TY - JOUR A1 - Akhrif, Atae A1 - Romanos, Marcel A1 - Domschke, Katharina A1 - Schmitt-Boehrer, Angelika A1 - Neufang, Susanne T1 - Fractal Analysis of BOLD Time Series in a Network Associated With Waiting Impulsivity JF - Frontiers in Physiology N2 - 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. KW - fMRI KW - Hurst Exponent KW - frontal cortex KW - nucleus accumbens KW - biomarker KW - impulse control disorders Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189191 SN - 1664-042X VL - 9 ER - TY - JOUR A1 - Albrecht, Franziska A1 - Mueller, Karsten A1 - Ballarini, Tommaso A1 - Lampe, Leonie A1 - Diehl-Schmid, Janine A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Jahn, Holger A1 - Jech, Robert A1 - Kassubek, Jan A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Ludolph, Albert C. A1 - Lyros, Epameinondas A1 - Prudlo, Johannes A1 - Schneider, Anja A1 - Synofzik, Matthis A1 - Wiltfang, Jens A1 - Danek, Adrian A1 - Otto, Markus A1 - Schroeter, Matthias L. T1 - Unraveling corticobasal syndrome and alien limb syndrome with structural brain imaging JF - Cortex N2 - Alien limb phenomenon is a rare syndrome associated with a feeling of non-belonging and disowning toward one's limb. In contrast, anarchic limb phenomenon leads to involuntary but goal-directed movements. Alien/anarchic limb phenomena are frequent in corticobasal syndrome (CBS), an atypical parkinsonian syndrome characterized by rigidity, akinesia, dystonia, cortical sensory deficit, and apraxia. The structure function relationship of alien/anarchic limb was investigated in multi centric structural magnetic resonance imaging (MRI) data. Whole-group and single subject comparisons were made in 25 CBS and eight CBS-alien/anarchic limb patients versus controls. Support vector machine was used to see if CBS with and without alien/anarchic limb could be distinguished by structural MRI patterns. Whole-group comparison of CBS versus controls revealed asymmetric frontotemporal atrophy. CBS with alien/anarchic limb syndrome versus controls showed frontoparietal atrophy including the supplementary motor area contralateral to the side of the affected limb. Exploratory analysis identified frontotemporal regions encompassing the pre-/and postcentral gyrus as compromised in CBS with alien limb syndrome. Classification of CBS patients yielded accuracies of 79%. CBS-alien/anarchic limb syndrome was differentiated from CBS patients with an accuracy of 81%. Predictive differences were found in the cingulate gyrus spreading to frontomedian cortex, postcentral gyrus, and temporoparietoocipital regions. We present the first MRI-based group analysis on CBS-alien/anarchic limb. Results pave the way for individual clinical syndrome prediction and allow understanding the underlying neurocognitive architecture. (C) 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). KW - Alien limb syndrome KW - Anarchic limb syndrome KW - Corticobasal syndrome KW - Diagnosis prediction KW - Support vector machine Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221040 VL - 117 ER - TY - JOUR A1 - Appel, Patricia A1 - Schuler, Michael A1 - Vogel, Heiner A1 - Oezelsel, Amina A1 - Faller, Hermann T1 - Short Questionnaire for Workplace Analysis (KFZA): factorial validation in physicians and nurses working in hospital settings JF - Journal of Occupational Medicine and Toxicology N2 - Background: In recent years, there has been an increasing interest in psychosocial workplace risk assessments in Germany. One of the questionnaires commonly employed for this purpose is the Short Questionnaire for Workplace Analysis (KFZA). Originally, the KFZA was developed and validated for office workers. The aim of the present study was to examine the factorial validity of the KFZA when applied to hospital settings. Therefore, we examined the factorial structure of a questionnaire that contained all the original items plus an extension adding 11 questions specific to hospital workplaces and analyzed both, the original version and the extended version. Methods: We analyzed questionnaire data of a total of 1731 physicians and nurses obtained over a 10-year period. Listwise exclusion of data sets was applied to account for variations in questionnaire versions and yielded 1163 questionnaires (1095 for the extended version) remaining for factor analysis. To examine the factor structure, we conducted a principal component factor analysis. The number of factors was determined using the Kaiser criterion and scree-plot methods. Factor interpretation was based on orthogonal Varimax rotation as well as oblique rotation. Results: The Kaiser criterion revealed a 7-factor solution for the 26 items of the KFZA, accounting for 62.0% of variance. The seven factors were named: “Social Relationships”, “Job Control”, “Opportunities for Participation and Professional Development”, “Quantitative Work Demands”, “Workplace Environment”, “Variability” and “Qualitative Work Demands”. The factor analysis of the 37 items of the extended version yielded a 9-factor solution. The two additional factors were named “Consequences of Strain” and “Emotional Demands”. Cronbach’s α ranged from 0.63 to 0.87 for these scales. Conclusions: Overall, the KFZA turned out to be applicable to hospital workers, and its content-related structure was replicated well with some limitations. However, instead of the 11 factors originally proposed for office workers, a 7-factor solution appeared to be more suitable when employed in hospitals. In particular, the items of the KFZA factor “Completeness of Task” might need adaptation for the use in hospitals. Our study contributes to the assessment of the validity of this popular instrument and should stimulate further psychometric testing. KW - KFZA KW - mental health KW - work-related stress KW - hospital KW - psychosocial workplace risk assessment KW - validation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157510 VL - 12 IS - 11 ER - TY - THES A1 - Araragi, Naozumi T1 - Electrophysiological investigation of two animal models for emotional disorders - serotonin transporter knockout mice and tryptophan hydroxylase 2 knockout mice T1 - Elektrophysiologische Untersuchung bei zwei Tiermodellen für emotionale Störungen - Serotonin Transporter knockout Mäuse und Tryptophan Hydroxylase 2 knockout Mäuse N2 - Serotonin (5-HT) has been implicated in the regulation of emotions as well as in its pathological states, such as anxiety disorders and depression. Mice with targeted deletion of genes encoding various mediators of central serotonergic neurotransmission therefore provides a powerful tool in understanding contributions of such mediators to homeostatic mechanisms as well as to the development of human emotional disorders. Within this thesis a battery of electrophysiological recordings were conducted in the dorsal raphe nucleus (DRN) and the hippocampus of two murine knockout lines with deficient serotonergic systems. Serotonin transporter knockout mice (5-Htt KO), which lack protein responsible for reuptake of 5-HT from the extracellular space and tryptophan hydroxylase 2 knockout (Tph2 KO) mice, which lack the gene encoding the neuronal 5-HT-synthesising enzyme. First, 5-HT1A receptor-mediated autoinhibition of serotonergic neuron firing in the DRN was assessed using the loose-seal cell-attached configuration. Stimulation of 5-HT1A receptors by a selective agonist, R-8-hydroxy-2-(di-n-propylamino)tetralin (R-8-OH-DPAT), showed a mild sensitisation and a marked desensitisation of these receptors in Tph2 KO and 5-Htt KO mice, respectively. While application of tryptophan, a precursor of 5-HT and a substrate of Tph2, did not cause autoinhibition in Tph2 KO mice due to the lack of endogenously produced 5-HT, data from 5-Htt KO mice as well as heterozygous mice of both KO mice lines demonstrated the presence of autoinhibitory mechanisms as normal as seen in wildtype (WT) controls. When the Tph2-dependent step in the 5-HT synthesis pathway was bypassed by application of 5-hydroxytryptophan (5-HTP), serotonergic neurons of both Tph2 KO and 5-Htt KO mice showed decrease in firing rates at lower concentrations of 5-HTP than in WT controls. Elevated responsiveness of serotonergic neurons from Tph2 KO mice correspond to mild sensitisation of 5-HT1A receptors, while responses from 5-Htt KO mice suggest that excess levels of extracellular 5-HT, created by the lack of 5-Htt, stimulates 5-HT1A receptors strong enough to overcome desensitisation of these receptors. Second, the whole-cell patch clamp recording data from serotonergic neurons in the DRN showed no differences in basic electrophysiological properties between Tph2 KO and WT mice, except lower membrane resistances of neurons from KO mice. Moreover, the whole-cell patch clamp recording from CA1 pyramidal neurons in the hippocampus of 5-Htt KO mice showed increased conductance both at a steady state and at action potential generation. Lastly, magnitude of long-term potentiation (LTP) induced by the Schaffer collateral/commissural pathway stimulation in the ventral hippocampus showed no differences among Tph2 KO, 5-Htt KO, and WT counterparts. Taken together, lack and excess of extracellular 5-HT caused sensitisation and desensitisation of autoinhibitory 5-HT1A receptors, respectively. However, this may not directly translate to the level of autoinhibitory regulation of serotonergic neuron firing when these receptors are stimulated by endogenously synthesised 5-HT. In general, KO mice studied here showed an astonishing level of resilience to genetic manipulations of the central serotonergic system, maintaining overall electrophysiological properties and normal LTP inducibility. This may further suggest existence of as-yet-unknown compensatory mechanisms buffering potential alterations induced by genetic manipulations. N2 - Serotonin (5-HT) ist an der Regulation von der Emotionen, sowie ihrer pathologischen Zustände, wie Angststörungen und Depressionen beteiligt. Mäuse denen, mittels einer zielgerichteteten Deletion von Genen, die verschiedenste Proteine involviert in der zentralen serotonergen Nerotransmission fehlen, dienen daher als ein nützliches Tiermodell, um die Rolle dieser Mediatoren bei Homöostasemechanismen und der Entwicklung emotionaler Störungen beim Menschen zu verstehen. Im Rahmen dieser Thesis wurde eine Batterie von elektrophysiologischen Ableitungen im Hippocampus sowie in der dorsalen Raphe Nucleus (DRN) zweier Knockout-Mauslinien mit einem defizienten serotonergen Systems durchgeführt. Serotonintransporter Knockout-Mäuse (5-Htt KO), denen das Protein zur Wiederaufnahme von 5-HT aus dem extrazellulären Raum fehlt und Tryptophanhydroxylase 2 Knockout-Mäuse (Tph2 KO), denen das Gen für das 5-HT-synthetisierende Enzym im Gehirn fehlt. Zunächst wurde mittels der “loose-seal cell-attached” Aufnahmemethode die Eigenhemmung der serotonergen Neuronen untersucht, die durch 5-HT1A Rezeptoren in der DRN vermittelt wird. Stimulierung der 5-HT1A Rezeptoren durch einen selektiven Agonist, R-8-hydroxy-2-(di-n-propylamino)tetralin (R-8-OH-DPAT), zeigte eine milde Sensibilisierung und eine deutliche Desensibilisierung dieser Rezeptoren in Tph2 KO bzw. in 5-Htt KO Mäusen. Während die Anwendung von Tryptophan, eine Vorstufe von 5-HT und ein Substrat der Tph2, keine Eigenhemmung, aufgrund des Mangels an endogen produziertem 5-HT, in Tph2 KO Mäusen verursachte, wiesen Daten von 5-Htt KO Mäusen sowie von heterozygoten Mäusen beider KO Mauslinien die Existenz der Eigenhemmungsmechanismen wie in den Wildtypen (WT) nach. Wurde der Tph2-abhängige Schritt im 5-HT Syntheseweg durch Anwendung von 5-Hydroxytryptophan (5-HTP) umgangen, zeigten sowohl Tph2 KO als auch 5-Htt KO Mäuse eine Verminderung der serotonergen neuronalen Feuerungsrate bei niedrigeren Konzentrationen von 5-HTP im Vergleich zu den WT. Die erhöhte Reaktionsfähigkeit der serotonergen Neuronen von Tph2 KO Mäusen entsprechen der milden Sensibilisierung der 5-HT1A Rezeptoren. Stattdessen deuten die Reaktionen der serotonergen Neuronen von 5-Htt KO Mäusen darauf hin, dass das überschüssige Niveau von extrazellularem 5-HT, welches durch den Mangel an 5-Htt verursacht wird, 5-HT1A Rezeptoren stark genug stimuliert, um eine Desensibilisierung dieser Rezeptoren zu überwinden. Zweitens zeigten die Daten der whole-cell Patch Clamp Ableitung von serotonergen Neuronen im DRN keine Unterschiede in grundlegenden elektrophysiologischen Eigenschaften zwischen Tph2 KO und WT, außer niedrigen Membranwiderständen in KO Mäusen. Darüber hinaus zeigte die whole-cell Patch Clamp Ableitungen von CA1 Pyramidenzellen im Hippocampus der 5-Htt KO Mäuse eine erhöhte Leitfähigkeit sowohl bei Ruheständen als auch bei Aktionspotentialerzeugungen. Schließlich zeigte die Stärke der Langzeitpotenzierung (long-term potentiation: LTP) durch die Stimulation der Schaffer-Kollateralen/kommissuralen Fasern im ventralen Hippocampus keine Unterschiede zwischen Tph2 KO, 5-Htt KO, und jeweiligen WT. Zusammengefasst verursachten der Mangel und der Überschuss von extrazellularen 5-HT eine Sensibilisierung bzw. Desensibilisierung der autoinhibitorischen 5-HT1A Rezeptoren. Dies kann jedoch nicht direkt in die Regulierung von serotonergen Neuronen Feuerung umgesetzt werden, wenn die 5-HT1A Rezeptoren durch endogen synthetisiertes 5-HT stimuliert werden. Im Allgemeinen zeigten die hier untersuchten KO Mäuse, ein erstaunliches Maß an Widerstandskraft, die die allgemeinen elektrophysiologischen Eigenschaften und die normale LTP Induzierbarkeit trotz genetischer Manipulationen des zentralen serotonergen Systems aufrechterhielt. Weiterhin deutet dies auf die Existenz noch unbekannter Kompensationsmechanismen hin, die diese potentiellen Veränderungen abzudämpfen scheinen. KW - Serotonin KW - Elektrophysiologie KW - Tryptophan hydroxylase 2 KW - Knockout KW - Serotonin transporter KW - Depression KW - Anxiety KW - Knockout KW - Maus Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-83265 ER - TY - JOUR A1 - Araragi, Naozumi A1 - Mlinar, Boris A1 - Baccini, Gilda A1 - Gutknecht, Lise A1 - Lesch, Klaus-Peter A1 - Corradetti, Renato T1 - Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT) neurons in mice with altered 5-HT homeostasis JF - Frontiers in Neuropharmacology N2 - Firing activity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert-/-) and tryptophan hydroxylase-2 knockout (Tph2-/-) mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+)-8-hydroxy-2-(di-n-propylamino)tetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2-/- mice and Sert-/- mice, respectively. While 5-HT neurons from Tph2-/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert-/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP), neurons from both Tph2-/- and Sert-/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling. KW - serotonin transporter KW - tryptophan hydroxylase-2 KW - knockout KW - dorsal raphe nucleus KW - autoinhibition KW - 5-HT1A receptor Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97098 ER - TY - THES A1 - Asthana, Manish T1 - Associative learning – Genetic modulation of extinction and reconsolidation and the effects of transcranial Direct Current Stimulation (tDCS) T1 - Assoziatives Lernen - Genetische Modulation der Auslöschung und Rück-verfestigung und die Auswirkungen der transkraniellen Gleichstromstimulation (tDCS) N2 - Scientific surveys provide sufficient evidence that anxiety disorders are one of the most common psy-chiatric disorders in the world. The lifetime prevalence rate of anxiety disorder is 28.8% (Kessler, et al., 2005). The most widely studied anxiety disorders are as follows panic disorder (PD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), social phobia (or social anxiety disorder), specific phobias, and generalized anxiety disorder (GAD). (NIMH Article, 2009). Classical conditioning is the stable paradigm used from the last one century to understand the neurobi-ology of fear learning. Neurobiological mechanism of fear learning is well documented with the condi-tioning studies. In the therapy of anxiety disorders, exposure based therapies are known to be the most effective approaches. Flooding is a form of exposure therapy in which a participant is exposed to the fear situation and kept in that situation until their fear dissipates. The exposure therapy is based on the phenomena of extinction; this means that a conditioned response diminishes if the conditioned stimulus (CS) is repeatedly presented without an unconditioned stimulus (UCS). One problem with extinction as well as with exposure-based therapy is the problem of fear return (for e.g. renewal, spontaneous recov-ery and reinstatement) after successful extinction. Therefore, extinction does not delete the fear memory trace. It has been well documented that memory processes can be modulated or disrupted using several sci-entific paradigms such as behavioral (for e.g. exposure therapy), pharmacological (for e.g. drug manipu-lation), non-invasive stimulation (for e.g. non-invasive stimulation such as electroconvulsive shock (ECS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), etc. However, modulation of memory processes after reactivation or via non-invasive stimulation is still not clear, which is the focus of the current study. In addition, study of genetic variant suggests that genetic differences play a vital role in the psychiatric disorder especially in fear learning. Hence, it is also one of the concerns of the current dissertation to investigate the interaction between gene and reconsolidation of memory. With respect to fear-conditioning, there are three findings in the current dissertation, which are as fol-lows: (i) In the first study we investigated that non-invasive weak electrical stimulation interferes with the consolidation process and disrupts the fear consolidation to attain stable form. This might offer an effective treatment in the pathological memories, for e.g. PTSD, PD, etc. (ii) In the second study we demonstrated whether a brief single presentation of the CS will inhibit the fear recovery. Like earlier studies we also found that reactivation followed by reconsolidation douses fear return. Attenuation of fear recovery was observed in the reminder group compared to the no-reminder group. (iii) Finally, in our third study we found a statistically significant role of brain derived neurotrophic factor (BDNF) polymorphism in reconsolidation. Results of the third study affirm the involvement of BDNF variants (Met vs. Val) in the modulation of conditioned fear memory after its reactivation. In summary, we were able to show in the current thesis modulation of associative learning and recon-solidation via transcranial direct current stimulation and genetic polymorphism. N2 - Mit einer lebenslangen Prävalenz von etwa 28% (Kessler Rc, 2005) stellen Angststörungen eine der häufigsten psychischen Störungen weltweit dar. Zu den am besten untersuchten Angststörungen gehö-ren Panikstörungen (PD), posttraumatische Belastungsstörungen (PTSD), Zwangsstörungen (OCD), soziale Phobien (oder soziale Angststörungen), spezifische Phobien und generalisierte Angststörungen (GAD) (NIMH Artikel, 2009). Die klassische Konditionierung ist das seit dem letzten Jahrhundert gültige Paradigma zur Erforschung der neurobiologischen Mechanismen des Angstlernens. Bei der Behandlung von Angststörungen haben sich Konfrontationstherapien als äußerst wirksam herausgestellt. Reizüberflutung (Flooding) ist bei-spielsweise eine Form der Konfrontationstherapie, bei der der Teilnehmer einer furchteinflößenden Situation ausgesetzt und in ihr gehalten wird, bis seine Furcht vergeht. Die Konfrontationstherapie ba-siert auf dem Phänomen der Extinktion, also dem Rückgang eines konditionierten Verhaltens nach wie-derholter Präsentation eines konditionierten Stimulus (CS) ohne einen unkonditionierten Stimulus (UCS). Ein Problem der Extinktion und der Konfrontationstherapien ist, dass das Furchtgefühl nach einer erfolgreichen Extinktion zurückkehren kann, was darauf hinweist, dass eine Extinktion nicht die Spuren des Angstgedächtnisses löscht. Vieles deutet darauf, dass der Erinnerungsprozess mittels verschiedenener wissenschaftlicher Para-digmen moduliert oder unterbrochen werden kann. Hierzu gehören etwa behavioristische (z.B. Kon-frontationstherapie), pharmakologische oder nicht-invasive Interventionen (z.B. Elektrokonvulsions-therapie (ECS), transkranielle Magnetstimulation (TMS) oder transkranielle Gleichstromstimulation (tDCS)). Da die Modulation von Erinnerungsprozessen nach einer Reaktivierung oder durch eine nicht-invasive Stimulation derzeit noch unzureichend erforscht ist, wurde der Schwerpunkt der vorliegenden Studie auf diese Thematik gelegt. Ein weiteres Ziel ist es, die Wechselwirkung bestimmter Gene mit der Rekonsolidierung des Gedächtnisses zu untersuchen, also Prozesse, denen eine entscheidende Rolle für Angststörungen im Allgemeinen und Furcht-Lernen im Speziellen zugeschrieben wird. Die vorliegende Dissertation umfasst drei zentrale Ergebnisse zur konditionierten Angst: (i.) In der ers-ten Studie wurde herausgefunden, dass eine nicht-invasive, schwache Stimulation den Konsolidie-rungsprozess beeinflusst und verhindert, dass die Angstkonsolidierung eine stabile Form erreicht. Dies könnte eine neue Möglichkeit darstellen, pathologische Gedächtnisinhalte, die z.B. bei Störungen wie PTSD oder PD vorkommen, effektiv zu behandeln. (ii.) Die zweite Studie untersuchte, ob eine kurze, einfache Präsentation des CS das Wiederaufkommen von Angst hemmen kann. Ähnlich wie in früheren Studien beschrieben, fanden auch wir, dass eine Reaktivierung gefolgt von einer Rekonsolidierung die Rückkehr der Angst unterbindet. Insbesondere wurde in der Gruppe, deren Teilnehmer erneut kon-frontiert wurden (reminder), im Vergleich zur Kontroll-Gruppe (no-reminder) ein verringertes Wieder-aufkommen von Angst beobachtet. (iii.) Die dritte Studie zeigte, dass ein Polymorphismus im BDNF-Gen (Met vs Val) eine signifikante Rolle für die Rekonsolidierung und die Modulation des konditionierten Angstgedächtnisses nach seiner Reaktivierung spielt. KW - Konditionierung KW - Angststörung KW - Associative learning KW - transcranial Direct Current Stimulation (tDCS) KW - Elektrotherapie KW - Brain-derived neurotrophic factor KW - Assoziatives Lernen KW - transkranielle Gleichstromstimulation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-84158 ER - TY - JOUR A1 - Asthana, Manish Kumar A1 - Brunhuber, Bettina A1 - Mühlberger, Andreas A1 - Reif, Andreas A1 - Schneider, Simone A1 - Herrmann, Martin J. T1 - Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism JF - International Journal of Neuropsychopharmacology N2 - Background: Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. Methods: An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. Results: The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Conclusions: Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans. KW - BDNF KW - brain derived neurotrophic factor KW - fear conditioning KW - genetics memory KW - reconsolidation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166217 VL - 19 IS - 6 ER - TY - JOUR A1 - Baader, Anna A1 - Kiani, Behnaz A1 - Brunkhorst-Kanaan, Nathalie A1 - Kittel-Schneider, Sarah A1 - Reif, Andreas A1 - Grimm, Oliver T1 - A within-sample comparison of two innovative neuropsychological tests for assessing ADHD JF - Brain Sciences N2 - New innovative neuropsychological tests in attention deficit hyperactivity disorder ADHD have been proposed as objective measures for diagnosis and therapy. The current study aims to investigate two different commercial continuous performance tests (CPT) in a head-to-head comparison regarding their comparability and their link with clinical parameters. The CPTs were evaluated in a clinical sample of 29 adult patients presenting in an ADHD outpatient clinic. Correlational analyses were performed between neuropsychological data, clinical rating scales, and a personality-based measure. Though inattention was found to positively correlate between the two tests (r = 0.49, p = 0.01), no association with clinical measures and inattention was found for both tests. While hyperactivity did not correlate between both tests, current ADHD symptoms were positively associated with Nesplora Aquarium's motor activity (r = 0.52 to 0.61, p < 0.05) and the Qb-Test's hyperactivity (r = 0.52 to 0.71, p < 0.05). Conclusively, the overall comparability of the tests was limited and correlation with clinical parameters was low. While our study shows some interesting correlation between clinical symptoms and sub-scales of these tests, usage in clinical practice is not recommended. KW - ADHD KW - neuropsychology KW - continuous performance test KW - Qb-Test KW - Nesplora Aquarium KW - attention KW - hyperactivity KW - GHQ-28 KW - UPPS KW - impulsivity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-220089 SN - 2076-3425 VL - 11 IS - 1 ER - TY - JOUR A1 - Barteit, Sandra A1 - Hoepffner, Philip A1 - Huwendiek, Sören A1 - Karamagi, Angela A1 - Munthali, Charles A1 - Theurer, Antje A1 - Neuhann, Florian T1 - Self-directed e-learning at a tertiary hospital in Malawi - a qualitative evaluation and lessons learnt JF - GMS Journal for Medical Education N2 - Background: Malawi faces a severe lack of health workers. Despite initiatives to address this problem, a critical shortage of health care staff remains. This lack challenges the education and training of junior medical staff, especially medical interns in their final and crucial training year before they independently work as medical doctors. Project description: We have introduced an e-learning platform in the medical department of the Kamuzu Central Hospital (KCH) in Malawi. With the support of computer-assisted instruction, we aimed to improve the quality of medical training and education, as well as access to current medical materials, in particular for interns. Method: From March to April 2012, we conducted a qualitative evaluation to assess relevance and appropriateness of the e-learning platform. Data was collected via face-to-face interviews, a guided group discussion and a checklist based observation log. Evaluation data was recorded and coded using content analysis, interviewees were chosen via purposive sampling. Results: E-learning proved to be technically feasible in this setting. Users considered the e-learning platform to be relevant and appropriate. Concerns were raised about sustainability, accessibility and technical infrastructure, as well as limited involvement and responsibilities of Malawian partners. Interest in e-learning was high, yet, awareness of and knowledge about the e-learning platform among potential users was low. Evaluation results indicated that further adaptions to local needs are necessary to increase usage and accessibility. Conclusions: Interview results and our project experiences showed that, in the given setting, e-learning requires commitment from local stakeholders, adequate technical infrastructure, identification and assignation of responsibilities, as well as specific adaption to local needs. T2 - Selbstgesteuertes medizinisches Lernen via E-Learning an einem Lehrkrankenhaus in Malawi: Aufbau,Erkenntnisse und Erfahrungen KW - computer-assisted instruction KW - capacity KW - multimedia, KW - ICT KW - virtual patients KW - medical Education KW - understaffed KW - teaching hospital KW - Sub-saharan Africa Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150208 N1 - Deutschsprachige Version des Artikels ab Seite 8 des Dokuments. VL - 32 IS - 1 ER - TY - JOUR A1 - Bartl, Jasmin A1 - Scholz, Claus-Jürgen A1 - Hinterberger, Margareta A1 - Jungwirth, Susanne A1 - Wichart, Ildiko A1 - Rainer, Michael K. A1 - Kneitz, Susanne A1 - Danielczyk, Walter A1 - Tragl, Karl H. A1 - Fischer, Peter A1 - Riederer, Peter A1 - Grünblatt, Edna T1 - Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzymegene JF - BMC Medical Genetics N2 - Background Insulin-degrading enzyme (IDE) is the ubiquitously expressed enzyme responsible for insulin and amyloid beta (Aβ) degradation. IDE gene is located on chromosome region 10q23-q25 and exhibits a well-replicated peak of linkage with Type 2 diabetes mellitus (T2DM). Several genetic association studies examined IDE gene as a susceptibility gene for Alzheimer's disease (AD), however with controversial results. Methods We examined associations of three IDE polymorphisms (IDE2, rs4646953; IDE7, rs2251101 and IDE9, rs1887922) with AD, Aβ42 plasma level and T2DM risk in the longitudinal Vienna Transdanube Aging (VITA) study cohort. Results The upstream polymorphism IDE2 was found to influence AD risk and to trigger the Aβ42 plasma level, whereas the downstream polymorphism IDE7 modified the T2DM risk; no associations were found for the intronic variant IDE9. Conclusions Based on our SNP and haplotype results, we delineate the model that IDE promoter and 3' untranslated region/downstream variation may have different effects on IDE expression, presumably a relevant endophenotype with disorder-specific effects on AD and T2DM susceptibility. KW - Insulin Degrading Enzyme Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137744 VL - 12 IS - 151 ER -