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Abstract Non-invasive brain stimulation has been suggested as a potential treatment for improving symptomology and cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD), the most common childhood neurodevelopmental disorder. Here, we examined whether a novel form of stimulation, high-frequency transcranial random noise stimulation (tRNS), applied with cognitive training (CT), may impact symptoms and neural oscillations in children with ADHD. We conducted a randomized, double-blind, sham-controlled trial in 23 unmedicated children with ADHD, who received either tRNS over the right inferior frontal gyrus (rIFG) and left dorsolateral prefrontal cortex (lDLPFC) or sham stimulation for 2 weeks, combined with CT. tRNS + CT yielded significant clinical improvements (reduced parent-reported ADHD rating-scale scores) following treatment, compared to the control intervention. These improvements did not change significantly at a 3-week follow-up. Moreover, resting state (RS)-EEG periodic beta bandwidth of the extracted peaks was reduced in the experimental compared to control group immediately following treatment, with further reduction at follow-up. A lower aperiodic exponent, which reflects a higher cortical excitation/inhibition (E/I) balance and has been related to cognitive improvement, was seen in the experimental compared to control group. This replicates previous tRNS findings in adults without ADHD but was significant only when using a directional hypothesis. The experimental group further exhibited longer sleep onset latencies and more wake-up times following treatment compared to the control group. No significant group differences were seen in executive functions, nor in reported adverse events. We conclude that tRNS + CT has a lasting clinical effect on ADHD symptoms and on beta activity. These results provide a preliminary direction towards a novel intervention in pediatric ADHD.

In recent years, there has been debate about the effectiveness of treatments from different fields, such as neurostimulation, neurofeedback, brain training, and pharmacotherapy. This debate has been fuelled by contradictory and nuanced experimental findings. Notably, the effectiveness of a given treatment is commonly evaluated by comparing the effect of the active treatment versus the placebo on human health and/or behaviour. However, this approach neglects the individual’s subjective experience of the type of treatment she or he received in establishing treatment efficacy. Here, we show that individual differences in subjective treatment - the thought of receiving the active or placebo condition during an experiment - can explain variability in outcomes better than the actual treatment. We analysed four independent datasets (N = 387 participants), including clinical patients and healthy adults from different age groups who were exposed to different neurostimulation treatments (transcranial magnetic stimulation: Studies 1 and 2; transcranial direct current stimulation: Studies 3 and 4). Our findings show that the inclusion of subjective treatment can provide a better model fit either alone or in interaction with objective treatment (defined as the condition to which participants are assigned in the experiment). These results demonstrate the significant contribution of subjective experience in explaining the variability of clinical, cognitive, and behavioural outcomes. We advocate for existing and future studies in clinical and non-clinical research to start accounting for participants’ subjective beliefs and their interplay with objective treatment when assessing the efficacy of treatments. This approach will be crucial in providing a more accurate estimation of the treatment effect and its source, allowing the development of effective and reproducible interventions.

Previous research has highlighted the role of the excitation/inhibition (E/I) ratio for typical and atypical development, mental health, cognition, and learning. Other research has highlighted the benefits of high-frequency transcranial random noise stimulation (tRNS)—an excitatory form of neurostimulation—on learning. We examined the E/I as a potential mechanism and studied whether tRNS effect on learning depends on E/I as measured by the aperiodic exponent as its putative marker. In addition to manipulating E/I using tRNS, we also manipulated the level of learning (learning/overlearning) that has been shown to influence E/I. Participants (n = 102) received either sham stimulation or 20-minute tRNS over the dorsolateral prefrontal cortex (DLPFC) during a mathematical learning task. We showed that tRNS increased E/I, as reflected by the aperiodic exponent, and that lower E/I predicted greater benefit from tRNS specifically for the learning task. In contrast to previous magnetic resonance spectroscopy (MRS)-based E/I studies, we found no effect of the level of learning on E/I. A further analysis using a different data set suggest that both measures of E/I (EEG versus MRS) may reflect, at least partly, different biological mechanisms. Our results highlight the role of E/I as a marker for neurostimulation efficacy and learning. This mechanistic understanding provides better opportunities for augmented learning and personalized interventions. Previous work has suggested that the excitation/inhibition ratio (E/I) contributes to typical and atypical development, mental health, cognition and learning. This study reveals that the E/I ratio in the brain plays an important role in neurostimulation efficacy and is a possible marker for learning.

Previous research has highlighted the role of the excitation/inhibition (E/I) ratio for typical and atypical development, mental health, cognition, and learning. Other research has highlighted the benefits of high-frequency transcranial random noise stimulation (tRNS)-an excitatory form of neurostimulation-on learning. We examined the E/I as a potential mechanism and studied whether tRNS effect on learning depends on E/I as measured by the aperiodic exponent as its putative marker. In addition to manipulating E/I using tRNS, we also manipulated the level of learning (learning/overlearning) that has been shown to influence E/I. Participants (n = 102) received either sham stimulation or 20-minute tRNS over the dorsolateral prefrontal cortex (DLPFC) during a mathematical learning task. We showed that tRNS increased E/I, as reflected by the aperiodic exponent, and that lower E/I predicted greater benefit from tRNS specifically for the learning task. In contrast to previous magnetic resonance spectroscopy (MRS)-based E/I studies, we found no effect of the level of learning on E/I. A further analysis using a different data set suggest that both measures of E/I (EEG versus MRS) may reflect, at least partly, different biological mechanisms. Our results highlight the role of E/I as a marker for neurostimulation efficacy and learning. This mechanistic understanding provides better opportunities for augmented learning and personalized interventions.

Previously we found perspective taking (PT) influenced affect ratings of negative pictures more than neutral pictures. The current follow-up experiments extend that research to explore effects of perspective taking with positive valence pictures. We used stimuli consisting of neutral, happy and sad pictures. Stimuli were presented either mixed within blocks (Experiment 1) or separated by emotion (neutrals + happy/sad) into two separate blocks (Experiment 2). Participants rated (from 1‐ to 7 based on emotional strength) stimuli from different perspectives (sensitive/tough/their own, i.e., “me”). Emotional strength rating was a dependent variable. A significant interaction between valence and PT was found in both experiments. The difference between adopting sensitive and tough perspectives toward sadness was larger than toward the neutral condition, replicating our results from the previous study. The same difference (sensitive-tough) was larger toward the happiness condition than toward the neutral one (this was a trend in Experiment 1 and was significant in Experiment 2) and toward the sadness condition than toward the happy one. These results suggest that PT effects on emotional ratings are modulated by valence of stimuli.

Environmental cues can influence basic perceptual and attentional processes especially in an emotional context. In the current study, we aimed to investigate the effect of a non-emotional common environmental cue-a traffic light-on a higher cognitive operation-inhibition. In two experiments, we administered a novel version of the stop-signal task, in which the go task was to determine the color of a traffic light. In order to investigate the influence of each of the cues on inhibitory processes, separate tracking procedures (one for each cue) were applied simultaneously to the stop-signal delay. In Experiment 1, we found that reaction time in no-stop-signal trials was faster when a green traffic light was present, whereas stop-signal reaction time was longer when a red traffic light was present. In Experiment 2, neutral control cues were used in addition to a red and green light. The results indicate that the differences between red and green stem from an association between the color red and stop processes (rather than from the green-go association). These results strengthen previous findings showing the effect of environmental cues on attentional processes and go beyond them by showing that the effect is not restricted to emotional cues. Most importantly, the current study results suggest that environmental cues can also influence complex cognitive operations such as inhibitory control. These results might have specific implications for our understanding of the processes that underlie specific psychiatric disorders characterized by inhibitory deficit.