Unilateral Prefrontal Direct Current Stimulation Effects are Modulated by Working Memory Load and Gender Oded Meiron a, * , Michal Lavidor a, b a The Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan, Israel b Department of Psychology, University of Hull, UK article info Article history: Received 1 November 2011 Received in revised form 7 May 2012 Accepted 31 May 2012 Available online 27 June 2012 Keywords: Transcranial direct current stimulation (tDCS) Dorsolateral prefrontal cortex (DLPFC) Working memory (WM) Executive attention and verbal WM load abstract Background: Recent studies revealed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may improve verbal working memory (WM) performance in humans. In the present study, we evaluated executive attention, which is the core of WM capacity, considered to be significantly involved in tasks that require active maintenance of memory represen- tations in interference-rich conditions, and is highly dependent on DLPFC function. Objectives: We investigated verbal WM accuracy using a WM task that is highly sensitive to executive attention function. We were interested in how verbal WM accuracy may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. Methods: We utilized a modified verbal n-Back task hypothesized to increase demands on executive attention. We examined “online” WM performance while participants received transcranial direct current stimulation (tDCS), and implicit learning performance in a post-stimulation WM task. Results: Significant lateralized “online” stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. Conclusions: Our findings support the idea that lateralized stimulation effects in high verbal WM load may be gender-dependent. Further, our post-stimulation results support the idea that increased left hemisphere activity may be important for encoding verbal information into episodic memory as well as for facilitating retrieval of context-specific targets from semantic memory. Ó 2013 Elsevier Inc. All rights reserved. Introduction Recent studies have demonstrated that weak transcranial direct current stimulation (tDCS) can induce significant effects on working memory function in humans [1e4]. Some of these studies revealed that anodal tDCS to the left prefrontal cortex, presumably the dorsolateral prefrontal cortex of healthy participants, improves working memory, specifically its verbal domains [2,5]. These stimulation effects are considered to be a result of transient cortical excitability changes in the resting membrane potential of neurons underlying the electrode, or a result of modulating their sponta- neous firing rate [6]. This facilitation is usually accomplished by delivering a constant weak current of either 1, or 2 mA for 10 up to 30 min over the left dorsolateral prefrontal cortex (left e DLPFC). The facilitation is polarity-dependent as anodal tDCS usually has an excitatory effect on underlying cortical networks, while cathodal tDCS decreases cortical excitability in the region below the elec- trode [1,5]. More so, tDCS effects could impact electrophysiological activity of remote interconnected cortical networks, and are not solely limited to the particular area below the electrodes [5]. Working memory (WM), the ability to temporarily hold and manipulate task-relevant information, includes an attentional- control function (i.e., central executive), a subordinate system that temporarily holds visual spatial information (i.e. visual spatial sketchpad), and a subordinate verbal-auditory system called the phonological loop [7]. In the present tDCS study, we investigated a prefrontal cognitive sub-function of WM central executive system, called executive attention [7]. Executive attention is conceptualized as the core of WM capacity, a prefrontal mechanism responsible for maintaining memory representations in a highly active state in the This study was supported by an ERC starting grant awarded to ML (Inspire 200512). * Corresponding author. Cognitive Neuroscience Lab, Brain Research Center, Bar Ilan University, 52900 Ramat Gan, Israel. Tel.: þ972 3 531 8171; fax: þ972 3 5352184. E-mail address: neuron.o.d.m@gmail.com (O. Meiron). Contents lists available at SciVerse ScienceDirect Brain Stimulation journal homepage: www.brainstimjrnl.com 1935-861X/$ e see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.brs.2012.05.014 Brain Stimulation 6 (2013) 440e447