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@ARTICLE{Manos:845953,
      author       = {Manos, Thanos and Zeitler, Magteld and Tass, Peter A.},
      title        = {{H}ow stimulation frequency and intensity impact on the
                      long-lasting effects of coordinated reset stimulation},
      journal      = {PLoS Computational Biology},
      volume       = {14},
      number       = {5},
      issn         = {1553-7358},
      address      = {San Francisco, Calif.},
      publisher    = {Public Library of Science},
      reportid     = {FZJ-2018-03131},
      pages        = {e1006113 -},
      year         = {2018},
      note         = {The study was funded by the Helmholtz Society (TM, MZ,
                      PAT). The funders had no role in study design, data
                      collection and analysis, decision to publish, or preparation
                      of the manuscript.},
      abstract     = {Several brain diseases are characterized by abnormally
                      strong neuronal synchrony. Coordinated Reset (CR)
                      stimulation was computationally designed to specifically
                      counteract abnormal neuronal synchronization processes by
                      desynchronization. In the presence of spike-timing-dependent
                      plasticity (STDP) this may lead to a decrease of synaptic
                      excitatory weights and ultimately to an anti-kindling, i.e.
                      unlearning of abnormal synaptic connectivity and abnormal
                      neuronal synchrony. The long-lasting desynchronizing impact
                      of CR stimulation has been verified in pre-clinical and
                      clinical proof of concept studies. However, as yet it is
                      unclear how to optimally choose the CR stimulation
                      frequency, i.e. the repetition rate at which the CR stimuli
                      are delivered. This work presents the first computational
                      study on the dependence of the acute and long-term outcome
                      on the CR stimulation frequency in neuronal networks with
                      STDP. For this purpose, CR stimulation was applied with
                      Rapidly Varying Sequences (RVS) as well as with Slowly
                      Varying Sequences (SVS) in a wide range of stimulation
                      frequencies and intensities. Our findings demonstrate that
                      acute desynchronization, achieved during stimulation, does
                      not necessarily lead to long-term desynchronization after
                      cessation of stimulation. By comparing the long-term effects
                      of the two different CR protocols, the RVS CR stimulation
                      turned out to be more robust against variations of the
                      stimulation frequency. However, SVS CR stimulation can
                      obtain stronger anti-kindling effects. We revealed specific
                      parameter ranges that are favorable for long-term
                      desynchronization. For instance, RVS CR stimulation at weak
                      intensities and with stimulation frequencies in the range of
                      the neuronal firing rates turned out to be effective and
                      robust, in particular, if no closed loop adaptation of
                      stimulation parameters is (technically) available. From a
                      clinical standpoint, this may be relevant in the context of
                      both invasive as well as non-invasive CR stimulation.},
      cin          = {INM-7},
      ddc          = {570},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {572 - (Dys-)function and Plasticity (POF3-572)},
      pid          = {G:(DE-HGF)POF3-572},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29746458},
      UT           = {WOS:000434012100011},
      doi          = {10.1371/journal.pcbi.1006113},
      url          = {https://juser.fz-juelich.de/record/845953},
}