Gereon R Fink

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

Are you Gereon R Fink?

Claim your profile

Publications (561)2449.09 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The cholinergic system plays a central role in episodic memory-related processes in health and disease. Cerebral acetycholinesterase (AChE) activity, a measure of the integrity of the cholinergic system, can be assessed in vivo using positron emission tomography (PET) and [(11)C]N-methyl-4-piperidyl acetate (MP4A). A close relationship between the kinetic constant k3 of MP4A and mnestic functions has been demonstrated for patients suffering from amnestic mild cognitive impairment and Alzheimer's disease. Under the hypothesis that AChE activity and memory are intimately linked in older age, we obtained MP4A-PET and structural magnetic resonance images as well as neuropsychological data from fourteen healthy older adults. Multiple regression analysis revealed that AChE activity in areas previously implicated in mnestic functions predicted episodic memory performance irrespective of cortical atrophy. Data suggest that in older adults the integrity of the cholinergic system underlies inter-individual variability in memory function.
    NeuroImage 06/2014; · 6.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others' (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region.
    Brain Structure and Function 06/2014; · 7.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuroinflammation with microglia activation (MA) constitutes a key tissue response in acute stroke. Until now, its course in the chronic stage is less well defined. Here, we investigated (i) neuroinflammation in the chronic stage of a rat model of embolic stroke (n=6), and (ii) whether this process can be visualized in vivo by multimodal imaging using Magnetic Resonance Imaging (MRI) and Positron-Emission-Tomography (PET). Imaging data were verified using histology and immunohistochemistry. Repetitive PET studies until week 6 after stroke reveal poststroke inflammation as a dynamic process that involved the infarct, the surrounding tissue and secondary degenerating areas in a complex fashion. At the end, 7 months after stroke, neuroinflammation had almost completely vanished at the lesion side. In contrast, remote from the primarily infarcted areas, a marked T2⁎- hypointensity was detected in the ipsilateral thalamus. In the corresponding area, [(11)C]PK11195-PET detected microglia activation. Immunohistochemistry confirmed activated microglia in the ipsilateral thalamus with signs of extensive phagocytosis and iron deposition around plaque-like amyloid deposition. Neuronal staining (NeuN) revealed pronounced neuronal loss as an endpoint of neurodegeneration in these areas. In conclusion, the data demonstrate not only ongoing thalamic neuroinflammation but also marked neurodegeneration remote from the lesion site in the chronic phase after stroke in rats. Both, neuroinflammation and neurodegeneration were accessible to (immuno-) histochemical methods as well as to in vivo methods using [(11)C]PK11195-PET and T2⁎-weighted MRI. Although the functional roles of these dynamic processes remain to be elucidated, ongoing destruction of neuronal tissue is conceivable. Its inhibition using anti-inflammatory substances may be beneficial in chronic post-stroke conditions, while multimodal imaging can be used to evaluate putative therapeutic effects in vivo.
    Brain research. 06/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Handedness denotes the individual predisposition to consistently use the left or right hand for most types of skilled movements. A putative neurobiological mechanism for handedness consists in hemisphere-specific differences in network dynamics that govern unimanual movements. We, therefore, used functional magnetic resonance imaging and dynamic causal modeling to investigate effective connectivity between key motor areas during fist closures of the dominant or non-dominant hand performed by 18 right- and 18 left-handers. Handedness was assessed employing the Edinburgh-Handedness-Inventory (EHI). The network of interest consisted of key motor regions in both hemispheres including primary motor cortex (M1), supplementary motor area (SMA), ventral premotor cortex (PMv), motor putamen (Put) and motor cerebellum (Cb). The connectivity analysis revealed that in right-handed subjects movements of the dominant hand were associated with significantly stronger coupling of contralateral (left, i.e., dominant) SMA with ipsilateral SMA, ipsilateral PMv, contralateral motor putamen and contralateral M1 compared to equivalent connections in left-handers. The degree of handedness as indexed by the individual EHI scores also correlated with coupling parameters of these connections. In contrast, we found no differences between right- and left-handers when testing for the effect of movement speed on effective connectivity. In conclusion, the data show that handedness is associated with differences in effective connectivity within the human motor network with a prominent role of SMA in right-handers. Left-handers featured less asymmetry in effective connectivity implying different hemispheric mechanisms underlying hand motor control compared to right-handers.
    NeuroImage 05/2014; · 6.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Conventional mass-univariate analyses have been previously used to test for group differences in neural signals. However, machine learning algorithms represent a multivariate decoding approach that may help to identify neuroimaging patterns associated with functional impairment in "individual" patients. We investigated whether fMRI allows classification of individual motor impairment after stroke using support vector machines (SVMs). Forty acute stroke patients and 20 control subjects underwent resting-state fMRI. Half of the patients showed significant impairment in hand motor function. Resting-state connectivity was computed by means of whole-brain correlations of seed time-courses in ipsilesional primary motor cortex (M1). Lesion location was identified using diffusion-weighted images. These features were used for linear SVM classification of unseen patients with respect to motor impairment. SVM results were compared with conventional mass-univariate analyses. Resting-state connectivity classified patients with hand motor deficits compared with controls and nonimpaired patients with 82.6-87.6% accuracy. Classification was driven by reduced interhemispheric M1 connectivity and enhanced connectivity between ipsilesional M1 and premotor areas. In contrast, lesion location provided only 50% sensitivity to classify impaired patients. Hence, resting-state fMRI reflects behavioral deficits more accurately than structural MRI. In conclusion, multivariate fMRI analyses offer the potential to serve as markers for endophenotypes of functional impairment.
    Cerebral cortex (New York, N.Y. : 1991). 05/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity.
    Journal of Neuroscience 05/2014; 34(20):6849-59. · 6.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The neural cell adhesion molecule (NCAM) plays a role in neurite outgrowth, synaptogenesis, and neuronal differentiation. The NCAM mimetic peptide FG Loop (FGL) promotes neuronal survival in vitro and enhances spatial learning and memory in rats. We here investigated the effects of FGL on neural stem cells (NSC) in vitro and in vivo. In vitro, cell proliferation of primary NSC was assessed after exposure to various concentrations of NCAM or FGL. The differentiation potential of NCAM- or FGL-treated cells was assessed immunocytochemically. To investigate its influence on endogenous NSC in vivo, FGL was injected subcutaneously into adult rats. The effects on NSC mobilization were studied both via non-invasive positron emission tomography (PET) imaging using the tracer [(18)F]-fluoro-L-thymidine ([(18)F]FLT), as well as with immunohistochemistry. Only FGL significantly enhanced NSC proliferation in vitro, with a maximal effect at 10 μg/ml. During differentiation, NCAM promoted neurogenesis, while FGL induced an oligodendroglial phenotype; astrocytic differentiation was neither affected by NCAM or FGL. Those differential effects of NCAM and FGL on differentiation were mediated through different receptors. After FGL-injection in vivo, proliferative activity of NSC in the subventricular zone (SVZ) was increased (compared to placebo-treated animals). Moreover, non-invasive imaging of cell proliferation using [(18)F]FLT-PET supported an FGL-induced mobilization of NSC from both the SVZ and the hippocampus. We conclude that FGL robustly induces NSC mobilization in vitro and in vivo, and supports oligodendroglial differentiation. This capacity renders FGL a promising agent to facilitate remyelinization, which may eventually make FGL a drug candidate for demyelinating neurological disorders.
    Stem cell reviews 05/2014; · 5.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: . Previous findings suggest that language disorders may occur in severely brain-injured patients and could interfere with behavioral assessments of consciousness. However, no study investigated to what extent language impairment could affect patients' behavioral responses. . To estimate the impact of receptive and/or productive language impairments on consciousness assessment. . Twenty-four acute and subacute stroke patients with different types of aphasia (global, n = 11; Broca, n = 4; Wernicke, n = 3; anomic, n = 4; mixed, n = 2) were recruited in neurology and neurosurgery units as well as in rehabilitation centers. The Coma Recovery Scale-Revised (CRS-R) was administered. . We observed that 25% (6 out of 24) of stroke patients with a diagnosis of aphasia and 54% (6 out of 11) of patients with a diagnosis of global aphasia did not reach the maximal CRS-R total score of 23. An underestimation of the consciousness level was observed in 3 patients with global aphasia who could have been misdiagnosed as being in a minimally conscious state, even in the absence of any documented period of coma. More precisely, lower subscores were observed on the communication, motor, oromotor, and arousal subscales. . Consciousness assessment may be complicated by the co-occurrence of severe language deficits. This stresses the importance of developing new tools or identifying items in existing scales, which may allow the detection of language impairment in severely brain-injured patients.
    Neurorehabilitation and neural repair 04/2014; · 4.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th-DBS) on dystonic head tremor and dystonia in a single-blind design.Methods Dystonic head tremor and dystonia before and 3 months after surgery were quantified via blinded video-ratings using the Fahn-Tolosa-Marin-Tremor-Scale and the Burke-Fahn-Marsden-Dystonia-Rating-Scale in seven patients with idiopathic cervical or segmental dystonia, dystonic head tremor, and bilateral Th-DBS. Pain, side effects, adverse events, and stimulation parameters were assessed.ResultsTh-DBS improved dystonic tremor and dystonia (P < 0.05; 57.1% and 70.4%, respectively). Head tremor amplitude and pain were also improved (P < 0.05; 77.5% and 90.0%, respectively). Side effects included dysarthria, gait disturbance, slowness of movement, and weight gain.Conclusion Dystonic head tremor and dystonia can be improved with Th-DBS. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 04/2014; · 4.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PET using O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) provides important diagnostic information in addition to that from conventional MR imaging on tumor extent and activity of cerebral gliomas. Recent studies suggest that perfusion-weighted MR imaging (PWI), especially maps of regional cerebral blood volume (rCBV), may provide similar diagnostic information. In this study, we directly compared (18)F-FET PET and PWI in patients with brain tumors. Fifty-six patients with gliomas were investigated using static (18)F-FET PET and PWI. For comparison, 8 patients with meningiomas were included. We generated a set of tumor and reference volumes of interest (VOIs) based on morphologic MR imaging and transferred these VOIs to the corresponding (18)F-FET PET scans and PWI maps. From these VOIs, tumor-to-brain ratios (TBR) were calculated, and normalized histograms were generated for (18)F-FET PET and rCBV maps. Furthermore, in rCBV maps and in (18)F-FET PET scans, tumor volumes, their spatial congruence, and the distance between the local hot spots were assessed. For patients with glioma, TBR was significantly higher in (18)F-FET PET than in rCBV maps (TBR, 2.28 ± 0.99 vs. 1.62 ± 1.13; P < 0.001). Histogram analysis of the VOIs revealed that (18)F-FET scans could clearly separate tumor from background. In contrast, deriving this information from rCBV maps was difficult. Tumor volumes were significantly larger in (18)F-FET PET than in rCBV maps (tumor volume, 24.3 ± 26.5 cm(3) vs. 8.9 ± 13.9 cm(3); P < 0.001). Accordingly, spatial overlap of both imaging parameters was poor (congruence, 11.0%), and mean distance between the local hot spots was 25.4 ± 16.1 mm. In meningioma patients, TBR was higher in rCBV maps than in (18)F-FET PET (TBR, 5.33 ± 2.63 vs. 2.37 ± 0.32; P < 0.001) whereas tumor volumes were comparable. In patients with cerebral glioma, tumor imaging with (18)F-FET PET and rCBV yields different information. (18)F-FET PET shows considerably higher TBRs and larger tumor volumes than rCBV maps. The spatial congruence of both parameters is poor. The locations of the local hot spots differ considerably. Taken together, our data show that metabolically active tumor tissue of gliomas as depicted by amino acid PET is not reflected by rCBV as measured with PWI.
    Journal of Nuclear Medicine 02/2014; · 5.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A moon near to the horizon is perceived larger than a moon at the zenith, although-obviously-the moon does not change its size. In this study, the neural mechanisms underlying the "moon illusion" were investigated using a virtual 3-D environment and fMRI. Illusory perception of an increased moon size was associated with increased neural activity in ventral visual pathway areas including the lingual and fusiform gyri. The functional role of these areas was further explored in a second experiment. Left V3v was found to be involved in integrating retinal size and distance information, thus indicating that the brain regions that dynamically integrate retinal size and distance play a key role in generating the moon illusion.
    Journal of Cognitive Neuroscience 02/2014; · 4.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hypokinetic gait is a common and very disabling symptom of Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) over the motor cortex has been used with variable effectiveness to treat hypokinesia in PD. Preconditioning rTMS by transcranial direct current stimulation (tDCS) may enhance its effectiveness to treat hypokinetic gait in PD. Three-dimensional kinematic gait analysis was performed (1) prior to, (2) immediately after and (3) 30 min after low-frequency rTMS (1 Hz, 900 pulses, 80 % of resting motor threshold) over M1 contralateral to the more affected body side preconditioned by (1) cathodal, (2) anodal or (3) sham tDCS (amperage: 1 mA, duration: 10 min) in ten subjects with PD (7 females, mean age 63 ± 9 years) and ten healthy subjects (four females, mean age 50 ± 11 years). The effects of tDCS-preconditioned rTMS on gait kinematics were assessed by the following parameters: number of steps, step length, stride length, double support time, cadence, swing and stance phases. Our data suggest a bilateral improvement of hypokinetic gait in PD after 1 Hz rTMS over M1 of the more affected body side preceded by anodal tDCS. In contrast, 1 Hz rTMS alone (preceded by sham tDCS) and 1 Hz rTMS preceded by cathodal tDCS were ineffective to improve gait kinematics in PD. In healthy subjects, gait kinematics was unaffected by either intervention. Preconditioning motor cortex rTMS by tDCS is a promising approach to treat hypokinetic gait in PD.
    Journal of Neural Transmission 02/2014; · 3.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: When movements indicate meaningful actions, even nonbiological objects induce the impression of "having a mind" or animacy. This basic social ability was investigated in adults with high-functioning autism (HFA, n = 13, and matched controls, n = 13) by systematically varying motion properties of simple geometric shapes. Critically, trial-by-trial variations of (1) motion complexity of stimuli, and of (2) participants' individual animacy ratings were separately correlated with neural activity to dissociate cognitive strategies relying more closely on stimulus analysis vs. subjective experience. Increasing motion complexity did not yield any significant group differences, and in both groups, it correlated with neural activity in regions involved in perceptual and evaluative processing, including the ventral medial prefrontal cortex (mPFC), superior temporal gyrus (STG) and posterior cingulate cortex (PCC). In contrast, although there were no significant behavioral differences between the groups, increasing animacy ratings correlated with neural activity in the insula, STG, amygdala, dorsal mPFC and PCC more strongly in controls than in HFA. These results indicate that in HFA the evaluation of stimulus properties cuing for animacy is intact, while increasing subjective ratings do not seem to be robustly related to social processing, including spontaneous mental state inferences and experience of salience.
    Social neuroscience 02/2014; · 3.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: When movements indicate meaningful actions, even nonbiological objects induce the impression of “having a mind” or animacy. This basic social ability was investigated in adults with high-functioning autism (HFA, n = 13, and matched controls, n = 13) by systematically varying motion properties of simple geometric shapes. Critically, trial-by-trial variations of (1) motion complexity of stimuli, and of (2) participants’ individual animacy ratings were separately correlated with neural activity to dissociate cognitive strategies relying more closely on stimulus analysis vs. subjective experience. Increasing motion complexity did not yield any significant group differences, and in both groups, it correlated with neural activity in regions involved in perceptual and evaluative processing, including the ventral medial prefrontal cortex (mPFC), superior temporal gyrus (STG) and posterior cingulate cortex (PCC). In contrast, although there were no significant behavioral differences between the groups, increasing animacy ratings correlated with neural activity in the insula, STG, amygdala, dorsal mPFC and PCC more strongly in controls than in HFA. These results indicate that in HFA the evaluation of stimulus properties cuing for animacy is intact, while increasing subjective ratings do not seem to be robustly related to social processing, including spontaneous mental state inferences and experience of salience.
    Social Neuroscience 02/2014; · 2.79 Impact Factor
  • Christian Grefkes, Gereon R Fink
    [Show abstract] [Hide abstract]
    ABSTRACT: After focal damage, cerebral networks reorganise their structural and functional anatomy to compensate for both the lesion itself and remote effects. Novel developments in the analysis of functional neuroimaging data enable us to assess in vivo the specific contributions of individual brain areas to recovery of function and the effect of treatment on cortical reorganisation. Connectivity analyses can be used to investigate the effect of stroke on cerebral networks, and help us to understand why some patients make a better recovery than others. This systems-level view also provides insights into how neuromodulatory interventions might target pathological network configurations associated with incomplete recovery. In the future, such analyses of connectivity could help to optimise treatment regimens based on the individual network pathology underlying a particular neurological deficit, thereby opening the way for stratification of patients based on the possible response to an intervention.
    The Lancet Neurology 02/2014; 13(2):206-16. · 23.92 Impact Factor
  • Fortschritte der Neurologie · Psychiatrie 01/2014; 82(1):55-56. · 0.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a non-current-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control.
    Neurology 01/2014; · 8.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inconsistent findings regarding effects of dopaminergic medication (MED) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) on decision making processes and impulsivity in Parkinson´s disease (PD) patients have been reported. This study investigated the influence of MED and STN-DBS on decision-making under risk. Eighteen non-demented PD patients, treated with both MED and STN-DBS (64.3 ± 10.2years, UPDRS III MED off, DBS off 45.5 ± 17.1) were tested with the Game of Dice Task (GDT) which probes decision-making under risk during four conditions: MED on / DBS on, MED on / DBS off, MED off / DBS on, and MED off / DBS off. Task performance across conditions was compared analyzing two GDT-parameters: (i) the "net score" indicating advantageous decisions, and (ii) the patient's ability to use negative feedback. Significantly higher GDT net scores were observed in Med on in contrast to Med off conditions as well as in DBS on versus DBS off conditions. However, no effect of therapy for the patient's ability to make use of negative feedback could be detected. The data suggest a positive influence of both MED and STN-DBS on making decisions under risk in PD patients, an effect which seems to be mediated by mechanisms other than the use of negative feedback.
    Experimental Neurology 01/2014; · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cerebral ischemia triggers a cascade of cellular processes, which induce neuroprotection, inflammation, apoptosis and regeneration. At the neural network level, lesions concomitantly induce cerebral plasticity. Yet, many stroke survivors are left with a permanent motor deficit, and only little is known about the neurobiological factors that determine functional outcome after stroke. Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) are non-invasive approaches that allow insights into the functional (re-) organization of the cortical motor system. We here combined neuronavigated TMS, MRI and analyses of connectivity to investigate to which degree recovery of hand function depends on corticospinal tract (CST) damage and biomarkers of cerebral plasticity like cortical excitability and motor network effective connectivity. As expected, individual motor performance of 12 stroke patients with persistent motor deficits was found to depend upon the degree of CST damage but also motor cortex excitability and interhemispheric connectivity. In addition, the data revealed a strong correlation between reduced ipsilesional motor cortex excitability and reduced interhemispheric inhibition in severely impaired patients. Interindividual differences in ipsilesional motor cortex excitability were stronger related to the motor deficit than abnormal interhemispheric connectivity or CST damage. Multivariate linear regression analysis combining the three factors accounted for more than 80 % of the variance in functional impairment. The inter-relation of cortical excitability and reduced interhemispheric inhibition provides direct multi-modal evidence for the disinhibition theory of the contralesional hemisphere following stroke. Finally, our data reveal a key mechanism (i.e., the excitability-related reduction in interhemispheric inhibition) accounting for the rehabilitative potential of novel therapeutic approaches which aim at modulating cortical excitability in stroke patients.
    Brain Structure and Function 01/2014; · 7.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To assess the effects of different frequencies of thalamic Deep-Brain-Stimulation (DBS) on cognitive performance of patients suffering from Essential Tremor (ET). Methods In 17 ET-patients with thalamic-DBS, tremor rating scale (TRS), standardized phonemic and semantic verbal fluency (VF), Stroop-Color-Word-Test and Digit-span-test were investigated in three randomized stimulation-settings: i. high-frequency stimulation (HFS), ii. low-frequency stimulation (LFS) and iii. OFF-stimulation (DBS-OFF). Paired-samples t-test for TRS and one-way repeated measures analysis of variance for cognitive performance were calculated. Results Tremor was reduced during HFS (MeanTRS-HFS = 12.9 ± 9.6) compared to DBS-OFF (MeanTRS-OFF = 44.4 ± 19.8, p<.001) and to LFS (MeanTRS-10Hz = 50.0 ± 24.2; p<.001). While performance of Stroop-task and digit-span remained unaffected by stimulation-settings (p>.05), phonemic and semantic VF differed significantly between the three conditions (FPvf = 5.28, FSvf = 3.41, both p<.05). Post-hoc comparisons revealed significant differences for both phonemic and semantic VF between LFS (MeanPvf-10Hz = 54.6 ± 9.2, MeanSvf-10Hz = 56.4 ± 7.9) and HFS (MeanPvf-ON = 48.3 ± 11.4, MeanSvf-ON = 51.1 ± 11.0, both p<.05), while DBS-OFF (MeanPvf-OFF = 51.2 ± 9.3, MeanSvf-OFF = 53.6 ± 12.9) and HFS and DBS-OFF and LFS did not differ significantly (p>.05). Conclusions HFS compared to LFS or DBS-OFF significantly reduced tremor but simultaneously worsened VF while working memory and cognitive inhibition remained unaffected. In contrast, LFS enhanced VF but did not ameliorate tremor. The data emphasize the relevance of thalamocortical loops for verbal fluency but also suggest that more sophisticated DBS-regimes in ET may improve both motor and cognitive performance.
    Brain Stimulation 01/2014; · 4.54 Impact Factor

Publication Stats

20k Citations
2,449.09 Total Impact Points

Institutions

  • 1991–2014
    • University of Cologne
      • • Department of Neurology
      • • Department of Psychiatry and Psychotherapy
      • • Institute of Anatomy I
      Köln, North Rhine-Westphalia, Germany
  • 2013
    • McGill University
      Montréal, Quebec, Canada
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 2002–2013
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
  • 1991–2013
    • Max Planck Institute for Neurological 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
    • University of Geneva
      Genève, Geneva, Switzerland
    • South China Normal University
      Shengcheng, Guangdong, China
  • 2011–2012
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
  • 2007–2012
    • University College London
      • Wellcome Department of Imaging Neuroscience
      London, ENG, United Kingdom
    • Ludwig-Maximilian-University of Munich
      • Institute of Medical Psychology (IMP)
      München, Bavaria, Germany
    • Lancaster University
      • Department of Psychology
      Lancaster, ENG, United Kingdom
    • University of Leipzig
      • Faculty of Biosciences, Pharmacy and Psychology
      Leipzig, Saxony, Germany
  • 2003–2012
    • RWTH Aachen University
      • • Institut für Psychologie
      • • Department of Neurology
      • • Department of Child and Adolescent Psychiatry and Psychotherapy
      • • Department of Psychiatry, Psychotherapy and Psychosomatics
      Aachen, North Rhine-Westphalia, Germany
  • 2001–2012
    • Forschungszentrum Jülich
      • • Institut für Neurowissenschaften und Medizin (INM)
      • • Kognitive Neurologie (INM-3)
      Düren, North Rhine-Westphalia, Germany
    • Università degli studi di Parma
      • Dipartimento di Neuroscienze
      Parma, Emilia-Romagna, Italy
    • Ruhr-Universität Bochum
      • Allgemeine Zoologie und Neurobiologie
      Bochum, North Rhine-Westphalia, Germany
  • 2003–2010
    • Bielefeld University
      • • Physiologische Psychologie
      • • BINAS - Bielefeld Institute for Biophysics and Nanoscience
      Bielefeld, North Rhine-Westphalia, Germany
  • 2009
    • Park University
      Parkville, Missouri, United States
    • Deutsche Forschungsgemeinschaft
      Bonn, North Rhine-Westphalia, Germany
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
  • 2004–2009
    • Scuola Internazionale Superiore di Studi Avanzati di Trieste
      • Cognitive Neuroscience Group
      Trst, Friuli Venezia Giulia, Italy
    • University Medical Center Schleswig-Holstein
      Kiel, Schleswig-Holstein, Germany
  • 1999–2009
    • Heinrich-Heine-Universität Düsseldorf
      • • Klinik und Poliklinik für Psychiatrie und Psychotherapie der HHU, Rheinische Kliniken Düsseldorf
      • • Neurologische Klinik
      • • Institut für Neuropathologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2008
    • University of Rostock
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie
      Rostock, Mecklenburg-Vorpommern, Germany
    • University of Bergen
      • Department of Biological and Medical Psychology
      Bergen, Hordaland Fylke, Norway
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom
  • 2007–2008
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany
    • Carl von Ossietzky Universität Oldenburg
      • Department of Biology and Environmental Sciences (IBU)
      Oldenburg, Lower Saxony, Germany
  • 2005
    • Medical Research Council (UK)
      Londinium, England, United Kingdom
    • Neurologische Klinik Westend
      Бад Вилдунген, Hesse, Germany
    • Universitätsklinikum Schleswig - Holstein
      Kiel, Schleswig-Holstein, Germany
    • University of Cambridge
      • Department of Psychiatry
      Cambridge, ENG, United Kingdom
    • IME Metallurgy
      Aachen, North Rhine-Westphalia, Germany
  • 2002–2004
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2001–2004
    • University of Bonn
      Bonn, North Rhine-Westphalia, Germany
  • 1997–2003
    • University of Oxford
      • • Nuffield Department of Clinical Neurosciences
      • • Department of Experimental Psychology
      Oxford, ENG, United Kingdom
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • The University of Arizona
      • Department of Psychiatry
      Tucson, AZ, United States