Neuroanatomical predictors of transcranial direct current stimulation (tDCS)-induced modifications in neurocognitive task performance in typically developing individuals.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typical developing (TD) individuals that may be used for the prediction of individual responses to tDCS. 57 TD male and female children received 2mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporo-parietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, Flanker, Mooney Faces Detection, Attentional Emotional Recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3-Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using a general linear model. Machine learning (ML) algorithms were employed to predict responses to tDCS. Overall, vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioural variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioural measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.Significance statement Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that has recently gained more attention in neurodevelopmental disorders (NDDs), such as autism and attention-deficit/hyperactivity disorder. However, due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical biomarkers in typical developing individuals that may be used for the prediction of individual responses to tDCS. Our findings suggest that it may be possible to accurately predict individual responses to tDCS for some behavioural measures using measures of neuroanatomy. In the future, our models might be extended to predict treatment outcome in individuals with clinical diagnoses, and may allow for more individualized, person-centred interventions.

Stratification of responses to tDCS intervention in a healthy pediatric population based on resting-state EEG profiles.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique with a wide variety of clinical and research applications. As increasingly acknowledged, its effectiveness is subject dependent, which may lead to time consuming and cost ineffective treatment development phases. We propose the combination of electroencephalography (EEG) and unsupervised learning for the stratification and prediction of individual responses to tDCS. A randomized, sham-controlled, double-blind crossover study design was conducted within a clinical trial for the development of pediatric treatments based on tDCS. The tDCS stimulation (sham and active) was applied either in the left dorsolateral prefrontal cortex or in the right inferior frontal gyrus. Following the stimulation session, participants performed 3 cognitive tasks to assess the response to the intervention: the Flanker Task, N-Back Task and Continuous Performance Test (CPT). We used data from 56 healthy children and adolescents to implement an unsupervised clustering approach that stratify participants based on their resting-state EEG spectral features before the tDCS intervention. We then applied a correlational analysis to characterize the clusters of EEG profiles in terms of participant's difference in the behavioral outcome (accuracy and response time) of the cognitive tasks when performed after a tDCS-sham or a tDCS-active session. Better behavioral performance following the active tDCS session compared to the sham tDCS session is considered a positive intervention response, whilst the reverse is considered a negative one. Optimal results in terms of validity measures was obtained for 4 clusters. These results show that specific EEG-based digital phenotypes can be associated to particular responses. While one cluster presents neurotypical EEG activity, the remaining clusters present non-typical EEG characteristics, which seem to be associated with a positive response. Findings suggest that unsupervised machine learning can be successfully used to stratify and eventually predict responses of individuals to a tDCS treatment.

No effects of prefrontal multichannel tACS at individual alpha frequency on phonological decisions.

OBJECTIVE: Alpha oscillations are linked to inhibitory capabilities in higher cognitive processing. Transcranial alternating current stimulation (tACS) at 10 Hz can enhance alpha oscillations and modulate behaviour. One possibility to increase the efficacy of tACS may be stimulating at the individual alpha frequency (IAF). The present work addresses this issue (among others) to increase the current understanding of the functional role of alpha oscillations in higher cognitive tasks. METHODS: Twenty-two healthy and 13 dyslexic participants performed two word decision tasks while receiving IAF-tACS over the left prefrontal cortex. Resting EEG was recorded to detect electrophysiological changes. Cortical excitability was assessed with TMS. RESULTS: Dyslexic participants performed worse in the phonological task. However, no significant tACS effects were found. Interestingly, higher cortical excitability was correlated with faster responses in healthy controls. In dyslexics this association significantly differed in the phonological task. CONCLUSION: The non-significant modulation by tACS might be explained by methodological limitations. Alternatively, it may indicate that alpha oscillations do not play a functional role in phonological decisions. The findings on cortical excitability expands the existing literature and may reflect the specific phonological deficit in dyslexics. SIGNIFICANCE: Our critical discussion of these null findings expands the systematic knowledge on alpha-tACS for future studies.

Multichannel anodal tDCS over the left dorsolateral prefrontal cortex in a paediatric population.

Methodological studies investigating transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) in paediatric populations are limited. Therefore, we investigated in a paediatric population whether stimulation success of multichannel tDCS over the lDLPFC depends on concurrent task performance and individual head anatomy. In a randomised, sham-controlled, double-blind crossover study 22 healthy participants (10-17 years) received 2 mA multichannel anodal tDCS (atDCS) over the lDLPFC with and without a 2-back working memory (WM) task. After stimulation, the 2-back task and a Flanker task were performed. Resting state and task-related EEG were recorded. In 16 participants we calculated the individual electric field (E-field) distribution. Performance and neurophysiological activity in the 2-back task were not affected by atDCS. atDCS reduced reaction times in the Flanker task, independent of whether atDCS had been combined with the 2-back task. Flanker task related beta oscillation increased following stimulation without 2-back task performance. atDCS effects were not correlated with the E-field. We found no effect of multichannel atDCS over the lDLPFC on WM in children/adolescents but a transfer effect on interference control. While this effect on behaviour was independent of concurrent task performance, neurophysiological activity might be more sensitive to cognitive activation during stimulation. However, our results are limited by the small sample size, the lack of an active control group and variations in WM performance.

Individual Baseline Performance and Electrode Montage Impact on the Effects of Anodal tDCS Over the Left Dorsolateral Prefrontal Cortex.

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.

The Effects of 1 mA tACS and tRNS on Children/Adolescents and Adults: Investigating Age and Sensitivity to Sham Stimulation.

The aim of this study was to investigate the effect of transcranial random noise (tRNS) and transcranial alternating current (tACS) stimulation on motor cortex excitability in healthy children and adolescents. Additionally, based on our recent results on the individual response to sham in adults, we explored this effect in the pediatric population. We included 15 children and adolescents (10-16 years) and 28 adults (20-30 years). Participants were stimulated four times with 20 Hz and 140 Hz tACS, tRNS, and sham stimulation (1 mA) for 10 minutes over the left M1HAND. Single-pulse MEPs (motor evoked potential), short-interval intracortical inhibition, and facilitation were measured by TMS before and after stimulation (baseline, 0, 30, 60 minutes). We also investigated aspects of tolerability. According to the individual MEPs response immediately after sham stimulation compared to baseline (Wilcoxon signed-rank test), subjects were regarded as responders or nonresponders to sham. We did not find a significant age effect. Regardless of age, 140 Hz tACS led to increased excitability. Incidence and intensity of side effects did not differ between age groups or type of stimulation. Analyses on responders and nonresponders to sham stimulation showed effects of 140 Hz, 20 Hz tACS, and tRNS on single-pulse MEPs only for nonresponders. In this study, children and adolescents responded to 1 mA tRNS and tACS comparably to adults regarding the modulation of motor cortex excitability. This study contributes to the findings that noninvasive brain stimulation is well tolerated in children and adolescents including tACS, which has not been studied before. Finally, our study supports a modulating role of sensitivity to sham stimulation on responsiveness to a broader stimulation and age range.