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@ARTICLE{Keute:140868,
      author       = {Keute, Marius and Demirezen, Mustafa and Graf, Alina and
                      Müller, Notger and Zaehle, Tino},
      title        = {{N}o modulation of pupil size and event-related pupil
                      response by transcutaneous auricular vagus nerve stimulation
                      (ta{VNS}).},
      journal      = {Scientific reports},
      volume       = {9},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DZNE-2020-07190},
      pages        = {11452},
      year         = {2019},
      abstract     = {Transcutaneous auricular vagus nerve stimulation (taVNS)
                      bears therapeutic potential for a wide range of medical
                      conditions. However, previous studies have found substantial
                      interindividual variability in responsiveness to taVNS, and
                      no reliable predictive biomarker for stimulation success has
                      been developed so far. In this study, we investigate pupil
                      size and event-related pupil response as candidate
                      biomarkers. Both measures have a direct physiological link
                      to the activity of the locus coeruleus (LC), a brainstem
                      structure and the main source of norepinephrine in the
                      brain. LC activation is considered one of the key mechanisms
                      of action of taVNS, therefore, we expected a clear increase
                      of the pupillary measures under taVNS compared to sham
                      (placebo) stimulation, such that it could serve as a
                      prospective predictor for individual clinical and
                      physiological taVNS effects in future studies. We studied
                      resting pupil size and pupillary responses to target stimuli
                      in an auditory oddball task in 33 healthy young volunteers.
                      We observed stronger pupil responses to target than to
                      standard stimuli. However, and contrary to our hypothesis,
                      neither pupil size nor the event-related pupil response nor
                      behavioral performance were modulated by taVNS. We discuss
                      potential explanations for this negative finding and its
                      implications for future clinical investigation and
                      development of taVNS.},
      keywords     = {Adult / Depression: therapy / Ear Auricle: innervation /
                      Electrodes / Epilepsy: therapy / Female / Healthy Volunteers
                      / Humans / Locus Coeruleus: physiology / Male / Pupil:
                      physiology / Skin: innervation / Transcutaneous Electric
                      Nerve Stimulation: instrumentation / Transcutaneous Electric
                      Nerve Stimulation: methods / Vagus Nerve: physiology / Vagus
                      Nerve Stimulation: instrumentation / Vagus Nerve
                      Stimulation: methods / Young Adult},
      cin          = {AG Müller},
      ddc          = {600},
      cid          = {I:(DE-2719)1310003},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31391505},
      pmc          = {pmc:PMC6685960},
      doi          = {10.1038/s41598-019-47961-4},
      url          = {https://pub.dzne.de/record/140868},
}