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Noradrenergic enhancement improves motor network connectivity in stroke patients

Authors

  • Ling E. Wang PhD,

    1. Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany
    2. International Graduate School of Neuroscience, Ruhr University Bochum, Bochum, Germany
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  • Gereon R. Fink MD, PhD,

    1. Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany
    2. Department of Neurology, University of Cologne, Cologne, Germany
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  • Svenja Diekhoff MSc,

    1. Neuromodulation & Neurorehabilitation Section, Max Planck Institute for Neurological Research, Cologne, Germany
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  • Anne K. Rehme MSc,

    1. Neuromodulation & Neurorehabilitation Section, Max Planck Institute for Neurological Research, Cologne, Germany
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  • Simon B. Eickhoff MD,

    1. Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany
    2. Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany
    3. Juelich-Aachen Research Alliance (JARA-Brain), Juelich, Germany
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  • Christian Grefkes MD

    Corresponding author
    1. Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Centre Juelich, Juelich, Germany
    2. Department of Neurology, University of Cologne, Cologne, Germany
    3. Neuromodulation & Neurorehabilitation Section, Max Planck Institute for Neurological Research, Cologne, Germany
    • Neuromodulation & Neurorehabilitation, Max Planck Institute for Neurological Research, Gleueler Str. 50, 50931 Köln, Germany
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Abstract

Objective

Both animal and human data suggest that noradrenergic stimulation may enhance motor performance after brain damage. We conducted a placebo-controlled, double-blind and crossover design study to investigate the effects of noradrenergic stimulation on the cortical motor system in hemiparetic stroke patients.

Methods

Stroke patients (n = 11) in the subacute or chronic stage with mild-to-moderate hand paresis received a single oral dose of 6mg reboxetine (RBX), a selective noradrenaline reuptake inhibitor. We used functional magnetic resonance imaging and dynamic causal modeling to assess changes in neural activity and interregional effective connectivity while patients moved their paretic hand.

Results

RBX stimulation significantly increased maximum grip power and index finger-tapping frequency of the paretic hand. Enhanced motor performance was associated with a reduction of cortical “hyperactivity” toward physiological levels as observed in healthy control subjects, especially in the ipsilesional ventral premotor cortex (vPMC) and supplementary motor area (SMA), but also in the temporoparietal junction and prefrontal cortex. Connectivity analyses revealed that in stroke patients neural coupling with SMA or vPMC was significantly reduced compared with healthy controls. This “hypoconnectivity” was partially normalized when patients received RBX, especially for the coupling of ipsilesional SMA with primary motor cortex.

Interpretation

The data suggest that noradrenergic stimulation by RBX may help to modulate the pathologically altered motor network architecture in stroke patients, resulting in increased coupling of ipsilesional motor areas and thereby improved motor function. Ann Neurol 2011.

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