title: Combining TMS and tACS for Closed-Loop Phase-Dependent Modulation of Corticospinal Excitability: A Feasibility Study.
abstract: BACKGROUND
  The corticospinal excitability indexed by motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) of the sensorimotor cortex is characterized by large variability. The instantaneous phase of cortical oscillations at the time of the stimulation has been suggested as a possible source of this variability. To explore this hypothesis, a specific phase needs to be targeted by TMS pulses with high temporal precision.
  
  
  OBJECTIVE
  The aim of this feasibility study was to introduce a methodology capable of exploring the effects of phase-dependent stimulation by the concurrent application of alternating current stimulation (tACS) and TMS.
  
  
  METHODS
  We applied online calibration and closed-loop TMS to target four specific phases (0°, 90°, 180° and 270°) of simultaneous 20 Hz tACS over the primary motor cortex (M1) of seven healthy subjects.
  
  
  RESULTS
  The integrated stimulation system was capable of hitting the target phase with high precision (SD ± 2.05 ms, i.e., ± 14.45°) inducing phase-dependent MEP modulation with a phase lag (CI95% = -40.37° to -99.61°) which was stable across subjects (p = 0.001).
  
  
  CONCLUSIONS
  The combination of different neuromodulation techniques facilitates highly specific brain state-dependent stimulation, and may constitute a valuable tool for exploring the physiological and therapeutic effect of phase-dependent stimulation, e.g., in the context of neurorehabilitation.
authors.affiliation: Division of Functional and Restorative Neurosurgery, and Centre for Integrative Neuroscience, Eberhard Karls University Tübingen Baden-Württemberg, Germany.
authors.forename: Valerio
authors.initials: V
authors.lastname: Raco
authors.affiliation: Division of Functional and Restorative Neurosurgery, and Centre for Integrative Neuroscience, Eberhard Karls University Tübingen Baden-Württemberg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Division of Functional and Restorative Neurosurgery, and Centre for Integrative Neuroscience, Eberhard Karls University Tübingen Baden-Württemberg, Germany.
authors.forename: Srikandarajah
authors.initials: S
authors.lastname: Tharsan
authors.affiliation: Division of Functional and Restorative Neurosurgery, and Centre for Integrative Neuroscience, Eberhard Karls University Tübingen Baden-Württemberg, Germany.
authors.forename: Alireza
authors.initials: A
authors.lastname: Gharabaghi
keywords: adaptive; beta oscillations; brain state-dependent; phase-dependent; targeted modulation