@phdthesis{Seeger2023, author = {Seeger, Fabian Reinhard}, title = {Moderators of exposure-based treatment outcome in anxiety disorders: an fMRI approach}, doi = {10.25972/OPUS-21435}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214356}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Even though exposure-based cognitive behavioral therapy (CBT) constitutes a first-line treatment for anxiety disorders, a substantial proportion of patients does not respond in a clinically significant manner. The identification of pre-treatment patient characteristics that are associated with treatment outcome might aid in improving response rates. Therefore, the present doctoral thesis aimed at investigating moderators of treatment outcome in anxiety disorders: first, we investigated the neural correlates of comorbidity among primary panic disorder/agoraphobia (PD/AG) and secondary social anxiety disorder (SAD) moderating treatment outcome towards exposure-based CBT. Second, pre-treatment functional resting-state connectivity signatures of treatment response in specific phobia were studied. Within the first study, we compared PD/AG patients with or without secondary SAD regarding their clinical and neurofunctional outcome towards a manualized CBT treatment focusing on PD/AG symptoms. Prior to treatment, PD/AG+SAD compared to PD/AG-SAD patients exhibited a specific neural signature within the temporal lobe, which was attenuated to the level of PD/AG-SAD patients afterwards. CBT was equally effective in both groups. Thus, comorbidity among those two anxiety disorders did not alter treatment outcome substantially. This might be due to the high overlap of shared pathophysiological features within both disorders. In the second study, we assessed pre-treatment functional resting-state connectivity within a sample of spider phobic patients that were treated with massed in virtuo exposure. We found responders already prior to treatment to be characterized by stronger inhibitory frontolimbic connectivity as well as heightened connectivity between the amygdala and regions related to the ventral visual stream. Furthermore, patients demonstrating high within-session extinction exhibited pronounced intrinsic prefrontal connectivity. Our results point to responders exhibiting a brain prepared for the mechanism of action of exposure. Taken together, results highlight the major impact of pre-treatment characteristics on treatment outcome. Both, PD/AG+SAD patients as well as responders within the SpiderVR study exhibited heightened activation or connectivity within the ventral visual pathway and the amygdala. Pronounced visual processing together with enhanced executive control and emotion regulation seem to constitute a fruitful soil for successful exposure. The results provide starting points for personalized treatment approaches in order to improve treatment success in the anxiety disorders. Future studies are needed to investigate the benefit of neuroscientifically informed CBT augmentation strategies such as repetitive transcranial magnetic stimulation.}, subject = {Angstst{\"o}rung}, language = {en} } @phdthesis{Siminski2023, author = {Siminski, Niklas}, title = {Temporal predictability of threat: Evaluation of differential involvement of amygdala and BNST, and relevance for therapy response prediction in spider phobia}, doi = {10.25972/OPUS-24664}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246643}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Predictability of threat is one of the key modulators of neural activity in fear and anxiety-related threat processes and there is a considerable number of studies focusing on the exact contribution of centromedial amygdala and Bed nucleus of stria terminalis (BNST) in animals as well as in humans. In this research field, some studies already investigated the differential involvement of both areas during temporally predictable and unpredictable threat processes in humans. However, these studies showed several limitations e.g. small sample size, no predictable threat conditions, no separation of anticipation and confrontation processes, which should be addressed in future studies. Furthermore, evidence for group-based inter-individual differences of amygdala and BNST activity during predictable and unpredictable threat processes have not been studied extensively. Several studies suggest a relevant role of the amygdala and BNST activity in phobic processes in patients with specific phobia, but no study so far has investigated the exact contribution of centromedial amygdala (CM) and BNST during temporally predictable and unpredictable threat processes in specific phobia. This thesis consisted of three studies and aimed to evaluate the exact contribution of CM and BNST during temporally predictable and unpredictable threat anticipation and confrontation with the use of an optimized functional magnetic resonance imaging (fMRI) paradigm, which aimed to solve methodological limitations of recent studies. Study 1 used a large sample of healthy participants who were grouped based on NPSR1 genotype, and study 2 and study 3 used a sample of patients with spider phobia. In sum, the results of all three studies indicated, that BNST is more relevant for anticipation processes as compared to the CM. Contrary, during the confrontation phase the CM displays a greater relevance for threat confrontation processes. In recent years, various studies have investigated the extent to which treatment success can be predicted in patients with anxiety disorders based on pre-treatment fMRI activity. Therefore, this was investigated for the first time in study 3 in patients with spider phobia during temporally predictable and unpredictable threat processes. Results indicated that independent of temporal predictability lower anterior cingulate cortex (ACC) activity during threat anticipation and engaged BNST during threat confrontation might be benefitting factors for successful therapy response in spider phobia.}, subject = {Amygdala}, language = {en} } @article{BuffBrinkmannBruchmannetal.2017, author = {Buff, Christine and Brinkmann, Leonie and Bruchmann, Maximilian and Becker, Michael P.I. and Tupak, Sara and Herrmann, Martin J. and Straube, Thomas}, title = {Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder}, series = {Social Cognitive and Affective Neuroscience}, volume = {12}, journal = {Social Cognitive and Affective Neuroscience}, number = {11}, doi = {10.1093/scan/nsx103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173298}, pages = {1766-1774}, year = {2017}, abstract = {Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD.}, language = {en} } @article{WeissIotzovZhouetal.2022, author = {Weiß, Martin and Iotzov, Vassil and Zhou, Yuqing and Hein, Grit}, title = {The bright and dark sides of egoism}, series = {Frontiers in Psychiatry}, volume = {13}, journal = {Frontiers in Psychiatry}, issn = {1664-0640}, doi = {10.3389/fpsyt.2022.1054065}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297183}, year = {2022}, abstract = {Despite its negative reputation, egoism - the excessive concern for one's own welfare - can incite prosocial behavior. So far, however, egoism-based prosociality has received little attention. Here, we first provide an overview of the conditions under which egoism turns into a prosocial motive, review the benefits and limitations of egoism-based prosociality, and compare them with empathy-driven prosocial behavior. Second, we summarize studies investigating the neural processing of egoism-based prosocial decisions, studies investigating the neural processing of empathy-based prosocial decisions, and the small number of studies that compared the neural processing of prosocial decisions elicited by the different motives. We conclude that there is evidence for differential neural networks involved in egoism and empathy-based prosocial decisions. However, this evidence is not yet conclusive, because it is mainly based on the comparison of different experimental paradigms which may exaggerate or overshadow the effect of the different motivational states. Finally, we propose paradigms and research questions that should be tackled in future research that could help to specify how egoism can be used to enhance other prosocial behavior and motivation, and the how it could be tamed.}, language = {en} } @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} } @article{SaulinHornLotzeetal.2022, author = {Saulin, Anne and Horn, Ulrike and Lotze, Martin and Kaiser, Jochen and Hein, Grit}, title = {The neural computation of human prosocial choices in complex motivational states}, series = {NeuroImage}, volume = {247}, journal = {NeuroImage}, doi = {10.1016/j.neuroimage.2021.118827}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265852}, year = {2022}, abstract = {Motives motivate human behavior. Most behaviors are driven by more than one motive, yet it is unclear how different motives interact and how such motive combinations affect the neural computation of the behaviors they drive. To answer this question, we induced two prosocial motives simultaneously (multi-motive condition) and separately (single motive conditions). After the different motive inductions, participants performed the same choice task in which they allocated points in favor of the other person (prosocial choice) or in favor of themselves (egoistic choice). We used fMRI to assess prosocial choice-related brain responses and drift diffusion modeling to specify how motive combinations affect individual components of the choice process. Our results showed that the combination of the two motives in the multi-motive condition increased participants' choice biases prior to the behavior itself. On the neural level, these changes in initial prosocial bias were associated with neural responses in the bilateral dorsal striatum. In contrast, the efficiency of the prosocial decision process was comparable between the multi-motive and the single-motive conditions. These findings provide insights into the computation of prosocial choices in complex motivational states, the motivational setting that drives most human behaviors .}, language = {en} } @phdthesis{Roesler2020, author = {R{\"o}sler, Lara}, title = {Behavioral and Neural Mechanisms of Social Attention}, doi = {10.25972/OPUS-21609}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216092}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Humans in our environment are of special importance to us. Even if our minds are fixated on tasks unrelated to their presence, our attention will likely be drawn towards other people's appearances and their actions. While we might remain unaware of this attentional bias at times, various studies have demonstrated the preferred visual scanning of other humans by recording eye movements in laboratory settings. The present thesis aims to investigate the circumstances under and the mechanisms by which this so-called social attention operates. The first study demonstrates that social features in complex naturalistic scenes are prioritized in an automatic fashion. After 200 milliseconds of stimulus presentation, which is too brief for top-down processing to intervene, participants targeted image areas depicting humans significantly more often than would be expected from a chance distribution of saccades. Additionally, saccades towards these areas occurred earlier in time than saccades towards non-social image regions. In the second study, we show that human features receive most fixations even when bottom-up information is restricted; that is, even when only the fixated region was visible and the remaining parts of the image masked, participants still fixated on social image regions longer than on regions without social cues. The third study compares the influence of real and artificial faces on gaze patterns during the observation of dynamic naturalistic videos. Here we find that artificial faces, belonging to humanlike statues or machines, significantly predicted gaze allocation but to a lesser extent than real faces. In the fourth study, we employed functional magnetic resonance imaging to investigate the neural correlates of reflexive social attention. Analyses of the evoked blood-oxygenation level dependent responses pointed to an involvement of striate and extrastriate visual cortices in the encoding of social feature space. Collectively, these studies help to elucidate under which circumstances social features are prioritized in a laboratory setting and how this prioritization might be achieved on a neuronal level. The final experimental chapter addresses the question whether these laboratory findings can be generalized to the real world. In this study, participants were introduced to a waiting room scenario in which they interacted with a confederate. Eye movement analyses revealed that gaze behavior heavily depended on the social context and were influenced by whether an interaction is currently desired. We further did not find any evidence for altered gaze behavior in socially anxious participants. Alleged gaze avoidance or hypervigilance in social anxiety might thus represent a laboratory phenomenon that occurs only under very specific real-life conditions. Altogether the experiments described in the present thesis thus refine our understanding of social attention and simultaneously challenge the inferences we can draw from laboratory research.}, subject = {Aufmerksamkeit}, language = {en} } @phdthesis{Geiger2020, author = {Geiger, Maximilian Johannes}, title = {Das neuronale Aufmerksamkeitsnetzwerk aus dem Gleichgewicht - Ein ‚imaging genetics' Modell der Panikst{\"o}rung}, doi = {10.25972/OPUS-16178}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161787}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Hintergrund: Eine Panikattacke beginnt typischerweise mit der Wahrnehmung einer physiologischen oder psychischen Ver{\"a}nderung, die von der Person als bedrohlich eingestuft wird. W{\"a}hrend in klassischen neuroanatomischen Modellen der Panikst{\"o}rung die Amygdala in der sich anschließenden aufschaukelnden Symptomatik in den Mittelpunkt gestellt wurde, erweitern aktuelle Studien dieses amygdalozentrische Bild und lenken die Aufmerksamkeit auf extratemporale neuronale Netzwerke. Dysfunktionen im neuronalen Aufmerksamkeitsnetzwerk, relevant f{\"u}r die Wahrnehmung und Regulierung exterozeptiver und interozeptiver Prozesse, k{\"o}nnten zur Entstehung einer Panikst{\"o}rung beitragen. Weiterhin scheinen bestimmte Risikogenotypen f{\"u}r die Panikst{\"o}rung wie z.B. im Adenosin Rezeptor 2A (ADORA2A) oder dem Neuropeptid S Rezeptor (NPSR1) Gen und die entsprechenden Neurotransmittersysteme in der Regulierung der Aufmerksamkeitsnetzwerke involviert zu sein. Fragestellung: Dysfunktionen im noradrenergen bottom-up Alertingnetzwerk und in der dopaminergen exekutiven top-down Aufmerksamkeitskontrolle k{\"o}nnten in einem neurokognitiven Entstehungsmodell der Panikst{\"o}rung eine wichtige Rolle spielen. Mit Hilfe funktioneller Bildgebung soll die Funktion des neuronalen Aufmerksamkeitsnetzwerkes in einer nichtklinischen Stichprobe abh{\"a}ngig von genetischen Risikofaktoren und einer klinischen Stichprobe von und nach einer kognitiven Verhaltenstherapie untersucht werden. Methoden: Im nichtklinischen Teil der Untersuchung wurden in Studie 1 47 gesunde Versuchspersonen f{\"u}r die NPSR1 rs324981 Variante stratifiziert rekrutiert. Mittels fMRT wurde die Aktivit{\"a}t des Alertingnetzwerks und des Executive Control Netzwerks auf neuronaler Ebene mit dem Attentional Networt Test (ANT) untersucht. In Studie 2 wurde bei N=65 Versuchspersonen stratifiziert f{\"u}r die ADORA2A rs5751876 Variante als zus{\"a}tzliches Verhaltensmaß die F{\"a}higkeit zur interozeptiven Wahrnehmung in Bezug zur Konnektivit{\"a}t im insul{\"a}ren Ruhenetzwerk untersucht. Im klinischen Teil der Untersuchung (Studie 3) wurden 44 Patienten mit Panikst{\"o}rung sowie eine entsprechend große und gematchte Kontrollgruppe rekrutiert. Es wurden fMRT Ruhemessungen vor und nach Abschluss einer kognitiven Verhaltenstherapie erhoben. Als zus{\"a}tzliches Verhaltensmaß wurde die selbstberichtete Aufmerksamkeitskontrolle zwischen der Patienten- und der Kontrollgruppe verglichen. Ergebnisse: Tr{\"a}ger des NPSR1 TT und des ADORA2A TT Risikogenotyps f{\"u}r Angst und Angsterkrankungen zeigten eine erh{\"o}hte Aktivit{\"a}t in Teilen des Alertingnetzwerks. Die Aktivit{\"a}t im Executive Control Netzwerk war arealabh{\"a}ngig teilweise erh{\"o}ht, teilweise reduziert. Innerhalb eines interozeptiven Netzwerks zeigten Tr{\"a}ger des ADORA2A TT Genotyps Hinweise auf eine dysfunktionale fronto-striatale-insul{\"a}re Interaktion. Im klinischen Teil der Studie zeigten Patienten mit Panikst{\"o}rung eine reduzierte Konnektivit{\"a}t des dorsolateralen Pr{\"a}frontalkortex (dlPFC) im fronto-parietalen Aufmerksamkeitsnetzwerk. Die Konnektivit{\"a}t innerhalb dieses Netzwerks korrelierte mit Defiziten in selbstberichteter Aufmerksamkeitskontrolle bei Patienten mit Panikst{\"o}rung. Nach Abschluss der Therapie zeigte sich bei Patienten, die von der Therapie profitiert hatten, wieder eine Zunahme oder Verbesserung der Konnektivit{\"a}t mit dem dlPFC. Schlussfolgerung: Die Ergebnisse dieser Untersuchung betonen die Rolle dysfunktionaler interozeptiver und exterozeptiver Aufmerksamkeitsnetzwerke in der Entstehung von Angsterkrankungen. Bei Patienten mit Panikst{\"o}rung sowie gesunden Versuchspersonen mit bestimmten pr{\"a}disponierenden genetischen Variationen scheint eine Dysbalance des neuronalen Aufmerksamkeitsnetzwerks bzgl. der Abstimmung von bottom-up und top-down Netzwerken vorzuliegen.}, subject = {Angstst{\"o}rung}, language = {de} } @article{AkhrifRomanosDomschkeetal.2018, author = {Akhrif, Atae and Romanos, Marcel and Domschke, Katharina and Schmitt-Boehrer, Angelika and Neufang, Susanne}, title = {Fractal Analysis of BOLD Time Series in a Network Associated With Waiting Impulsivity}, series = {Frontiers in Physiology}, volume = {9}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2018.01378}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189191}, pages = {1378}, year = {2018}, abstract = {Fractal phenomena can be found in numerous scientific areas including neuroscience. Fractals are structures, in which the whole has the same shape as its parts. A specific structure known as pink noise (also called fractal or 1/f noise) is one key fractal manifestation, exhibits both stability and adaptability, and can be addressed via the Hurst exponent (H). FMRI studies using H on regional fMRI time courses used fractality as an important characteristic to unravel neural networks from artificial noise. In this fMRI-study, we examined 103 healthy male students at rest and while performing the 5-choice serial reaction time task. We addressed fractality in a network associated with waiting impulsivity using the adaptive fractal analysis (AFA) approach to determine H. We revealed the fractal nature of the impulsivity network. Furthermore, fractality was influenced by individual impulsivity in terms of decreasing fractality with higher impulsivity in regions of top-down control (left middle frontal gyrus) as well as reward processing (nucleus accumbens and anterior cingulate cortex). We conclude that fractality as determined via H is a promising marker to quantify deviations in network functions at an early stage and, thus, to be able to inform preventive interventions before the manifestation of a disorder.}, language = {en} } @article{MouraoMirandaHardoonHahnetal.2011, author = {Mour{\~a}o-Miranda, Janaina and Hardoon, David R. and Hahn, Tim and Marquand, Andre F. and Williams, Steve C.R. and Shawe-Taylor, John and Brammer, Michael}, title = {Patient classification as an outlier detection problem: An application of the One-Class Support Vector Machine}, series = {NeuroImage}, volume = {58}, journal = {NeuroImage}, number = {3}, doi = {10.1016/j.neuroimage.2011.06.042}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141412}, pages = {793-804}, year = {2011}, abstract = {Pattern recognition approaches, such as the Support Vector Machine (SVM), have been successfully used to classify groups of individuals based on their patterns of brain activity or structure. However these approaches focus on finding group differences and are not applicable to situations where one is interested in accessing deviations from a specific class or population. In the present work we propose an application of the one-class SVM (OC-SVM) to investigate if patterns of fMRI response to sad facial expressions in depressed patients would be classified as outliers in relation to patterns of healthy control subjects. We defined features based on whole brain voxels and anatomical regions. In both cases we found a significant correlation between the OC-SVM predictions and the patients' Hamilton Rating Scale for Depression (HRSD), i.e. the more depressed the patients were the more of an outlier they were. In addition the OC-SVM split the patient groups into two subgroups whose membership was associated with future response to treatment. When applied to region-based features the OC-SVM classified 52\% of patients as outliers. However among the patients classified as outliers 70\% did not respond to treatment and among those classified as non-outliers 89\% responded to treatment. In addition 89\% of the healthy controls were classified as non-outliers.}, language = {en} }