Julich Aachen Research Alliance JARA Brain

Aachen, Germany

Julich Aachen Research Alliance JARA Brain

Aachen, Germany
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Behrwind S.D.,RWTH Aachen | Dafotakis M.,RWTH Aachen | Dafotakis M.,Alexianer Psychiatric Hospital | Halfter S.,RWTH Aachen | And 6 more authors.
Behavioural Brain Research | Year: 2011

Background: Antisaccade deficits are a well-documented pathophysiological characteristic in schizophrenia. However, it is yet unclear whether these findings reflect a specific oculomotor deficit, general psychomotor impairment or disturbance in executive control mechanisms. Methods: Performance in a manual stimulus-response compatibility (SRC) task and a neuropsychological test-battery covering different cognitive and motor domains were obtained in 28 patients with chronic schizophrenia. It was compared with a normative cohort of healthy subjects and validated by comparison with a sub-sample of that cohort consisting of 28 age, gender and education matched controls. Results: Patients showed significantly worse performance than controls in tests requiring maintenance or manipulating of multiple components but were unimpaired in simple motor, memory or executive tasks. In the SRC task patients had a significantly worse performance in the congruent condition and also a significantly higher increase in error rate from the congruent to the incongruent condition. There were, however, neither a group difference nor a group-by-condition interaction with respect to reaction times. Interpretation:: Our results provide evidence against an isolated oculomotor deficit but also against an undifferentiated psychomotor dysfunction in chronic schizophrenia. Rather, in synopsis with previous reports on antisaccade performance, it becomes evident that the degree of impairment follows closely the amount of executive control required in a task, which in turn may relate to dysfunctional top-down bias of the prefrontal cortex arising from unstable task instructions. © 2011 Elsevier B.V.

Papadelis C.,RIKEN | Papadelis C.,University of Trento | Eickhoff S.B.,Jülich Research Center | Eickhoff S.B.,RWTH Aachen | And 4 more authors.
NeuroImage | Year: 2011

This study combines source analysis imaging data for early somatosensory processing and the probabilistic cytoarchitectonic maps (PCMs). Human somatosensory evoked fields (SEFs) were recorded by stimulating left and right median nerves. Filtering the recorded responses in different frequency ranges identified the most responsive frequency band. The short-latency averaged SEFs were analyzed using a single equivalent current dipole (ECD) model and magnetic field tomography (MFT). The identified foci of activity were superimposed with PCMs. Two major components of opposite polarity were prominent around 21 and 31. ms. A weak component around 25. ms was also identified. For the most responsive frequency band (50-150. Hz) ECD and MFT revealed one focal source at the contralateral Brodmann area 3b (BA3b) at the peak of N20. The component ~. 25. ms was localised in Brodmann area 1 (BA1) in 50-150. Hz. By using ECD, focal generators around 28-30. ms located initially in BA3b and 2. ms later to BA1. MFT also revealed two focal sources - one in BA3b and one in BA1 for these latencies. Our results provide direct evidence that the earliest cortical response after median nerve stimulation is generated within the contralateral BA3b. BA1 activation few milliseconds later indicates a serial mode of somatosensory processing within cytoarchitectonic SI subdivisions. Analysis of non-invasive magnetoencephalography (MEG) data and the use of PCMs allow unambiguous and quantitative (probabilistic) interpretation of cytoarchitectonic identity of activated areas following median nerve stimulation, even with the simple ECD model, but only when the model fits the data extremely well. © 2010 Elsevier Inc.

Jakobs O.,RWTH Aachen | Jakobs O.,Heinrich Heine University Düsseldorf | Jakobs O.,Jülich Research Center | Langner R.,RWTH Aachen | And 14 more authors.
NeuroImage | Year: 2012

Bidirectional integration between sensory stimuli and contextual framing is fundamental to action control. Stimuli may entail context-dependent actions, while temporal or spatial characteristics of a stimulus train may establish a contextual framework for upcoming stimuli. Here we aimed at identifying core areas for stimulus-context integration and delineated their functional connectivity (FC) using meta-analytic connectivity modeling (MACM) and analysis of resting-state networks.In a multi-study conjunction, consistently increased activity under higher demands on stimulus-context integration was predominantly found in the right temporo-parietal junction (TPJ), which represented the largest cluster of overlap and was thus used as the seed for the FC analyses. The conjunction between task-dependent (MACM) and task-free (resting state) FC of the right TPJ revealed a shared network comprising bilaterally inferior parietal and frontal cortices, anterior insula, premotor cortex, putamen and cerebellum, i.e., a 'ventral' action/attention network. Stronger task-dependent (vs. task-free) connectivity was observed with the pre-SMA, dorsal premotor cortex, intraparietal sulcus, basal ganglia and primary sensori motor cortex, while stronger resting-state (vs. task-dependent) connectivity was found with the dorsolateral prefrontal and medial parietal cortex.Our data provide strong evidence that the right TPJ may represent a key region for the integration of sensory stimuli and contextual frames in action control. Task-dependent associations with regions related to stimulus processing and motor responses indicate that the right TPJ may integrate 'collaterals' of sensory processing and apply (ensuing) contextual frames, most likely via modulation of preparatory loops. Given the pattern of resting-state connectivity, internal states and goal representations may provide the substrates for the contextual integration within the TPJ in the absence of a specific task. © 2012 Elsevier Inc..

Laoutidis Z.G.,RWTH Aachen | Laoutidis Z.G.,Heinrich Heine University Düsseldorf | Mathiak K.,RWTH Aachen | Mathiak K.,Julich Aachen Research Alliance JARA BRAIN | Mathiak K.,Jülich Research Center
BMC Psychiatry | Year: 2013

Background: Over the past thirty years a number of studies have suggested that antidepressants can be effective in the treatment of depressive symptoms in patients with cancer. The aim of this paper was to review randomized controlled trials (RCTs) and to perform a meta-analysis in order to quantify their overall effect.Methods: Pubmed and the Cochrane libraries were searched for the time period between 1980 and 2010.Results: Nine RCTs were identified and reviewed. Six of them (with a total of 563 patients) fulfilled the criteria for meta-analysis, but exhibited an unclear risk for bias. The estimated effect size was 1.56 with 95% CI: 1.07- 2.28 (p= 0.021). There were no differences in discontinuation rates between antidepressants and placebo groups (RR= 0.86 with 95% CI 0.47- 1.56, p=0.62).Conclusions: This meta-analysis suggests that antidepressants can be effective in treating depressive symptoms beside clinical depression. When considering the risk of side effects and interactions and the heterogeneity among the mostly small studies, a general recommendation cannot be made until well-controlled studies are conducted. © 2013 Laoutidis and Mathiak; licensee BioMed Central Ltd.

Schreckenbach T.,RWTH Aachen | Schreckenbach T.,Julich Aachen Research Alliance JARA Brain | Henn W.,Saarland University | Kress W.,Institute for Human Genetics | And 12 more authors.
Muscle and Nerve | Year: 2013

Introduction: Reducing body myopathy is a rare X-linked myopathy. It is characterized by intracytoplasmic inclusions that stain with menadione-nitroblue tetrazolium. It is caused by mutations in the FHL1 gene, which encodes the four-and-a-half LIM domain 1 protein (FHL1). Methods: We performed a clinical, muscle MRI, and histopathological characterization and immunoblot and genetic analysis of the FHL1 protein in a family with 4 individuals affected by reducing body myopathy. Results: We identified a novel missense mutation in FHL1 (c.449G>C; p.C150S). The patients presented with asymmetric proximal weakness and scoliosis. Both of the boys had a more severe course with earlier onset, contractures, and death due to heart failure at 14 and 18 years of age, respectively. MRI revealed fatty infiltration of posteromedial thigh and paraspinal muscles. Histopathological findings showed FHL1-immunoreactive inclusions. Immunoblot analysis revealed a 50% reduction of FHL1 protein. Conclusion: In this study we highlighted diagnostic clues in this myopathy and compared our data with the literature. © 2012 Wiley Periodicals, Inc.

Sarid L.,Institute of Life science | Feldmeyer D.,Jülich Research Center | Feldmeyer D.,RWTH Aachen | Feldmeyer D.,Julich Aachen Research Alliance JARA Brain | And 5 more authors.
Cerebral Cortex | Year: 2015

This computational study integrates anatomical and physiological data to assess the functional role of the lateral excitatory connections between layer 2/3 (L2/3) pyramidal cells (PCs) in shaping their response during early stages of intracortical processing of a whisker deflection (WD). Based on in vivo and in vitro recordings, and 3D reconstructions of connected pairs of L2/3 PCs, our model predicts that: 1) AMPAR and NMDAR conductances/synapse are 0.52 ± 0.24 and 0.40 ± 0.34 nS, respectively; 2) following WD, connection between L2/3 PCs induces a composite EPSPs of 7.6 ± 1.7 mV, well below the threshold for action potential (AP) initiation; 3) together with the excitatory feedforward L4-to-L2/3 connection, WD evoked a composite EPSP of 16.3 ± 3.5 mV and a probability of 0.01 to generate an AP. When considering the variability in L4 spiny neurons responsiveness, it increased to 17.8 ± 11.2 mV; this 3-fold increase in the SD yielded AP probability of 0.35; 4) the interaction between L4-to-L2/3 and L2/3-to-L2/3 inputs is highly nonlinear; 5) L2/3 dendritic morphology significantly affects L2/3 PCs responsiveness. We conclude that early stages of intracortical signaling of WD are dominated by a combination of feedforward L4-L2/3 and L2/3-L2/3 lateral connections. © The Author 2013. Published by Oxford University Press.

Derntl B.,RWTH Aachen | Derntl B.,Julich Aachen Research Alliance JARA BRAIN | Derntl B.,Jülich Research Center | Krajnik J.,Medical University of Vienna | And 6 more authors.
BMC Pregnancy and Childbirth | Year: 2015

Background: While the application of fetal MRI in high-risk pregnant women is steadily rising, little is known about the psychological consequences of this procedure. The aim of the present study was to investigate emotional and psychophysiological reactions of females undergoing fetal MRI. Methods: Sixty women (17-44 ys), assigned for fetal MRI, were included. Affective state was assessed by standardized measures of anxiety, emotional states and depressive symptoms. Stress coping strategies were assessed using a self-report questionnaire. Stress responses were determined using skin conductance levels (SCL) during fetal MRI as well as measurement of salivary cortisol levels immediately before and after fetal MRI. Results: Analysis of fast and slow physiological stress measures revealed significant differences between women with and without a supporting person accompanying them to the examination. For SCLs, lower levels of stress during MRI emerged in accompanied women. Women with well-marked stress-coping-strategies experienced lower levels of stress during the examination. Although fast and slow stress measures before and after MRI did not show significant correlations, a significant difference of SCLs pre and post examination was clearly detectable, as well as a trend of decreased cortisol levels for both time points. Conclusions: The results imply that the elevation of SCLs is an accurate instrument to assess fast stress alterations in patients during fetal MRI. Stress coping strategies and whether women are accompanied or not play an important role in the experience of anxiety and depressive symptoms. These factors should be considered especially in patients with high-risk-pregnancies to improve patient care. © Derntl et al.; licensee BioMed Central.

Butler E.K.,RWTH Aachen | Butler E.K.,University of Gottingen | Voigt A.,RWTH Aachen | Lutz A.K.,Ludwig Maximilians University of Munich | And 9 more authors.
PLoS Genetics | Year: 2012

Overexpression or mutation of α-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T]α-Synuclein-induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T]α-Synuclein expression. In addition, decreased TRAP1 expression in [A53T]α-Synuclein-expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T]α-Synuclein-induced sensitivity to rotenone treatment. In human (non)neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T]α-Synuclein-induced sensitivity to oxidative stress treatment. [A53T]α-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T]α-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T]α-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to α-Synuclein. © 2012 Butler et al.

Prussing K.,RWTH Aachen | Voigt A.,RWTH Aachen | Schulz J.B.,RWTH Aachen | Schulz J.B.,Julich Aachen Research Alliance JARA Brain
Molecular Neurodegeneration | Year: 2013

Drosophila melanogaster provides an important resource for in vivo modifier screens of neurodegenerative diseases. To study the underlying pathogenesis of Alzheimer's disease, fly models that address Tau or amyloid toxicity have been developed. Overexpression of human wild-type or mutant Tau causes age-dependent neurodegeneration, axonal transport defects and early death. Large-scale screens utilizing a neurodegenerative phenotype induced by eye-specific overexpression of human Tau have identified several kinases and phosphatases, apoptotic regulators and cytoskeleton proteins as determinants of Tau toxicity in vivo. The APP ortholog of Drosophila (dAPPl) shares the characteristic domains with vertebrate APP family members, but does not contain the human Aβ42 domain. To circumvent this drawback, researches have developed strategies by either direct secretion of human Aβ42 or triple transgenic flies expressing human APP, β-secretase and Drosophila γ-secretase presenilin (dPsn). Here, we provide a brief overview of how fly models of AD have contributed to our knowledge of the pathomechanisms of disease. © 2013 Prüßing et al.; licensee BioMed Central Ltd.

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