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Dive into the research topics where Manuel Dafotakis is active.

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Featured researches published by Manuel Dafotakis.


Annals of Neurology | 2008

Cortical connectivity after subcortical stroke assessed with functional magnetic resonance imaging

Christian Grefkes; Dennis A. Nowak; Simon B. Eickhoff; Manuel Dafotakis; Jutta Küst; Hans Karbe; Gereon R. Fink

This study aimed at identifying the impact of subcortical stroke on the interaction of cortical motor areas within and across hemispheres during the generation of voluntary hand movements.


NeuroImage | 2008

Dynamic intra- and interhemispheric interactions during unilateral and bilateral hand movements assessed with fMRI and DCM

Christian Grefkes; Simon B. Eickhoff; Dennis A. Nowak; Manuel Dafotakis; Gereon R. Fink

Any motor action results from a dynamic interplay of various brain regions involved in different aspects of movement preparation and execution. Establishing a reliable model of how these areas interact is crucial for a better understanding of the mechanisms underlying motor function in both healthy subjects and patients. We used fMRI and dynamic causal modeling to reveal the specific excitatory and inhibitory influences within the human motor system for the generation of voluntary hand movements. We found an intrinsic balance of excitatory and inhibitory couplings among core motor regions within and across hemispheres. Neural coupling within this network was specifically modulated upon uni- and bimanual movements. During unimanual movements, connectivity towards the contralateral primary motor cortex was enhanced while neural coupling towards ipsilateral motor areas was reduced by both transcallosal inhibition and top-down modulation. Bimanual hand movements were associated with a symmetric facilitation of neural activity mediated by both increased intrahemispheric connectivity and enhanced transcallosal coupling of SMA and M1. The data suggest that especially the supplementary motor area represents a key structure promoting or suppressing activity in the cortical motor network driving uni- and bilateral hand movements. Our data demonstrate that fMRI in combination with DCM allows insights into intrinsic properties of the human motor system and task-dependent modulations thereof.


NeuroImage | 2010

Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling

Christian Grefkes; Dennis A. Nowak; Ling E. Wang; Manuel Dafotakis; Simon B. Eickhoff; Gereon R. Fink

Data derived from transcranial magnetic stimulation (TMS) studies suggest that transcallosal inhibition mechanisms between the primary motor cortex of both hemispheres may contribute to the reduced motor performance of stroke patients. We here investigated the potential of modulating pathological interactions between cortical motor areas by means of repetitive TMS using functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM). Eleven subacute stroke patients were scanned 1-3 months after symptom onset while performing whole hand fist closure movements. After a baseline scan, patients were stimulated with inhibitory 1-Hz rTMS applied over two different locations: (i) vertex (control stimulation) and (ii) primary motor cortex (M1) of the unaffected (contralesional) hemisphere. Changes in the endogenous and task-dependent effective connectivity were assessed by DCM of a bilateral network comprising M1, lateral premotor cortex, and the supplementary motor area (SMA). The results showed that rTMS applied over contralesional M1 significantly improved the motor performance of the paretic hand. The connectivity analysis revealed that the behavioral improvements were significantly correlated with a reduction of the negative influences originating from contralesional M1 during paretic hand movements. Concurrently, endogenous coupling between ipsilesional SMA and M1 was significantly enhanced only after rTMS applied over contralesional M1. Therefore, rTMS applied over contralesional M1 may be used to transiently remodel the disturbed functional network architecture of the motor system. The connectivity analyses suggest that both a reduction of pathological transcallosal influences (originating from contralesional M1) and a restitution of ipsilesional effective connectivity between SMA and M1 underlie improved motor performance.


JAMA Neurology | 2008

Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Contralesional Primary Motor Cortex on Movement Kinematics and Neural Activity in Subcortical Stroke

Dennis A. Nowak; Christian Grefkes; Manuel Dafotakis; Simon B. Eickhoff; Jutta Küst; Hans Karbe; Gereon R. Fink

BACKGROUND Following the concept of interhemispheric competition, downregulation of the contralesional primary motor cortex (M1) may improve the dexterity of the affected hand after stroke. OBJECTIVE To determine the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the contralesional M1 on movement kinematics and neural activation within the motor system in the subacute phase after subcortical stroke. DESIGN Crossover investigation. SETTING A university hospital. METHODS Fifteen right-handed patients with impaired dexterity due to subcortical middle cerebral artery stroke received 1-Hz rTMS for 10 minutes applied to the vertex (control stimulation) and contralesional M1. For behavioral testing, patients performed finger and grasp movements with both hands at 2 baseline conditions, separated by 1 week, and following each rTMS application. For functional magnetic resonance imaging, patients performed hand grip movements with their affected or unaffected hand before and after each rTMS application. RESULTS Application of rTMS to the contralesional M1 improved the kinematics of finger and grasp movements in the affected hand. At the neural level, rTMS applied to the contralesional M1 reduced overactivity in the contralesional primary and nonprimary motor areas. There was no significant correlation between the rTMS-induced reduction in blood oxygen level-dependent responses within the contralesional M1 and the degree of behavioral improvement of the affected hand. Overactivity of the contralesional dorsal premotor cortex, contralesional parietal operculum, and ipsilesional mesial frontal cortex at baseline predicted improvement of movement kinematics with the affected hand after rTMS of the contralesional M1. CONCLUSION The functional magnetic resonance imaging data suggest that rTMS of the contralesional M1 may normalize neural activation within the cortical motor network after subcortical stroke. Identifying patients suitable for rTMS intervention based on individual patterns of cortical activation may help to implement rTMS in motor rehabilitation after stroke.


Neuropsychologia | 2008

Enhancing language performance with non-invasive brain stimulation—A transcranial direct current stimulation study in healthy humans

Roland Sparing; Manuel Dafotakis; Ingo G. Meister; Nivethida Thirugnanasambandam; Gereon R. Fink

In humans, transcranial direct current stimulation (tDCS) can be used to induce, depending on polarity, increases or decreases of cortical excitability by polarization of the underlying brain tissue. Cognitive enhancement as a result of tDCS has been reported. The purpose of this study was to test whether weak tDCS (current density, 57 microA/cm(2)) can be used to modify language processing. Fifteen healthy subjects performed a visual picture naming task before, during and after tDCS applied over the posterior perisylvian region (PPR), i.e. an area which includes Wernickes area [BA 22]. Four different sessions were carried out: (1) anodal and (2) cathodal stimulation of left PPR and, for control, (3) anodal stimulation of the homologous region of the right hemisphere and (4) sham stimulation. We found that subjects responded significantly faster following anodal tDCS to the left PPR (p<0.01). No decreases in performance were detected. Our finding of a transient improvement in a language task following the application of tDCS together with previous studies which investigated the modulation of picture naming latency by transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS) suggest that tDCS applied to the left PPR (including Wernickes area [BA 22]) can be used to enhance language processing in healthy subjects. Whether this safe, low cost, and easy to use brain stimulation technique can be used to ameliorate deficits of picture naming in aphasic patients needs further investigations.


European Journal of Neuroscience | 2007

Dexterity is impaired at both hands following unilateral subcortical middle cerebral artery stroke.

Dennis A. Nowak; Christian Grefkes; Manuel Dafotakis; Jutta Küst; Hans Karbe; Gereon R. Fink

Dexterity was investigated in right‐handed subjects in the subacute phase of a first unilateral subcortical middle cerebral artery stroke affecting the left or right hemisphere and right‐handed healthy subjects. Dexterity was quantified at both hands by kinematic recordings of finger and hand tapping, a reach‐to‐grasp movement, quantitative analysis of grip forces in a grasp‐lift task and clinical rating scales. Stroke subjects exhibited significant deficits in timing and coordination of tapping movements at both the contralesional and ipsilesional hands, irrespective of the hemisphere affected. Likely for the reach‐to‐grasp and grasp‐lift movements a bilateral impairment was found in stroke subjects. In particular, slowing of hand transport towards the object, deficient timing and scaling of grasp formation, discoordination between grip and lift forces and inefficient scaling of grip forces were observed. The severity of impairment was independent of the hemisphere affected and evident for both the reach (involving more proximal muscles of the arm) and grasp (involving more distal muscles of the arm and hand) components of the task. Strong correlations were found between clinical scores of hand function and loss of sensibility with the deficits in timing, coordination and efficiency of movement of the contralesional and ipsilesional hand. These data provide evidence that dexterity is impaired at both hands after subcortical middle cerebral artery stroke.


Experimental Neurology | 2008

Effects of rTMS on grip force control following subcortical stroke

Manuel Dafotakis; Christian Grefkes; Simon B. Eickhoff; Hans Karbe; Gereon R. Fink; Dennis A. Nowak

Within the concept of interhemispheric competition we tested the effect of inhibitory 1 Hz repetitive transcranial magnetic stimulation (rTMS), applied over the primary motor cortex of the unaffected hemisphere, upon dexterity of the affected hand in subcortical stroke patients. Subjects grasped, lifted and held an instrumented object between the index finger and thumb with both the affected and unaffected hand prior to (baseline) and following 1 Hz rTMS applied over (i) the vertex (control stimulation) and (ii) the primary motor cortex of the unaffected hemisphere. Compared to baseline, 1 Hz rTMS applied over the unaffected primary motor cortex, but not the vertex, improved the efficiency and timing of grasping and lifting with the affected hand. Our data support the interhemispheric competition concept and furthermore reinforce current efforts to implement rTMS in novel approaches to stroke rehabilitation.


Neuropsychologia | 2008

Action Verbs and the Primary Motor Cortex: A Comparative TMS Study of Silent Reading, Frequency Judgments, and Motor Imagery.

Barbara Tomasino; Gereon R. Fink; Roland Sparing; Manuel Dafotakis; Peter H. Weiss

Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS(M1) vs. TMS(vertex)) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation within the same experiment: subjects indicated with their left foot when they (i) had finished reading, (ii) had judged whether the corresponding movement involved a hand rotation after simulating the hand movement, and (iii) had judged whether they would frequently encounter the action verb in a newspaper (TASK: silent reading, motor imagery, and frequency judgment). Response times were compared between TMS(M1) and TMS(vertex), both applied at different time points after stimulus onset (DELAY: 150, 300, 450, 600, and 750 ms). TMS(M1) differentially modulated task performance: there was a significant facilitatory effect of TMS(M1) for the imagery task only (about 88 ms), with subjects responding about 10% faster (compared to TMS(vertex)). In contrast, response times for silent reading and frequency judgments were unaffected by TMS(M1). No differential effect of the time point of TMS(M1) was observed. The differential effect of TMS(M1) when subjects performed a motor imagery task (relative to performing silent reading or frequency judgments with the same set of verbs) suggests that the primary motor cortex is critically involved in processing action verbs only when subjects are simulating the corresponding movement. This task-dependent effect of hand motor cortex TMS on the processing of hand-related action verbs is discussed with respect to the notion of embodied cognition and the associationist theory.


Brain Research | 2008

On the role of the ventral premotor cortex and anterior intraparietal area for predictive and reactive scaling of grip force.

Manuel Dafotakis; Roland Sparing; Simon B. Eickhoff; Gereon R. Fink; Dennis A. Nowak

When lifting objects of different mass but identical visual appearance, we apply grip forces that match the expected mass of the object. Here we study the role of the primary motor cortex (M1), the ventral premotor cortex (PMv) and the anterior intraparietal area (AIP) for predictive and reactive scaling of grip forces. Participants performed a precision grip between the index finger and thumb of the right hand to lift two different masses of identical visual appearance in random order. Neuronavigated single pulse transcranial magnetic stimulation (TMS) over (i) left M1, (ii) left PMv, (iii) left AIP and (iv) the vertex (for control) was applied at two time points of the grasping movement after an unexpected change in mass had occurred: (a) at the time of movement onset and (b) at the time of peak grasp aperture. TMS over the PMv, but not over the vertex, M1 or the AIP, interfered with the predictive scaling of grip forces according to the most recent lift when applied at the time of peak grasp aperture. In contrast, TMS over AIP, but not over the vertex, M1 or PMv, disrupted the reactive adjustment of grip force to the novel mass of the object at hand. The findings highlight the differential involvement of PMv in the predictive scaling of grip force and of AIP in the reactive online adjustment of grip force during object manipulation.


Lancet Neurology | 2015

Biological and clinical characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) cohort: a cross-sectional analysis of baseline data.

Kathrin Reetz; Imis Dogan; Ana S. Costa; Manuel Dafotakis; Kathrin Fedosov; Paola Giunti; Michael H Parkinson; Mary G. Sweeney; Caterina Mariotti; Marta Panzeri; Lorenzo Nanetti; Javier Arpa; Irene Sanz-Gallego; Alexandra Durr; Perrine Charles; Sylvia Boesch; Wolfgang Nachbauer; Thomas Klopstock; Ivan Karin; Chantal Depondt; Jennifer Müller vom Hagen; Ludger Schöls; Ilaria Giordano; Thomas Klockgether; Katrin Bürk; Massimo Pandolfo; Jörg B. Schulz

BACKGROUND Friedreichs ataxia is a rare autosomal recessive neurodegenerative disorder. Here we report cross-sectional baseline data to establish the biological and clinical characteristics for a prospective, international, European Friedreichs ataxia database registry. METHODS Within the European Friedreichs Ataxia Consortium for Translational Studies (EFACTS) framework, we assessed a cohort of patients with genetically confirmed Friedreichs ataxia. The primary outcome measure was the Scale for the Assessment and Rating of Ataxia (SARA) and secondary outcome measures were the Inventory of Non-Ataxia Signs (INAS), the performance-based coordination test Spinocerebellar Ataxia Functional Index (SCAFI), the neurocognitive phonemic verbal fluency test, and two quality-of-life measures: the activities of daily living (ADL) part of the Friedreichs Ataxia Rating Scale and EQ-5D. The Friedreichs ataxia cohort was subdivided into three groups: early disease onset (≤14 years), intermediate onset (15-24 years), and late onset (≥25 years), which were compared for clinical characteristics and outcome measures. We used linear regression analysis to estimate the annual decline of clinical outcome measures based on disease duration. This study is registered with ClinicalTrials.gov, number NCT02069509. FINDINGS We enrolled 592 patients with genetically confirmed Friedreichs ataxia between Sept 15, 2010, and April 30, 2013, at 11 sites in seven European countries. Age of disease onset was inversely correlated with the number of GAA repeats in the frataxin (FXN) gene: every 100 GAA repeats on the smaller repeat allele was associated with a 2·3 year (SE 0·2) earlier onset. Regression analyses showed significant estimated annual worsening of SARA (regression coefficient 0·86 points [SE 0·05], INAS (0·14 points [0·01]), SCAFI Z scores (-0·09 [0·01]), verbal fluency (-0·34 words [0·07]), and ADL (0·64 points [0·04]) during the first 25 years of disease; the regression slope for health-related quality-of-life state from EQ-5D was not significant (-0·33 points [0·18]). For SARA, the predicted annual rate of worsening was significantly higher in early-onset patients (n=354; 1·04 points [0·13]) and intermediate-onset patients (n=137; 1·17 points [0·22]) than in late-onset patients (n=100; 0·56 points [0·10]). INTERPRETATION The results of this cross-sectional baseline analysis of the EFACTS cohort suggest that earlier disease onset is associated with larger numbers of GAA repeats and more rapid disease progression. The differential estimated progression of ataxia symptoms related to age of onset have implications for the design of clinical trials in Friedreichs ataxia, for which SARA might be the most suitable measure to monitor disease progression. FUNDING European Commission.

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Karl Zilles

University of Düsseldorf

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F. Block

RWTH Aachen University

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