Testing the limits: Investigating the effect of tDCS dose on working memory enhancement in healthy controls
Introduction
tDCS involves the application of a very weak electrical current via two surface electrodes (anode and cathode) applied to the scalp. It has been shown to alter the excitability of neurons by shifting their membrane potentials in a de- or hyperpolarizing direction; thus making them more or less likely to fire (Nitsche et al., 2008). Anodal stimulation has been shown to depolarise neurons leading to an increase in brain activity while cathodal stimulation is hyperpolarizing and generally results in reductions in brain activity (Jacobson et al., 2012, Nitsche et al., 2008, Weiss and Lavidor, 2012).
In recent years, investigations into the use of tDCS to enhance cognition via prefrontal cortex (PFC) stimulation have increased considerably (Jacobson et al., 2012). Many of these studies have investigated the effects of tDCS on working memory (WM) enhancement in healthy controls and have consistently found positive effects of anodal tDCS to the left PFC (Hoy and Fitzgerald, 2010, Jacobson et al., 2012, Nitsche et al., 2008). The importance of enhancing WM performance in particular is significant. WM is essentially the capacity to keep information ‘in mind’ for short periods of time, often to allow manipulation of the information in concert with the other frontally mediated ‘executive’ brain functions (i.e. language, learning, problem solving etc.), and improvements in WM have indeed been shown to enhance more complex thought and action (Jaušovec & Jaušovec, 2012). Therefore, tDCS induced improvements in WM may have considerable consequences for broader cognitive abilities. While the exact means by which tDCS is able to enhance cognition remains unknown; one posited mechanism involves the modulation of cortical oscillatory activity.
Cortical oscillations refer to the synchronous firing of groups of neurons at specific frequencies and are thought to reflect a variety of functional processes. Theta (4–8 Hz) and alpha (8–13 Hz) oscillations in particular are believed to reflect cognitive processes (Klimesch, 1999). WM functioning has been associated with both increased theta event-related synchronisation (ERS) and greater alpha event-related desynchronisation (ERD), with greater effects shown as WM demands increase (Krause et al., 2000; Peneson, Hamalainen, & Krause, 2007). Recently, research has shown that anodal PFC tDCS does indeed modulate cortical oscillatory activity and that this is associated with the improvements seen in cognitive performances, including in WM (Meinzer et al., 2012, Zaehle et al., 2011). These studies provide preliminary evidence that tDCS is enhancing cognition by directly targeting the intrinsic underlying neurophysiological processes involved.
While studies demonstrating the improvement in cognition produced with tDCS present an exciting avenue for the treatment of cognitive dysfunction, they have also generated some debate around the possibilities and ethics of cognitive enhancement in healthy individuals (Fox, 2011, Kadosh et al., 2012). Both the excitement and concerns regarding the potential applications of tDCS in the healthy population, however, are contingent on the ability of tDCS to meaningfully improve cognitive performance. If substantial effects are possible in healthy controls, one might expect the presence of a dose related effect with greater, and perhaps longer lasting, benefits apparent at higher doses. Dose effects are indeed seen in brain stimulation; Boggio et al. (2006) for example showed enhancement of WM in patients with Parkinson's disease following 2 mA but not with 1 mA stimulation and recent clinical trials of Transcranial Magnetic Stimulation (TMS) for depression have shown greater improvements with higher stimulation doses (Hadley et al., 2011). To date the relationship between dose of tDCS and the degree and duration of induced cognitive enhancement in healthy controls has not been investigated.
Therefore, the aim of the current study was to compare the behavioural and neurophysiological effects of 1 mA and 2 mA tDCS within a standard sham-controlled tDCS protocol for WM enhancement (assessed using 2-back and 3-back) at three time points post-stimulation (0, 20 and 40 min). We hypothesised that active tDCS would improve WM to a greater degree and for a greater duration than sham, and that the most significant improvements would be seen with 2 mA. In addition, we hypothesised greater theta ERS and alpha ERD would be seen in the left PFC following active stimulation compared with sham, and again that the greatest effects would be seen with 2 mA.
Section snippets
Participants
Eighteen healthy participants were recruited for the study (11 females, 7 males; mean age±SD, 24.71±6.97). Participants were excluded if they had a history of any neurological or serious medical conditions, or were currently pregnant. Written consent was obtained from participants prior to commencement of the study. Ethical approval was granted by Monash University and the Alfred Hospital ethics committees.
Procedure
Participants each attended for three experimental sessions held at least one week apart
Reaction time
For reaction time on the 2-back there were significant main effects of current (F(2,32)=3.782, p=0.034) and time (F(2,32)=4.902, p=0.014) and a significant time by current interaction (F(4,64)=2.619, p=0.043) (see Fig. 2).
Post-hoc analysis of the main effect of current using pairwise comparisons revealed that overall participants exhibited significantly faster reaction times following 1 mA compared to either 2 mA (mean difference=−31.792, p=0.038) or sham (mean difference=−57.773, p=0.046).
Discussion
This is the first investigation to look at the effect of tDCS dose on the magnitude and duration of cognitive enhancement post-stimulation using both behavioural and neurophysiological outcome measures in healthy controls. While there has been previous research looking at the effects of tDCS dose (for example, Teo, Hoy, Daskalakis, & Fitzgerald, 2011), none have included investigation of the underlying neurophysiological processes nor examined post-stimulation effects up to 40 min. Participants
Disclosures
PF has received equipment for research from Brainsway Ltd., Medtronic Ltd. and MagVenture A/S and funding for research from Cervel Neurotech and Neuronetics Ltd. PF has received consultancy fees as a scientific advisor for Bionomics. ZD has received research support from Brainsway Ltd., Aspect Medical Inc. and Neuronetics Ltd. ZD has received a travel allowance from Pfizer. There are no other relevant conflicts of interest.
Acknowledgements
This research was supported by grants from the National Health and Medical Research Council and Monash University.
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