title: Enhancement of Neuromodulation with Novel Pulse Shapes Generated by Controllable Pulse Parameter Transcranial Magnetic Stimulation.
abstract: BACKGROUND
  Standard repetitive transcranial magnetic stimulation (rTMS) devices generate bidirectional biphasic sinusoidal pulses that are energy efficient, but may be less effective than monophasic pulses that induce a more unidirectional electric field. To enable pulse shape optimization, we developed a controllable pulse parameter TMS (cTMS) device.
  
  
  OBJECTIVE
  We quantified changes in cortical excitability produced by conventional sinusoidal bidirectional pulses and by three rectangular-shaped cTMS pulses, one bidirectional and two unidirectional (in opposite directions), and compared their efficacy in modulating motor evoked potentials (MEPs) produced by stimulation of motor cortex.
  
  
  METHODS
  Thirteen healthy subjects completed four sessions of 1 Hz rTMS of the left motor cortex. In each session, the rTMS electric field pulse had one of the four shapes. Excitability changes due to rTMS were measured by applying probe TMS pulses before and after rTMS, and comparing resultant MEP amplitudes. Separately, we measured the latency of the MEPs evoked by each of the four pulses.
  
  
  RESULTS
  While the three cTMS pulses generated significant mean inhibitory effects in the subject group, the conventional biphasic cosine pulses did not. The strongest inhibition resulted from a rectangular unidirectional pulse with dominant induced current in the posterior-anterior direction. The MEP latency depended significantly on the pulse shape.
  
  
  CONCLUSIONS
  The pulse shape is an important factor in rTMS-induced neuromodulation. The standard cosine biphasic pulse showed the smallest effect on cortical excitability, while the greatest inhibition was observed for an asymmetric, unidirectional, rectangular pulse. Differences in MEP latency across the various rTMS pulse shapes suggest activation of distinct subsets of cortical microcircuitry.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA.
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Goetz
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA; Department of Psychology and Neuroscience, Duke University, Durham, NC 27710, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Luber
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA; Department of Psychology and Neuroscience, Duke University, Durham, NC 27710, USA.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Lisanby
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA.
authors.forename: David L K
authors.initials: DL
authors.lastname: Murphy
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA.
authors.forename: I Cassie
authors.initials: IC
authors.lastname: Kozyrkov
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA; Department of Neurobiology, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA; Department of Electrical and Computer Engineering, Duke University, Durham, NC 27710, USA.
authors.forename: Warren M
authors.initials: WM
authors.lastname: Grill
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA; Department of Electrical and Computer Engineering, Duke University, Durham, NC 27710, USA. Electronic address: angel.peterchev@duke.edu.
authors.forename: Angel V
authors.initials: AV
authors.lastname: Peterchev
mesh_terms: D000293:Adolescent; D000328:Adult; D019054:Evoked Potentials, Motor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000502:physiology; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
keywords: Inhibitory; Latency; Low frequency; Pulse shape; Repetitive transcranial magnetic stimulation; cTMS