@article{BiehlEhlisMuelleretal.2013, author = {Biehl, Stefanie C. and Ehlis, Ann-Christine and M{\"u}ller, Laura D. and Niklaus, Andrea and Pauli, Paul and Herrmann, Martin J.}, title = {The impact of task relevance and degree of distraction on stimulus processing}, series = {BMC Neuroscience}, journal = {BMC Neuroscience}, doi = {10.1186/1471-2202-14-107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97271}, year = {2013}, abstract = {Background The impact of task relevance on event-related potential amplitudes of early visual processing was previously demonstrated. Study designs, however, differ greatly, not allowing simultaneous investigation of how both degree of distraction and task relevance influence processing variations. In our study, we combined different features of previous tasks. We used a modified 1-back task in which task relevant and task irrelevant stimuli were alternately presented. The task irrelevant stimuli could be from the same or from a different category as the task relevant stimuli, thereby producing high and low distracting task irrelevant stimuli. In addition, the paradigm comprised a passive viewing condition. Thus, our paradigm enabled us to compare the processing of task relevant stimuli, task irrelevant stimuli with differing degrees of distraction, and passively viewed stimuli. EEG data from twenty participants was collected and mean P100 and N170 amplitudes were analyzed. Furthermore, a potential connection of stimulus processing and symptoms of attention deficit hyperactivity disorder (ADHD) was investigated. Results Our results show a modulation of peak N170 amplitudes by task relevance. N170 amplitudes to task relevant stimuli were significantly higher than to high distracting task irrelevant or passively viewed stimuli. In addition, amplitudes to low distracting task irrelevant stimuli were significantly higher than to high distracting stimuli. N170 amplitudes to passively viewed stimuli were not significantly different from either kind of task irrelevant stimuli. Participants with more symptoms of hyperactivity and impulsivity showed decreased N170 amplitudes across all task conditions. On a behavioral level, lower N170 enhancement efficiency was significantly correlated with false alarm responses. Conclusions Our results point to a processing enhancement of task relevant stimuli. Unlike P100 amplitudes, N170 amplitudes were strongly influenced by enhancement and enhancement efficiency seemed to have direct behavioral consequences. These findings have potential implications for models of clinical disorders affecting selective attention, especially ADHD.}, language = {en} } @article{KopfDreslerReichertsetal.2013, author = {Kopf, Juliane and Dresler, Thomas and Reicherts, Philipp and Herrmann, Martin J. and Reif, Andreas}, title = {The Effect of Emotional Content on Brain Activation and the Late Positive Potential in a Word n-back Task}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0075598}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96687}, year = {2013}, abstract = {Introduction There is mounting evidence for the influence of emotional content on working memory performance. This is particularly important in light of the emotion processing that needs to take place when emotional content interferes with executive functions. In this study, we used emotional words of different valence but with similar arousal levels in an n-back task. Methods We examined the effects on activation in the prefrontal cortex by means of functional near-infrared spectroscopy (fNIRS) and on the late positive potential (LPP). FNIRS and LPP data were examined in 30 healthy subjects. Results Behavioral results show an influence of valence on the error rate depending on the difficulty of the task: more errors were made when the valence was negative and the task difficult. Brain activation was dependent both on the difficulty of the task and on the valence: negative valence of a word diminished the increase in activation, whereas positive valence did not influence the increase in activation, while difficulty levels increased. The LPP also differentiated between the different valences, and in addition was influenced by the task difficulty, the more difficult the task, the less differentiation could be observed. Conclusions Summarized, this study shows the influence of valence on a verbal working memory task. When a word contained a negative valence, the emotional content seemed to take precedence in contrast to words containing a positive valence. Working memory and emotion processing sites seemed to overlap and compete for resources even when words are carriers of the emotional content.}, language = {en} } @article{BonnSchmittLeschetal.2013, author = {Bonn, M. and Schmitt, A. and Lesch, K.-P. and Van Bockstaele, E. J. and Asan, E.}, title = {Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei}, series = {Brain Structure and Function}, volume = {218}, journal = {Brain Structure and Function}, number = {2}, doi = {10.1007/s00429-012-0406-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132591}, pages = {421-435}, year = {2013}, abstract = {Pharmacobehavioral studies in experimental animals, and imaging studies in humans, indicate that serotonergic transmission in the amygdala plays a key role in emotional processing, especially for anxiety-related stimuli. The lateral and basolateral amygdaloid nuclei receive a dense serotonergic innervation in all species studied to date. We investigated interrelations between serotonergic afferents and neuropeptide Y (NPY)-producing neurons, which are a subpopulation of inhibitory interneurons in the rat lateral and basolateral nuclei with particularly strong anxiolytic properties. Dual light microscopic immunolabeling showed numerous appositions of serotonergic afferents on NPY-immunoreactive somata. Using electron microscopy, direct membrane appositions and synaptic contacts between serotonin-containing axon terminals and NPY-immunoreactive cellular profiles were unequivocally established. Double in situ hybridization documented that more than 50 \%, and about 30-40 \% of NPY mRNA-producing neurons, co-expressed inhibitory 5-HT1A and excitatory 5-HT2C mRNA receptor subtype mRNA, respectively, in both nuclei with no gender differences. Triple in situ hybridization showed that individual NPY mRNA-producing interneurons co-express both 5-HT1A and 5-HT2C mRNAs. Co-expression of NPY and 5-HT3 mRNA was not observed. The results demonstrate that serotonergic afferents provide substantial innervation of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei. Studies of serotonin receptor subtype co-expression indicate a differential impact of the serotonergic innervation on this small, but important, population of anxiolytic interneurons, and provide the basis for future studies of the circuitry underlying serotonergic modulation of emotional stimulus processing in the amygdala.}, language = {en} } @article{HenningsKohliCzamaraetal.2013, author = {Hennings, Johannes M. and Kohli, Martin A. and Czamara, Darina and Giese, Maria and Eckert, Anne and Wolf, Christiane and Heck, Angela and Domschke, Katharina and Arolt, Volker and Baune, Bernhard T. and Horstmann, Sonja and Br{\"u}ckl, Tanja and Klengel, Torsten and Menke, Andreas and M{\"u}ller-Myhsok, Bertram and Ising, Marcus and Uhr, Manfred and Lucae, Susanne}, title = {Possible Associations of NTRK2 Polymorphisms with Antidepressant Treatment Outcome: Findings from an Extended Tag SNP Approach}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0065636}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130924}, pages = {e64947}, year = {2013}, abstract = {Background: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. Methods: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. Results: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (\(P_{corr}\) = .018, \(P_{corr}\) = .015 and \(P_{corr}\) = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients. Conclusions/Limitations: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies.}, language = {en} } @phdthesis{Tupak2013, author = {Tupak, Sara}, title = {Modulators of Prefrontal Fear Network Function: An Integrative View}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85673}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Regulating our immediate feelings, needs, and urges is a task that we are faced with every day in our lives. The effective regulation of our emotions enables us to adapt to society, to deal with our environment, and to achieve long-term goals. Deficient emotion regulation, in contrast, is a common characteristic of many psychiatric and neurological conditions. Particularly anxiety disorders and subclinical states of increased anxiety are characterized by a range of behavioral, autonomic, and neural alterations impeding the efficient down-regulation of acute fear. Established fear network models propose a downstream prefrontal-amygdala circuit for the control of fear reactions but recent research has shown that there are a range of factors acting on this network. The specific prefrontal cortical networks involved in effective regulation and potential mediators and modulators are still a subject of ongoing research in both the animal and human model. The present research focused on the particular role of different prefrontal cortical regions during the processing of fear-relevant stimuli in healthy subjects. It is based on four studies, three of them investigating a different potential modulator of prefrontal top-down function and one directly challenging prefrontal regulatory processes. Summarizing the results of all four studies, it was shown that prefrontal functioning is linked to individual differences in state anxiety, autonomic flexibility, and genetic predisposition. The T risk allele of the neuropeptide S receptor gene, a recently suggested candidate gene for pathologically elevated anxiety, for instance, was associated with decreased prefrontal cortex activation to particularly fear-relevant stimuli. Furthermore, the way of processing has been found to crucially determine if regulatory processes are engaged at all and it was shown that anxious individuals display generally reduced prefrontal activation but may engage in regulatory processes earlier than non-anxious subjects. However, active manipulation of prefrontal functioning in healthy subjects did not lead to the typical behavioral and neural patterns observed in anxiety disorder patients suggesting that other subcortical or prefrontal structures can compensate for an activation loss in one specific region. Taken together, the current studies support prevailing theories of the central role of the prefrontal cortex for regulatory processes in response to fear-eliciting stimuli but point out that there are a range of both individual differences and peculiarities in experimental design that impact on or may even mask potential effects in neuroimaging research on fear regulation.}, subject = {Neurogenetik}, language = {en} } @article{HahnDreslerPykaetal.2013, author = {Hahn, Tim and Dresler, Thomas and Pyka, Martin and Notebaert, Karolien and Fallgatter, Andreas J.}, title = {Local Synchronization of Resting-State Dynamics Encodes Gray's Trait Anxiety}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0058336}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131057}, pages = {e58336}, year = {2013}, abstract = {The Behavioral Inhibition System (BIS) as defined within the Reinforcement Sensitivity Theory (RST) modulates reactions to stimuli indicating aversive events. Gray's trait Anxiety determines the extent to which stimuli activate the BIS. While studies have identified the amygdala-septo-hippocampal circuit as the key-neural substrate of this system in recent years and measures of resting-state dynamics such as randomness and local synchronization of spontaneous BOLD fluctuations have recently been linked to personality traits, the relation between resting-state dynamics and the BIS remains unexplored. In the present study, we thus examined the local synchronization of spontaneous fMRI BOLD fluctuations as measured by Regional Homogeneity (ReHo) in the hippocampus and the amygdala in twenty-seven healthy subjects. Correlation analyses showed that Gray's trait Anxiety was significantly associated with mean ReHo in both the amygdala and the hippocampus. Specifically, Gray's trait Anxiety explained 23\% and 17\% of resting-state ReHo variance in the left amygdala and the left hippocampus, respectively. In summary, we found individual differences in Gray's trait Anxiety to be associated with ReHo in areas previously associated with BIS functioning. Specifically, higher ReHo in resting-state neural dynamics corresponded to lower sensitivity to punishment scores both in the amygdala and the hippocampus. These findings corroborate and extend recent findings relating resting-state dynamics and personality while providing first evidence linking properties of resting-state fluctuations to Gray's BIS.}, language = {en} } @article{DuernerReineckerCsef2013, author = {D{\"u}rner, Julia and Reinecker, Hans and Csef, Herbert}, title = {Individual quality of life in patients with multiple myeloma}, series = {SpringerPlus}, volume = {2}, journal = {SpringerPlus}, number = {397}, doi = {10.1186/2193-1801-2-397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130529}, year = {2013}, abstract = {Objective: The situation of patients with multiple myeloma, whose treatment often implies high-dose chemotherapy and stem cell transplantation that can be associated with severe symptoms and psychological distress, has gained attention in recent psychooncological research. This study followed an idiographic approach in order to identify the areas of life most relevant for the interviewed myeloma patients' quality of life (QoL) as well as their current satisfaction with these. Methods: 64 patients took part in semi-structured interviews according to the SEIQoL-DW Manual (Schedule for the Evaluation of Individual Quality of Life - Direct Weighting). Visual analogue scales (VAS) were used to gain additional information about a general assessment of the present QoL. Qualitative data evaluation preceded quantitative processing. Groups were compared according to the time elapsed since diagnosis regarding specified areas of life, satisfaction with these and their relative weighting. SEIQoL-DW-indices were correlated to the VAS to reflect on an interindividually comparable parameter. Results: Personal social relationships were mentioned significantly more often as important for QoL than healthrelated aspects, and in direct comparison were weighted significantly stronger. Regarding the change of areas relevant for QoL over the time elapsed since diagnosis, there was a significant difference between groups concerning the area of spirituality. Satisfaction differed significantly between groups for the field of leisure. Conclusion: The results for the interviewed patients with multiple myeloma point out the need to take into account the importance of social and individual aspects when reflecting on QoL. Similar findings have been reported for different samples. The relevance of an individualized approach is illustrated by the fact that individually named areas of life were rated comparatively strongly in their importance for the patients' QoL. An overall assessment for the current QoL by means of VAS is regarded as an adequate supplement to the SEIQoL-Profile and an alternative to the SEIQoL-DW-Index.}, language = {en} } @article{HornSchellerduPlessisetal.2013, author = {Horn, Anne and Scheller, Carsten and du Plessis, Stefan and Arendt, Gabriele and Nolting, Thorsten and Joska, John and Sopper, Sieghart and Maschke, Matthias and Obermann, Mark and Husstedt, Ingo W. and Hain, Johannes and Maponga, Tongai and Riederer, Peter and Koutsilieri, Eleni}, title = {Increases in CSF dopamine in HIV patients are due to the dopamine transporter 10/10-repeat allele which is more frequent in HIV-infected individuals}, series = {Journal of Neural Transmission}, volume = {120}, journal = {Journal of Neural Transmission}, doi = {10.1007/s00702-013-1086-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132385}, pages = {1411-1419}, year = {2013}, abstract = {Dysfunction of dopaminergic neurotransmission has been implicated in HIV infection. We showed previously increased dopamine (DA) levels in CSF of therapy-na{\"i}ve HIV patients and an inverse correlation between CSF DA and CD4 counts in the periphery, suggesting adverse effects of high levels of DA on HIV infection. In the current study including a total of 167 HIV-positive and negative donors from Germany and South Africa (SA), we investigated the mechanistic background for the increase of CSF DA in HIV individuals. Interestingly, we found that the DAT 10/10-repeat allele is present more frequently within HIV individuals than in uninfected subjects. Logistic regression analysis adjusted for gender and ethnicity showed an odds ratio for HIV infection in DAT 10/10 allele carriers of 3.93 (95 \% CI 1.72-8.96; p = 0.001, Fishers exact test). 42.6 \% HIV-infected patients harbored the DAT 10/10 allele compared to only 10.5 \% uninfected DAT 10/10 carriers in SA (odds ratio 6.31), whereas 68.1 versus 40.9 \%, respectively, in Germany (odds ratio 3.08). Subjects homozygous for the 10-repeat allele had higher amounts of CSF DA and reduced DAT mRNA expression but similar disease severity compared with those carrying other DAT genotypes. These intriguing and novel findings show the mutual interaction between DA and HIV, suggesting caution in the interpretation of CNS DA alterations in HIV infection solely as a secondary phenomenon to the virus and open the door for larger studies investigating consequences of the DAT functional polymorphism on HIV epidemiology and progression of disease.}, language = {en} } @article{SchaefferKuehnSchmittetal.2013, author = {Schaeffer, Evelin L. and K{\"u}hn, Franziska and Schmitt, Angelika and Gattaz, Wagner F. and Gruber, Oliver and Schneider-Axmann, Thomas and Falkai, Peter and Schmitt, Andrea}, title = {Increased cell proliferation in the rat anterior cingulate cortex following neonatal hypoxia: relevance to schizophrenia}, series = {Journal of Neural Transmission}, volume = {120}, journal = {Journal of Neural Transmission}, number = {1}, doi = {10.1007/s00702-012-0859-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125890}, pages = {187-195}, year = {2013}, abstract = {As a consequence of obstetric complications, neonatal hypoxia has been discussed as an environmental factor in the pathophysiology of schizophrenia. However, the biological consequences of hypoxia are unclear. The neurodevelopmental hypothesis of schizophrenia suggests that the onset of abnormal brain development and neuropathology occurs perinatally, whereas symptoms of the disease appear in early adulthood. In our animal model of chronic neonatal hypoxia, we have detected behavioral alterations resembling those known from schizophrenia. Disturbances in cell proliferation possibly contribute to the pathophysiology of this disease. In the present study, we used postnatal rats to investigate cell proliferation in several brain areas following neonatal hypoxia. Rats were repeatedly exposed to hypoxia (89 \% N2, 11 \% O2) from postnatal day (PD) 4-8. We then evaluated cell proliferation on PD 13 and 39, respectively. These investigations were performed in the anterior cingulate cortex (ACC), caudate-putamen (CPU), dentate gyrus, and subventricular zone. Rats exposed to hypoxia exhibited increased cell proliferation in the ACC at PD 13, normalizing at PD 39. In other brain regions, no alterations have been detected. Additionally, hypoxia-treated rats showed decreased CPU volume at PD 13. The results of the present study on the one hand support the assumption of chronic hypoxia influencing transient cell proliferation in the ACC, and on the other hand reveal normalization during ageing.}, language = {en} } @article{BorchersMuellerSynofziketal.2013, author = {Borchers, Svenja and M{\"u}ller, Laura and Synofzik, Matthis and Himmelbach, Marc}, title = {Guidelines and quality measures for the diagnosis of optic ataxia}, series = {Frontiers in Human Neuroscience}, volume = {7}, journal = {Frontiers in Human Neuroscience}, number = {324}, issn = {1662-5161}, doi = {10.3389/fnhum.2013.00324}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122439}, year = {2013}, abstract = {Since the first description of a systematic mis-reaching by Balint in 1909, a reasonable number of patients showing a similar phenomenology, later termed optic ataxia (OA), has been described. However, there is surprising inconsistency regarding the behavioral measures that are used to detect OA in experimental and clinical reports, if the respective measures are reported at all. A typical screening method that was presumably used by most researchers and clinicians, reaching for a target object in the peripheral visual space, has never been evaluated. We developed a set of instructions and evaluation criteria for the scoring of a semi-standardized version of this reaching task. We tested 36 healthy participants, a group of 52 acute and chronic stroke patients, and 24 patients suffering from cerebellar ataxia. We found a high interrater reliability and a moderate test-retest reliability comparable to other clinical instruments in the stroke sample. The calculation of cut-off thresholds based on healthy control and cerebellar patient data showed an unexpected high number of false positives in these samples due to individual outliers that made a considerable number of errors in peripheral reaching. This study provides first empirical data from large control and patient groups for a screening procedure that seems to be widely used but rarely explicitly reported and prepares the grounds for its use as a standard tool for the description of patients who are included in single case or group studies addressing optic ataxia similar to the use of neglect, extinction, or apraxia screening tools.}, language = {en} }