Coordinated reset neuromodulation for Parkinson's disease: Proof-of-concept study

Authors

  • Ilya Adamchic MD,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
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  • Christian Hauptmann PhD,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
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  • Utako Brigit Barnikol MD,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
    2. Department of Neuromodulation, University of Cologne, Cologne, Germany
    3. Department of Child- and Adolescent Psychiatry, University of Cologne, Cologne, Germany
    4. Clinic for Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany
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  • Norbert Pawelczyk,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
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  • Oleksandr Popovych PhD,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
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  • Thomas Theo Barnikol MD,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
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  • Alexander Silchenko PhD,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
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  • Jens Volkmann MD,

    1. Department of Neurology, University Würzburg, Würzburg, Germany
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  • Günter Deuschl MD,

    1. Department of Neurology, University Kiel, Kiel, Germany
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  • Wassilios G Meissner MD, PhD,

    1. Institut des Maladies Neurodégénératives, Univ. de Bordeaux, Bordeaux, France
    2. CNRS Institut des Maladies Neurodégénératives, Bordeaux, France
    3. Service de Neurologie, CHU de Bordeaux, Pessac, France
    4. Centre de référence atrophie multisystématisée, CHU de Bordeaux, Pessac, France
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  • Mohammad Maarouf MD,

    1. Clinic for Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany
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  • Volker Sturm MD,

    1. Clinic for Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany
    2. Department of Neurology, University Würzburg, Würzburg, Germany
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  • Hans-Joachim Freund MD,

    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
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  • Peter Alexander Tass MD, PhD

    Corresponding author
    1. Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, Jülich, Germany
    2. Department of Neuromodulation, University of Cologne, Cologne, Germany
    3. Clinic for Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany
    • Correspondence to: Prof. Peter A. Tass, Institute of Neuroscience and Medicine-Neuromodulation, Jülich Research Center, 52425 Jülich, Germany, E-mail: p.tass@fz-juelich.de

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  • Funding agencies: The authors reported no financial support.

  • Relevant conflicts of interest/financial disclosures: Dr. Tass is employed by the Jülich Research Center; formerly working with ANM GmbH (Cologne, Germany) to develop an implantable device for CR neuromodulation in patients, shareholder of ANM GmbH. He has received research funding from the European Community, the Federal Ministry of Education and Research (Germany), the Deutsche Forschungsgemeinschaft, the Helmholtz Association, Biomedical Primate, and the Michael J Fox Foundation. Dr. Hauptmann is employed by the Jülich Research Center and formerly employed by ANM GmbH (to develop an implantable device for CR neuromodulation in patients). He has received research funding from the European Community, the Federal Ministry of Education and Research (Germany), the Deutsche Forschungsgemeinschaft, and the Helmholtz Association. Dr. Freund is employed by the International Neuroscience Institute, Hannover; formely working with ANM GmbH (Cologne, Germany) to develop an implantable device for CR neuromodulation in patients; and is a shareholder of ANM GmbH. Dr. Sturm is employed by the University Clinic Würzburg; was formerly employed by the University Clinic Cologne; formerly working with ANM GmbH (Cologne, Germany) to develop an implantable device for CR neuromodulation in patients, shareholder of ANM GmbH. He has received research funding from the Federal Ministry of Education and Research (Germany). Drs. Adamich, Barnikol, Pawelczyk, Popovych, Barnikol, Silchenko, Maarouf, Volkmann, Deuschl, and Meissner report no disclosures related to research covered in this article. Several patents protect electrical CR neuromodulation, for example, the US patent 7,917,221 “Device for the desynchronization of neuronal activity.” The inventor of this patent is Peter A. Tass, assignee is Forschungszentrum Juelich GmbH, Juelich, Germany.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Background

The discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinson's disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony.

Methods

In this prospective case series, six PD patients were evaluated before and after coordinated reset neuromodulation according to a standardized protocol that included both electrophysiological recordings and clinical assessments.

Results

Coordinated reset neuromodulation of the subthalamic nucleus (STN) applied to six PD patients in an externalized setting during three stimulation days induced a significant and cumulative reduction of beta band activity that correlated with a significant improvement of motor function.

Conclusions

These results highlight the potential effects of coordinated reset neuromodulation of the STN in PD patients and encourage further development of this approach as an alternative to conventional high-frequency deep brain stimulation in PD. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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