Gereon R Fink

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

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Publications (391)2118.35 Total impact

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    ABSTRACT: Voluntary movements depend on a well-regulated interplay between the primary motor cortex (M1) and premotor areas. While to date the neural underpinnings of hand movements are relatively well understood, we only have rather limited knowledge on the cortical control of lower-limb movements. Given that our hands and feet have different roles for activities of daily living, with hand movements being more frequently used in a lateralized fashion, we hypothesized that such behavioral differences also impact onto network dynamics underlying upper and lower limb movements. We, therefore, used functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to investigate differences in effective connectivity underlying isolated movements of the hands or feet in 16 healthy subjects. The connectivity analyses revealed that both movements of the hand and feet were accompanied by strong facilitatory coupling of the respective contralateral M1 representations with premotor areas of both hemispheres. However, excitatory influences were significantly lower for movements of the feet compared to hand movements. During hand movements, the M1hand representation ipsilateral to the movement was strongly inhibited by premotor regions and the contralateral M1 homologue. In contrast, interhemispheric inhibition was absent between the M1foot representations during foot movements. Furthermore, M1foot ipsilateral to the moving foot exerted promoting influences onto contralateral M1foot. In conclusion, the generally stronger and more lateralized coupling pattern associated with hand movements suggest distinct fine-tuning of cortical control to underlie voluntary movements with the upper compared to the lower limb. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 06/2015; DOI:10.1016/j.neuroimage.2015.05.101 · 6.13 Impact Factor
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    ABSTRACT: The responsiveness to non-invasive neuromodulation protocols shows high inter-individual variability, the reasons of which remain poorly understood. We here tested whether the response to intermittent theta-burst stimulation (iTBS) - an effective repetitive transcranial magnetic stimulation (rTMS) protocol for increasing cortical excitability - depends on network properties of the cortical motor system. We furthermore investigated whether the responsiveness to iTBS is dose-dependent. To this end, we used a sham-stimulation controlled, single-blinded within-subject design testing for the relationship between iTBS aftereffects and (i) motor-evoked potentials (MEPs) as well as (ii) resting-state functional connectivity (rsFC) in 16 healthy subjects. In each session, three blocks of iTBS were applied, separated by 15 min. We found that non-responders (subjects not showing an MEP increase of ≥10% after one iTBS block) featured stronger rsFC between the stimulated primary motor cortex (M1) and premotor areas before stimulation compared to responders. However, only the group of responders showed increases in rsFC and MEPs, while most non-responders remained close to baseline levels after all three blocks of iTBS. Importantly, there was still a large amount of variability in both groups. Our data suggest that responsiveness to iTBS at the local level (i.e., M1 excitability) depends upon the pre-interventional network connectivity of the stimulated region. Of note, increasing iTBS dose did not turn non-responders into responders. The finding that higher levels of pre-interventional connectivity precluded a response to iTBS could reflect a ceiling effect underlying non-responsiveness to iTBS at the systems level. Copyright © 2015. Published by Elsevier Inc.
    NeuroImage 06/2015; 118. DOI:10.1016/j.neuroimage.2015.06.004 · 6.13 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is associated with distinct metabolic covariance patterns that relate to the motor and cognitive manifestations of the disorder. It is not known, however, how the expression of these patterns relates to measurements of nigrostriatal dopaminergic activity from the same individuals. To explore these associations, we studied 106 PD subjects who underwent cerebral PET with both (18) F-fluorodeoxyglucose (FDG) and (18) F-fluoro-L-dopa (FDOPA). Expression values for the PD motor- and cognition-related metabolic patterns (PDRP and PDCP, respectively) were computed for each subject; these measures were correlated with FDOPA uptake on a voxel-by-voxel basis. To explore the relationship between dopaminergic function and local metabolic activity, caudate and putamen FDOPA PET signal was correlated voxel-wise with FDG uptake over the entire brain. PDRP expression correlated with FDOPA uptake in caudate and putamen (P < 0.001), while PDCP expression correlated with uptake in the anterior striatum (P < 0.001). While statistically significant, the correlations were only of modest size, accounting for less than 20% of the overall variation in these measures. After controlling for PDCP expression, PDRP correlations were significant only in the posterior putamen. Of note, voxel-wise correlations between caudate/putamen FDOPA uptake and whole-brain FDG uptake were significant almost exclusively in PDRP regions. Overall, the data indicate that PDRP and PDCP expression correlates significantly with PET indices of presynaptic dopaminergic functioning obtained in the same individuals. Even so, the modest size of these correlations suggests that in PD patients, individual differences in network activity cannot be explained solely by nigrostriatal dopamine loss. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 06/2015; DOI:10.1002/hbm.22863 · 6.92 Impact Factor
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    ABSTRACT: We evaluated the diagnostic value of static and dynamic O-(2-[(18)F]fluoroethyl)-l-tyrosine ((18)F-FET) PET parameters in patients with progressive or recurrent glioma. We retrospectively analyzed 132 dynamic (18)F-FET PET and conventional MRI scans of 124 glioma patients (primary World Health Organization grade II, n = 55; grade III, n = 19; grade IV, n = 50; mean age, 52 ± 14 y). Patients had been referred for PET assessment with clinical signs and/or MRI findings suggestive of tumor progression or recurrence based on Response Assessment in Neuro-Oncology criteria. Maximum and mean tumor/brain ratios of (18)F-FET uptake were determined (20-40 min post-injection) as well as tracer uptake kinetics (ie, time to peak and patterns of the time-activity curves). Diagnoses were confirmed histologically (95%) or by clinical follow-up (5%). Diagnostic accuracies of PET and MR parameters for the detection of tumor progression or recurrence were evaluated by receiver operating characteristic analyses/chi-square test. Tumor progression or recurrence could be diagnosed in 121 of 132 cases (92%). MRI and (18)F-FET PET findings were concordant in 84% and discordant in 16%. Compared with the diagnostic accuracy of conventional MRI to diagnose tumor progression or recurrence (85%), a higher accuracy (93%) was achieved by (18)F-FET PET when a mean tumor/brain ratio ≥2.0 or time to peak <45 min was present (sensitivity, 93%; specificity, 100%; accuracy, 93%; positive predictive value, 100%; P < .001). Static and dynamic (18)F-FET PET parameters differentiate progressive or recurrent glioma from treatment-related nonneoplastic changes with higher accuracy than conventional MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Neuro-Oncology 05/2015; DOI:10.1093/neuonc/nov088 · 5.29 Impact Factor
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    ABSTRACT: Osteopontin (OPN) is a phosphoglycoprotein with important roles in tissue homeostasis, wound healing, immune regulation, and stress responses. It is expressed constitutively in the brain and upregulated during neuroinflammatory responses, e.g., after focal cerebral ischemia. To date, its effects on neural stem cells (NSC) remain to be elucidated and are, accordingly, subject of this study. Primary fetal rat NSC were cultured as homogenous monolayers and treated with different concentrations of OPN. Fundamental properties of NSC were assessed following OPN exposure, including proliferative activity, survival under oxidative stress, migration, and differentiation potential. To elucidate a putative action of OPN via the CXC chemokine receptor type 4 (CXCR4), the latter was blocked with AMD3100. To investigate effects of OPN on endogenous NSC in vivo, recombinant OPN was injected into the brain of healthy adult rats as well as rats subjected to focal cerebral ischemia. Effects of OPN on NSC proliferation and neurogenesis in the subventricular zone (SVZ) were studied immunohistochemically. OPN dose-dependently increased the number of NSC in vitro. As hypothesized, this effect was mediated through CXCR4. The increase in NSC number was due to both enhanced cell proliferation and increased survival, and was confirmed in vivo. Additionally, OPN dose-dependently stimulated the migration of NSC via CXCR4. Moreover, in the presence of OPN, differentiation of NSC led to a significant increase in neurogenesis both in vitro as well as in vivo after cerebral ischemia. Data show positive effects of OPN on survival, proliferation, migration, and neuronal differentiation of NSC. At least in part these effects were mediated via CXCR4. Results suggest that OPN is a promising substance for the targeted activation of NSC in future experimental therapies for neurological disorders such as stroke.
    Stem Cell Research & Therapy 05/2015; 6(1):99. DOI:10.1186/s13287-015-0098-x · 4.63 Impact Factor
  • The Lancet 05/2015; 385(9979):1802. DOI:10.1016/S0140-6736(15)60451-2 · 45.22 Impact Factor
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    ABSTRACT: The synthesis of the neurotransmitters serotonin (5-HT) and dopamine (DA) in the brain can be directly altered by dietary manipulation of their relevant precursor amino acids (AA). There is evidence that altered serotonergic and dopaminergic neurotransmission are both associated with impaired attentional control. Specifically, phasic alertness is one specific aspect of attention that has been linked to changes in 5-HT and DA availability in different neurocircuitries related to attentional processes. The present study investigated the impact of short-term reductions in central nervous system 5-HT and DA synthesis, which was achieved by dietary depletion of the relevant precursor AA, on phasic alertness in healthy adult volunteers; body weight-adapted dietary tryptophan and phenylalanine-tyrosine depletion (PTD) techniques were used. The study employed a double-blind between-subject design. Fifty healthy male and female subjects were allocated to three groups in a randomized and counterbalanced manner and received three different dietary challenge conditions: acute tryptophan depletion (ATD, for the depletion of 5-HT; N=16), PTD (for the depletion of DA; N=17), and a balanced AA load (BAL; N=17), which served as a control condition. Three hours after challenge intake (ATD/PTD/BAL), phasic alertness was assessed using a standardized test battery for attentional performance (TAP). Blood samples for AA level analyses were obtained at baseline and 360 min after the challenge intake. Overall, there were no significant differences in phasic alertness for the different challenge conditions. Regarding PTD administration, a positive correlation between the reaction times and the DA-related depletion magnitude was detected via the lower plasma tyrosine levels and the slow reaction times of the first run of the task. In contrast, higher tryptophan concentrations were associated with slower reaction times in the fourth run of the task in the same challenge group. The present study is the first to demonstrate preliminary data that support an association between decreased central nervous system DA synthesis, which was achieved by dietary depletion strategies, and slower reaction times in specific runs of a task designed to assess phasic alertness in healthy adult volunteers; these findings are consistent with previous evidence that links phasic alertness with dopaminergic neurotransmission. A lack of significant differences between the three groups could be due to compensatory mechanisms and the limited sample size, as well as the dietary challenge procedures administered to healthy participants and the strict exclusion criteria used. The potential underlying neurochemical processes related to phasic alertness should be the subject of further investigations.
    Food & Nutrition Research 04/2015; 59:26407. DOI:10.3402/fnr.v59.26407 · 1.79 Impact Factor
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    ABSTRACT: Background Subthalamic deep brain stimulation (STN-DBS) can ameliorate gait disturbances in Parkinson's disease (PD). Using motor imagery and positron emission tomography (PET), we investigated how STN-DBS interacts with supraspinal locomotor centers in PD.Methods Ten PD patients with bilateral STN-DBS actually walked or stood still under STN-DBS ON or OFF conditions. Directly thereafter, subjects imagined walking or standing while changes in regional cerebral blood flow were measured by PET.ResultsIndependent of STN-DBS, imagined walking distance correlated with imagery duration. Compared with STN-DBS OFF, STN-DBS ON improved actual gait and increased imagined walking distance. Imagery of gait (vs. stance) induced activity in the supplementary motor area and the right superior parietal lobule for both STN-DBS conditions. The improvement of imagined gait during STN-DBS ON led to activity changes in the pedunculopontine nucleus/mesencephalic locomotor region (PPN/MLR).Conclusions Data suggest that STN-DBS improves Parkinsonian gait by modulating PPN/MLR activity. © 2015 International Parkinson and Movement Disorder Society
    Movement Disorders 04/2015; DOI:10.1002/mds.26229 · 5.63 Impact Factor
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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; 22(5):1-19. 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; 35:330-341. 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. clinicaltrials.gov Identifier: NCT01829581.
    JAMA The Journal of the American Medical Association 02/2015; 313(8):824-36. DOI:10.1001/jama.2015.0846 · 30.39 Impact Factor
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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; 27(7):1-10. DOI:10.1162/jocn_a_00784 · 4.69 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 · 1.82 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

Publication Stats

16k Citations
2,118.35 Total Impact Points

Institutions

  • 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
  • 2002–2007
    • RWTH Aachen University
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
    • 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
  • 2000–2005
    • Neurologische Klinik Westend
      Бад Вилдунген, Hesse, Germany
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany