title: Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects.
abstract: The safety and tolerability of limited output transcranial electrical stimulation (tES) in clinical populations support a non-significant risk designation. The tolerability of long-term use in a healthy population had remained untested.
  
  
  
  We tested the tolerability and compliance of two tES waveforms, transcranial direct current stimulation (tDCS) and modulated high frequency transcranial pulsed current stimulation (MHF-tPCS) compared to sham-tDCS, applied to healthy subjects for three to five days (17-20 minutes per day) per week for up to six weeks in a communal setting. MHF-tPCS consisted of asymmetric high-frequency pulses (7-11 kHz) having a peak amplitude of 10-20 mA peak, adjusted by subject, resulting in an average current of 5-7 mA.
  
  
  
  A total of 100 treatment blind healthy subjects were randomly assigned to one of three treatment groups: tDCS (n = 33), MHF-tPCS (n = 30), or sham-tDCS (n = 37). In order to test the role of waveform, electrode type and montage were fixed across tES and sham-tDCS arms: high-capacity self-adhering electrodes on the right lateral forehead and back of the neck. We conducted 1905 sessions (636 sham-tDCS, 623 tDCS, and 646 MHF-tPCS sessions) on study volunteers over a period of six weeks.
  
  
  
  Common adverse events were primarily restricted to influences upon the skin and included skin tingling, itching, and mild burning sensations. The incidence of these events in the active tES treatment arms (MHF-tPCS, tDCS) was equivalent or significantly lower than their incidence in the sham-tDCS treatment arm. Other adverse events had a rarity (<5% incidence) that could not be significantly distinguished across the treatment groups. Some subjects were withdrawn from the study due to atypical headache (sham-tDCS n = 2, tDCS n = 2, and MHF-tPCS n = 3), atypical discomfort (sham-tDCS n = 0, tDCS n = 1, and MHF-tPCS n = 1), or atypical skin irritation (sham-tDCS n = 2, tDCS n = 8, and MHF-tPCS n = 1). The rate of compliance, elected sessions completed, for the MHF-tPCS group was significantly greater than the sham-tDCS group's compliance (p = 0.007). There were no serious adverse events in any treatment condition.
  
  
  
  We conclude that repeated application of limited output tES across extended periods, limited to the hardware, electrodes, and protocols tested here, is well tolerated in healthy subjects, as previously observed in clinical populations.
authors.affiliation: Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Paneri
authors.affiliation: Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Adair
authors.affiliation: Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Thomas
authors.affiliation: Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Khadka
authors.affiliation: Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Patel
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287 USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Tyler
authors.affiliation: Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA.
authors.forename: Lucas
authors.initials: L
authors.lastname: Parra
authors.affiliation: Department of Biomedical Engineering, The City College of New York, CUNY, 160 Convent Ave., New York 10031, USA. Electronic address: bikson@ccny.cuny.edu.
authors.forename: Marom
authors.initials: M
authors.lastname: Bikson
mesh_terms: D000293:Adolescent; D000328:Adult; D004566:Electrodes; D005260:Female; D006261:Headache / Q000209:etiology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011537:Pruritus / Q000209:etiology*; D065908:Transcranial Direct Current Stimulation / Q000009:adverse effects* / Q000379:methods; D055815:Young Adult
keywords: Compliance; Extended use; Healthy population; MHF-tPCS; Tolerability; tDCS