{\"a}tigen, dass es m{\"o}glich ist die physiologische Reaktion bei emotionaler Anspannung durch tDCS des rIFG zu regulieren. Dar{\"u}ber hinaus k{\"o}nnen wir dadurch die angenommene Rolle des rIFG in der Emotionsregulation best{\"a}tigen. Dieser scheint daher ein vielversprechender Stimulationsort f{\"u}r tDCS zur Verst{\"a}rkung der emotionalen Kontrolle zu sein. Auf Basis unserer Ergebnisse, k{\"o}nnte in zuk{\"u}nftigen Studien tDCS des rIFG in Kombination mit Verhaltenstherapie bei Angsterkrankungen oder zur Modulation von Vermeidungsverhalten eingesetzt werden. Durch unseren Versuch konnte damit ein grundlegender Beitrag f{\"u}r zuk{\"u}nftige Therapiestudien im Zusammenhang mit tDCS geleistet werden.}, language = {de} } @phdthesis{Rubo2019, author = {Rubo, Marius}, title = {Social Attention in the Laboratory, in Real Life and in Virtual Reality}, doi = {10.25972/OPUS-18845}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188452}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Social attention is a ubiquitous, but also enigmatic and sometimes elusive phenomenon. We direct our gaze at other human beings to see what they are doing and to guess their intentions, but we may also absorb social events en passant as they unfold in the corner of the eye. We use our gaze as a discrete communication channel, sometimes conveying pieces of information which would be difficult to explicate, but we may also find ourselves avoiding eye-contact with others in moments when self-disclosure is fear-laden. We experience our gaze as the most genuine expression of our will, but research also suggests considerable levels of predictability and automaticity in our gaze behavior. The phenomenon's complexity has hindered researchers from developing a unified framework which can conclusively accommodate all of its aspects, or from even agreeing on the most promising research methodologies. The present work follows a multi-methods approach, taking on several aspects of the phenomenon from various directions. Participants in study 1 viewed dynamic social scenes on a computer screen. Here, low-level physical saliency (i.e. color, contrast, or motion) and human heads both attracted gaze to a similar extent, providing a comparison of two vastly different classes of gaze predictors in direct juxtaposition. In study 2, participants with varying degrees of social anxiety walked in a public train station while their eye movements were tracked. With increasing levels of social anxiety, participants showed a relative avoidance of gaze at near compared to distant people. When replicating the experiment in a laboratory situation with a matched participant group, social anxiety did not modulate gaze behavior, fueling the debate around appropriate experimental designs in the field. Study 3 employed virtual reality (VR) to investigate social gaze in a complex and immersive, but still highly controlled situation. In this situation, participants exhibited a gaze behavior which may be more typical for real-life compared to laboratory situations as they avoided gaze contact with a virtual conspecific unless she gazed at them. This study provided important insights into gaze behavior in virtual social situations, helping to better estimate the possible benefits of this new research approach. Throughout all three experiments, participants showed consistent inter-individual differences in their gaze behavior. However, the present work could not resolve if these differences are linked to psychologically meaningful traits or if they instead have an epiphenomenal character.}, subject = {Aufmerksamkeit}, language = {en} } @phdthesis{Ghafoor2020, author = {Ghafoor, Hina}, title = {Coping with Psychosocial Stress: Examining the Roles of Emotional Intelligence and Coping Strategies in Germany and Pakistan}, doi = {10.25972/OPUS-19351}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193519}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Maladaptive coping mechanisms influence health-related quality of life (HRQoL) of individuals facing acute and chronic stress. Trait emotional intelligence (EI) may provide a protective shield against the debilitating effects of maladaptive coping thus contributing to maintained HRQoL. Low trait EI, on the other hand, may predispose individuals to apply maladaptive coping, consequently resulting in lower HRQoL. The current research is comprised of two studies. Study 1 was designed to investigate the protective effects of trait EI and its utility for efficient coping in dealing with the stress caused by chronic heart failure (CHF) in a cross-cultural setting (Pakistan vs Germany). N = 200 CHF patients were recruited at cardiology institutes of Multan, Pakistan and W{\"u}rzburg as well as Brandenburg, Germany. Path analysis confirmed the expected relation between low trait EI and low HRQoL and revealed that this association was mediated by maladaptive metacognitions and negative coping strategies in Pakistani but not German CHF patients. Interestingly, also the specific coping strategies were culture-specific. The Pakistani sample considered religious coping to be highly important, whereas the German sample was focused on adopting a healthy lifestyle such as doing exercise. These findings are in line with cultural characteristics suggesting that German CHF patients have an internal locus of control as compared to an external locus of control in Pakistani CHF patients. Finally, the findings from study 1 corroborate the culture-independent validity of the metacognitive model of generalized anxiety disorder. In addition to low trait EI, high interoception accuracy (IA) may predispose individuals to interpret cardiac symptoms as threatening, thus leading to anxiety. To examine this proposition, Study 2 compared individuals with high vs low IA in dealing with a psychosocial stressor (public speaking) in an experimental lab study. In addition, a novel physiological intervention named transcutaneous vagus nerve stimulation (t-VNS) and cognitive reappraisal (CR) were applied during and after the anticipation of the speech in order to facilitate coping with stress. N= 99 healthy volunteers participated in the study. Results showed interesting descriptive results that only reached trend level. They suggested a tendency of high IA individuals to perceive the situation as more threatening as indicated by increased heart rate and reduced heart rate variability in the high-frequency spectrum as well as high subjective anxiety during anticipation of and actual performance of the speech. This suggests a potential vulnerability of high IA individuals for developing anxiety disorders, specifically social anxiety disorder, in case negative self-focused attention and negative evaluation is applied to the (more prominently perceived) increased cardiac responding during anticipation of and the actual presentation of the public speech. The study did not reveal any significant protective effects of t-VNS and CR. In summary, the current research suggested that low trait EI and high IA predicted worse psychological adjustment to chronic and acute distress. Low trait EI facilitated maladaptive metacognitive processes resulting in the use of negative coping strategies in Study 1; however, increased IA regarding cardioceptions predicted high physiological arousal in study 2. Finally, the German vs. the Pakistani culture greatly affected the preference for specific coping strategies. These findings have implications for caregivers to provide culture-specific treatments on the one hand. On the other hand, they highlight high IA as a possible vulnerability to be targeted for the prevention of (social) anxiety.}, subject = {Deutschland}, language = {en} } @phdthesis{LangeneSoehnchen2020, author = {Lange [n{\´e} S{\"o}hnchen], Bastian}, title = {Influence of social anxiety on social attention and corresponding changes in action patterns}, doi = {10.25972/OPUS-18900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189001}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {People who suffer Social Anxiety Disorder (SAD) are under substantial personal distress and endure impaired normal functioning in at least some parts of everyday life. Next, to the personal suffering, there are also the immense public health costs to consider, as SAD is the most common anxiety disorder and thereby one of the major psychiatric disorders in general. Over the last years, fundamental research found cognitive factors as essential components in the development and maintenance of social fears. Following leading cognitive models, avoidance behaviors are thought to be an important factor in maintaining the developed social anxieties. Therefore, this thesis aims to deepen the knowledge of avoidance behaviors exhibited in social anxiety, which allows to get a better understanding of how SAD is maintained. To reach this goal three studies were conducted, each using a different research approach. In the first study cutting-edge Virtual Reality (VR) equipment was used to immerse participants in a virtual environment. In this virtual setting, High Socially Anxious (HSA) individuals and matched controls had to execute a social Approach-Avoidance Task (AAT). In the task, participants had to pass a virtual person displaying neutral or angry facial expressions. By using a highly immersive VR apparatus, the first described study took the initial step in establishing a new VR task for the implicit research on social approach-avoidance behaviors. By moving freely through a VR environment, participants experienced near real-life social situations. By tracking body and head movements, physical and attentional approach-avoidance processes were studied. The second study looked at differences in attention shifts initiated by gaze-cues of neutral or emotional faces. Comparing HSA and controls, enabled a closer look at attention re-allocation with special focus on social stimuli. Further, context conditioning was used to compare task performance in a safe and in a threatening environment. Next to behavioral performance, the study also investigated neural activity using Electroencephalography (EEG) primarily looking at the N2pc component. In the third study, eye movements of HSA and Low Socially Anxious (LSA) were analyzed using an eye-tracking apparatus while participants executed a computer task. The participants' tasks consisted of the detection of either social or non-social stimuli in complex visual settings. The study intended to compare attention shifts towards social components between these two tasks and how high levels of social anxiety influence them. In other words, the measurements of eye movements enabled the investigation to what extent social attention is task-dependent and how it is influenced by social anxiety. With the three described studies, three different approaches were used to get an in-depth understanding of what avoidance behaviors in SAD are and to which extent they are exhibited. Overall, the results showed that HSA individuals exhibited exaggerated physical and attentional avoidance behavior. Furthermore, the results highlighted that the task profoundly influences attention allocation. Finally, all evidence indicates that avoidance behaviors in SAD are exceedingly complex. They are not merely based on the fear of a particular stimulus, but rather involve highly compound cognitive processes, which surpass the simple avoidance of threatening stimuli. To conclude, it is essential that further research is conducted with special focus on SAD, its maintaining factors, and the influence of the chosen research task and method.}, subject = {Sozialangst}, language = {en} } @phdthesis{Vietz2022, author = {Vietz, Melanie Sabrina}, title = {Pr{\"a}vention von Angsterkrankungen: Etablierung und Validierung des Kognitiven Angstsensitivit{\"a}tstrainings (KAST) - Deutsche Version}, doi = {10.25972/OPUS-22312}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223122}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {Angsterkrankungen stellen mit einer 12-Monats-Pr{\"a}valenz von 14\% die h{\"a}ufigsten psychischen Erkrankungen in der westlichen Gesellschaft dar. Angesichts der hohen querschnittlichen wie sequentiellen Komorbidit{\"a}t von Angsterkrankungen, der ausgepr{\"a}gten individuellen Einschr{\"a}nkungen sowie der hohen {\"o}konomischen Belastung f{\"u}r das Gesundheitssystem ist neben therapeutischen Behandlungsans{\"a}tzen die Entwicklung von kurzzeitigen, kosteng{\"u}nstigen und leicht zug{\"a}nglichen Pr{\"a}ventionsmaßnahmen von großer Bedeutung und steht zunehmend im Fokus des gesundheitspolitischen Interesses, um die Inzidenz von Angsterkrankungen zu reduzieren. Voraussetzung f{\"u}r die Entwicklung von gezielten und damit den effektivsten Pr{\"a}ventionsmaßnahmen sind valide Risikofaktoren, die die Entstehung von Angsterkrankungen beg{\"u}nstigen. Ein Konstrukt, das in der Literatur als subklinisches Symptom in Form einer kognitiven Vulnerabilit{\"a}t f{\"u}r Angsterkrankungen und damit als Risikofaktor angesehen wird, ist die sogenannte Angstsensitivit{\"a}t (AS). AS umfasst die individuelle Tendenz, angstbezogene k{\"o}rperliche Symptome generell als bedrohlich einzustufen und mit aversiven Konsequenzen zu assoziieren. Das Ziel der vorliegenden Arbeit war daher die Etablierung und Validierung eines Pr{\"a}ventionsprogramms zur Reduktion der AS an einer nicht-klinischen Stichprobe von 100 Probanden (18-30 Jahre) mit einer erh{\"o}hten AS (Anxiety Sensitivity Index [ASI-3] ≥17) sowie die Rekrutierung von 100 alters- und geschlechtsangeglichenen Probanden mit niedriger Angstsensitivit{\"a}t (ASI-3 <17). In einem randomisiert-kontrollierten Studiendesign durchliefen die Probanden mit hoher AS entweder das {\"u}ber f{\"u}nf Wochen angelegte „Kognitive Angstsensitivit{\"a}tstraining" (KAST) als erste deutschsprachige {\"U}bersetzung des Computer-basierten „Cognitive Anxiety Sensitivity Treatment" (CAST) von Schmidt et al. (2014) oder wurden der Wartelisten-Kontrollgruppe zugeteilt. Das KAST Training bestand aus einer einmaligen Vermittlung kognitiv-behavioraler Psychoedukation zum Thema Stress und Anspannung sowie deren Auswirkungen auf den K{\"o}rper und der Anleitung von zwei interozeptiven Expositions{\"u}bungen (‚Strohhalm-Atmung' und ‚Hyperventilation'), die {\"u}ber den anschließenden Zeitraum von f{\"u}nf Wochen in Form von Hausaufgaben wiederholt wurden. Es konnte gezeigt werden, dass die Teilnehmer des KAST-Programms nach Beendigung des Trainings (T1) eine signifikant niedrigere AS-Auspr{\"a}gung im Vergleich zur Wartelisten-Kontrollgruppe aufwiesen und diese Reduktion auch {\"u}ber den Katamnese-Zeitraum von sechs Monaten (T2) stabil blieb. Erg{\"a}nzend wurde auch die Targetierbarkeit weiterer intermedi{\"a}rer Risikomarker wie der Trennungsangst (TA), des Index der kardialen Sensitivit{\"a}t sowie der Herzratenvariabilit{\"a}t (HRV) untersucht, die jedoch nicht durch das KAST-Training direkt ver{\"a}ndert werden konnten. Im Vergleich der Subgruppen von Probanden mit hoher AS und gleichzeitig hoher TA (Adult Separation Anxiety Questionnaire [ASA-27] ≥22) und Probanden mit hoher AS, aber niedriger TA (ASA-27 <22) zeigte sich, dass die AS-TA-Hochrisikogruppe ebenfalls gut von der KAST-Intervention profitieren und eine signifikante Reduktion der AS erzielen konnte, indem sie sich bei T1 dem Niveau der Gruppe mit niedriger TA anglich. Zudem korrelierte die prozentuale Ver{\"a}nderung der Einstiegswerte der inneren Anspannung w{\"a}hrend der Strohhalm-Atmungs{\"u}bung positiv mit der prozentualen Ver{\"a}nderung der dimensionalen TA bei T1. Zusammenfassend weisen die Ergebnisse der vorliegenden Arbeit erstmalig auf die Wirksamkeit der deutschsprachigen {\"U}bersetzung des CAST-Programms (Schmidt et al., 2014), eines Computer-basierten, und damit leicht zu implementierenden sowie kosteng{\"u}nstigen Programms, in Bezug auf die Reduktion der AS sowie indirekt der TA hin und k{\"o}nnen damit zur indizierten und demnach besonders effektiven Pr{\"a}vention von Angsterkrankungen in Hochrisikogruppen beitragen.}, subject = {Angstst{\"o}rung}, language = {de} } @phdthesis{Schwarzmeier2023, author = {Schwarzmeier, Hanna}, title = {From fear extinction to exposure therapy: neural mechanisms and moderators of extinction}, doi = {10.25972/OPUS-22330}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223304}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Emotional-associative learning processes such as fear conditioning and extinction are highly relevant to not only the development and maintenance of anxiety disorders (ADs), but also to their treatment. Extinction, as the laboratory analogue to behavioral exposure, is assumed a core process underlying the treatment of ADs. Although exposure-based treatments are highly effective for the average patient suffering from an AD, there remains a gap in treatment efficacy with over one third of patients failing to achieve clinically significant symptom relief. There is ergo a pressing need for intensified research regarding the underlying neural mechanisms of aberrant emotional-associative learning processes and the neurobiological moderators of treatment (non-)response in ADs. The current thesis focuses on different applications of the fundamental principles of fear conditioning and extinction by using two example cases of ADs from two different multicenter trials. First, we targeted alterations in fear acquisition, extinction, and its recall as a function of psychopathology in panic disorder (PD) patients compared to healthy subjects using fMRI. Second, exposure-based therapy and pre-treatment patient characteristics exerting a moderating influence on this essential learning process later on (i.e. treatment outcome) were examined using multimodal functional and structural neuroimaging in spider phobia. We observed aberrations in emotional-associative learning processes in PD patients compared to healthy subjects indicated by an accelerated fear acquisition and an attenuated extinction recall. Furthermore, pre-treatment differences related to defensive, regulatory, attentional, and perceptual processes may exert a moderating influence on treatment outcome to behavioral exposure in spider phobia. Although the current results need further replication, on an integrative meta level, results point to a hyperactive defensive network system and deficient emotion regulation processes (including extinction processes) and top-down control in ADs. This speaks in favor of transdiagnostic deficits in important functional domains in ADs. Deficits in transdiagnostic domains such as emotion regulation processes could be targeted by enhancing extinction learning or by means of promising tools like neurofeedback. The detection of pre-treatment clinical response moderators, for instance via machine learning frameworks, may help in supporting clinical decision making on individually tailored treatment approaches or, respectively, to avoid ineffective treatment and its related financial costs. In the long run, the identification of neurobiological markers which are capable of detecting non-responders a priori represents an ultimate goal.}, subject = {Extinktion}, language = {en} } @phdthesis{Slyschak2022, author = {Slyschak, Anna}, title = {Fear conditioning, its generalization and extinction in children and adolescents under consideration of trait anxiety and anxiety sensitivity}, doi = {10.25972/OPUS-26780}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267806}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2022}, abstract = {The propounded thesis investigated fear learning including fear conditioning, its generalization as well as its extinction in 133 healthy children and adolescents aged 8 to 17 years. The main goal was to analyze these processes also in the course of childhood and adolescence due to far less research in this age span compared to adults. Of note, childhood is the typical period for the onset of anxiety disorders. To achieve this, an aversive discriminative fear conditioning, generalization and extinction paradigm, which based on the "screaming lady paradigm" from Lau et al. (2008) and was adapted by Schiele \& Reinhard et al. (2016), was applied. All probands traversed the pre-acquisition (4 x CS-, 4 x CS+, no US), the acquisition (12 x CS-, 12 x CS+, reinforcement rate: 83\%), the generalization (12 x CS-, 12 x GS4, 12 x GS3, 12 x GS2, 12 x GS1, 12 x CS+, reinforcement rate: 50\%) and the extinction (18 x CS-, 18 x CS+, no US). The generalization stimuli, i.e. GS1-GS4, were built out of CS- and CS+ in different mixtures on a percentage basis in steps of 20\% from CS- to CS+. Pictures of faces of two actresses with a neutral expression were used for the discriminative conditioning, whereby the CS+ was paired with a 95-dB loud female scream at the same time together with a fearful facial expression (US). CS- and GS1-GS4 were never followed by the US. Subjective ratings (arousal, valence and US expectancy) were collected and further the psychophysiological measure of the skin conductance response (SCR). The hypotheses were 1) that underage probands show a negative correlation between age and overgeneralization and 2) that anxiety is positively correlated with overgeneralization in the same sample. ANOVAs with repeated measures were conducted for all four dependent variables with phase (pre-acquisition phase, 1. + 2. acquisition phase, 1. + 2. generalization phase, 1. - 3. extinction phase) and stimulus type (CS-, CS+, GS1-GS4) as within-subject factors. For the analyses of the modulatory effects of age and anxiety in additional separate ANCOVAs were conducted including a) age, b) the STAIC score for trait anxiety and c) the CASI score for anxiety sensitivity as covariates. Sex was always included as covariate of no interest. On the one hand, findings indicated that the general extent of the reactions (arousal, valence and US expectancy ratings and the SCR) decreased with growing age, i.e. the older the probands the lower their reactions towards the stimuli regardless of the type of dependent variable. On the other hand, ratings of US expectancy, i.e. the likelihood that a stimulus is followed by a US (here: female scream coupled with a fearful facial expression), showed better discrimination skills the older the probands were, resulting in a smaller overgeneralization within older probands. It must be emphasized very clearly that no causality can be derived. Thus, it was only an association revealed between 15 age and generalization of conditioned fear, which is negative. Furthermore, no obvious impact of trait anxiety could be detected on the different processes of fear learning. Especially, no overgeneralization was expressed by the probands linked to higher trait anxiety. In contrast to trait anxiety, for anxiety sensitivity there was an association between its extent and the level of fear reactions. This could be described best with a kind of parallel shifts: the higher the anxiety sensitivity, the stronger the fear reactions. Likewise, for anxiety sensitivity no overgeneralization due to a stronger extent of anxiety sensitivity could be observed. Longitudinal follow-up examinations and, furthermore, neurobiological investigations are needed for replication purposes and purposes of gaining more supporting or opposing insights, but also for the profound exploration of the impact of hormonal changes during puberty and of the maturation processes of different brain structures. Finally, the question whether enhanced generalization of conditioned fear facilitates the development of anxiety disorders or vice versa remains unsolved yet.}, subject = {Furcht}, language = {en} } @phdthesis{Aster2023, author = {Aster, Hans-Christoph}, title = {Characterization of subgroups in fibromyalgia syndrome}, doi = {10.25972/OPUS-31304}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313049}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {The present cumulative dissertation summarizes three clinical studies, which examine subgroups of patients within the fibromyalgia syndrome (FMS). FMS entails chronic pain and associated symptoms, and its pathophysiology is incompletely understood (1). Previous studies show that there is a subgroup of patients with FMS with objective histological pathology of the small nerve fibers of the peripheral nervous system (PNS). Another subgroup of FMS patients does not show any signs of pathological changes of the small nerve fibers. The aim of this dissertation was to compare FMS patients with healthy controls, and these two FMS subgroups for differences in the central nervous system (CNS) in order to explore possible interactions between PNS and the CNS. Regarding the CNS, differences of FMS patients with healthy controls have already been found in studies with small sample sizes, but no subgroups have yet been identified. Another aim of this thesis was to test whether the subgroups show a different response to different classes of pain medication. The methods used in this thesis are structural and functional magnetic resonance imaging (MRI), magnetic resonance diffusion imaging and magnetic resonance spectroscopy. For the evaluation of clinical symptoms, we used standardized questionnaires. The subgroups with and without pathologies of the PNS were determined by skin biopsies of the right thigh and lower leg based on the intraepidermal nerve fiber density (IENFD) of the small nerve fibers. 1) In the first MRI study, 43 female patients with the diagnosis of FMS and 40 healthy control subjects, matched in age and body mass index, were examined with different MRI sequences. Cortical thickness was investigated by structural T1 imaging, white matter integrity by diffusion tensor imaging and functional connectivity within neuronal networks by functional resting state MRI. Compared to the controls, FMS patients had a lower cortical volume in bilateral frontotemporoparietal regions and the left insula, but a higher cortical volume in the left pericalcarine cortex. Compared to the subgroup without PNS pathology, the subgroup with PNS pathology had lower cortical volume in both pericalcarine cortices. Diffusion tensor imaging revealed an increased fractional anisotropy (FA) of FMS patients in corticospinal pathways such as the corona radiata, but also in regions of the limbic systems such as the fornix and cingulum. Subgroup comparison again revealed lower mean FA values of the posterior thalamic radiation and the posterior limb of the left internal capsule in the subgroup with PNS pathology. In the functional connectivity analysis FMS patients, compared to controls, showed a hypoconnectivity between the right median frontal gyrus and the posterior cerebellum and the right crus cerebellum, respectively. In the subgroup comparisons, the subgroup with PNS pathology showed a hyperconnectivity between both inferior frontal gyri, the right posterior parietal cortex and the right angular gyrus. In summary, these results show that differences in brain morphology and functional connectivity exist between FMS patients with and without PNS pathology. These differences were not associated with symptom duration or severity and, in some cases, have not yet been described in the context of FMS. The differences in brain morphology and connectivity between subgroups could also lead to a differential response to treatment with centrally acting drugs. Further imaging studies with FMS patients should take into account this heterogeneity of FMS patient cohorts. 2) Following the results from the first MRI study, drug therapies of FMS patients and their treatment response were compared between PNS subgroups. As there is no licensed drug for FMS in Europe, the German S3 guideline recommends amitriptyline, duloxetine and pregabalin for temporary use. In order to examine the current drug use in FMS patients in Germany on a cross-sectional basis, 156 patients with FMS were systematically interviewed. The drugs most frequently used to treat pain in FMS were non-steroidal anti-inflammatory drugs (NSAIDs) (28.9\%), metamizole (15.4\%) and amitriptyline (8.8\%). Pain relief assessed by patients on a numerical rating scale from 0-10 averaged 2.2 points for NSAIDs, 2.0 for metamizole and 1.5 for amitriptyline. Drugs that were discontinued for lack of efficacy and not for side effects were acetaminophen (100\%), flupirtine (91.7\%), selective serotonin reuptake inhibitors (81.8\%), NSAIDs (83.7\%) and weak opioids (74.1\%). Patients were divided into subgroups with and without PNS pathology as determined by skin biopsies. We found no differences in drug use and effect between the subgroups. Taken together, these results show that many FMS patients take medication that is not in accordance with the guidelines. The reduction of symptoms was best achieved with metamizole and NSAIDs. Further longitudinal studies on medication in FMS are necessary to obtain clearer treatment recommendations. 3) Derived from previous pharmacological and imaging studies (with smaller case numbers), there is a hypothesis in the FMS literature that hyperreactivity of the insular cortex may have an impact on FMS. The hyperreactivity seems to be due to an increased concentration of the excitatory neurotransmitter glutamate in the insular cortex of FMS patients. The hypothesis is supported by magnetic resonance spectroscopy studies with small number of cases, as well as results from pharmacological studies with glutamate-inhibiting medication. Studies from animal models have also shown that an artificially induced increase in glutamate in the insular cortex can lead to reduced skin innervation. Therefore, the aim of this study was to compare glutamate and GABA concentrations in the insular cortex of FMS patients with those of healthy controls using magnetic resonance imaging. There was no significant difference of both neurotransmitters between the groups. In addition, there was no correlation between the neurotransmitter concentrations and the severity of clinical symptoms. There were also no differences in neurotransmitter concentrations between the subgroups with and without PNS pathology. In conclusion, our study could not show any evidence of a correlation of glutamate and GABA concentrations with the symptoms of FMS or the pathogenesis of subgroups with PNS pathologies.}, subject = {Fibromyalgie}, language = {en} } @phdthesis{RiechelmannverhSteinbacher2021, author = {Riechelmann [verh. Steinbacher], Eva Katharina}, title = {Gaze interaction: Cognitive mechanisms of oculomotor action control}, doi = {10.25972/OPUS-21527}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215279}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Humans use their eyes not only as visual input devices to perceive the environment, but also as an action tool in order to generate intended effects in their environment. For instance, glances are used to direct someone else's attention to a place of interest, indicating that gaze control is an important part of social communication. Previous research on gaze control in a social context mainly focused on the gaze recipient by asking how humans respond to perceived gaze (gaze cueing). So far, this perspective has hardly considered the actor's point of view by neglecting to investigate what mental processes are involved when actors decide to perform an eye movement to trigger a gaze response in another person. Furthermore, eye movements are also used to affect the non-social environment, for instance when unlocking the smartphone with the help of the eyes. This and other observations demonstrate the necessity to consider gaze control in contexts other than social communication whilst at the same time focusing on commonalities and differences inherent to the nature of a social (vs. non-social) action context. Thus, the present work explores the cognitive mechanisms that control such goal-oriented eye movements in both social and non-social contexts. The experiments presented throughout this work are built on pre-established paradigms from both the oculomotor research domain and from basic cognitive psychology. These paradigms are based on the principle of ideomotor action control, which provides an explanatory framework for understanding how goal-oriented, intentional actions come into being. The ideomotor idea suggests that humans acquire associations between their actions and the resulting effects, which can be accessed in a bi-directional manner: Actions can trigger anticipations of their effects, but the anticipated resulting effects can also trigger the associated actions. According to ideomotor theory, action generation involves the mental anticipation of the intended effect (i.e., the action goal) to activate the associated motor pattern. The present experiments involve situations where participants control the gaze of a virtual face via their eye movements. The triggered gaze responses of the virtual face are consistent to the participant's eye movements, representing visual action effects. Experimental situations are varied with respect to determinants of action-effect learning (e.g., contingency, contiguity, action mode during acquisition) in order to unravel the underlying dynamics of oculomotor control in these situations. In addition to faces, conditions involving changes in non-social objects were included to address the question of whether mechanisms underlying gaze control differ for social versus non-social context situations. The results of the present work can be summarized into three major findings. 1. My data suggest that humans indeed acquire bi-directional associations between their eye movements and the subsequently perceived gaze response of another person, which in turn affect oculomotor action control via the anticipation of the intended effects. The observed results show for the first time that eye movements in a gaze-interaction scenario are represented in terms of their gaze response in others. This observation is in line with the ideomotor theory of action control. 2. The present series of experiments confirms and extends pioneering results of Huestegge and Kreutzfeldt (2012) with respect to the significant influence of action effects in gaze control. I have shown that the results of Huestegge and Kreutzfeldt (2012) can be replicated across different contexts with different stimulus material given that the perceived action effects were sufficiently salient. 3. Furthermore, I could show that mechanisms of gaze control in a social gaze-interaction context do not appear to be qualitatively different from those in a non-social context. All in all, the results support recent theoretical claims emphasizing the role of anticipation-based action control in social interaction. Moreover, my results suggest that anticipation-based gaze control in a social context is based on the same general psychological mechanisms as ideomotor gaze control, and thus should be considered as an integral part rather than as a special form of ideomotor gaze control.}, subject = {Verhaltenskontrolle}, language = {en} }