Optimal random frequency range in transcranial pulsed current stimulation indexed by quantitative electroencephalography Leon Morales-Quezada a,b , Laura Castillo-Saavedra a , Camila Cosmo a , Deniz Doruk a , Ibrahim Sharaf a , Alejandra Malavera a and Felipe Fregni a Given the recent results provided by previous investigations on transcranial pulsed current stimulation (tPCS) demonstrating its modulatory effects on cortical connectivity; we aimed to explore the application of different random pulsed frequencies. The utility of tPCS as a neuromodulatory technique for cognition performance will come as additional frequency ranges are tested with the purpose to find optimal operational parameters for tPCS. This study was designed to analyze the effects of tPCS using the following random frequencies; 1–5, 6–10, and 11–15 Hz compared with sham on quantitative electroencephalographic changes in the spectral power and interhemispheric coherence of each electroencephalographic frequency band. This was a parallel, randomized, double-blinded, sham-controlled trial. Forty healthy individuals older than 18 years were eligible to participate. The main outcomes were differences in the spectral power analysis and interhemispheric coherence as measured by quantitative electroencephalography. Participants were randomly allocated to four groups of random frequency stimulation and received a single session of stimulation for 20 min with a current intensity of 2 mA delivered by bilateral periauricular electrode clips. We found that a random pulsed frequency between 6–10 Hz significantly increased the power and coherence in frontal and central areas for the alpha band compared with sham stimulation, while 11–15 Hz tPCS decreased the power for the alpha and theta bandwidth. Our findings corroborate the hypothesis that a random frequency ranging into the boundaries of 6–10 Hz induces changes in the naturally occurring alpha oscillatory activity, providing additional data for further studies with tPCS. NeuroReport 26:747–752 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. NeuroReport 2015, 26:747–752 Keywords: intensity, interhemispheric coherence, quantitative electroencephalography, transcranial pulsed current stimulation a Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, Massachusetts, USA and b Department of Physical Medicine and Rehabilitation, School of Health Sciences, De Montfort University, Leicester, UK Correspondence to Felipe Fregni, MD, PhD, Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, 79/96 13th Street, Charlestown, Boston, MA 02129, USA Tel: + 1 617 952 6156; fax: + 1 717 952 6153; e-mails: ffregni@mgh.harvard.edu and felipe.fregni@ppcr.hms.harvard.edu Received 31 May 2015 accepted 11 June 2015 Introduction Transcranial pulsed current stimulation (tPCS) is a simple technique that uses an alternating current delivered to the brain through surface electrodes [1]. It can interact with endogenous oscillatory activity inducing changes in cortical excitability. When the alternating current behaves ran- domly within predefined boundaries, the ongoing cortical electrical activity can be modulated and the magnitude of these modulations will be detected by quantitative elec- troencephalography (qEEG) measurements [2,3]. One of the important parameters that has demonstrated a significant impact in tPCS effects is the frequency of the stimulation [4,5]. Previous studies assessing different sti- mulation properties found that a random frequency para- meter (1–5 Hz) increased functional connectivity when compared with nonrandom and also sham stimulation [2,3]. Given that these studies only assessed one random fre- quency range, it is conceivable that other stimulation ranges, such as alpha-like rate (6–10 Hz), would also be associated with significant qEEG changes. This assumption can be analyzed by taking into consideration the effects of random noise stimulation on brain dynamics. When naturally- generated frequencies from neural assemblies interact with a noninvasive electrical stimulation, the recorded electro- encephalography (EEG) outcome will be dependent on the externally-induced frequency if an alternating current is injected. In biological systems where the signals tend to have nonlinear properties, the use of random noise stimu- lation actually increases the power for its detection [6], creating an enhancing effect on the signal [7]. As this phe- nomenon can be used to manipulate the power and con- nectivity of certain neural oscillations, it makes sense to use different random frequencies especially those contained within the EEG frequency bands, to induce changes in the expression of internal oscillations. This study aims to explore the effects of different ran- domly oscillating frequencies of stimulation (1–5, 6–10, or 11–15 Hz) as compared with sham on qEEG changes in the power and coherence of the EEG frequency bands. We hypothesized that, in addition to the range of Clinical neuroscience 747 0959-4965 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/WNR.0000000000000415 Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.