% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Manos:845004,
      author       = {Manos, Thanos and Zeitler, Magteld and Tass, Peter A.},
      title        = {{S}hort-{T}erm {D}osage {R}egimen for
                      {S}timulation-{I}nduced {L}ong-{L}asting
                      {D}esynchronization},
      journal      = {Frontiers in physiology},
      volume       = {9},
      issn         = {1664-042X},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {FZJ-2018-02334},
      pages        = {376},
      year         = {2018},
      abstract     = {In this paper, we computationally generate hypotheses for
                      dose-finding studies in the context of desynchronizing
                      neuromodulation techniques. Abnormally strong neuronal
                      synchronization is a hallmark of several brain disorders.
                      Coordinated Reset (CR) stimulation is a spatio-temporally
                      patterned stimulation technique that specifically aims at
                      disrupting abnormal neuronal synchrony. In networks with
                      spike-timing-dependent plasticity CR stimulation may
                      ultimately cause an anti-kindling, i.e., an unlearning of
                      abnormal synaptic connectivity and neuronal synchrony. This
                      long-lasting desynchronization was theoretically predicted
                      and verified in several pre-clinical and clinical studies.
                      We have shown that CR stimulation with rapidly varying
                      sequences (RVS) robustly induces an anti-kindling at low
                      intensities e.g., if the CR stimulation frequency (i.e.,
                      stimulus pattern repetition rate) is in the range of the
                      frequency of the neuronal oscillation. In contrast, CR
                      stimulation with slowly varying sequences (SVS) turned out
                      to induce an anti-kindling more strongly, but less robustly
                      with respect to variations of the CR stimulation frequency.
                      Motivated by clinical constraints and inspired by the
                      spacing principle of learning theory, in this computational
                      study we propose a short-term dosage regimen that enables a
                      robust anti-kindling effect of both RVS and SVS CR
                      stimulation, also for those parameter values where RVS and
                      SVS CR stimulation previously turned out to be ineffective.
                      Intriguingly, for the vast majority of parameter values
                      tested, spaced multishot CR stimulation with
                      demand-controlled variation of stimulation frequency and
                      intensity caused a robust and pronounced anti-kindling. In
                      contrast, spaced CR stimulation with fixed stimulation
                      parameters as well as singleshot CR stimulation of equal
                      integral duration failed to improve the stimulation outcome.
                      In the model network under consideration, our short-term
                      dosage regimen enables to robustly induce long-term
                      desynchronization at comparably short stimulation duration
                      and low integral stimulation duration. Currently, clinical
                      proof of concept is available for deep brain CR stimulation
                      for Parkinson's therapy and acoustic CR stimulation for
                      tinnitus therapy. Promising first in human data is available
                      for vibrotactile CR stimulation for Parkinson's treatment.
                      For the clinical development of these treatments it is
                      mandatory to perform dose-finding studies to reveal optimal
                      stimulation parameters and dosage regimens. Our findings can
                      straightforwardly be tested in human dose-finding studies.},
      cin          = {INM-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {574 - Theory, modelling and simulation (POF3-574)},
      pid          = {G:(DE-HGF)POF3-574},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000429829800001},
      pubmed       = {pmid:29706900},
      doi          = {10.3389/fphys.2018.00376},
      url          = {https://juser.fz-juelich.de/record/845004},
}