@article{BremGruenblattDrechsleretal.2014, author = {Brem, Silvia and Gr{\"u}nblatt, Edna and Drechsler, Renate and Riederer, Peter and Walitza, Susanne}, title = {The neurobiological link between OCD and ADHD}, series = {Attention Deficit and Hyperactivity Disorders}, volume = {6}, journal = {Attention Deficit and Hyperactivity Disorders}, number = {3}, doi = {10.1007/s12402-014-0146-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121312}, pages = {175-202}, year = {2014}, abstract = {Obsessive compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) are two of the most common neuropsychiatric diseases in paediatric populations. The high comorbidity of ADHD and OCD with each other, especially of ADHD in paediatric OCD, is well described. OCD and ADHD often follow a chronic course with persistent rates of at least 40-50 \%. Family studies showed high heritability in ADHD and OCD, and some genetic findings showed similar variants for both disorders of the same pathogenetic mechanisms, whereas other genetic findings may differentiate between ADHD and OCD. Neuropsychological and neuroimaging studies suggest that partly similar executive functions are affected in both disorders. The deficits in the corresponding brain networks may be responsible for the perseverative, compulsive symptoms in OCD but also for the disinhibited and impulsive symptoms characterizing ADHD. This article reviews the current literature of neuroimaging, neurochemical circuitry, neuropsychological and genetic findings considering similarities as well as differences between OCD and ADHD.}, 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} } @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{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} } @phdthesis{Endres2019, author = {Endres, Ralph Julian}, title = {Networks of fear: Functional connectivity of the amygdala, the insula and the anterior cingulate cortex in two subtypes of specific phobia}, doi = {10.25972/OPUS-18095}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180950}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Neuroimaging research has highlighted the relevance of well-balanced functional brain interactions as an essential basis for efficient emotion regulation. In contrast, abnormal coupling of fear-processing regions such as the amygdala, the anterior cingulate cortex (ACC) and the insula could be an important feature of anxiety disorders. Although activity alterations of these regions have been frequently reported in specific phobia, little is known about their functional interactions during phobogenic stimulus processing. To explore these interrelationships in two subtypes of specific phobia - i.e., the blood-injection-injury subtype and the animal subtype - functional connectivity (FC) was analyzed in three fMRI studies. Two studies examined fear processing in a dental phobia group (DP), a snake phobia group (SP) and a healthy control group (HC) during visual phobogenic stimuli presentation while a third study investigated differences between auditory and visual stimuli presentation in DP and HC. Due to a priori hypotheses of impaired interactions between the amygdala, the ACC and the insula, a first analysis was conducted to explore the FC within these three regions of interest. Based on emerging evidence of functionally diverse subregions, the ACC was further divided into a subgenual, pregenual and dorsal ACC and the insula was divided into a ventral-anterior, dorsal-anterior and posterior region. Additionally, an exploratory seed-to-voxel analysis using the amygdala, ACC and insula as seeds was conducted to scan for connectivity patterns across the whole brain. The analyses revealed a negative connectivity of the ACC and the amygdala during phobogenic stimulus processing in controls. This connectivity was predominantly driven by the affective ACC subdivision. By contrast, SP was characterized by an increased mean FC between the examined regions. Interestingly, this phenomenon was specific for auditory, but not visual symptom provocation in DP. During visual stimulus presentation, however, DP exhibited further FC alterations of the ACC and the insula with pre- and orbitofrontal regions. These findings mark the importance of balanced interactions between fear-processing regions in specific phobia, particularly of the inhibitory connectivity between the ACC and the amygdala. Theoretically, this is assumed to reflect top-down inhibition by the ACC during emotion regulation. The findings support the suggestion that SP particularly is characterized by excitatory, or missing inhibitory, (para-) limbic connectivity, reflecting an overshooting fear response based on evolutionary conserved autonomic bottom-up pathways. Some of these characteristics applied to DP as well but only under the auditory stimulation, pointing to stimulus dependency. DP was further marked by altered pre- and orbitofrontal coupling with the ACC and the insula which might represent disturbances of superordinate cognitive control on basal emotion processes. These observations strengthen the assumption that DP is predominantly based on evaluation-based fear responses. In conclusion, the connectivity patterns found may depict an intermediate phenotype that possibly confers risks for inappropriate phobic fear responses. The findings presented could also be of clinical interest. Particularly the ACC - amygdala circuit may be used as a predictive biomarker for treatment response or as a promising target for neuroscience-focused augmentation strategies as neurofeedback or repetitive transcranial magnetic stimulation.}, subject = {Kernspintomografie}, language = {en} } @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} } @article{BiehlMerzDresleretal.2016, author = {Biehl, Stefanie C. and Merz, Christian J. and Dresler, Thomas and Heupel, Julia and Reichert, Susanne and Jacob, Christian P. and Deckert, J{\"u}rgen and Herrmann, Martin J.}, title = {Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty?}, series = {International Journal of Neuropsychopharmacology}, volume = {19}, journal = {International Journal of Neuropsychopharmacology}, number = {10}, doi = {10.1093/ijnp/pyw049}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147551}, pages = {pyw049}, year = {2016}, abstract = {Background: Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Methods: Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. Results: There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Conclusions: Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes.}, 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{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{XiuGeigerKlaver2015, author = {Xiu, Daiming and Geiger, Maximilian J. and Klaver, Peter}, title = {Emotional face expression modulates occipital-frontal effective connectivity during memory formation in a bottom-up fashion}, series = {Frontiers in Behavioral Neuroscience}, volume = {9}, journal = {Frontiers in Behavioral Neuroscience}, number = {90}, doi = {10.3389/fnbeh.2015.00090}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143211}, year = {2015}, abstract = {This study investigated the role of bottom-up and top-down neural mechanisms in the processing of emotional face expression during memory formation. Functional brain imaging data was acquired during incidental learning of positive ("happy"), neutral and negative ("angry" or "fearful") faces. Dynamic Causal Modeling (DCM) was applied on the functional magnetic resonance imaging (fMRI) data to characterize effective connectivity within a brain network involving face perception (inferior occipital gyrus and fusiform gyrus) and successful memory formation related areas (hippocampus, superior parietal lobule, amygdala, and orbitofrontal cortex). The bottom-up models assumed processing of emotional face expression along feed forward pathways to the orbitofrontal cortex. The top-down models assumed that the orbitofrontal cortex processed emotional valence and mediated connections to the hippocampus. A subsequent recognition memory test showed an effect of negative emotion on the response bias, but not on memory performance. Our DCM findings showed that the bottom-up model family of effective connectivity best explained the data across all subjects and specified that emotion affected most bottom-up connections to the orbitofrontal cortex, especially from the occipital visual cortex and superior parietal lobule. Of those pathways to the orbitofrontal cortex the connection from the inferior occipital gyrus correlated with memory performance independently of valence. We suggest that bottom-up neural mechanisms support effects of emotional face expression and memory formation in a parallel and partially overlapping fashion.}, language = {en} }