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Anodal transcranial direct current stimulation (tDCS), applied over the left dorsolateral prefrontal cortex (lDLPFC), can produce significant effects on working memory (WM) performance and associated neurophysiological activity. However, results from previous studies are inconsistent and occasionally contradictory. This inconsistency may be attributed to methodological and individual differences during experiments. This study therefore investigated two hypotheses: (1) A multichannel-optimized montage was expected to be more effective than a classical bipolar montage, because of increased focality. (2) The subjects were expected to benefit differently from the stimulation depending on their initial task performance. In a sham-controlled crossover study, 24 healthy participants received bipolar, multichannel, and sham stimulation for 20 min in randomized order, targeting the lDLPFC while performing a 2-back WM task. After stimulation, electroencephalography (EEG) was recorded at rest and during 2-back and nontarget continuous performance task (CPT) performance. Bipolar and multichannel stimulations were both well tolerated and effectively blinded. We found no effect of stimulation on behavioral performance or neuronal oscillations comparing the classical bipolar or multichannel montage with sham stimulation. We did, however, find an interaction between stimulation and initial task performance. For multichannel stimulation, initially low-performing participants tended to improve their WM performance while initially high-performing participants tended to worsen their performance compared to sham stimulation. Both tDCS montages induced changes in neural oscillatory power, which correlated with baseline performance. The worse the participants’ initial WM performance was, the more task-related theta power was induced by multichannel and bipolar stimulation. The same effect was observed for alpha power in the nontarget task following multichannel stimulation. Notably, we were not able to show a superiority of multichannel stimulation compared to bipolar stimulation. Still, comparing both montages with sham stimulation, multichannel stimulation led to stronger effects than bipolar stimulation. The current study highlights the importance of investigating different parameters with potential influence on tDCS effects in combination. Our results demonstrate how individual differences in cognitive performance and electrode montages influence effects of tDCS on neuropsychological performance. These findings support the idea of an individualized and optimized stimulation setting, potentially leading to increased tDCS effects.

Experimental evidence in rodents and humans suggests that long-term memory consolidation can be enhanced by the exploration of a novel environment presented during a vulnerable early phase of consolidation. This memory enhancing effect (behavioral tagging) is caused by dopaminergic and noradrenergic neuromodulation of hippocampal plasticity processes. In translation from animal to human research, we investigated whether behavioral tagging with novelty can be used to tackle memory problems observed in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). 34 patients with ADHD and 34 typically developing participants (age 9–15 years) explored either a previously familiarized or a novel virtual environment 45 min after they had learned a list of 20 words. Participants took a free recall test both immediately after learning the word list and after 24 h. Patients who explored a familiar environment showed significantly impaired memory consolidation compared to typically developing peers. Exploration of a novel environment led to significantly better memory consolidation in children and adolescents with ADHD. However, we did not observe a beneficial effect of novel environment exploration in typically developing participants. Our data rather suggested that increased exploration of a novel environment as well as higher feelings of virtual immersion compromised memory performance in typically developing children and adolescents, which was not the case for patients with ADHD. We propose that behavioral tagging with novel virtual environments is a promising candidate to overcome ADHD related memory problems. Moreover, the discrepancy between children and adolescents with and without ADHD suggests that behavioral tagging might only be able to improve memory consolidation for weakly encoded information.

The development of cognitive interventions in attention-deficit/hyperactivity disorder (ADHD) often requires the assessment of multiple cognitive functions. However, experimental settings consisting of various tasks are particularly strenuous for patients and can thus result in poor data quality. For the economical assessment of working memory and response inhibition, this study aims to validate a combined n-back/nogo paradigm by comparing it to single task versions and to demonstrate its applicability for ADHD research. Twenty-five healthy individuals and 34 ADHD patients between 9 and 16 years participated in this event-related potential (ERP) study. Healthy controls underwent single task versions of a 2-back working memory task and a go/nogo response inhibition task as well as the introduced combined 2-back/nogo task. This combined task demonstrated a comparable ERP structure for working memory and response inhibition aspects as single task versions. Behaviorally, higher working memory performance during the combined paradigm indicated lower task difficulty, while high correlations between combined and single task versions still indicated valid working memory measures. For response inhibition performance, different task versions resulted in similar outcomes. The application of the combined n-back/nogo paradigm in ADHD patients revealed the expected working memory and response inhibition deficits, increased omission errors, reaction times, and standard deviation of reaction time, as well as diminished n-back P3 and nogo P3 amplitudes. We conclude that the combined n-back/nogo task is an effective paradigm for the economical assessment of working memory and response inhibition deficits in ADHD on a behavioral and neurophysiological level.

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