title: Endogenous cortical oscillations constrain neuromodulation by weak electric fields.
abstract: BACKGROUND
  Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation modality that may modulate cognition by enhancing endogenous neocortical oscillations by application of sine-wave electric fields. Yet, the role of endogenous network activity in enabling and shaping the effects of tACS has remained unclear.
  
  
  OBJECTIVE
  We combined optogenetic stimulation and multichannel slice electrophysiology to elucidate how the effect of a weak sine-wave electric field depends on the ongoing cortical oscillatory activity. We hypothesized that endogenous cortical oscillations constrain neuromodulation by tACS.
  
  
  METHODS
  We studied the effect of weak sine-wave electric fields on oscillatory activity in mouse neocortical slices. Optogenetic control of the network activity enabled the generation of in vivo-like cortical oscillations for studying the temporal relationship between network activity and sine-wave electric field stimulation.
  
  
  RESULTS
  Weak electric fields enhanced endogenous oscillations but failed to induce a frequency shift of the ongoing oscillation for stimulation frequencies that were not matched to the endogenous oscillation. This constraint on the effect of electric field stimulation imposed by endogenous network dynamics was limited to the case of weak electric fields targeting in vivo-like network dynamics. Together, these results suggest that the key mechanism of tACS may be enhancing, but not overriding, intrinsic network dynamics.
  
  
  CONCLUSIONS
  Our results contribute to understanding the inconsistent tACS results from human studies and propose that stimulation precisely adjusted in frequency to the endogenous oscillations is key to rational design of non-invasive brain stimulation paradigms.
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Schmidt
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Apoorva K
authors.initials: AK
authors.lastname: Iyengar
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: A Alban
authors.initials: AA
authors.lastname: Foulser
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Boyle
authors.affiliation: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: flavio_frohlich@med.unc.edu.
authors.forename: Flavio
authors.initials: F
authors.lastname: Fröhlich
mesh_terms: D000818:Animals; D001683:Biological Clocks; D058256:Brain Waves / Q000502:physiology; D051379:Mice; D019579:Neocortex / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D062308:Optogenetics; D017966:Pyramidal Cells / Q000502:physiology; D065908:Transcranial Direct Current Stimulation
keywords: Electric field; Multielectrode array; Optogenetics; Resonance; Transcranial alternating current stimulation; tACS