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Behavioral and neurophysiological evidence for the enhancement of cognitive control under dorsal pallidal deep brain stimulation in Huntington’s disease

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Abstract

Deep brain stimulation of the dorsal pallidum (globus pallidus, GP) is increasingly considered as a surgical therapeutic option in Huntington’s disease (HD), but there is need to identify outcome measures useful for clinical trials. Computational models consider the GP to be part of a basal ganglia network involved in cognitive processes related to the control of actions. We examined behavioural and event-related potential (ERP) correlates of action control (i.e., error monitoring) and evaluated the effects of deep brain stimulation (DBS). We did this using a standard flanker paradigm and evaluated error-related ERPs. Patients were recruited from a prospective pilot trial for pallidal DBS in HD (trial number NCT00902889). From the initial four patients with Huntington’s chorea, two patients with chronic external dorsal pallidum stimulation were available for follow-up and able to perform the task. The results suggest that the external GP constitutes an important basal ganglia element not only for error processing and behavioural adaptation but for general response monitoring processes as well. Response monitoring functions were fully controllable by switching pallidal DBS stimulation on and off. When stimulation was switched off, no neurophysiological and behavioural signs of error and general performance monitoring, as reflected by the error-related negativity and post-error slowing in reaction times were evident. The modulation of response monitoring processes by GP-DBS reflects a side effect of efforts to alleviate motor symptoms in HD. From a clinical neurological perspective, the results suggest that DBS in the external GP segment can be regarded as a potentially beneficial treatment with respect to cognitive functions.

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Acknowledgments

This work was supported by a Grant from the Deutsche Forschungsgemeinschaft (DFG) BE4045/10-1. The initial clinical trial was supported with a seed funding by the European Huntington´s Disease Network (EHDN). We thank the patients for their cooperation.

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Authors and Affiliations

  1. Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Schubertstrasse 42, 01309, Dresden, Germany

    Christian Beste & Moritz Mückschel

  2. Movement Disorders and Neuromodulation, Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany

    Saskia Elben, Christian J Hartmann, Alfons Schnitzler & Lars Wojtecki

  3. Medical Faculty, Institute of Clinical Neuroscience and Medical Psychology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany

    Saskia Elben, Christian J Hartmann, Alfons Schnitzler & Lars Wojtecki

  4. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

    Cameron C McIntyre

  5. Department of Neurology, St. Josef Hospital, Ruhr-Universität Bochum, Bochum, Germany

    Carsten Saft

  6. Stereotaxy and Functional Neurosurgery, Department of Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany

    Jan Vesper

Authors
  1. Christian Beste
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  2. Moritz Mückschel
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  3. Saskia Elben
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  4. Christian J Hartmann
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  5. Cameron C McIntyre
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  6. Carsten Saft
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  7. Jan Vesper
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  8. Alfons Schnitzler
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  9. Lars Wojtecki
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Correspondence to Christian Beste or Lars Wojtecki.

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Beste, C., Mückschel, M., Elben, S. et al. Behavioral and neurophysiological evidence for the enhancement of cognitive control under dorsal pallidal deep brain stimulation in Huntington’s disease. Brain Struct Funct 220, 2441–2448 (2015). https://doi.org/10.1007/s00429-014-0805-x

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  • DOI: https://doi.org/10.1007/s00429-014-0805-x

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