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@ARTICLE{Weiss:137841,
      author       = {Weiss, Daniel and Klotz, Rosa and Govindan, Rathinaswamy B
                      and Scholten, Marlieke and Naros, Georgios and
                      Ramos-Murguialday, Ander and Bunjes, Friedemann and Meisner,
                      Christoph and Plewnia, Christian and Krüger, Rejko and
                      Gharabaghi, Alireza},
      title        = {{S}ubthalamic stimulation modulates cortical motor network
                      activity and synchronization in {P}arkinson's disease.},
      journal      = {Brain},
      volume       = {138},
      number       = {3},
      issn         = {1460-2156},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2020-04163},
      pages        = {679-693},
      year         = {2015},
      abstract     = {Dynamic modulations of large-scale network activity and
                      synchronization are inherent to a broad spectrum of
                      cognitive processes and are disturbed in neuropsychiatric
                      conditions including Parkinson's disease. Here, we set out
                      to address the motor network activity and synchronization in
                      Parkinson's disease and its modulation with subthalamic
                      stimulation. To this end, 20 patients with idiopathic
                      Parkinson's disease with subthalamic nucleus stimulation
                      were analysed on externally cued right hand finger movements
                      with 1.5-s interstimulus interval. Simultaneous recordings
                      were obtained from electromyography on antagonistic muscles
                      (right flexor digitorum and extensor digitorum) together
                      with 64-channel electroencephalography. Time-frequency
                      event-related spectral perturbations were assessed to
                      determine cortical and muscular activity. Next,
                      cross-spectra in the time-frequency domain were analysed to
                      explore the cortico-cortical synchronization. The
                      time-frequency modulations enabled us to select a
                      time-frequency range relevant for motor processing. On these
                      time-frequency windows, we developed an extension of the
                      phase synchronization index to quantify the global
                      cortico-cortical synchronization and to obtain topographic
                      differentiations of distinct electrode sites with respect to
                      their contributions to the global phase synchronization
                      index. The spectral measures were used to predict clinical
                      and reaction time outcome using regression analysis. We
                      found that movement-related desynchronization of cortical
                      activity in the upper alpha and beta range was significantly
                      facilitated with 'stimulation on' compared to 'stimulation
                      off' on electrodes over the bilateral parietal,
                      sensorimotor, premotor, supplementary-motor, and prefrontal
                      areas, including the bilateral inferior prefrontal areas.
                      These spectral modulations enabled us to predict both
                      clinical and reaction time improvement from subthalamic
                      stimulation. With 'stimulation on', interhemispheric
                      cortico-cortical coherence in the beta band was
                      significantly attenuated over the bilateral sensorimotor
                      areas. Similarly, the global cortico-cortical phase
                      synchronization was attenuated, and the topographic
                      differentiation revealed stronger desynchronization over the
                      (ipsilateral) right-hemispheric prefrontal, premotor and
                      sensorimotor areas compared to 'stimulation off'. We further
                      demonstrated that the cortico-cortical phase synchronization
                      was largely dominated by genuine neuronal coupling. The
                      clinical improvement with 'stimulation on' compared to
                      'stimulation off' could be predicted from this cortical
                      decoupling with multiple regressions, and the reduction of
                      synchronization over the right prefrontal area showed a
                      linear univariate correlation with clinical improvement. Our
                      study demonstrates wide-spread activity and synchronization
                      modulations of the cortical motor network, and highlights
                      subthalamic stimulation as a network-modulating therapy.
                      Accordingly, subthalamic stimulation may release bilateral
                      cortical computational resources by facilitating
                      movement-related desynchronization. Moreover, the
                      subthalamic nucleus is critical to balance inhibitory and
                      facilitatory cortical players within the motor program.},
      keywords     = {Adult / Aged / Antiparkinson Agents: therapeutic use /
                      Cortical Synchronization: drug effects / Cortical
                      Synchronization: physiology / Deep Brain Stimulation:
                      methods / Evoked Potentials, Motor: physiology / Female /
                      Humans / Levodopa: therapeutic use / Longitudinal Studies /
                      Male / Middle Aged / Motor Cortex: physiopathology / Nerve
                      Net: physiopathology / Neural Pathways: physiopathology /
                      Parkinson Disease: pathology / Parkinson Disease: therapy /
                      Psychomotor Performance: drug effects / Subthalamus:
                      physiology / Time Factors / Treatment Outcome /
                      Antiparkinson Agents (NLM Chemicals) / Levodopa (NLM
                      Chemicals)},
      cin          = {AG Gasser / Tübingen common / Ext HIH},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)6000018 /
                      I:(DE-2719)5000057},
      pnm          = {345 - Population Studies and Genetics (POF3-345)},
      pid          = {G:(DE-HGF)POF3-345},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:25558877},
      pmc          = {pmc:PMC4408429},
      doi          = {10.1093/brain/awu380},
      url          = {https://pub.dzne.de/record/137841},
}