Gereon R Fink

Forschungszentrum Jülich, Jülich, North Rhine-Westphalia, Germany

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Publications (394)2075.28 Total impact

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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. Because decline of dopaminergic innervation leads to impaired function of the basal ganglia and prefrontal cortex in Parkinson’s disease (PD), we hypothesised that PD patients would show increased temporal variability in the action segmentation task, especially under medication withdrawal (hypothesis 1). Another crucial aspect of action segmentation is its reliance on a semantic representation of actions. There is no evidence to suggest that action representations are substantially altered, or cannot be accessed, in non-demented PD patients. We therefore expected action segmentation judgments to follow the same overall patterns in PD patients and healthy controls (hypothesis 2), resulting in comparable segmentation profiles. Both hypotheses were tested with a novel classification approach. We present evidence for both hypotheses in the present study: classifier performance was slightly decreased when it was tested for its ability to predict the identity of movies segmented by PD patients, and a measure of normativity of response behaviour was decreased when patients segmented movies under medication-withdrawal without access to an episodic memory of the sequence. This pattern of results is consistent with hypothesis 1. However, the classifier analysis also revealed that responses given by patients and controls create very similar action-specific patterns, thus delivering evidence in favour hypothesis 2. In terms of methodology, the use of classifiers in the present study allowed us to establish similarity of behaviour across groups (hypothesis 2). The approach opens up a new avenue that standard statistical methods often fail to provide and is discussed in terms of its merits to measure hypothesised similarities across study populations.
    Neuropsychologia 09/2015; DOI:10.1016/j.neuropsychologia.2015.09.034 · 3.30 Impact Factor
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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.
    Neuropsychologia 09/2015; DOI:10.1016/j.neuropsychologia.2015.09.017 · 3.30 Impact Factor
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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.
    Brain Stimulation 08/2015; DOI:10.1016/j.brs.2015.08.005 · 4.40 Impact Factor
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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.
    Human Brain Mapping 08/2015; DOI:10.1002/hbm.22936 · 5.97 Impact Factor
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    ABSTRACT: Theories of lateralized cognitive functions propose a dominance of the left hemisphere for motor control and of the right hemisphere for spatial attention. Accordingly, spatial attention deficits (e.g., neglect) are more frequently observed after right-hemispheric stroke, whereas apraxia is a common consequence of left-hemispheric stroke. Clinical reports of spatial attentional deficits after left hemisphere (LH) stroke also exist, but are often neglected. By applying parallel analysis (PA) and voxel-based lesion-symptom mapping (VLSM) to data from a comprehensive neuropsychological assessment of 74 LH stroke patients, we here systematically investigate the relationship between spatial inattention and apraxia and their neural bases. PA revealed that apraxic (and language comprehension) deficits loaded on one common component, while deficits in attention tests were explained by another independent component. Statistical lesion analyses with the individual component scores showed that apraxic (and language comprehension) deficits were significantly associated with lesions of the left superior longitudinal fascicle (SLF). Data suggest that in LH stroke spatial attention deficits dissociate from apraxic (and language comprehension) deficits. These findings contribute to models of lateralised cognitive functions in the human brain. Moreover, our findings strongly suggest that LH stroke patients should be assessed systematically for spatial attention deficits so that these can be included in their rehabilitation regime. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Cortex 07/2015; 71:349-358. DOI:10.1016/j.cortex.2015.07.023 · 5.13 Impact Factor
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    ABSTRACT: In patients with small-fiber neuropathy (SFN), noninvasive diagnostic tests that allow accurate monitoring of disease progression are urgently needed. The aim of this study was to assess corneal trigeminal small sensory nerves and immune cells by in vivo corneal confocal microscopy (CCM) in SFN. In this prospective single-center study, 14 patients with histologically confirmed SFN were analyzed. CCM parameters [corneal nerve fiber density (NFD); the total number of nerves, main trunks, and branches; nerve tortuosity; and dendritic cell density] were compared with 14 age-matched healthy controls and correlated with clinical symptoms, disease course, and histopathological findings. Corneal NFD (15,489.3 ± 5927.6 μm/mm vs. 22,687.1 ± 4328.7 μm/mm; P = 0.001) and the total number of nerves (10.4 ± 4.6/frame vs. 18.5 ± 4.8/frame; P < 0.0001) were significantly reduced in patients with SFN. In contrast, nerve tortuosity was significantly increased (2.2 ± 0.3 vs. 1.7 ± 0.5; P = 0.02). Corneal NFD did not correlate with intraepidermal NFD (ρ = -0.158; P = 0.5) or clinical symptoms (cold P = 0.1; prickling P = 0.2; burning P = 0.8; formication P = 0.7; stabbing P = 0.4; rubbing 0.1; pressure P = 0.1). The average dendritic cell density was increased in SFN (33.5 ± 57.5 cells/mm vs. 16.1 ± 13.7 cells/mm) but did not reach significance (P = 0.7). CCM provides parameters that reliably indicate injury to sensory afferents of the trigeminal nerve in patients with SFN. Our data suggest that CCM may serve both as a noninvasive diagnostic test and as a surrogate marker in SFN.
    Cornea 07/2015; 34(9). DOI:10.1097/ICO.0000000000000535 · 2.04 Impact Factor
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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; 119. DOI:10.1016/j.neuroimage.2015.05.101 · 6.36 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 · 6.36 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; 36(9). DOI:10.1002/hbm.22863 · 5.97 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:
    Neuro-Oncology 05/2015; 17(9). DOI:10.1093/neuonc/nov088 · 5.56 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 · 3.37 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; 30(8). DOI:10.1002/mds.26229 · 5.68 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. Identifier: NCT01829581.
    JAMA The Journal of the American Medical Association 02/2015; 313(8):824-36. DOI:10.1001/jama.2015.0846 · 35.29 Impact Factor
  • Lucia B Roy · Roland Sparing · Gereon R Fink · Maike D Hesse
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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; 74. DOI:10.1016/j.neuropsychologia.2015.02.028 · 3.30 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 · 3.36 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.
    Journal of the International Neuropsychological Society 02/2015; 21(03):1-10. DOI:10.1017/S1355617715000107 · 2.96 Impact Factor

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17k Citations
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  • 2001–2015
    • 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
      • • Department of Psychiatry and Psychotherapy
      • • Institute of Anatomy I
      Köln, 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