Gereon R Fink

MediaPark Klinik Köln, Köln, North Rhine-Westphalia, Germany

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Publications (690)2953.81 Total impact

  • Simone Vossel · Ralph Weidner · Katharina Moos · Gereon R. Fink
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    ABSTRACT: Modelling psychophysical data using the Theory of Visual Attention (TVA) allows for a quantification of attentional sub-processes, such as the resolution of competition among multiple stimuli by top-down control signals for target selection (TVA-parameter α). This fMRI study investigated the neural correlates of α by comparing activity differences and changes of effective connectivity between conditions where a target was accompanied by a distractor or by a second target. Twenty-five participants performed a partial report task inside the MRI scanner. The left angular gyrus (ANG), medial frontal, and posterior cingulate cortex showed higher activity when a target was accompanied by a distractor as opposed to a second target. The reverse contrast yielded activation of a bilateral fronto-parietal network, the anterior insula, anterior cingulate cortex, and left inferior occipital gyrus. A psychophysiological interaction analysis revealed that the connectivity between left ANG and the left and right supramarginal gyrus (SMG), left anterior insula, and right putamen was enhanced in the target-distractor condition in participants with worse attentional top-down control. Dynamic causal modelling suggested that the connection from left ANG to right SMG during distractor presence was modulated by α. Our data show that interindividual differences in attentional processing are reflected in changes of effective connectivity without significant differences in activation strength of network nodes.
    No preview · Article · Jan 2016 · NeuroImage
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    ABSTRACT: Inflammatory cells such as microglia need energy to exert their functions and to maintain their cellular integrity and membrane potential. Subsequent to cerebral ischemia, inflammatory cells infiltrate tissue with limited blood flow where neurons and astrocytes died due to insufficient supply with oxygen and glucose. Using dual tracer positron emission tomography (PET), we found that concomitant with the presence of inflammatory cells, transport and consumption of glucose increased up to normal levels but returned to pathological levels as soon as inflammatory cells disappeared. Thus, inflammatory cells established sufficient glucose supply to satisfy their energy demands even in regions with insufficient supply for neurons and astrocytes to survive. Our data suggest that neurons and astrocytes died from oxygen deficiency and inflammatory cells metabolized glucose non-oxidatively in regions with residual availability. As a consequence, glucose metabolism of inflammatory cells can mask metabolic deficits in neurodegenerative diseases. We further found that the PET tracer did not bind to inflammatory cells in severely hypoperfused regions and thus only a part of the inflammation was detected. We conclude that glucose consumption of inflammatory cells should be taken into account when analyzing disease-related alterations of local cerebral metabolism.
    Preview · Article · Dec 2015 · NeuroImage
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    ABSTRACT: Apraxia typically results from left-hemispheric (LH), but also from right-hemispheric (RH) stroke, and often impairs gesture imitation. Especially in LH stroke, it is important to differentiate apraxia-induced gesture imitation deficits from those due to co-morbid aphasia and associated semantic deficits, possibly influencing the imitation of meaningful (MF) gestures. To explore this issue, we first investigated if the ten supposedly meaningless (ML) gestures of a widely used finger imitation test really carry no meaning, or if the test also contains MF gestures, by asking healthy subjects (n=45) to classify these gestures as MF or ML. Most healthy subjects (98%) classified three of the ten gestures as clearly MF. Only two gestures were considered predominantly ML. We next assessed how imitation in stroke patients (255 LH, 113 RH stroke) is influenced by gesture meaning and how aphasia influences imitation of LH stroke patients (n=208). All patients and especially patients with imitation deficits (17% of LH, 27% of RH stroke patients) imitated MF gestures significantly better than ML gestures. Importantly, meaningfulness-scores of all 10 gestures significantly predicted imitation scores of patients with imitation deficits. Furthermore, especially in LH stroke patients with imitation deficits, the severity of aphasia significantly influenced the imitation of MF, but not ML gestures. Our findings in a large patient cohort support current cognitive models of imitation and strongly suggest that ML gestures are particularly sensitive to detect imitation deficits while minimizing confounding effects of aphasia which affect the imitation of MF gestures in LH stroke patients.
    No preview · Article · Dec 2015 · Neuropsychologia
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    Full-text · Dataset · Dec 2015
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    ABSTRACT: The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta-analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Nov 2015 · Human Brain Mapping
  • Pascasie L. Dombert · Gereon R. Fink · Simone Vossel
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    ABSTRACT: Allocation of attentional resources rests on predictions about the likelihood of events. While this effect has been extensively studied in the spatial attention domain where the location of a target stimulus is pre-cued, less is known about the cueing of stimulus features such as the color of a behaviorally relevant target. Moreover, there is disagreement about which types of color cues are effective for biasing attention. Here we investigated the effects of probabilistic context (percentage of cue validity, %CV) for different levels of cue abstraction to elucidate how feature-based search information is processed and used to direct attention. The color of a target was cued by presenting the perceptual color, the color word, or two-letter abbreviations. %CV, i.e., the probability that the cue indicated the color correctly, changed unpredictably between 50, 70, and 90 %. Response times (RTs) for valid and invalid trials in each %CV condition were recorded in 60 datasets and analyzed with analyses of variance. The results showed that all cues were associated with comparable RT costs after invalid cueing. The modulation of RT costs by probabilities, however, depended upon level of cue abstraction and time on task: While a strong, immediate impact of %CV was found for two-letter cueing, the effect was solely observed in the second half of the experiment for perceptual and word cues. These results demonstrate that probabilistic feature-based information is processed differently for different levels of cue abstraction. Moreover, the modulatory effect of the environmental statistics differentially depends on the time on task for different feature cues.
    No preview · Article · Nov 2015 · Experimental Brain Research
  • Sylvia Kreutzer · Gereon R. Fink · Ralph Weidner
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    ABSTRACT: The current study determined in healthy subjects (n = 16) whether size adaptation occurs at early, i.e., preattentive, levels of processing or whether higher cognitive processes such as attention can modulate the illusion. To investigate this issue, bottom-up stimulation was kept constant across conditions by using a single adaptation display containing both small and large adapter stimuli. Subjects' attention was directed to either the large or small adapter stimulus by means of a luminance detection task. When attention was directed toward the small as compared to the large adapter, the perceived size of the subsequent target was significantly increased. Data suggest that different size adaptation effects can be induced by one and the same stimulus depending on the current allocation of attention. This indicates that size adaptation is subject to attentional modulation. These findings are in line with previous research showing that transient as well as sustained attention modulates visual features, such as contrast sensitivity and spatial frequency, and influences adaptation in other contexts, such as motion adaptation (Alais & Blake, 1999; Lankheet & Verstraten, 1995). Based on a recently suggested model (Pooresmaeili, Arrighi, Biagi, & Morrone, 2013), according to which perceptual adaptation is based on local excitation and inhibition in V1, we conclude that guiding attention can boost these local processes in one or the other direction by increasing the weight of the attended adapter. In sum, perceptual adaptation, although reflected in changes of neural activity at early levels (as shown in the aforementioned study), is nevertheless subject to higher-order modulation.
    No preview · Article · Nov 2015 · Journal of Vision
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    ABSTRACT: The human brain readily perceives fluent movement from static input. Using functional magnetic resonance imaging, we investigated brain mechanisms that mediate fluent apparent biological motion (ABM) perception from sequences of body postures. We presented body and nonbody stimuli varying in objective sequence duration and fluency of apparent movement. Three body postures were ordered to produce a fluent (ABC) or a nonfluent (ACB) apparent movement. This enabled us to identify brain areas involved in the perceptual reconstruction of body movement from identical lower-level static input. Participants judged the duration of a rectangle containing body/nonbody sequences, as an implicit measure of movement fluency. For body stimuli, fluent apparent motion sequences produced subjectively longer durations than nonfluent sequences of the same objective duration. This difference was reduced for nonbody stimuli. This body-specific bias in duration perception was associated with increased blood oxygen level-dependent responses in the primary (M1) and supplementary motor areas. Moreover, fluent ABM was associated with increased functional connectivity between M1/SMA and right fusiform body area. We show that perceptual reconstruction of fluent movement from static body postures does not merely enlist areas traditionally associated with visual body processing, but involves cooperative recruitment of motor areas, consistent with a "motor way of seeing".
    Full-text · Article · Nov 2015 · Cerebral Cortex
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    ABSTRACT: Mobilizing endogenous neural stem cells (NSCs) in the adult brain is designed to enhance the brain's regenerative capacity after cerebral lesions, e.g., as a result of stroke. Cerebral ischemia elicits neuroinflammatory processes affecting NSCs in multiple ways, the precise mechanisms of which currently remain elusive. An inhibitory effect of minocycline on microglia activation, a hallmark of postischemic neuroinflammation, has already been demonstrated in clinical trials, showing minocycline to be safe and potentially effective in ischemic stroke. Here we investigate the direct effects of minocycline and of proinflammatory cytokines on the differentiation potential of NSCs in vitro and in vivo. Primary fetal rat NSCs were treated with minocycline plus a combination of the proinflammatory cytokines tumor necrosis factor-α, interleukin 1β, and interleukin 6. The differentiation fate of NSCs was assessed immunocytochemically. To investigate the effects of minocycline and inflammation in vivo, minocycline or lipopolysaccharides were injected intraperitoneally into adult rats, with subsequent immunohistochemistry. Minocycline alone did not affect the differentiation potential of NSCs in vivo or in vitro. In contrast, proinflammatory cytokines accelerated the differentiation of NSCs, promoting an astrocytic fate while inhibiting neurogenesis in vitro and in vivo. It is interesting to note that minocycline counteracted this cytokine-induced rapid astrocytic differentiation and restored the neurogenic and oligodendrogliogenic potential of NSCs. Data suggest that minocycline antagonizes the rapid glial differentiation induced by proinflammatory cytokines following cerebral ischemia but without having a direct effect on the differentiation potential of NSCs. Thus, minocycline constitutes a promising drug for stroke research, counteracting the detrimental effects of postischemic neuroinflammation in multiple ways. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Nov 2015 · Journal of Neuroscience Research
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    Preview · Article · Nov 2015 · Neuro-Oncology
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    ABSTRACT: Data is inconsistent concerning the question whether cognitive-physical training (CPT) yields stronger cognitive gains than cognitive training (CT). Effects of additional counseling, neurobiological mechanisms, and predictors have scarcely been studied. Healthy older adults were trained with CT (n = 20), CPT (n = 25), or CPT with counseling (CPT+C; n = 23). Cognition, physical fitness, BDNF, IGF-1, and VEGF were assessed at pre- and post-test. No interaction effects were found except for one effect showing that CPT+C led to stronger gains in verbal fluency than CPT (p = 0.03). However, this superiority could not be assigned to additional physical training gains. Low baseline cognitive performance and BDNF, not carrying apoE4, gains in physical fitness and the moderation of gains in physical fitness × gains in BDNF predicted training success. Although all types of interventions seem successful to enhance cognition, our data do not support the hypotheses that CPT shows superior CT gains compared to CT or that CPT+C adds merit to CPT. However, as CPT leads to additional gains in physical fitness which in turn is known to have positive impact on cognition in the long-term, CPT seems more beneficial. Training success can partly be predicted by neuropsychological, neurobiological, and genetic parameters. Unique Identifier: WHO ICTRP (; ID: DRKS00005194.
    Full-text · Article · Oct 2015 · Frontiers in Aging Neuroscience
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    ABSTRACT: Transcranial direct current stimulation (tDCS) constitutes a promising approach for promoting recovery of function after stroke, although the underlying neurobiological mechanisms are unclear. To conduct translational research in animal models, stimulation parameters should not lead to neuronal lesions. Liebetanz et al. recommend charge densities for cathodal stimulation in rats, but parameters for mice are not established. We established tDCS in the wild-type mouse, enabling studies with genetically-engineered mice (GEM). tDCS equipment was adapted to fit the mouse skull. Using different polarities and charge densities, tDCS was safe to apply in the mouse where the charge density was below 198 kC/m(2) for single or repeated stimulations. These findings are crucial for future investigations of the neurobiological mechanisms underlying tDCS using GEM.
    No preview · Article · Oct 2015 · Laboratory Animals
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    ABSTRACT: During rehabilitation after stroke motor sequence learning is of particular importance because considerable effort is devoted to (re)acquiring lost motor skills. Previous studies suggest that implicit motor sequence learning is preserved in stroke patients but were restricted to the spatial dimension, although the timing of single action components is as important as their spatial order. As the left parietal cortex is known to play a critical role in implicit timing and spatiotemporal integration, in this study we applied an adapted version of the SRT task designed to assess both spatial (different stimulus locations) and temporal (different response-stimulus intervals) aspects of motor learning to 24 right-handed patients with a single left-hemisphere (LH) stroke and 24 age-matched healthy controls. Implicit retrieval of sequence knowledge was tested both at Day 1 and after 24 hr (Day 2). Additionally, voxel-based lesion symptom mapping was used to investigate the neurobiological substrates of the behavioral effects. Although LH stroke patients showed a combined spatiotemporal learning effect that was comparable to that observed in controls, LH stroke patients did not show learning effects for the learning probes in which only one type of sequence information was maintained whereas the other one was randomized. Particularly on Day 2, patients showed significantly smaller learning scores for these two learning probes than controls. Voxel-based lesion symptom mapping analyses revealed for all learning probes that diminished learning scores on Day 2 were associated with lesions of the striatum. This might be attributed to its role in motor chunking and offline consolidation as group differences occurred on Day 2 only. The current results suggest that LH stroke patients rely on multimodal information (here: temporal and spatial information) when retrieving motor sequence knowledge and are very sensitive to any disruption of the learnt sequence information as they seem to build very rigid chunks preventing them from forming independent spatial and temporal sequence representations.
    No preview · Article · Oct 2015 · Journal of Cognitive Neuroscience
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    ABSTRACT: Action observation is known to trigger predictions of the ongoing course of action and thus considered a hallmark example for predictive perception. A related task, which explicitly taps into the ability to predict actions based on their internal representations, is action segmentation; the task requires participants to demarcate where one action step is completed and another one begins. It thus benefits from a temporally precise prediction of the current action. Formation and exploitation of these temporal predictions of external events is now closely associated with a network including the basal ganglia and prefrontal cortex.
    Full-text · Article · Sep 2015 · Neuropsychologia
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    ABSTRACT: Cognitive impairment in Parkinson's disease (PD) is often attributed to dopamine deficiency in the prefrontal-basal ganglia-thalamo-cortical loops. Although recent studies point to a close interplay between motor and cognitive abilities in PD, the so-called "motor loop" connecting supplementary motor area (SMA) and putamen has been considered solely with regard to the patients' motor impairment. Our study challenges this view by testing patients with the serial prediction task (SPT), a cognitive task that requires participants to predict stimulus sequences and particularly engages premotor sites of the motor loop. We hypothesized that affection of the motor loop causes impaired SPT performance, especially when the internal sequence representation is challenged by suspension of external stimuli. As shown for motor tasks, we further expected this impairment to be compensated by hyperactivity of the lateral premotor cortex (PM). We tested 16 male PD patients ON and OFF dopaminergic medication and 16 male age-matched healthy controls in an functional Magnetic Resonance Imaging study. All subjects performed two versions of the SPT: one with on-going sequences (SPT0), and one with sequences containing non-informative wildcards (SPT+) increasing the demands on mnemonic sequence representation. Patients ON (compared to controls) revealed an impaired performance coming along with hypoactivity of SMA and putamen. Patients OFF compared to ON medication, while showing poorer performance, exhibited a significantly increased PM activity for SPT+ vs. SPT0. Furthermore, patients' performance positively co-varied with PM activity, corroborating a compensatory account. Our data reveal a contribution of the motor loop to cognitive impairment in PD, and suggest a close interplay of SMA and PM beyond motor control.
    No preview · Article · Sep 2015 · Neuropsychologia
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    ABSTRACT: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and relevant side effect of antineoplastic agents such as cisplatin, paclitaxel, vincristine and bortezomib. Over the last years, significant progress has been achieved in elucidating the underlying pathomechanisms of CIPN using both in vivo and in vitro models. These studies suggest that mitochondrial toxicity, disturbed axonal transport, toxic effects on Schwann cells and activation of the immune system contribute to the pathogenesis of CIPN. This review provides an overview of the current pathogenetic concepts of CIPN. In addition, experimental approaches that aim at preventing or ameliorating neurotoxic effects of antineoplastic agents are discussed.
    No preview · Article · Sep 2015 · Fortschritte der Neurologie · Psychiatrie
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is often linked with impulsive and aggressive behaviour, indexed by high comorbidity rates between ADHD and disruptive behaviour disorders (DBD). The present study aimed to investigate underlying neural activity of reactive aggression in children with ADHD and comorbid DBD using functional neuroimaging techniques (fMRI). Eighteen boys with ADHD (age 9-14 years, 10 subjects with comorbid DBD) and 18 healthy controls were administered a modified fMRI-based version of the 'Point Subtraction Aggression Game' to elicit reactive aggressive behaviour. Trials consisted of an 'aggression phase' (punishment for a fictitious opponent) and an 'outcome phase' (presentation of the trial outcome). During the aggression phase, higher aggressive responses of control children were accompanied by higher activation of the ventral anterior cingulate cortex and the temporoparietal junction. Patients displayed inverted results. During the outcome phase, comparison between groups and conditions showed differential activation in the dorsal striatum and bilateral insular when subjects gained points. Losing points was accompanied by differential activation of regions belonging to the insula and the middle temporal sulcus. Data support the hypothesis that deficient inhibitory control mechanisms are related to increased impulsive aggressive behaviour in young people with ADHD and comorbid DBD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Aug 2015 · Acta Psychiatrica Scandinavica
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    ABSTRACT: Background STN-DBS is well established to improve motor symptoms and quality of life in patients with PD. While non-motor symptoms are crucial for quality of life in these patients, only neuropsychiatric and neuropsychological symptoms have been systematically studied in a longitudinal design so far. However, these are only a part of the non-motor symptoms spectrum. Hypothesis We hypothesized that STN-DBS is associated with a beneficial effect on a range of non-motor symptoms. Methods In this multicenter, open, prospective, international study (EuroInf-study, UKCRN10084/DRKS00006735) we investigated non-motor effects of STN-DBS in “real-life” use. We evaluated Non-motor Symptom Scale, and Questionnaire, PD Questionnaire-8, Scales for Outcomes of PD motor examination and complications, and activities of daily living preoperatively and at 6 months follow-up in 60 consecutive patients (35 male, mean age: 61.6 ± 7.8 years, mean disease duration: 10.4 ± 4.2 years). Results All outcomes improved significantly at 6 months follow-up (PD Questionaire-8, p = 0.006; activities of daily living, p = 0.012; all others, p < 0.001; Wilcoxon signed-rank, respectively paired t-test; Bonferroni-correction). Post-hoc analyses of Non-motor Symptom Scale domains showed a significant reduction of sleep/fatigue and miscellaneous domains (p ≤ 0.001), perceptual problems/hallucinations (p = 0.036), and urinary (p = 0.018) scores. Effect sizes were “moderate” for Non-motor Symptom Scale, and motor complications, “large” for motor examination, and “small” for other outcomes. Conclusions This study provides evidence that bilateral STN-DBS improves non-motor burden in patients with PD and opens the door to a more balanced evaluation of DBS outcomes. Further randomized studies are needed to confirm these findings and compare DBS non-motor effects to other invasive therapies of advanced PD.
    No preview · Article · Aug 2015 · Brain Stimulation

  • No preview · Article · Aug 2015
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    ABSTRACT: Several neurobiological factors have been found to correlate with functional recovery after brain lesions. However, predicting the individual potential of recovery remains difficult. Here we used multivariate support vector machine (SVM) classification to explore the prognostic value of functional magnetic resonance imaging (fMRI) to predict individual motor outcome at 4–6 months post-stroke. To this end, 21 first-ever stroke patients with hand motor deficits participated in an fMRI hand motor task in the first few days post-stroke. Motor impairment was quantified assessing grip force and the Action Research Arm Test. Linear SVM classifiers were trained to predict good versus poor motor outcome of unseen new patients. We found that fMRI activity acquired in the first week post-stroke correctly predicted the outcome for 86% of all patients. In contrast, the concurrent assessment of motor function provided 76% accuracy with low sensitivity (<60%). Furthermore, the outcome of patients with initially moderate impairment and high outcome variability could not be predicted based on motor tests. In contrast, fMRI provided 87.5% prediction accuracy in these patients. Classifications were driven by activity in ipsilesional motor areas and contralesional cerebellum. The accuracy of subacute fMRI data (two weeks post-stroke), age, time post-stroke, lesion volume, and location were at 50%-chance-level. In conclusion, multivariate decoding of fMRI data with SVM early after stroke enables a robust prediction of motor recovery. The potential for recovery is influenced by the initial dysfunction of the active motor system, particularly in those patients whose outcome cannot be predicted by behavioral tests. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Aug 2015 · Human Brain Mapping

Publication Stats

31k Citations
2,953.81 Total Impact Points


  • 2015
    • MediaPark Klinik Köln
      Köln, North Rhine-Westphalia, Germany
  • 1999-2015
    • Forschungszentrum Jülich
      • • Institute of Neurosciences and Medicine (INM)
      • • Kognitive Neurologie (INM-3)
      Jülich, North Rhine-Westphalia, Germany
  • 1991-2015
    • University of Cologne
      • • Department of Neurology
      • • Institute of Anatomy I
      Köln, North Rhine-Westphalia, Germany
  • 2012
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom
  • 2007-2008
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany
  • 2002-2008
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 2002-2007
    • RWTH Aachen University
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
    • Università degli studi di Parma
      • Department of Neurosciences
      Parma, Emilia-Romagna, Italy
  • 2000-2006
    • Neurologische Klinik Westend
      Бад Вилдунген, Hesse, Germany
    • University College London
      • Institute of Neurology
      Londinium, England, United Kingdom
  • 2005
    • Scuola Internazionale Superiore di Studi Avanzati di Trieste
      Trst, Friuli Venezia Giulia, Italy
    • Fraunhofer Institute for Molecular Biology and Applied Ecology IME
      Aachen, North Rhine-Westphalia, Germany
  • 2004
    • Bielefeld University
      • Physiologische Psychologie
      Bielefeld, North Rhine-Westphalia, Germany
  • 1999-2002
    • Heinrich-Heine-Universität Düsseldorf
      • • Department of Urology
      • • Institute of Diagnostic and interventional radiology
      • • Neurologische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1997
    • University of Oxford
      • Department of Experimental Psychology
      Oxford, England, United Kingdom
  • 1991-1997
    • Max Planck Institute for Metabolism Research
      Köln, North Rhine-Westphalia, Germany