title: Nerve excitation using an amplitude-modulated signal with kilohertz-frequency carrier and non-zero offset.
abstract: Incorporating kilohertz-frequency signals in transcutaneous electrical stimulation has been proposed as a means to overcome the impedance of the skin, thereby reaching deeper nerves. In particular, a transdermal amplitude modulated signal (TAMS), composed of a 210 kHz non-zero offset carrier modulated by rectangular pulses, was introduced recently for the treatment of overactive bladder. However, the contribution of the components of TAMS to nerve fiber activation has not been quantified.
  
  
  
  We conducted in vivo experiments and applied direct stimulation to the sciatic nerve of cats and rats. We measured electromyogram and compound action potential activity evoked by pulses, TAMS and modified versions of TAMS in which we varied the size of the carrier.
  
  
  
  Nerve fiber activation using TAMS showed no difference with respect to activation with conventional pulse for carrier frequencies of 20 kHz and higher, regardless the relative amplitude of the carrier. For frequencies lower than 20 kHz, the offset needed to generate half of the maximal evoked response decreased significantly with respect to the pulse. Results of simulations in a computational model of nerve fiber stimulation using the same stimulation waveforms closely matched our experimental measurements.
  
  
  
  Taken together, these results suggest that a TAMS with carrier frequencies >20 kHz does not offer any advantage over conventional pulses, even with larger amplitudes of the carrier, and this has implications for design of waveforms for efficient and effective transcutaneous stimulation.
authors.affiliation: Department of Biomedical Engineering, Duke University, Fitzpatrick CIEMAS, Room 1427, Box 90281, Durham, NC, 27708-0281, USA.
authors.forename: Leonel E
authors.initials: LE
authors.lastname: Medina
authors.affiliation: Department of Biomedical Engineering, Duke University, Fitzpatrick CIEMAS, Room 1427, Box 90281, Durham, NC, 27708-0281, USA. warren.grill@duke.edu.|Department of Neurobiology, Duke University Medical Center, Durham, NC, USA. warren.grill@duke.edu.|Department of Surgery, Duke University Medical Center, Durham, NC, USA. warren.grill@duke.edu.|Department of Electrical and Computer Engineering, Duke University, Durham, NC, USA. warren.grill@duke.edu.
authors.forename: Warren M
authors.initials: WM
authors.lastname: Grill
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002415:Cats; D003198:Computer Simulation; D051381:Rats; D012584:Sciatic Nerve / Q000502:physiology*; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*
keywords: Computational modeling; Kilohertz frequency nerve stimulation; Nerve stimulation; Transdermal amplitude modulated signal