@article{BiehlDreslerReifetal.2011, author = {Biehl, Stefanie C. and Dresler, Thomas and Reif, Andreas and Scheuerpflug, Peter and Deckert, J{\"u}rgen and Herrmann, Martin J.}, title = {Dopamine Transporter (DAT1) and Dopamine Receptor D4 (DRD4) Genotypes Differentially Impact on Electrophysiological Correlates of Error Processing}, series = {PLoS One}, volume = {6}, journal = {PLoS One}, number = {12}, doi = {10.1371/journal.pone.0028396}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137930}, pages = {e28396}, year = {2011}, abstract = {Recent studies as well as theoretical models of error processing assign fundamental importance to the brain's dopaminergic system. Research about how the electrophysiological correlates of error processing—the error-related negativity (ERN) and the error positivity (Pe)—are influenced by variations of common dopaminergic genes, however, is still relatively scarce. In the present study, we therefore investigated whether polymorphisms in the DAT1 gene and in the DRD4 gene, respectively, lead to interindividual differences in these error processing correlates. One hundred sixty participants completed a version of the Eriksen Flanker Task while a 26-channel EEG was recorded. The task was slightly modified in order to increase error rates. During data analysis, participants were split into two groups depending on their DAT1 and their DRD4 genotypes, respectively. ERN and Pe amplitudes after correct responses and after errors as well as difference amplitudes between errors and correct responses were analyzed. We found a differential effect of DAT1 genotype on the Pe difference amplitude but not on the ERN difference amplitude, while the reverse was true for DRD4 genotype. These findings are in line with predictions from theoretical models of dopaminergic transmission in the brain. They furthermore tie results from clinical investigations of disorders impacting on the dopamine system to genetic variations known to be at-risk genotypes.}, language = {en} } @article{EgetemeirStennekenKoehleretal.2011, author = {Egetemeir, Johanna and Stenneken, Prisca and Koehler, Saskia and Fallgatter, Andreas J. and Herrmann, Martin J.}, title = {Exploring the neural basis of real-life joint action: measuring brain activation during joint table setting with functional near-infrared spectroscopy}, series = {FRONTIERS IN HUMAN NEUROSCIENCE}, volume = {5}, journal = {FRONTIERS IN HUMAN NEUROSCIENCE}, number = {9, Artikel 95}, doi = {10.3389/fnhum.2011.00095}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137054}, pages = {1-9}, year = {2011}, abstract = {Many every-day life situations require two or more individuals to execute actions together. Assessing brain activation during naturalistic tasks to uncover relevant processes underlying such real-life joint action situations has remained a methodological challenge. In the present study, we introduce a novel joint action paradigm that enables the assessment of brain activation during real-life joint action tasks using functional near-infrared spectroscopy (fNIRS). We monitored brain activation of participants who coordinated complex actions with a partner sitting opposite them. Participants performed table setting tasks, either alone (solo action) or in cooperation with a partner (joint action), or they observed the partner performing the task (action observation). Comparing joint action and solo action revealed stronger activation (higher [oxy-Hb]-concentration) during joint action in a number of areas. Among these were areas in the inferior parietal lobule (IPL) that additionally showed an overlap of activation during action observation and solo action. Areas with such a close link between action observation and action execution have been associated with action simulation processes. The magnitude of activation in these IPL areas also varied according to joint action type and its respective demand on action simulation. The results validate fNIRS as an imaging technique for exploring the functional correlates of interindividual action coordination in real-life settings and suggest that coordinating actions in real-life situations requires simulating the actions of the partner.}, language = {en} } @article{HerrmannGlotzbachMuehlbergeretal.2011, author = {Herrmann, Martin J. and Glotzbach, Evelyn and M{\"u}hlberger, Andreas and Gschwendtner, Kathrin and Fallgatter, Andreas J. and Pauli, Paul}, title = {Prefrontal Brain Activation During Emotional Processing: A Functional Near Infrared Spectroscopy Study (fNIRS)}, series = {The Open Neuroimaging Journal}, journal = {The Open Neuroimaging Journal}, doi = {10.2174/1874440001105010033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97437}, year = {2011}, abstract = {The limbic system and especially the amygdala have been identified as key structures in emotion induction and regulation. Recently research has additionally focused on the influence of prefrontal areas on emotion processing in the limbic system and the amygdala. Results from fMRI studies indicate that the prefrontal cortex (PFC) is involved not only in emotion induction but also in emotion regulation. However, studies using fNIRS only report prefrontal brain activation during emotion induction. So far it lacks the attempt to compare emotion induction and emotion regulation with regard to prefrontal activation measured with fNIRS, to exclude the possibility that the reported prefrontal brain activation in fNIRS studies are mainly caused by automatic emotion regulation processes. Therefore this work tried to distinguish emotion induction from regulation via fNIRS of the prefrontal cortex. 20 healthy women viewed neutral pictures as a baseline condition, fearful pictures as induction condition and reappraised fearful pictures as regulation condition in randomized order. As predicted, the view-fearful condition led to higher arousal ratings than the view-neutral condition with the reappraise-fearful condition in between. For the fNIRS results the induction condition showed an activation of the bilateral PFC compared to the baseline condition (viewing neutral). The regulation condition showed an activation only of the left PFC compared to the baseline condition, although the direct comparison between induction and regulation condition revealed no significant difference in brain activation. Therefore our study underscores the results of previous fNIRS studies showing prefrontal brain activation during emotion induction and rejects the hypothesis that this prefrontal brain activation might only be a result of automatic emotion regulation processes.}, language = {en} } @article{KlaukeWinterGajewskaetal.2012, author = {Klauke, Benedikt and Winter, Bernward and Gajewska, Agnes and Zwanzger, Peter and Reif, Andreas and Herrmann, Martin J. and Dlugos, Andrea and Warrings, Bodo and Jacob, Christian and M{\"u}hlberger, Andreas and Arolt, Volker and Pauli, Paul and Deckert, J{\"u}rgen and Domschke, Katharina}, title = {Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {6}, doi = {10.1371/journal.pone.0039709}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132184}, pages = {e39709}, year = {2012}, abstract = {The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.}, language = {en} } @article{VernerHerrmannTrocheetal.2013, author = {Verner, Martin and Herrmann, Martin J. and Troche, Stefan J. and Roebers, Claudia M. and Rammsayer, Thomas H.}, title = {Cortical oxygen consumption in mental arithmetic as a function of task difficulty: a near-infrared spectroscopy approach}, series = {Frontiers in Human Neuroscience}, volume = {7}, journal = {Frontiers in Human Neuroscience}, number = {217}, issn = {1662-5161}, doi = {10.3389/fnhum.2013.00217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122449}, year = {2013}, abstract = {The present study investigated changes in cortical oxygenation during mental arithmetic using near-infrared spectroscopy (NIRS). Twenty-nine male volunteers were examined using a 52-channel continuous wave system for analyzing activity in prefrontal areas. With the help of a probabilistic mapping method, three regions of interest (ROIs) on each hemisphere were defined: The inferior frontal gyri (IFG), the middle frontal gyri (MFG), and the superior frontal gyri (SFG). Oxygenation as an indicator of functional brain activation was compared over the three ROI and two levels of arithmetic task difficulty (simple and complex additions). In contrast to most previous studies using fMRI or NIRS, in the present study arithmetic tasks were presented verbally in analogue to many daily life situations. With respect to task difficulty, more complex addition tasks led to higher oxygenation in all defined ROI except in the left IFG compared to simple addition tasks. When compared to the channel positions covering different gyri of the temporal lobe, the observed sensitivity to task complexity was found to be restricted to the specified ROIs. As to the comparison of ROIs, the highest oxygenation was found in the IFG, while MFG and SFG showed significantly less activation compared to IFG. The present cognitive-neuroscience approach demonstrated that NIRS is a suitable and highly feasible research tool for investigating and quantifying neural effects of increasing arithmetic task difficulty.}, 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{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{ManishNueckelMuehlbergeretal.2013, author = {Manish, Asthana and Nueckel, Katharina and M{\"u}hlberger, Andreas and Neueder, Dorothea and Polak, Thomas and Domschke, Katharina and Deckert, J{\"u}rgen and Herrmann, Martin J.}, title = {Effects of transcranial direct current stimulation on consolidation of fear memory}, series = {Frontiers in Neuropsychiatric Imaging and Stimulation}, journal = {Frontiers in Neuropsychiatric Imaging and Stimulation}, doi = {10.3389/fpsyt.2013.00107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97294}, year = {2013}, abstract = {It has been shown that applying transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) influences declarative memory processes. This study investigates the efficacy of tDCS on emotional memory consolidation, especially experimental fear conditioning. We applied an auditory fear-conditioning paradigm, in which two differently colored squares (blue and yellow) were presented as conditioned stimuli (CS) and an auditory stimulus as unconditioned stimulus (UCS). Sixty-nine participants were randomly assigned into three groups: anodal, cathodal, and sham stimulation. The participants of the two active groups (i.e., anodal and cathodal) received tDCS over the left DLPFC for 12 min after fear conditioning. The effect of fear conditioning and consolidation (24 h later) was measured by assessing the skin conductance response (SCR) to the CS. The results provide evidence that cathodal stimulation of the left DLPFC leads to an inhibitory effect on fear memory consolidation compared to anodal and sham stimulation, as indicated by decreased SCRs to CS+ presentation during extinction training at day 2. In conclusion, current work suggests that cathodal stimulation interferes with processes of fear memory consolidation.}, language = {en} } @article{SchecklmannGianiTupaketal.2014, author = {Schecklmann, Martin and Giani, Anette and Tupak, Sara and Langguth, Berthold and Raab, Vincent and Polak, Thomas and Varallyay, Csanad and Harnisch, Wilma and Herrmann, Martin J. and Fallgatter, Andreas J.}, title = {Functional Near-Infrared Spectroscopy to Probe State- and Trait-Like Conditions in Chronic Tinnitus: A Proof-of-Principle Study}, series = {Neural Plasticity}, journal = {Neural Plasticity}, number = {894203}, issn = {1687-5443}, doi = {10.1155/2014/894203}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117801}, pages = {8}, year = {2014}, abstract = {Objective. Several neuroscience tools showed the involvement of auditory cortex in chronic tinnitus. In this proof-of-principle study we probed the capability of functional near-infrared spectroscopy (fNIRS) for the measurement of brain oxygenation in auditory cortex in dependence from chronic tinnitus and from intervention with transcranial magnetic stimulation. Methods. Twenty-three patients received continuous theta burst stimulation over the left primary auditory cortex in a randomized sham-controlled neuronavigated trial (verum = 12; placebo = 11). Before and after treatment, sound-evoked brain oxygenation in temporal areas was measured with fNIRS. Brain oxygenation was measured once in healthy controls (n = 12). Results. Sound-evoked activity in right temporal areas was increased in the patients in contrast to healthy controls. Left-sided temporal activity under the stimulated area changed over the course of the trial; high baseline oxygenation was reduced and vice versa. Conclusions. By demonstrating that rTMS interacts with auditory evoked brain activity, our results confirm earlier electrophysiological findings and indicate the sensitivity of fNIRS for detecting rTMS induced changes in brain activity. Moreover, our findings of trait-and state-related oxygenation changes indicate the potential of fNIRS for the investigation of tinnitus pathophysiology and treatment response.}, language = {en} } @article{GuhnDreslerAndreattaetal.2014, author = {Guhn, Anne and Dresler, Thomas and Andreatta, Marta and M{\"u}ller, Laura D. and Hahn, Tim and Tupak, Sara V. and Polak, Thomas and Deckert, J{\"u}rgen and Herrmann, Martin J.}, title = {Medial prefrontal cortex stimulation modulates the processing of conditioned fear}, doi = {10.3389/fnbeh.2014.00044}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111309}, year = {2014}, abstract = {The extinction of conditioned fear depends on an efficient interplay between the amygdala and the medial prefrontal cortex (mPFC). In rats, high-frequency electrical mPFC stimulation has been shown to improve extinction by means of a reduction of amygdala activity. However, so far it is unclear whether stimulation of homologues regions in humans might have similar beneficial effects. Healthy volunteers received one session of either active or sham repetitive transcranial magnetic stimulation (rTMS) covering the mPFC while undergoing a 2-day fear conditioning and extinction paradigm. Repetitive TMS was applied offline after fear acquisition in which one of two faces (CS+ but not CS-) was associated with an aversive scream (UCS). Immediate extinction learning (day 1) and extinction recall (day 2) were conducted without UCS delivery. Conditioned responses (CR) were assessed in a multimodal approach using fear-potentiated startle (FPS), skin conductance responses (SCR), functional near-infrared spectroscopy (fNIRS), and self-report scales. Consistent with the hypothesis of a modulated processing of conditioned fear after high-frequency rTMS, the active group showed a reduced CS+/CS- discrimination during extinction learning as evident in FPS as well as in SCR and arousal ratings. FPS responses to CS+ further showed a linear decrement throughout both extinction sessions. This study describes the first experimental approach of influencing conditioned fear by using rTMS and can thus be a basis for future studies investigating a complementation of mPFC stimulation to cognitive behavioral therapy (CBT).}, language = {en} } @article{HerrmannBeierSimonsetal.2016, author = {Herrmann, Martin J. and Beier, Jennifer S. and Simons, Bibiane and Polak, Thomas}, title = {Transcranial Direct Current Stimulation (tDCS) of the Right Inferior Frontal Gyrus Attenuates Skin Conductance Responses to Unpredictable Threat Conditions}, series = {Frontiers in Human Neuroscience}, volume = {10}, journal = {Frontiers in Human Neuroscience}, number = {352}, doi = {10.3389/fnhum.2016.00352}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146486}, year = {2016}, abstract = {Patients with panic and post-traumatic stress disorders seem to show increased psychophysiological reactions to conditions of unpredictable (U) threat, which has been discussed as a neurobiological marker of elevated levels of sustained fear in these disorders. Interestingly, a recent study found that the right inferior frontal gyrus (rIFG) is correlated to the successful regulation of sustained fear during U threat. Therefore this study aimed to examine the potential use of non-invasive brain stimulation to foster the rIFG by means of anodal transcranial direct current stimulation (tDCS) in order to reduce psychophysiological reactions to U threat. Twenty six participants were randomly assigned into an anodal and sham stimulation group in a double-blinded manner. Anodal and cathodal electrodes (7 * 5 cm) were positioned right frontal to target the rIFG. Stimulation intensity was I = 2 mA applied for 20 min during a task including U threat conditions (NPU-task). The effects of the NPU paradigm were measured by assessing the emotional startle modulation and the skin conductance response (SCR) at the outset of the different conditions. We found a significant interaction effect of condition × tDCS for the SCR (F(2,48) = 6.3, p < 0.01) without main effects of condition and tDCS. Post hoc tests revealed that the increase in SCR from neutral (N) to U condition was significantly reduced in verum compared to the sham tDCS group (t(24) = 3.84, p < 0.001). Our results emphasize the causal role of rIFG for emotional regulation and the potential use of tDCS to reduce apprehension during U threat conditions and therefore as a treatment for anxiety disorders.}, 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} } @article{AsthanaBrunhuberMuehlbergeretal.2016, author = {Asthana, Manish Kumar and Brunhuber, Bettina and M{\"u}hlberger, Andreas and Reif, Andreas and Schneider, Simone and Herrmann, Martin J.}, title = {Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism}, series = {International Journal of Neuropsychopharmacology}, volume = {19}, journal = {International Journal of Neuropsychopharmacology}, number = {6}, doi = {10.1093/ijnp/pyv137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166217}, year = {2016}, abstract = {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.}, 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{KatzorkeZellerMuelleretal.2017, author = {Katzorke, Andrea and Zeller, Julia B. M. and M{\"u}ller, Laura D. and Lauer, Martin and Polak, Thomas and Reif, Andreas and Deckert, J{\"u}rgen and Herrmann, Martin J.}, title = {Reduced activity in the right inferior frontal gyrus in elderly APOE-E4 carriers during a verbal fluency task}, series = {Frontiers in Human Neuroscience}, volume = {11}, journal = {Frontiers in Human Neuroscience}, doi = {10.3389/fnhum.2017.00046}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171892}, year = {2017}, abstract = {Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer's disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS). We compared performance and hemodynamic response of high risk APOE-E4/E4, -E3/E4 carriers with neutral APOE-E3/E3 non-demented subjects (N = 288; 70-77 years). No difference in performance was found. APOE-E4/E4, -E3/E4 carriers had a decreased hemodynamic response in the right inferior frontal junction (IFJ) with a corresponding higher response in the left middle frontal gyrus (MFG) during category fluency. Performance was correlated with the hemodynamic response in the MFG. We assume a compensation of decreased IFJ brain activation by utilizing the MFG during category fluency and thus resulting in no behavioral differences between APOE-groups during the performance of a VFT.}, language = {en} } @article{RosenbaumBlumSchweizeretal.2018, author = {Rosenbaum, David and Blum, Leonore and Schweizer, Paul and Fallgatter, Andreas J. and Herrmann, Martin J. and Ehlis, Ann-Christine and Metzger, Florian G.}, title = {Comparison of speed versus complexity effects on the hemodynamic response of the trail making test in block designs}, series = {Neurophotonics}, volume = {5}, journal = {Neurophotonics}, number = {4}, doi = {10.1117/1.NPh.5.4.045007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226982}, pages = {045007, 1-9}, year = {2018}, abstract = {The use of functional near-infrared spectroscopy (fNIRS) in block designs provides measures of cortical activity in ecologically valid environments. However, in some cases, the use of block designs may be problematic when data are not corrected for performance in a time-restricted block. We sought to investigate the effects of task complexity and processing speed on hemodynamic responses in an fNIRS block design. To differentiate the effects of task complexity and processing speed, 20 subjects completed the trail making test (TMT) in two versions (TMT-A versus TMT-B) and three different speed levels (slow versus moderate versus fast). During TMT-A, subjects are asked to connect encircled numbers in numerically ascending order (1-2-3 ... ). In the more complex TMT-B, subjects are instructed to connect encircled numbers and letters in alternating ascending order (1-A-2-B ... ). To illustrate the obscuring effects of processing speed on task complexity, we perform two different analyses. First, we analyze the classical measures of oxygenated blood, and second, we analyze the measures corrected for the number of processed items. Our results show large effects for processing speed within the bilateral inferior frontal gyrus, left dorsolateral prefrontal cortex, and superior parietal lobule (SPL). The TMT contrast did not show significant effects with classical measures, although trends are observed for higher activation during TMT-B. When corrected for processed items, higher activity for TMT-B in comparison to TMT-A is found within the SPL. The results are discussed in light of recent research designs, and simple to use correction methods are suggested. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.}, language = {en} } @article{SchieleZieglerKollertetal.2018, author = {Schiele, Miriam A. and Ziegler, Christiane and Kollert, Leonie and Katzorke, Andrea and Schartner, Christoph and Busch, Yasmin and Gromer, Daniel and Reif, Andreas and Pauli, Paul and Deckert, J{\"u}rgen and Herrmann, Martin J. and Domschke, Katharina}, title = {Plasticity of Functional MAOA Gene Methylation in Acrophobia}, series = {International Journal of Neuropsychopharmacology}, volume = {21}, journal = {International Journal of Neuropsychopharmacology}, number = {9}, doi = {10.1093/ijnp/pyy050}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228571}, pages = {822-827}, year = {2018}, abstract = {Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction.}, language = {en} } @article{DittertHuettnerPolaketal.2018, author = {Dittert, Natalie and H{\"u}ttner, Sandrina and Polak, Thomas and Herrmann, Martin J.}, title = {Augmentation of fear extinction by transcranial direct current stimulation (tDCS)}, series = {Frontiers in Behavioral Neuroscience}, volume = {12}, journal = {Frontiers in Behavioral Neuroscience}, number = {76}, doi = {10.3389/fnbeh.2018.00076}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176056}, year = {2018}, abstract = {Although posttraumatic stress disorder (PTSD; DSM-V 309.82) and anxiety disorders (DSM-V 300.xx) are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS) might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS) and a 95-dB female scream as unconditioned stimulus (UCS). We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC), which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR) and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84). The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS- discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS- in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be tested in a clinical context further investigation is needed to assess the reason for the reaction increase on CS-. If this negative side effect can be avoided, tDCS may be a tool to improve exposure-based anxiety therapies.}, language = {en} } @article{SchwarzmeierLeehrBoehnleinetal.2020, author = {Schwarzmeier, Hanna and Leehr, Elisabeth Johanna and B{\"o}hnlein, Joscha and Seeger, Fabian Reinhard and Roesmann, Kati and Gathmann, Bettina and Herrmann, Martin J. and Siminski, Niklas and Jungh{\"o}fer, Markus and Straube, Thomas and Grotegerd, Dominik and Dannlowski, Udo}, title = {Theranostic markers for personalized therapy of spider phobia: Methods of a bicentric external cross-validation machine learning approach}, series = {International Journal of Methods in Psychiatric Research}, volume = {29}, journal = {International Journal of Methods in Psychiatric Research}, number = {2}, doi = {10.1002/mpr.1812}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213430}, year = {2020}, abstract = {Objectives Embedded in the Collaborative Research Center "Fear, Anxiety, Anxiety Disorders" (CRC-TRR58), this bicentric clinical study aims at identifying biobehavioral markers of treatment (non-)response by applying machine learning methodology with an external cross-validation protocol. We hypothesize that a priori prediction of treatment (non-)response is possible in a second, independent sample based on multimodal markers. Methods One-session virtual reality exposure treatment (VRET) with patients with spider phobia was conducted on two sites. Clinical, neuroimaging, and genetic data were assessed at baseline, post-treatment and after 6 months. The primary and secondary outcomes defining treatment response are as follows: 30\% reduction regarding the individual score in the Spider Phobia Questionnaire and 50\% reduction regarding the individual distance in the behavioral avoidance test. Results N = 204 patients have been included (n = 100 in W{\"u}rzburg, n = 104 in M{\"u}nster). Sample characteristics for both sites are comparable. Discussion This study will offer cross-validated theranostic markers for predicting the individual success of exposure-based therapy. Findings will support clinical decision-making on personalized therapy, bridge the gap between basic and clinical research, and bring stratified therapy into reach. The study is registered at ClinicalTrials.gov (ID: NCT03208400).}, language = {en} } @article{ReimannStopperPolaketal.2020, author = {Reimann, Hauke and Stopper, Helga and Polak, Thomas and Lauer, Martin and Herrmann, Martin J. and Deckert, J{\"u}rgen and Hintzsche, Henning}, title = {Micronucleus frequency in buccal mucosa cells of patients with neurodegenerative diseases}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-78832-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231430}, year = {2020}, abstract = {Neurodegenerative diseases show an increase in prevalence and incidence, with the most prominent example being Alzheimer's disease. DNA damage has been suggested to play a role in the pathogenesis, but the exact mechanisms remain elusive. We enrolled 425 participants with and without neurodegenerative diseases and analyzed DNA damage in the form of micronuclei in buccal mucosa samples. In addition, other parameters such as binucleated cells, karyolytic cells, and karyorrhectic cells were quantified. No relevant differences in DNA damage and cytotoxicity markers were observed in patients compared to healthy participants. Furthermore, other parameters such as lifestyle factors and diseases were also investigated. Overall, this study could not identify a direct link between changes in buccal cells and neurogenerative diseases, but highlights the influence of lifestyle factors and diseases on the human buccal cytome.}, language = {en} }