The effect of c-tACS on working memory performance in healthy controls Kate E. Hoy a,⇑ , Neil Bailey a , Sara Arnold a , Kirstyn Windsor a , Joshua John a,b , Zafiris J. Daskalakis c , Paul B. Fitzgerald a a Monash Alfred Psychiatry Research Centre, The Alfred and Monash University, Central Clinical School, Victoria, Australia b Department of Psychology, University of South Carolina, Columbia, USA c Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Ontario, Canada article info Article history: Received 29 June 2015 Revised 27 October 2015 Accepted 2 November 2015 Keywords: tACS Gamma Working memory Cognitive load abstract Transcranial Direct Current Stimulation (tDCS) has been widely investigated for its potential to enhance cognition, and in particular working memory, however to date standard approaches to stimulation have shown only modest effects. Alternative, more specialised, forms of current delivery may be better suited to cognitive enhancement. One such method is transcranial Alternating Current Stimulation (tACS) which delivers stimulation at a specific frequency and has been shown to entrain endogenous cortical oscilla- tions which underlie cognitive functioning. To date there has been no comparison of the effects of tACS to those of tDCS on cognitive enhancement. In a randomised repeated-measures study design we assessed the effect of gamma (c)-tACS, tDCS and sham tDCS on working memory in 18 healthy partici- pants who attended three sessions held at least 72 h apart. Pre- and post-stimulation working memory performance was assessed using the 2 and 3-back. Our findings indicated the presence of a selective improvement in performance on the 3-back task following c-tACS compared with tDCS and sham stimulation. The current findings provide support for further and more detailed investigation of the role of c-tACS as a more specialised approach to neuromodulation. Ó 2015 Elsevier Inc. All rights reserved. 1. Introduction Non-invasive brain stimulation techniques, such as transcranial Direct Current Stimulation (tDCS), are being increasingly utilised in the cognitive neurosciences (Jacobson, Koslowsky, & Lavidor, 2012). tDCS involves the application of a weak electrical current applied to the scalp using two surface electrodes (anode and cath- ode). This current alters the excitability of brain cells by shifting their membrane potentials in a de- or hyperpolarising direction, thus making them more or less likely to fire (Nitsche & Fregni, 2007). Stimulation of brain cells under the anode appears to increase brain activity, whereas stimulation under the cathode generally has the opposite effect (Jacobson et al., 2012). Of note, findings in the motor cortex indicate that polarity is dependent upon stimulation parameters such as duration of stimulation, for example while 20 min of anodal tDCS has been shown to increase cortical excitability (Batsikadze, Moliadze, Paulus, Kuo, & Nitsche, 2013) the provision of 26 min of anodal stimulation has been shown to decrease excitability (Monte-Silva et al., 2013). The appli- cability of these findings outside the motor cortex is unclear, how- ever there is evidence that 20 min of anodal stimulation to the prefrontal cortex is behaviourally enhancing (Hoy et al., 2013). In addition to its acute effects on membrane potential thresholds, tDCS has been shown to induce changes outlasting the period of stimulation which are believed to be due to the induction of neu- roplastic processes such as Long Term Potentiation (LTP) and Long Term Depression (LTD) (Monte-Silva et al., 2013). These effects are consistent with the growing body of research showing that tDCS is able to induce post-stimulation enhancement in cognitive perfor- mance, with the majority of evidence to date in the domain of working memory (WM) (Brunoni & Vanderhasselt, 2014). In addition to tDCS, there is also growing interest in alternative forms of current delivery such as transcranial Alternating Current Stimulation (tACS) (Antal & Paulus, 2013). While tDCS delivers an electrical current which travels in a constant unipolar direction, tACS delivers a current that alternates at a specified frequency back and forth between the electrodes (Antal & Paulus, 2013; Helfrich et al., 2014). Stimulation with tACS in the EEG range (convention- ally: 0.1–80 Hz) is believed to directly modulate cortical oscilla- tions, with a growing number of studies showing entrainment of http://dx.doi.org/10.1016/j.bandc.2015.11.002 0278-2626/Ó 2015 Elsevier Inc. All rights reserved. ⇑ Corresponding author at: Monash Alfred Psychiatry Research Centre, Level 4, 607 St Kilda Road, Melbourne 3004, Australia. E-mail address: Kate.Hoy@monash.edu (K.E. Hoy). Brain and Cognition 101 (2015) 51–56 Contents lists available at ScienceDirect Brain and Cognition journal homepage: www.elsevier.com/locate/b&c