Effects of High-Definition and Conventional tDCS on Response Inhibition
Introduction
The human brain is capable of rapidly implementing a vast array of behavioral responses, yet this ability would be ill-suited to the real world without the capacity to stop responses that become irrelevant or inappropriate following changes in the environment [1]. This process, known as response inhibition, is critical to the executive control of behavior, and research aimed at identifying its neural substrates has received growing attention in recent years [2], [3]. Functional magnetic resonance imaging (fMRI) studies have identified a consistent network of brain regions that are engaged during response inhibition tasks, including pre-supplementary motor area (preSMA), inferior frontal cortex (IFC), and the subthalamic nucleus (STN) of the basal ganglia [4], [5], [6], [7]. The present study focuses on the IFC, which has been suggested to represent the key “brake” node in the response inhibition network, implementing the signal required to inhibit the performance of a planned response [2], [3].
Neuropsychological evidence has consistently linked inhibitory control function to regions of the prefrontal cortex [8], [9]. Supporting the view that the IFC is necessary for response inhibition, studies in patients with prefrontal brain lesions have shown that damage to this region impairs one's ability to refrain from either initiating a prepotent behavioral response [10] or stopping an ongoing response [11]. Furthermore, a causal role of the IFC in response inhibition has been reaffirmed by using transcranial magnetic stimulation (TMS) to disturb IFC function and impair response inhibition [12], [13]. Since disturbed IFC recruitment during response inhibition is a hallmark of several psychiatric and neurological disorders [14], [15], [16], studies that aim to promote regional activity in this area of the brain may offer promising new developments in the treatment of these conditions.
One promising method for enhancing regional brain activity is transcranial direct current stimulation (tDCS [17]). In conventional tDCS protocols, a mild electrical current (≈1–2 mA) is passed between two large electrode pads (≈25–35 cm2) placed in different arrangements on the scalp (electrode montage). One of the electrodes is an anode and the other is a cathode, and >10 minutes of tDCS delivery has been found to increase the excitability of cortical structures near the anode for as long as 90 minutes post-stimulation [18], [19]. Critically, this enhanced neuronal excitability has been associated with improvements in cognitive functions associated with structures nearer to the anodal electrode site. For example, tDCS with the anodal pad placed over the parietal cortex has been associated with improved performance on spatial attention and numerosity tasks [20], [21], [22], [23], whereas stimulation with the anode over prefrontal cortex has been shown to modulate planning [24], decision-making [25], [26], social reasoning [27], and working memory [28], [29]. Of particular relevance to the present study, researchers have started to investigate prefrontal tDCS as a tool for improving response inhibition.
Specifically, recent studies have demonstrated improved response inhibition following conventional tDCS with an anode placed over right IFC or pre-supplementary motor area (preSMA) and the cathodal electrode placed on the opposite side of the head [30], [31], [32], [33]. Given the well-established role of right IFC and preSMA in response inhibition [2], [3], the studies' authors argued that enhanced excitability at the structures underneath the anodal pad drove the observed behavioral improvement. However, computational neurostimulation1 studies have suggested that pad tDCS produces diffuse current through the brain including both cortical and deep structures (Fig. 1.1–2,4; [34], [35], [36]). This diffuse pattern of current flow is supported by evidence from combined tDCS/fMRI studies [37], [38], thereby making it difficult to establish causality between modulated activity at the nominal target site and resulting behavioral changes [39], [40], [41].
In an effort to improve the spatial focality of tDCS, researchers have recently developed high-definition tDCS (HD-tDCS) delivery systems [34], [35]. Typically, HD-tDCS involves passing a small direct electrical current (again, typically 1–2 mA) through a 4 × 1 montage of stimulating electrodes (1 cm diameter), with a single anodal electrode placed over the target brain region, and four return electrodes arranged in a ring surrounding the anode, each receiving 25% of the return current. Computational neurostimulation studies suggest that the focality of HD-tDCS is far superior to conventional tDCS, with current flow restricted to the circumscribed ring (Fig. 1.3) [35], [42]. The efficacy of HD-tDCS for inducing neurophysiological changes has been established in research on human motor system activity, by applying anodal stimulation over the primary motor cortex and demonstrating subsequent increases in corticospinal excitability [43], [44].
Although such findings in the domain of motor excitation have been established and replicated, similar effects in non-motor domains remain unreported. To our knowledge, only one study to date has examined the impact of HD-tDCS on neuropsychological task performance [45], with results demonstrating that HD-tDCS led to significant improvements on a variety of cognitive tasks (in comparison to stimulation in a control region). Furthermore, no studies have directly contrasted the cognitive effects of conventional and HD-tDCS in the same experimental paradigm. Given the potential spatial advantage of HD-tDCS for targeting brain regions relative to conventional tDCS, as well as the translational potential of both approaches in improving cognitive performance, there is a need to compare the impacts of the two stimulation techniques on cognitive functioning.
In order to address this need, we directly compared the effects of HD-tDCS and conventional tDCS on response inhibition in a group of healthy adult participants. Participants were randomly selected to receive either HD-tDCS or conventional tDCS to IFC during a response inhibition training task (Fig. 2A). Both HD- and conventional tDCS montages were designed to maximize current flow to the IFC (Fig. 1.2–3). A third group of participants received conventional tDCS targeting a mid-occipital control site (Fig. 1.4). Inclusion of an active tDCS control condition ensured the relative target specificity of any behavioral effect observed following HD- or conventional tDCS over the IFC [46]. Finally, in addition to the response inhibition task, participants completed a control training task unrelated to response inhibition (choice reaction time task, CRT, Fig. 2A [47]), during a separate testing session. As in the experimental training session, participants performed the control training task during stimulation, enabling us to determine whether task context during tDCS influences subsequent behavioral effects. Our central hypothesis was that both HD-tDCS and conventional tDCS would facilitate response inhibition training relative to mid-occipital stimulation, without influencing performance after training on the control task. Most importantly, the inclusion of both HD- and conventional tDCS in the same experimental paradigm allowed for the first direct comparison, to our knowledge, of the effects of these two techniques on a cognitive task.
Section snippets
Participants
Fifty-two individuals participated in the experiment for financial remuneration and were divided into three tDCS conditions: (1) conventional tDCS targeting the IFC (pad-IFC), n = 16; (2) HD-tDCS to IFC (HD-IFC), n = 16; and (3) conventional tDCS targeting the mid-occipital control site (pad-Oz), n = 20. Both gender (pad-IFC, p = 0.69 female; HD-IFC, p = 0.62 female; pad-Oz, p = 0.75 female; Χ2 =0.66, p = 0.72) and handedness (pad-IFC, p = 0.94 right-hand dominant; HD-IFC, p = 0.88 right-hand
Stop-signal reaction times
The primary measure used to index response inhibition performance was the stop-signal reaction time (SSRT), which estimates the amount of time subjects take to successfully inhibit an inappropriate planned response. The experiment was a 2 (time: pretest, posttest) × 2 (session: CRT, SST) × 3 (tDCS: pad-IFC, HD-IFC, pad-Oz) design. SSRTs were thus analyzed via three-way mixed ANOVA, which revealed a significant main effect of time [F(1,43) = 7.42, p = 0.009, η2 =0.14] due to significantly
Discussion
The present study compared the effects of conventional tDCS and HD-tDCS for targeting IFC in order to improve response inhibition. Response inhibition performance improved following stop-signal task (SST) training during both HD- and conventional tDCS targeting the right IFC, relative to conventional tDCS targeting a posterior control site. To our knowledge, these results provide the first evidence that HD-tDCS can improve response inhibition, or indeed, performance on any executive function
Acknowledgements
The authors would like to thank Valerie Mandoske and Aileen Chau for extensive help during participant recruitment and data collection. Support was provided by the Agency for Healthcare Research and Quality [K12 HS023011] and the Julius N. Frankel Foundation. Dr. Bikson is supported by grants from the NIH, NSF, DoD, Epilepsy Foundation, and Coulter Foundation, and has equity in Soterix Medical Inc. The City University of New York has patents on brain stimulation with Dr. Bikson as inventor.
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