Continuously changing environments require dynamic adaptation by means of filtering and evaluating internal and external stimuli to orchestrate goal-directed behaviour. This is especially important for situations in which distractions might influence efficient responses. Important information is maintained, while non-relevant stimuli must be suppressed or ignored. Dysfunctions of cognitive control (CC) processes are at the core of many psychopathological conditions [1,2], comprise the intentional selection of thoughts, emotions, and behaviours based on current task demands  involving functions of attention, memory, and emotional control , and are associated with altered patterns of brain activation [5,6]. The prefrontal cortex (PFC), particularly the dorsolateral prefrontal cortex (dlPFC), is known to be highly involved in CC processes  by means of processes related to working memory , encoding of task relevant rules and responses , and emotion regulation .
Transcranial direct current stimulation (tDCS) has been put forward as a means to influence these processes by modulating the likelihood of neuronal firing in response to a stimulus . At the macroscopic level, within the common and safe range of stimulation parameters (1–2 mA, up to 30 min of stimulation ), it is supposed that anodal tDCS predominantly enhances, while cathodal tDCS mainly reduces the excitability and spontaneous activity of the targeted and connected areas . This polarity-dependent modulation of brain activity by tDCS has a remarkable potential to influence corresponding cognition and behaviour [, , ]. However, tDCS does not induce cortical activity per se. It develops its effects particularly in interaction with spontaneous neuronal activity [17,18]. This activity-dependent influence on brain networks allows for a ‘functional targeting’ of stimulation when tDCS is directly coupled with the respective cognitive or behavioural process , where the target regions are activated (i.e. by a task) and further specifically modulated by the stimulation . Correspondingly, tDCS effects have been found especially in neuronal correlates of task features that were active during stimulation . Therefore, the combination of tDCS with task training is suggested to have a synergistic ‘neuroenhancing’ effect that is currently subject of extensive research [, , , ]. However, available data are still inconsistent as efficacy depends on stimulation parameters that vary widely between studies. For a meaningful clinical application, a sustainable enhancement of adaptive plasticity would be most desirable . Based on this notion, a specific activation of the CC network and concomitant tDCS holds promise to provide new treatment strategies for cognitive and behavioural disorders [, , ]. In a plethora of studies, stimulation has already shown to enhance CC by changing emotion regulation processes , improving frustration tolerance , modulating emotional vulnerability , dissolving attentional biases , augmenting working memory training , and increasing multitasking capacity . However, reliability of results and the plausibility of approaches leaves room for improvement, not at least because studies often yield varying results even for similar tasks [, , , ]. Therefore, reliable knowledge about the efficacy of parameter settings is mandatory for further advancements .
To this aim, we systematically tested different standard stimulation parameters (anodal/cathodal tDCS with 1/2 mA to the left/right dlPFC) in 162 healthy subjects, combining repeated CC training (6 sessions within 2 weeks) with tDCS, and additionally analysed pre- and post-training assessments. We applied a modified adaptive paced auditory serial addition task (PASAT) to challenge and train CC . This task requires continuous updating of working memory with parallel distracting performance feedback; it is known to activate CC , critically involves resources within the PFC , and adapts task difficulty to individual performance . We hypothesized that adding anodal but not cathodal tDCS to PASAT-induced neuronal activity of the dlPFC [43,44] can enhance cognitive training effects [45,46], improve performance of the PASAT or similar, even more challenging tasks [16,31,, , , , ], and that higher stimulation intensity does not increase efficacy . Furthermore, we wanted to test if the laterality of stimulation matters. Therefore, PASAT performance under eight different tDCS conditions (combined N = 119) was compared to a sham intervention group (N = 43). Analyses were conducted hierarchically, allowing us to narrow down the responsible factors for the most efficient combination of CC training and tDCS.[…]