R. Lange

Kliniken Schmieder Heidelberg, Allensbach, Baden-Württemberg, Germany

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Publications (25)78.67 Total impact

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    ABSTRACT: Introduction: The contralesional primary motor cortex (M1) has been suggested to be involved in the motor recovery after Mirror Therapy. But, whether the ipsilesional M1 is influenced by the contralesional M1 via the transcallosal interhemispheric inhibition (IHI) is still unclear. The present study investigated the change of IHI as well as the intracortical inhibition and the intracortical facilitation of both M1 induced by training in a mirror with the use of the transcranial magnetic stimulation (TMS). Methods: In this 2x2 factorial design (time x group) healthy subjects exercised standardized motor skills with their right hand on four consecutive days. Either a mirror (mirror-group) or a board (control-group) was positioned between both hands. Before and after training the TMS was applied along with training tests of both hands. Tests were the same motor skills daily exercised by both groups. Results: Test of the untrained left hand improved significantly more in the mirror-group than in the control-group after training (p = 0.02) and showed a close correlation with an increase of intracortical inhibition of M1left. IHI did not show any difference between both investigation time points and groups. Conclusion: The current study confirms previous suggestion of the involvement of the "contralesional"-left-sided (ipsilateral to the hand behind the mirror) M1 after Mirror Therapy, which is not mediated by IHI. Even with the same motor skill training (both groups performed same motor skills) but with different visual information, different networks are involved in training induced plasticity.
    Journal of Neurophysiology 09/2012; · 3.30 Impact Factor
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    ABSTRACT: Most neuroimaging studies on planning report bilateral activations of the dorsolateral prefrontal cortex (dlPFC). Recently, these concurrent activations of left and right dlPFC have been shown to double dissociate with different cognitive demands imposed by the planning task: Higher demands on the extraction of task-relevant information led to stronger activation in left dlPFC, whereas higher demands on the integration of interdependent information into a coherent action sequence entailed stronger activation of right dlPFC. Here, we used continuous theta-burst stimulation (cTBS) to investigate the supposed causal structure-function mapping underlying this double dissociation. Two groups of healthy subjects (left-lateralized stimulation, n = 26; right-lateralized stimulation, n = 26) were tested within-subject on a variant of the Tower of London task following either real cTBS over dlPFC or sham stimulation over posterior parietal cortex. Results revealed that, irrespective of specific task demands, cTBS over left and right dlPFC was associated with a global decrease and increase, respectively, in initial planning times compared to sham stimulation. Moreover, no interaction between task demands and stimulation type (real vs. sham) and/or stimulation side (left vs. right hemisphere) were found. Together, against expectations from previous neuroimaging data, lateralized cTBS did not lead to planning-parameter specific changes in performance, but instead revealed a global asymmetric pattern of faster versus slower task processing after left versus right cTBS. This global asymmetry in the absence of any task-parameter specific impact of cTBS suggests that different levels of information processing may span colocalized, but independent axes of functional lateralization in the dlPFC. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.
    Human Brain Mapping 10/2011; · 6.88 Impact Factor
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    ABSTRACT: Recent evidence from neuroimaging studies using visual tasks suggests that the right superior parietal cortex plays a pivotal role for the recovery of neglect. Importantly, neglect-related deficits are not limited to the visual system and have a rather multimodal nature. We employed somatosensory stimulation in patients with neglect in order to analyze activity changes in networks that are presumably associated with this condition. Eleven chronic neglect patients with right hemispherical stroke were investigated with a fMRI paradigm in which the affected and unaffected hand were passively moved. Brain activation was correlated with the performance in clinical neglect tests. Significant positive correlations with brain activation were found for the lesion duration, the performance in bells and letter cancellation tests and the line bisection test. These activated areas formed a distributed pattern in the right superior parietal cortex. The results suggest a shared representation of visual and somatosensory networks in the right superior parietal cortex in patients with right hemispherical strokes and neglect. The spatial pattern of activity in the superior parietal cortex points out to a different representation of changes related to lesion duration and neglect.
    Restorative neurology and neuroscience 04/2011; 29(4):253-63. · 2.93 Impact Factor
  • Clinical Neurophysiology - CLIN NEUROPHYSIOL. 01/2010; 121.
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    ABSTRACT: Cognitive functions are organized in distributed, overlapping, and interacting brain networks. Investigation of those large-scale brain networks is a major task in neuroimaging research. Here, we introduce a novel combination of functional and anatomical connectivity to study the network topology subserving a cognitive function of interest. (i) In a given network, direct interactions between network nodes are identified by analyzing functional MRI time series with the multivariate method of directed partial correlation (dPC). This method provides important improvements over shortcomings that are typical for ordinary (partial) correlation techniques. (ii) For directly interacting pairs of nodes, a region-to-region probabilistic fiber tracking on diffusion tensor imaging data is performed to identify the most probable anatomical white matter fiber tracts mediating the functional interactions. This combined approach is applied to the language domain to investigate the network topology of two levels of auditory comprehension: lower-level speech perception (i.e., phonological processing) and higher-level speech recognition (i.e., semantic processing). For both processing levels, dPC analyses revealed the functional network topology and identified central network nodes by the number of direct interactions with other nodes. Tractography showed that these interactions are mediated by distinct ventral (via the extreme capsule) and dorsal (via the arcuate/superior longitudinal fascicle fiber system) long- and short-distance association tracts as well as commissural fibers. Our findings demonstrate how both processing routines are segregated in the brain on a large-scale network level. Combining dPC with probabilistic tractography is a promising approach to unveil how cognitive functions emerge through interaction of functionally interacting and anatomically interconnected brain regions.
    NeuroImage 11/2009; 49(4):3187-97. · 6.25 Impact Factor
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    ABSTRACT: To investigate the effects of Modafinil on focused attention, motor function and motor excitability in patients with multiple sclerosis (MS) and fatigue. 21 MS patients with fatigue were enrolled in this double-blind placebo-controlled study. Modafinil (MOD) or placebo (PL) was administered for 8 weeks. The d2 alertness test, the Nine Hole Peg Test (9HPT) and several transcranial magnetic stimulation (TMS) techniques were applied prior to and after the first drug ingestion and well as after 8 weeks of drug intake. Prior to the first drug intake, the two groups were comparable. After the first drug ingestion, fatigue as measured by the Fatigue Severity Scale (FSS), performance of the d2 test and the 9HPT improved significantly in the MOD group and remained better than in the PL group after 8 weeks of treatment. Patients in the MOD group made fewer mistakes in the D2 test without being slower. They completed the 9HPT faster. Motor evoked potential amplitudes produced by paired pulse TMS were larger in the MOD group than the PL group. Motor thresholds and silent period durations remained unchanged. Compared to PL, MOD improved fatigue, focused attention and dexterity and enhanced motor cortex excitability in this group of patients. MOD may be helpful in MS patients with fatigue to improve cognitive and motor abilities.
    Journal of Neurology 05/2009; 256(4):645-50. · 3.58 Impact Factor
  • NeuroImage 01/2009; 47. · 6.25 Impact Factor
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    ABSTRACT: To infer interactions from functional magnetic resonance imaging (fMRI) data, structural equation modeling (SEM) as well as dynamic causal modeling (DCM) has been suggested. Directed partial correlation (dPC) is a measure which detects Granger causality in multivariate systems. To demonstrate the strengths as well as the limitations of directed partial correlation we first applied it to simulated data tailored to the problem at hand. Second, after dPC has proven to be useful for fMRI data analysis, we applied it to actual fMRI data.
    IEEE Journal of Selected Topics in Signal Processing 01/2009; · 3.30 Impact Factor
  • NeuroImage 01/2009; 47. · 6.25 Impact Factor
  • NeuroImage 01/2009; 47. · 6.25 Impact Factor
  • Klinische Neurophysiologie 01/2009; 120(1). · 0.33 Impact Factor
  • Brain Stimulation - BRAIN STIMUL. 01/2008; 1(3):280-281.
  • Clinical Neurophysiology 01/2008; 39(01). · 3.14 Impact Factor
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    ABSTRACT: Apart from being increasingly implicated in higher motor control, Broca's area is considered to play an important role in action understanding by coding the motor goal of an action. Moreover, recent findings suggest that parts of Broca's area may be able to code action content in a more abstract fashion, independent of modality, specific movement parameters or effector used. We performed functional magnetic resonance imaging to examine whether in humans processing object-directed hand actions presented either visually as video clips or verbally as spoken sentences relies on the same neural substrates. To control for action specificity, we included videos and sentences depicting inanimate motion events. In order to induce conceptual processing, we asked participants to make judgements about the acceptability of the stimuli. Results show that processing object-directed hand actions presented both visually and verbally leads to common activation of areas in parietal and frontal regions, most prominently in the pars opercularis of Broca's region. We conclude that the pars opercularis of Broca's area is endowed with polymodal capabilities, allowing the processing of higher-level conceptual aspects of action understanding.
    European Journal of Neuroscience 03/2007; 25(3):881-9. · 3.75 Impact Factor
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    ABSTRACT: Behavioural advantages for imitation of human movements over movements instructed by other visual stimuli are attributed to an 'action observation-execution matching' (AOEM) mechanism. Here, we demonstrate that priming/exogenous cueing with a videotaped finger movement stimulus (S1) produces specific congruency effects in reaction times (RTs) of imitative responses to a target movement (S2) at defined stimulus onset asynchronies (SOAs). When contrasted with a moving object at an SOA of 533 ms, only a human movement is capable of inducing an effect reminiscent of 'inhibition of return' (IOR), i.e. a significant advantage for imitation of a subsequent incongruent as compared to a congruent movement. When responses are primed by a finger movement at SOAs of 533 and 1,200 ms, inhibition of congruent or facilitation of incongruent responses, respectively, is stronger as compared to priming by a moving object. This pattern does not depend on whether S2 presents a finger movement or a moving object, thus effects cannot be attributed to visual similarity between S1 and S2. We propose that, whereas both priming by a finger movement and a moving object induces processes of spatial orienting, solely observation of a human movement activates AOEM. Thus, S1 immediately elicits an imitative response tendency. As an overt imitation of S1 is inadequate in the present setting, the response is inhibited which, in turn, modulates congruency effects.
    Experimental Brain Research 03/2007; 177(2):255-65. · 2.22 Impact Factor
  • R Lange, C Weiller, J Liepert
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    ABSTRACT: Enhancement of cortical excitability is thought to be beneficial for synaptic plasticity associated with motor skill acquisition. Single dose application of the selective norepinephrine reuptake inhibitor reboxetine (RBX) increases motor cortex excitability. In this study, we tested if a chronic dose application of RBX improved motor skill acquisition and modulated cortical excitability. The study was randomised, double blind and placebo-controlled. Twelve healthy subjects received four milligram RBX twice a day for four days preceded by two milligram RBX twice a day for two days. Each subject served as his own control. The time interval between the verum and the placebo session was 16 days or more. Measurement of cortical excitability by means of paired pulse transcranial magnetic stimulation (ppTMS) was conducted before and after the motor skill acquisition task in each session. The task was to lift two fingers of the right hand at once while the hand was positioned sprawled out on the table. The movements were self-paced and subjects had to perform as many moves as possible in 60 sec. Between seven blocks of self-paced movements six blocks with 60 single trials at a fixed interstimulus intervall were presented. Two equally difficult versions of the task using different finger combinations were established in order to avoid carry over effects in performance. The finger movements were recorded with a three-dimensional ultrasound movement analysis system (Zebris). All subjects had substantial gain in performance across the selfpaced blocks. Average increase in number of correct moves was 87% (from 27.8 to 51.9). There was no significant difference neither between the versions of the task nor between placebo vs. verum. Also, there was no significant difference between first and second session, indicating that there was no carry over effect in performance. ppTMS revealed no significant differences in cortical excitability between groups. The newly developed skill acquisition task yields robust single subject gain of performance. As the two versions of the task do not interact, it is suitable to be used in cross-over designs. In contrast to studies using single doses of RBX, motor cortex excitability seems to be unaffected in a steady-state induced by repeated drug applications. This could explain why RBX did not modulate motor behavior.
    Journal of Neural Transmission 01/2007; 114(8):1085-9. · 3.05 Impact Factor
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    ABSTRACT: Previous functional imaging studies of chronic stroke patients with aphasia suggest that recovery of language occurs in a pre-existing, bilateral network with an upregulation of undamaged areas and a recruitment of perilesional tissue and homologue right language areas. The present study aimed at identifying the dynamics of reorganization in the language system by repeated functional MRI (fMRI) examinations with parallel language testing from the acute to the chronic stage. We examined 14 patients with aphasia due to an infarction of the left middle cerebral artery territory and an age-matched control group with an auditory comprehension task in an event-related design. Control subjects were scanned once, whereas patients were scanned repeatedly at three consecutive dates. All patients recovered clinically as shown by a set of aphasia tests. In the acute phase [mean: 1.8 days post-stroke (dps)], patients' group analysis showed little early activation of non-infarcted left-hemispheric language structures, while in the subacute phase (mean: 12.1 dps) a large increase of activation in the bilateral language network with peak activation in the right Broca-homologue (BHo) was observed. A direct comparison of both examinations revealed the strongest increase of activation in the right BHo and supplementary motor area (SMA). These upregulated areas also showed the strongest correlation between improved language function and increased activation (r(BHo) = 0.88, r(SMA) = 0.92). In the chronic phase (mean: 321 dps), a normalization of activation with a re-shift of peak activation to left-hemispheric language areas was observed, associated with further language improvement. The data suggest that brain reorganization during language recovery proceeds in three phases: a strongly reduced activation of remaining left language areas in the acute phase is followed by an upregulation with recruitment of homologue language zones, which correlates with language improvement. Thereafter, a normalization of activation is observed, possibly reflecting consolidation in the language system.
    Brain 07/2006; 129(Pt 6):1371-84. · 10.23 Impact Factor
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    ABSTRACT: We explored interhemispheric facilitation (IHF) between (a) left and right primary motor cortex (M1) and (b) left dorsal premotor (dPM) and right M1 in 20 right-handed healthy human subjects using a paired pulse transcranial magnetic stimulation (TMS) protocol. A conditioning TMS pulse (CP) applied to left M1 or dPM with an intensity of 80% and 60% active motor threshold (CP(80%AMT) and CP(60%AMT), respectively) was followed by a test pulse (TP) over right M1 induced by anterior-posterior- or posterior-anterior- (TP(AP), TP(PA)) directed currents in the brain at interstimulus intervals (ISIs) of 3-8 and 10 ms. EMG was recorded from left first dorsal interosseous muscle. In the main experimental condition IHF was evoked by CP(80%AMT) over left M1 and TPAP at ISIs of 6 and 8 ms. The same CP(80%AMT) produced IHF at an ISI of 8 ms when applied over left dPM but only with TP(PA). In addition, when CP(60%AMT) was given to M1, IHF was present at an ISI of 6 ms (but not 8 ms) when followed by TP(PA), indicating that IHF elicited over dPM was not caused by current spread of the conditioning pulse to M1. We conclude that IHF can be induced differentially by conditioning M1 and dPM using subthreshold CP. These facilitatory interactions depended on the intensity and ISI of the CP as well as the current flow direction of the TP. We suggest that not only do the CPs activate separate anatomical pathways but also that these pathways project to different populations ofinterneurons in the receiving M1. These may correspond to elements involved in the generation of I3 and I1 waves, respectively.
    The Journal of Physiology 06/2006; 572(Pt 3):857-68. · 4.38 Impact Factor
  • Aktuelle Neurologie - AKTUEL NEUROL. 01/2006; 33.

Publication Stats

510 Citations
78.67 Total Impact Points

Institutions

  • 2011
    • Kliniken Schmieder Heidelberg
      Allensbach, Baden-Württemberg, Germany
  • 2009–2011
    • Universitätsklinikum Freiburg
      • Freiburg Brain Imaging (FBI)
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2006–2009
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2006–2007
    • University Medical Center Hamburg - Eppendorf
      • Department of Neurology
      Hamburg, Hamburg, Germany