Gereon R Fink

University of Cologne, Köln, North Rhine-Westphalia, Germany

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Publications (375)1989.52 Total impact

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    ABSTRACT: Cognitive training has been shown to be effective in improving cognitive functions in patients with Mild Cognitive Impairment (MCI). However, data on factors that may influence training gains including sociodemographic variables such as sex or age is rare. In this study, the impact of sex on cognitive training effects was examined in N = 32 age- and education-matched female (n = 16) and male (n = 16) amnestic MCI patients (total sample: age M = 74.97, SD = 5.21; education M = 13.50, SD = 3.11). Patients participated in a six-week multidomain cognitive training program including 12 sessions each 90 min twice weekly in mixed groups with both women and men. Various cognitive domains were assessed before and after the intervention. Despite comparable baseline performance in women and men, we found significant interaction effects Time × Sex in immediate (p = .04) and delayed verbal episodic memory (p= .045) as well as in working memory (p = .042) favoring the female MCI patients. In contrast, the overall analyses with the total sample did not reveal any significant within-subject effects Time. In conclusion, our results give preliminary evidence for stronger cognitive training improvements of female compared to male MCI patients. More generally, they emphasize the importance of sex-sensitive evaluations of cognitive training effects. Possible underlying mechanisms of the found sex differences are discussed and directions for future research are given.
    Aging Neuropsychology and Cognition 03/2015; DOI:10.1080/13825585.2015.1028883 · 1.07 Impact Factor
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    ABSTRACT: The ability to select, within the complexity of sensory input, the information most relevant for our purposes is influenced by both internal settings (i.e., top-down control) and salient features of external stimuli (i.e., bottom-up control). We here investigated using fMRI the neural underpinning of the interaction of top-down and bottom-up processes, as well as their effects on extrastriate areas processing visual stimuli in a category-selective fashion. We presented photos of bodies or buildings embedded into frequency-matched visual noise to the subjects. Stimulus saliency changed gradually due to an altered degree to which photos stood-out in relation to the surrounding noise (hence generating stronger bottom-up control signals). Top-down settings were manipulated via instruction: participants were asked to attend one stimulus category (i.e., "is there a body?" or "is there a building?"). Highly salient stimuli that were inconsistent with participants' attentional top-down template activated the inferior frontal junction and dorsal parietal regions bilaterally. Stimuli consistent with participants' current attentional set additionally activated insular cortex and the parietal operculum. Furthermore, the extrastriate body area (EBA) exhibited increased neural activity when attention was directed to bodies. However, the latter effect was found only when stimuli were presented at intermediate saliency levels, thus suggesting a top-down modulation of this region only in the presence of weak bottom-up signals. Taken together, our results highlight the role of the inferior frontal junction and posterior parietal regions in integrating bottom-up and top-down attentional control signals. Copyright © 2015 Elsevier Inc. All rights reserved.
    Consciousness and Cognition 02/2015; DOI:10.1016/j.concog.2015.02.006 · 2.31 Impact Factor
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    ABSTRACT: Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH). To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption. Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment. Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome. Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies. Identifier: NCT01829581.
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    ABSTRACT: Attention is a complex construct that comprises at least three major subcomponents: alerting, spatial (re-)orienting, and executive functions, all of which have specific neural correlates along frontoparietal networks. Attention deficits are a common consequence of brain damage. Transcranial direct current stimulation (tDCS) has been shown to modulate spatial attention. We investigated whether tDCS of different stimulation targets differentially modulates alerting, spatial (re-)orienting, and executive functions. Twenty-four healthy participants were included in this randomized, double-blinded study, which employed a within-subject design. On four different days, the effects of 1.5mA anodal tDCS (real and sham) on the left dorsolateral (EEG 10-20 point F3), left parietal (P3) and right parietal cortex (P4) were assessed using a modified attention network test. tDCS of the right parietal cortex enhanced spatial re-orienting, while tDCS of the other cortical targets did not modulate the assessed attention functions. With regard to visual field asymmetries in attentional processing, right parietal tDCS selectively enhanced mean network efficiency for targets presented in the contralateral left visual field. The observed visual field specific tDCS effects on reorienting suggest that systematic investigations into novel approaches for the treatment of patients suffering from spatial neglect patients are warranted. Copyright © 2015. Published by Elsevier Ltd.
    Neuropsychologia 02/2015; DOI:10.1016/j.neuropsychologia.2015.02.028 · 3.45 Impact Factor
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    ABSTRACT: In-vivo imaging of inflammatory processes is a valuable tool in stroke research. We here investigated the combination of two imaging modalities in the chronic phase after cerebral ischemia: magnetic resonance imaging (MRI) using intravenously applied ultra small supraparamagnetic iron oxide particles (USPIO), and positron emission tomography (PET) with the tracer [(11)C]PK11195. Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by the macrosphere model and monitored by MRI and PET for 28 or 56 days, followed by immunohistochemical endpoint analysis. To our knowledge, this is the first study providing USPIO-MRI data in the chronic phase up to eight weeks after stroke. Phagocytes with internalized USPIOs induced MRI-T2∗ signal alterations in the brain. Combined analysis with [(11)C]PK11195-PET allowed quantification of phagocytic activity and other neuroinflammatory processes. From four weeks after induction of ischemia, inflammation was dominated by phagocytes. Immunohistochemistry revealed colocalization of Iba1+ microglia with [(11)C]PK11195 and ED1/CD68 with USPIOs. USPIO-related iron was distinguished from alternatively deposited iron by assessing MRI before and after USPIO application. Tissue affected by non-phagocytic inflammation during the first week mostly remained in a viably vital but remodeled state after 4 or 8 weeks, while phagocytic activity was associated with severe injury and necrosis accordingly. We conclude that the combined approach of USPIO-MRI and [(11)C]PK11195-PET allows to observe post-stroke inflammatory processes in the living animal in an intraindividual and longitudinal fashion, predicting long-term tissue fate. The non-invasive imaging methods do not affect the immune system and have been applied to human subjects before. Translation into clinical applications is therefore feasible. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 02/2015; 292. DOI:10.1016/j.neuroscience.2015.02.024 · 3.33 Impact Factor
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    ABSTRACT: Objective: Patients with Parkinson's disease (PD) can show impaired self-awareness of motor deficits (ISAm). We developed a new scale that measures ISAm severity of hyper- and hypokinetic movements in PD during medication on state and defined its psychometric criteria. Method: Included were 104 right-handed, non-depressed, non-demented patients. Concerning ISAm, 38 motor symptoms were assessed using seven tasks, which were performed and self-rated concerning presence of deficit (yes/no) by all patients. The whole procedure was videotaped. Motor symptoms were then evaluated by two independent experts, blinded for patient's ratings, concerning presence, awareness of deficit, and severity. Exploratory principal component analysis (promax rotation) was applied to reduce items. Principal axis factoring was conducted to extract factors. Reliability was examined regarding internal consistency, split-half reliability, and interrater reliability. Validity was verified by applying two additional measures of ISAm. Results: Of the initial 38 symptoms, 15 remained, assessed in five motor tasks and merged to a total severity score. Factor analysis resulted in a four factor solution (dyskinesia, resting tremor right hand, resting tremor left hand, bradykinesia). For all subscales and the total score, measures of reliability (values 0.64-0.89) and validity (effect sizes>0.3) were satisfactory. Descriptive results showed that 66% of patients had signs of ISAm (median 2, range 0-15), with ISAm being most distinct for dyskinesia. Conclusions: We provide the first validation of a test for ISAm in PD. Using this instrument, future studies can further analyze the pathophysiology of ISAm, the psychosocial sequelae, therapeutic strategies and compliance with therapy. (JINS, 2015, 21, 1-10).
    Journal of the International Neuropsychological Society 02/2015; DOI:10.1017/S1355617715000107 · 3.01 Impact Factor
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    ABSTRACT: Transcranial direct current stimulation (tDCS) is used in numerous clinical studies and considered an effective and versatile add-on therapy in neurorehabilitation. To date, however, the underlying neurobiological mechanisms remain elusive. In a rat model of tDCS, we recently observed a polarity-dependent accumulation of endogenous neural stem cells (NSCs) in the stimulated cortex. Based upon these findings, we hypothesized that tDCS may exert a direct migratory effect on endogenous NSCs towards the stimulated cortex. Using noninvasive imaging, we here investigated whether tDCS may also cause a directed migration of engrafted NSCs. Murine NSCs were labeled with superparamagnetic particles of iron oxide (SPIOs) and implanted into rat striatum and corpus callosum. MRI was performed (i) immediately after implantation and (ii) after 10 tDCS sessions of anodal or cathodal polarity. Sham-stimulated rats served as control. Imaging results were validated ex vivo using immunohistochemistry. Overall migratory activity of NSCs almost doubled after anodal tDCS. However, no directed migration within the electric field (i.e. towards or away from the electrode) could be observed. Rather, an undirected outward migration from the center of the graft was detected. Xenograft transplantation induced a neuroinflammatory response that was significantly enhanced following cathodal tDCS. This inflammatory response did not impact negatively on the survival of implanted NSCs. Data suggest that anodal tDCS increases the undirected migratory activity of implanted NSCs. Since the electric field did not guide implanted NSCs over large distances, previously observed polarity-dependent accumulation of endogenous NSCs in the cortex might have originated from local proliferation. Results enhance our understanding of the neurobiological mechanisms underlying tDCS, and may thereby help to develop a targeted and sustainable application of tDCS in clinical practice. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
    NMR in Biomedicine 02/2015; 28(2). DOI:10.1002/nbm.3244 · 3.56 Impact Factor
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    ABSTRACT: History and presentation at admission | A 25-year-old male patient presented with acute left sided chest pain. The patient reported no physical exercise but daytime fasting (with neither food nor liquid intake) which he had started several days before. Investigations | ECG, echocardiography and chest X-ray were normal, but blood examination revealed elevated levels for creatine kinase (CK) and lactate dehydrogenase (LDH). Ischemic lactate ammonia test revealed no increase of lactate during exercise. Muscle biopsy confirmed suspected diagnosis of glycogen storage disease type V (McArdle's disease) Treatment and course | As causal treatments are unavailable for McArdle's disease, careful counselling regarding adequate exercise and regular, carbohydrate rich nutrition are mandatory to ameliorate symptoms. Conclusion | McArdle's disease represents a rare differential diagnosis of cardiac chest pain and somatoform myalgic complaints. When taking the patient's history, questions regarding the "Second wind"-phenomenon are helpful for initiating the adequate investigations early on. © Georg Thieme Verlag KG Stuttgart · New York.
  • Sylvia Kreutzer, Ralph Weidner, Gereon R Fink
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    ABSTRACT: Spatial and temporal context of an object influence its perceived size. Two visual illusions illustrate this nicely: the size adaptation effect and the Ebbinghaus illusion. Whereas size adaptation affects size rescaling of a target circle via a previously presented, differently sized adaptor circle, the Ebbinghaus illusion alters perceived size by virtue of surrounding circles. In the classical Ebbinghaus setting, the surrounding circles are shown simultaneously with the target. However, size underestimation persists when the surrounding circles precede the target. Such a temporal separation of inducer and target circles in both illusions permits the comparison of BOLD signals elicited by two displays that, although objectively identical, elicit different percepts. The current study combined both illusions in a factorial design to identify a presumed common central mechanism involved in rescaling retinal into perceived size. At the behavioral level, combining both illusions did not affect perceived size further. At the neural level, however, this combination induced functional activation beyond that induced by either illusion separately: An underadditive activation pattern was found within left lingual gyrus, right supramarginal gyrus, and right superior parietal cortex. These findings provide direct behavioral and functional evidence for the presence of a neural bottleneck in rescaling retinal into perceived size, a process vital for visual perception.
    Journal of Cognitive Neuroscience 01/2015; DOI:10.1162/jocn_a_00784 · 4.49 Impact Factor
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    ABSTRACT: Handedness is associated with differences in activation levels in various motor tasks performed with the dominant or non-dominant hand. Here we tested whether handedness is reflected in the functional architecture of the motor system even in the absence of an overt motor task. Using resting-state functional magnetic resonance imaging we investigated 18 right- and 18 left-handers. Whole-brain functional connectivity maps of the primary motor cortex (M1), supplementary motor area (SMA), dorsolateral premotor cortex (PMd), pre-SMA, inferior frontal junction and motor putamen were compared between right- and left-handers. We further used a multivariate linear support vector machine (SVM) classifier to reveal the specificity of brain regions for classifying handedness based on individual resting-state maps. Using left M1 as seed region, functional connectivity analysis revealed stronger interhemispheric functional connectivity between left M1 and right PMd in right-handers as compared to left-handers. This connectivity cluster contributed to the individual classification of right- and left-handers with 86.2% accuracy. Consistently, also seeding from right PMd yielded a similar handedness-dependent effect in left M1, albeit with lower classification accuracy (78.1%). Control analyses of the other resting-state networks including the speech and the visual network revealed no significant differences in functional connectivity related to handedness. In conclusion, our data revealed an intrinsically higher functional connectivity in right-handers. These results may help to explain that hand preference is more lateralized in right-handers than in left-handers. Furthermore, enhanced functional connectivity between left M1 and right PMd may serve as an individual marker of handedness. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 01/2015; 109. DOI:10.1016/j.neuroimage.2015.01.034 · 6.13 Impact Factor
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    ABSTRACT: Dear Sirs,We report a 46-year old woman who presented in 2009 with gait ataxia and dysarthria. Magnetic resonance (MR) imaging showed one isolated T2 hyperintense, slightly Gadolinium (Gd) enhancing lesion in the right cerebellar hemisphere. Oligoclonal bands in the cerebrospinal fluid (CSF) were positive, and the patient was diagnosed as clinically isolated syndrome. Over the next 2 years, symptoms partially remitted and repeated MRI scans confirmed regression of the cerebellar lesion. In August 2013 a relapse occurred, with gait ataxia and mild spastic paresis of the right arm. MRI scan at this time point demonstrated new periventricular and juxtacortical lesions (Fig. 1a, b). Subsequently immunomodulatory treatment with intramuscularly administered interferon beta-1a (Avonex®, 30 μg, weekly) was initiated.Fig. 1MR Imaging during interferon beta-1a treatment and development of PML: Axial T2-FLAIR (a, c, g) and Gd-enhanced T1-SE (e), coronal T2-FSE (d), and axial Double-Inversion Reco ...
    Journal of Neurology 01/2015; 262(3). DOI:10.1007/s00415-014-7620-4 · 3.84 Impact Factor
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    ABSTRACT: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune mediated peripheral neuropathy with multifocal involvement. Reliable biomarkers for diagnosis, disease progression and treatment response remain to be developed.We assessed the utility of corneal confocal microscopy (CCM) as a diagnostic marker for CIDP in 16 patients. CCM parameters including corneal nerve fiber density (NFD), nerve fiber length, number of main nerve trunks, number of nerve branches, nerve tortuosity, and dendritic cell density (DCD) were compared to those from 15 healthy controls and correlated with clinical and electrophysiological findings.CIDP patients had a significantly lower corneal NFD compared to healthy controls. The total nerve fiber length and the number of nerve branches were significantly decreased, whereas nerve tortuosity was increased in patients with CIDP. There was no positive correlation between corneal NFD and clinical or electrophysiological assessments. The average DCD was not significantly different in CIDP patients and controls.CCM measures suggest damage to small sensory afferents in the cornea in CIDP patients. Further studies are needed to compare different neuropathic conditions and to explore longitudinal changes of CCM parameters.
    Journal of the Peripheral Nervous System 01/2015; 19(4). DOI:10.1111/jns.12098 · 2.57 Impact Factor
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    ABSTRACT: Background Since 2000, systemic thrombolysis has been the only approved curative and causal treatment for acute ischemic stroke. In 2009, the guidelines of the German Society for Neurology were updated and the therapeutic window for performing thrombolysis was extended. The implementation of new therapies is influenced by many factors. We analyzed the factors at the organizational level that influence the implementation of thrombolysis in stroke patients.Methods The data published by the majority of German hospitals in their structured quality reports was assessed. We calculated a regression model in order to measure the influence of hospital/department-level characteristics (e.g., teaching status, ownership, location, and number of hospital beds) on the implementation of thrombolysis in 2006 (this is the earliest point in time that can be analyzed on this data basis). In order to measure the effect of the guideline update in 2009 on the thrombolysis rate (TR) change between 2008 and 2010, we performed a Wilcoxon signed-rank test and utilized a regression model.ResultsIn 2006, 61.5% of a total of 286 neurology departments performed systemic thrombolysis to treat ischemic strokes. The influencing factors for the use of systemic thrombolysis in 2006 were the existence of a stroke unit (+) and a hospital size of between 500 and 1,000 beds (¿). A significant increase of the mean departmental TR (thrombolysis rate) from 6.7% to 9.2% between 2008 and 2010 was observed after the guideline update in 2009. For the departments performing thrombolysis in 2008 and 2010, our analysis could not show any additional influencing factors on a structural level that would explain the TR rise during the period 2008¿2010.Conclusions Because ischemic stroke patients benefit from systemic thrombolysis, it is necessary to examine possible barriers at the organizational level that hinder the implementation. Our data shows that, organizational factors have an influence on the implementation of thrombolysis. However, the recent guideline update resulted in a TR rise that occurred at all hospitals, regardless of the measured structural conditions, as our analysis could not identify any structural factors that might have influenced the TR after the guideline update.
    Implementation Science 01/2015; 10(1):10. DOI:10.1186/s13012-014-0196-7 · 3.47 Impact Factor
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    ABSTRACT: Although characteristic motor symptoms of Parkinson's disease such as bradykinesia typically improve under dopaminergic medication, deficits in higher motor control are less responsive. We here investigated the dopaminergic modulation of network dynamics underlying basic motor performance, i.e. finger tapping, and higher motor control, i.e. internally and externally cued movement preparation and selection. Twelve patients, assessed ON and OFF medication, and 12 age-matched healthy subjects underwent functional magnetic resonance imaging. Dynamic causal modelling was used to assess effective connectivity in a motor network comprising cortical and subcortical regions. In particular, we investigated whether impairments in basic and higher motor control, and the effects induced by dopaminergic treatment are due to connectivity changes in (i) the mesial premotor loop comprising the supplementary motor area; (ii) the lateral premotor loop comprising lateral premotor cortex; and (iii) cortico-subcortical interactions. At the behavioural level, we observed a marked slowing of movement preparation and selection when patients were internally as opposed to externally cued. Preserved performance during external cueing was associated with enhanced connectivity between prefrontal cortex and lateral premotor cortex OFF medication, compatible with a context-dependent compensatory role of the lateral premotor loop in the hypodopaminergic state. Dopaminergic medication significantly improved finger tapping speed in patients, which correlated with a drug-induced coupling increase of prefrontal cortex with the supplementary motor area, i.e. the mesial premotor loop. In addition, only in the finger tapping condition, patients ON medication showed enhanced excitatory influences exerted by cortical premotor regions and the thalamus upon the putamen. In conclusion, the amelioration of bradykinesia by dopaminergic medication seems to be driven by enhanced connectivity within the mesial premotor loop and cortico-striatal interactions. In contrast, medication did not improve internal motor control deficits concurrent to missing effects at the connectivity level. This differential effect of dopaminergic medication on the network dynamics underlying motor control provides new insights into the clinical finding that in Parkinson's disease dopaminergic drugs especially impact on bradykinesia but less on executive functions. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
    Brain 01/2015; DOI:10.1093/brain/awu381 · 10.23 Impact Factor
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    ABSTRACT: Cognitive training (CT) has been reported to improve cognition in older adults. Its combination with protective factors such as physical activity (CPT) has rarely been studied, but it has been suggested that CPT might show stronger effects than pure CT. Healthy older adults (aged 50-85 years) were trained with CPT (n=15) or CT (n=15). Interventions were conducted in 90-minute sessions twice weekly for 6.5 weeks. Cognitive functions were assessed before and immediately after the interventions, and at 1-year follow-up. The main finding was an interaction effect on attention, with comparable gains from CPT and CT from pre- to post-test, but stronger effects of CPT to follow-up (P=0.02). Significant effects were found in subjects in terms of cognitive state (P=0.02), letter verbal fluency (P=0.00), and immediate (P=0.00) and delayed (P=0.01) verbal memory. Post hoc analyses indicated that these latter domains were affected differentially by CPT and CT. No significant between-subject effects were found. Our results suggest that CPT might lead to stronger long-term effects on attention. However, as the difference between CT and CPT was only evident at follow-up, these effects cannot be interpreted as a direct consequence of CPT; they may have been related to sustained physical activity after the training. Other domains were improved by both interventions, but no typical pattern could be identified. Possible underlying mechanisms are discussed, and directions for future research are suggested.
    Clinical Interventions in Aging 01/2015; 10:297-310. DOI:10.2147/CIA.S74071 · 2.65 Impact Factor
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    ABSTRACT: Experience regarding O-(2-[(18)F]-fluoroethyl)-L-tyrosine ((18)F-FET) PET in children and adolescents with brain tumors is limited. Sixty-nine (18)F-FET PET scans of 48 children and adolescents (median age, 13 years; range, 1-18 years) were analyzed retrospectively. Twenty-six scans were performed to assess newly diagnosed cerebral lesions; 24 scans for diagnosing tumor progression/recurrence; 8 scans for monitoring of chemotherapy effects; and 11 scans for the detection of residual tumor after resection. Maximum and mean tumor/brain ratios (TBRmax/mean) were determined at 20-40 min p.i. and time-activity curves of (18)F-FET uptake were assigned to three different patterns: (1) constant increase; (2) peak at > 20-40 min p.i. followed by a plateau; and (3) early peak (≤ 20 min) followed by a constant descent. Diagnostic accuracy of (18)F-FET PET was assessed by receiver-operating-characteristic (ROC) curve analyses using histology and/or clinical course as reference. In patients with newly diagnosed cerebral lesions, highest accuracy (77%) to detect neoplastic tissue (19 of 26 patients) was obtained when TBRmax was ≥ 1.7 (AUC, 0.80±0.09; sensitivity, 79%; specificity, 71%, PPV, 88%; P = 0.02). For diagnosing tumor progression/recurrence, highest accuracy (82%) was obtained when curve patterns 2 or 3 were present (AUC, 0.80±0.11; sensitivity, 75%; specificity, 90%, PPV, 90%; P = 0.02). During chemotherapy, a decrease of TBRs was associated with a stable clinical course and in two patients, PET detected residual tumor after presumably complete tumor resection. Our findings suggest that (18)F-FET PET can add valuable information for clinical decision-making in pediatric brain tumor patients. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 12/2014; DOI:10.2967/jnumed.114.148734 · 5.56 Impact Factor
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    ABSTRACT: Objective Nonhuman and human studies have documented the adverse effects of early life stress (ELS) on emotion regulation and underlying neural circuitry. Less is known about how these experiences shape social processes and neural circuitry. In this study we thus investigated how ELS impacts children’s perception of, and neural response to, negative social experiences in a social exclusion paradigm (CyberBall). Method Twenty-five foster or adopted children with ELS (age 10.6±1.8y, 13 male) and 26 matched non-separated controls (age 10.38 ±1.7y, 12 male) took part in a CyberBall paradigm during functional magnetic resonance imaging (fMRI). Results During peer rejection, children with ELS reported significantly more feelings of exclusion and frustration than non-separated controls. On the neural level, children with ELS showed reduced activation in the dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (dlPFC), and reduced connectivity between dlPFC-dACC, areas previously implicated in affect regulation. Conversely, children with ELS showed increased neural activation in brain regions involved in memory, arousal, and threat-related processing (middle temporal gyrus, thalamus, ventral tegmental area) relative to controls during social exclusion. The number of separation experiences before entering the permanent family predicted reductions in fronto-cingulate recruitment. The relationship between early separations and self-reported exclusion was mediated by dlPFC activity. Conclusion The findings suggest that ELS leads to alterations in neural circuitry implicated in the regulation of socioemotional processes. This neural signature may underlie foster children’s differential reactivity to rejection in everyday life and could increase risk for developing affective disorders.
    Journal of the American Academy of Child & Adolescent Psychiatry 12/2014; 53(12). DOI:10.1016/j.jaac.2014.09.004 · 6.35 Impact Factor
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    ABSTRACT: In digit-color synesthesia, a variant of grapheme-color synesthesia, digits trigger an additional color percept. Recent work on number processing in synesthesia suggests that colors can implicitly elicit numerical representations in digit-color synesthetes implying that synesthesia is bidirectional. Furthermore, morphometric investigations revealed structural differences in the parietal cortex of grapheme-color synesthetes, i.e., in the brain region where interactions between number and space occur in non-synesthetic subjects. Based upon these previous findings, we here examined whether implicitly evoked numerical representations interact with spatial representations in synesthesia in such a way that even a non-numerical, visuo-spatial task (here: line bisection) is modulated, i.e., whether synesthetes exhibit a systematic bisection bias for colored lines.Thirteen digit-color synesthetes were asked to bisect two sets of lines which were colored in their individual synesthetic colors associated with a small or a large digit, respectively. For all colored line stimuli combined, digit-color synesthetes showed - like control subjects (n=13, matched for age, gender, IQ and handedness) - a pseudo-neglect when bisecting colored lines. Measuring the color-induced change of the bisection bias (i.e., comparing the biases when bisecting lines colored according to a small number vs. those lines corresponding to a large number) revealed that only digit-color synesthetes were significantly influenced by line color.The results provide further evidence for the bidirectional nature of synesthesia and support the concept of a mental number line. In addition, they extend previous reports on bidirectionality in synesthesia by showing that even non-numerical, visuo-spatial performance can be modulated by implicit bidirectional processes.
    Cortex 11/2014; 64. DOI:10.1016/j.cortex.2014.11.001 · 6.04 Impact Factor
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    ABSTRACT: The follow-up of glioblastoma patients after radiochemotherapy with conventional MRI can be difficult since reactive alterations to the blood-brain barrier with contrast enhancement may mimic tumour progression (i.e. pseudoprogression, PsP). The aim of this study was to assess the clinical value of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET in the differentiation of PsP and early tumour progression (EP) after radiochemotherapy of glioblastoma. A group of 22 glioblastoma patients with new contrast-enhancing lesions or lesions showing increased enhancement (>25 %) on standard MRI within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median 7 weeks) were additionally examined using amino acid PET with (18)F-FET. Maximum and mean tumour-to-brain ratios (TBRmax, TBRmean) were determined. (18)F-FET uptake kinetic parameters (i.e. patterns of time-activity curves, TAC) were also evaluated. Classification as PsP or EP was based on the clinical course (no treatment change at least for 6 months), follow-up MR imaging and/or histopathological findings. Imaging results were also related to overall survival (OS). PsP was confirmed in 11 of the 22 patients. In patients with PsP, (18)F-FET uptake was significantly lower than in patients with EP (TBRmax 1.9 ± 0.4 vs. 2.8 ± 0.5, TBRmean 1.8 ± 0.2 vs. 2.3 ± 0.3; both P < 0.001) and presence of MGMT promoter methylation was significantly more frequent (P = 0.05). Furthermore, a TAC type II or III was more frequently present in patients with EP (P = 0.04). Receiver operating characteristic analysis showed that the optimal (18)F-FET TBRmax cut-off value for identifying PsP was 2.3 (sensitivity 100 %, specificity 91 %, accuracy 96 %, AUC 0.94 ± 0.06; P < 0.001). Univariate survival analysis showed that a TBRmax <2.3 predicted a significantly longer OS (median OS 23 vs. 12 months; P = 0.046). (18)F-FET PET may facilitate the diagnosis of PsP following radiochemotherapy of glioblastoma.
    European journal of nuclear medicine and molecular imaging 11/2014; 42(5). DOI:10.1007/s00259-014-2959-4 · 5.22 Impact Factor
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    ABSTRACT: It is debated how language and praxis are co-represented in the left hemisphere (LH). As voxel-based lesion-symptom mapping in LH stroke patients with aphasia and/or apraxia may contribute to this debate, we here investigated the relationship between language and praxis deficits at the behavioral and lesion levels in 50 sub-acute stroke patients. We hypothesized that language and (meaningful) action are linked via semantic processing in Broca's region. Behaviorally, half of the patients suffered from co-morbid aphasia and apraxia. While 24 % (n = 12) of all patients exhibited aphasia without apraxia, apraxia without aphasia was rare (n = 2, 4 %). Left inferior frontal, insular, inferior parietal, and superior temporal lesions were specifically associated with deficits in naming, reading, writing, or auditory comprehension. In contrast, lesions affecting the left inferior frontal gyrus, premotor cortex, and the central region as well as the inferior parietal lobe were associated with apraxic deficits (i.e., pantomime, imitation of meaningful and meaningless gestures). Thus, contrary to the predictions of the embodied cognition theory, lesions to sensorimotor and premotor areas were associated with the severity of praxis but not language deficits. Lesions of Brodmann area (BA) 44 led to combined apraxic and aphasic deficits. Data suggest that BA 44 acts as an interface between language and (meaningful) action thereby supporting parcellation schemes (based on connectivity and receptor mapping) which revealed a BA 44 sub-area involved in semantic processing.
    Brain Structure and Function 10/2014; DOI:10.1007/s00429-014-0925-3 · 7.84 Impact Factor

Publication Stats

15k Citations
1,989.52 Total Impact Points


  • 1991–2015
    • University of Cologne
      • • Department of Neurology
      • • Department of Psychiatry and Psychotherapy
      • • Institute of Anatomy I
      Köln, North Rhine-Westphalia, Germany
  • 2001–2014
    • Forschungszentrum Jülich
      • • Institut für Neurowissenschaften und Medizin (INM)
      • • Kognitive Neurologie (INM-3)
      Jülich, North Rhine-Westphalia, Germany
  • 1993–2013
    • Max Planck Institute for Metabolism Research
      • Group of Neuromodulation und Neurorehabilitation
      Köln, North Rhine-Westphalia, Germany
  • 2012
    • The Children's Hospital of Philadelphia
      • Center for Autism Research
      Philadelphia, PA, United States
  • 2007–2008
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany
  • 2003–2007
    • RWTH Aachen University
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 2002–2007
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 2005
    • Fraunhofer Institute for Molecular Biology and Applied Ecology IME
      Aachen, North Rhine-Westphalia, Germany
    • Scuola Internazionale Superiore di Studi Avanzati di Trieste
      Trst, Friuli Venezia Giulia, Italy
  • 2001–2005
    • Neurologische Klinik Westend
      Бад Вилдунген, Hesse, Germany
  • 2000
    • Heinrich-Heine-Universität Düsseldorf
      • Neurologische Klinik
      Düsseldorf, North Rhine-Westphalia, Germany