title: tACS Phase Locking of Frontal Midline Theta Oscillations Disrupts Working Memory Performance.
abstract: BACKGROUND
  Frontal midline theta (FMT) oscillations (4-8 Hz) are strongly related to cognitive and executive control during mental tasks such as memory processing, arithmetic problem solving or sustained attention. While maintenance of temporal order information during a working memory (WM) task was recently linked to FMT phase, a positive correlation between FMT power, WM demand and WM performance was shown. However, the relationship between these measures is not well understood, and it is unknown whether purposeful FMT phase manipulation during a WM task impacts FMT power and WM performance. Here we present evidence that FMT phase manipulation mediated by transcranial alternating current stimulation (tACS) can block WM demand-related FMT power increase (FMTΔpower) and disrupt normal WM performance.
  
  
  METHODS
  Twenty healthy volunteers were assigned to one of two groups (group A, group B) and performed a 2-back task across a baseline block (block 1) and an intervention block (block 2) while 275-sensor magnetoencephalography (MEG) was recorded. After no stimulation was applied during block 1, participants in group A received tACS oscillating at their individual FMT frequency over the prefrontal cortex (PFC) while group B received sham stimulation during block 2. After assessing and mapping phase locking values (PLV) between the tACS signal and brain oscillatory activity across the whole brain, FMT power and WM performance were assessed and compared between blocks and groups.
  
  
  RESULTS
  During block 2 of group A but not B, FMT oscillations showed increased PLV across task-related cortical areas underneath the frontal tACS electrode. While WM task-related FMTΔpower and WM performance were comparable across groups in block 1, tACS resulted in lower FMTΔpower and WM performance compared to sham stimulation in block 2.
  
  
  CONCLUSIONS
  tACS-related manipulation of FMT phase can disrupt WM performance and influence WM task-related FMTΔpower. This finding may have important implications for the treatment of brain disorders such as depression and attention deficit disorder associated with abnormal regulation of FMT activity or disorders characterized by dysfunctional coupling of brain activity, e.g., epilepsy, Alzheimer's or Parkinson's disease (AD/PD).
authors.affiliation: Applied Neurotechnology Lab, Department of Psychiatry and Psychotherapy, University Hospital of Tübingen Tübingen, Germany.
authors.forename: Bankim S
authors.initials: BS
authors.lastname: Chander
authors.affiliation: Applied Neurotechnology Lab, Department of Psychiatry and Psychotherapy, University Hospital of Tübingen Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Witkowski
authors.affiliation: MEG Center, University Hospital of TübingenTübingen, Germany; CIMeC, Center for Mind/Brain Sciences, University of TrentoTrento, Italy.
authors.forename: Christoph
authors.initials: C
authors.lastname: Braun
authors.affiliation: National Institute of Mental Health (NIMH), MEG Core Facility Bethesda, MD, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Robinson
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen Tübingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Born
authors.affiliation: National Institute of Neurological Disorders and Stroke (NINDS) Bethesda, MD, USA.
authors.forename: Leonardo G
authors.initials: LG
authors.lastname: Cohen
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen Tübingen, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Birbaumer
authors.affiliation: Applied Neurotechnology Lab, Department of Psychiatry and Psychotherapy, University Hospital of TübingenTübingen, Germany; MEG Center, University Hospital of TübingenTübingen, Germany.
authors.forename: Surjo R
authors.initials: SR
authors.lastname: Soekadar
keywords: entrainment; frontal midline theta (FMT); magnetoencephalography (MEG); transcranial alternating current stimulation (tACS); working memory performance