Functional neuroimaging and behavioral correlates of multisite tDCS as an add-on to language training in a person with post-stroke non-fluent aphasia: a year-long case study.

Mary, who experienced non-fluent aphasia as a result of an ischemic stroke, received 10 years of personalized language training (LT), resulting in transient enhancements in speech and comprehension. To enhance these effects, multisite transcranial Direct Current Stimulation (tDCS) was added to her LT regimen for 15 sessions. Assessment using the Reliable Change Index showed that this combination improved her left inferior frontal connectivity and speech production for two months and significantly improved comprehension after one month. The results indicate that using multisite transcranial direct current stimulation (tDCS) can improve the effectiveness of language therapy (LT) for individuals with non-fluent aphasia.

Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders.

BACKGROUND: Transcranial direct current stimulation has shown promising clinical results, leading to increased demand for an evidence-based review on its clinical effects. OBJECTIVE: We convened a team of transcranial direct current stimulation experts to conduct a systematic review of clinical trials with more than 1 session of stimulation testing: pain, Parkinson's disease motor function and cognition, stroke motor function and language, epilepsy, major depressive disorder, obsessive compulsive disorder, Tourette syndrome, schizophrenia, and drug addiction. METHODS: Experts were asked to conduct this systematic review according to the search methodology from PRISMA guidelines. Recommendations on efficacy were categorized into Levels A (definitely effective), B (probably effective), C (possibly effective), or no recommendation. We assessed risk of bias for all included studies to confirm whether results were driven by potentially biased studies. RESULTS: Although most of the clinical trials have been designed as proof-of-concept trials, some of the indications analyzed in this review can be considered as definitely effective (Level A), such as depression, and probably effective (Level B), such as neuropathic pain, fibromyalgia, migraine, post-operative patient-controlled analgesia and pain, Parkinson's disease (motor and cognition), stroke (motor), epilepsy, schizophrenia, and alcohol addiction. Assessment of bias showed that most of the studies had low risk of biases, and sensitivity analysis for bias did not change these results. Effect sizes vary from 0.01 to 0.70 and were significant in about 8 conditions, with the largest effect size being in postoperative acute pain and smaller in stroke motor recovery (nonsignificant when combined with robotic therapy). CONCLUSION: All recommendations listed here are based on current published PubMed-indexed data. Despite high levels of evidence in some conditions, it must be underscored that effect sizes and duration of effects are often limited; thus, real clinical impact needs to be further determined with different study designs.

Median nerve stimulation induced motor learning in healthy adults: A study of timing of stimulation and type of learning.

Median nerve stimulation (MNS) has been shown to change brain metaplasticity over the somatosensory networks, based on a bottom-up mechanism and may improve motor learning. This exploratory study aimed to test the effects of MNS on implicit and explicit motor learning as measured by the serial reaction time task (SRTT) using a double-blind, sham-controlled, randomized trial, in which participants were allocated to one of three groups: (a) online active MNS during acquisition, (b) offline active MNS during early consolidation and (c) sham MNS. SRTT was performed at baseline, during the training phase (acquisition period), and 30 min after training. We assessed the effects of MNS on explicit and implicit motor learning at the end of the training/acquisition period and at retest. The group receiving online MNS (during acquisition) showed a significantly higher learning index for the explicit sequences compared to the offline group (MNS during early consolidation) and the sham group. The offline group also showed a higher learning index as compared to sham. Additionally, participants receiving online MNS recalled the explicit sentence significantly more than the offline MNS and sham groups. MNS effects on motor learning have a specific effect on type of learning (explicit vs. implicit) and are dependent on timing of stimulation (during acquisition vs. early consolidation). More research is needed to understand and optimize the effects of peripheral electrical stimulation on motor learning. Taken together, our results show that MNS, especially when applied during the acquisition phase, is a promising tool to modulate motor leaning.

Study adherence in a tDCS longitudinal clinical trial with people with spinal cord injury.

STUDY DESIGN: Secondary analysis of a clinical trial. OBJECTIVES: To analyze adherence to 1-year transcranial Direct Current Stimulation (tDCS) clinical trial in people with chronic pain due to spinal cord injury (SCI). We also explore the association between dropout and several baseline variables such as age, depression levels, pain severity, number of days with pain in the last 7 days, walking ability, sleep, work, relationship with others, and enjoyment with life. SETTING: Boston, USA. METHODS: Forty-six participants were enrolled in this trial, and 33 participants were randomized to receive either active or sham tDCS. RESULTS: Using the full intention-to-treat (ITT) criteria, only 8 participants (24%) finished the study. The median time to dropout was seven (IQR:6,19) sessions (i.e., immediately after the first follow-up), regardless of the type of stimulation that participants received (active vs. sham tDCS) (χ2 = 0.025, p = 0.875). An exploratory analysis suggested that only the number of days with pain in the last 7 days was moderately associated with dropout, with people experiencing less pain being more prone to dropout from the study. CONCLUSIONS: Despite all the measures to improve study adherence (such as providing parking, flexibility to schedule sessions, follow-up with participants by phone), it seems that long follow-up periods may increase the likelihood of dropout. Given the need to understand long-term effects of interventions, longitudinal trials need to consider alternative designs or methods of treatment (for instance home treatment or home assessment) to decrease attrition rate.

Neuromodulating Attention and Mind-Wandering Processes with a Single Session Real Time EEG.

Our minds are continuously alternating between external attention (EA) and mind wandering (MW). An appropriate balance between EA and MW is important for promoting efficient perceptual processing, executive functioning, decision-making, auto-biographical memory, and creativity. There is evidence that EA processes are associated with increased activity in high-frequency EEG bands (e.g., SMR), contrasting with the dominance of low-frequency bands during MW (e.g., Theta). The aim of the present study was to test the effects of two distinct single session real-time EEG (rtEEG) protocols (SMR up-training/Theta down-training-SMR⇑Theta⇓; Theta up-training/SMR down-training-Theta⇑SMR⇓) on EA and MW processes. Thirty healthy volunteers were randomly assigned to one of two rtEEG training protocols (SMR⇑Theta⇓; Theta⇑SMR⇓). Before and after the rtEEG training, participants completed the attention network task (ANT) along with several MW measures. Both training protocols were effective in increasing SMR (SMR⇑Theta⇓) and theta (Theta⇑SMR⇓) amplitudes but not in decreasing the amplitude of down-trained bands. There were no significant effects of the rtEEG training in either EA or MW measures. However, there was a significant positive correlation between post-training SMR increases and the use of deliberate MW (rather than spontaneous) strategies. Additionally, for the Theta⇑SMR⇓ protocol, increase in post-training Theta amplitude was significantly associated with a decreased efficiency in the orientation network.

Duration Dependent Effects of Transcranial Pulsed Current Stimulation (tPCS) Indexed by Electroencephalography.

OBJECTIVE: To explore the duration of tPCS after effects given different durations of stimulation on power and interhemispheric coherence of the EEG frequency bands. Our hypothesis was that longer tPCS duration would induce a differential effect on the EEG analysis and a longer duration of after effects on the EEG frequency bands. MATERIALS AND METHODS: We conducted a double blind, sham controlled study in which forty healthy subjects were randomized to receive a single session of either 10, 20, 30 min of active (2 mA, random frequency between 6 and 10 Hz, ear clip montage) or sham tPCS. EEG was recorded before and after the intervention to assess tPCS induced after effects. RESULTS: We found that 10 and 20 min of active tPCS induced a significant increase in alpha (p = 0.004) and theta (p = 0.006) coherence in the frontal region as compared with the sham stimulation. No significant changes were found with 30 min of stimulation (p < 0.05). The Kaplan Meier analysis showed that 10 and 20 min of tPCS induced after effects that lasted 50 min. CONCLUSIONS: These results evidence the nonlinear relationship between the stimulation duration and the tPCS after effects, suggesting the presence of homeostatic mechanisms.

Cognitive effects and autonomic responses to transcranial pulsed current stimulation.

Transcranial pulsed current stimulation (tPCS) is emerging as an option in the field of neuromodulation; however, little is known about its effects on cognition and behavior and its neurophysiological correlates as indexed by autonomic responses. Our aim was to identify the effects of tPCS on arithmetic processing and risk-taking behavior, and to further categorize physiological autonomic responses by heart rate variability (HRV) and electrodermal activity measurements before, during, and after exposure to task performance and stimulation. Thirty healthy volunteers were randomized to receive a single session of sham or active stimulation with a current intensity of 2 mA and a random frequency between 1 and 5 Hz. Our results showed that tPCS has a modest and specific effect on cognitive performance as indexed by the cognitive tasks chosen in this study. There was a modest effect of active tPCS only on performance facilitation on a complex-level mathematical task as compared to sham stimulation. On autonomic responses, we observed that HRV total power increased while LF/HF ratio decreased in the tPCS active group compared to sham. There were no group differences for adverse effects. Based on our results, we conclude that tPCS, in healthy subjects, has a modest and specific cognitive effect as shown by the facilitation of arithmetical processing on complex mathematical task. These effects are accompanied by modulation of the central autonomic network providing sympathetic-vagal balance during stressful conditions. Although behavioral results were modest, they contribute to the understanding of tPCS effects and cognitive enhancement.

Deafness in patients with multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease and is considered the most debilitating neurological disorder among young adults. Sudden deafness has been reported in MS patients. This article describes cases of sudden deafness related to acute bouts in MS patients. A survey was conducted using 405 records of MS patients attended to at a reference center in the city of Rio de Janeiro between 2011 and 2012 to identify cases of sudden deafness. Seven patients were identified, 6 with a relapsing-remitting course and 1 with progressive disease at onset. Five patients had unilateral deafness and 2 bilateral. The recovery was complete in 4 and partial in 1, and there was no recovery in 2 patients. It was not possible to establish a topographical correlation between deafness and brainstem lesions. Audiometric examinations revealed severe hearing loss during the bout and recovery of hearing in 5 cases after remission.

Tailoring transcranial alternating current stimulation based on endogenous event-related P3 to modulate premature responses: a feasibility study.

Background: Transcranial alternating current stimulation (tACS) is a brain stimulation method for modulating ongoing endogenous oscillatory activity at specified frequency during sensory and cognitive processes. Given the overlap between event-related potentials (ERPs) and event-related oscillations (EROs), ERPs can be studied as putative biomarkers of the effects of tACS in the brain during cognitive/sensory task performance. Objective: This preliminary study aimed to test the feasibility of individually tailored tACS based on individual P3 (latency and frequency) elicited during a cued premature response task. Thus, tACS frequency was individually tailored to match target-P3 ERO for each participant. Likewise, the target onset in the task was adjusted to match the tACS phase and target-P3 latency. Methods: Twelve healthy volunteers underwent tACS in two separate sessions while performing a premature response task. Target-P3 latency and ERO were calculated in a baseline block during the first session to allow a posterior synchronization between the tACS and the endogenous oscillatory activity. The cue and target-P3 amplitudes, delta/theta ERO, and power spectral density (PSD) were evaluated pre and post-tACS blocks. Results: Target-P3 amplitude significantly increased after activetACS, when compared to sham. Evoked-delta during cue-P3 was decreased after tACS. No effects were found for delta ERO during target-P3 nor for the PSD and behavioral outcomes. Conclusion: The present findings highlight the possible effect of phase synchronization between individualized tACS parameters and endogenous oscillatory activity, which may result in an enhancement of the underlying process (i.e., an increase of target-P3). However, an unsuccessful synchronization between tACS and EEG activity might also result in a decrease in the evoked-delta activity during cue-P3. Further studies are needed to optimize the parameters of endogenous activity and tACS synchronization. The implications of the current results for future studies, including clinical studies, are further discussed since transcranial alternating current stimulation can be individually tailored based on endogenous event-related P3 to modulate responses.

Transcranial Direct Current Stimulation Decreases P3 Amplitude and Inherent Delta Activity during a Waiting Impulsivity Paradigm: Crossover Study.

The inability to wait for a target before initiating an action (i.e., waiting impulsivity) is one of the main features of addictive behaviors. Current interventions for addiction, such as transcranial Direct Current Stimulation (tDCS), have been suggested to improve this inability. Nonetheless, the effects of tDCS on waiting impulsivity and underlying electrophysiological (EEG) markers are still not clear. Therefore, this study aimed to evaluate the effects of neuromodulation over the right inferior frontal gyrus (rIFG) on the behavior and EEG markers of reward anticipation (i.e., cue and target-P3 and underlying delta/theta power) during a premature responding task. For that, forty healthy subjects participated in two experimental sessions, where they received active and sham tDCS over the rIFG combined with EEG recording during the task. To evaluate transfer effects, participants also performed two control tasks to assess delay discounting and motor inhibition. The active tDCS decreased the cue-P3 and target-P3 amplitudes, as well as delta power during target-P3. While no tDCS effects were found for motor inhibition, active tDCS increased the discounting of future rewards when compared to sham. These findings suggest a tDCS-induced modulation of the P3 component and underlying oscillatory activity during waiting impulsivity and the discounting of future rewards.

Efficacy and safety of repetitive Transcranial Magnetic Stimulation and transcranial Direct Current Stimulation in memory deficits in patients with Alzheimer's disease: Meta-analysis and systematic review.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are two of the most used non-pharmacological interventions for Alzheimer's Disease (AD). However, most of the clinical trials have focused on evaluating the effects on global cognition and not on specific cognitive functions. Therefore, considering that memory loss is one of the hallmark symptoms of AD, we aim to assess the efficacy and safety of tDCS and rTMS in memory deficits. For that, multilevel random effect models were performed considering the standardized mean difference (SMD) between active and sham stimulation. A total of 19 studies with 411 participants demonstrated positive effects in memory after tDCS (SMD=0.20, p = 0.04) and rTMS (SMD=0.44, p = 0.001). Subgroup analysis revealed that tDCS had greater efficacy when administered in temporal regions (SMD=0.32, p = 0.04), whereas rTMS was superior when applied in frontal regions (SMD=0.61, p < 0.001). Therefore, depending on the brain region of stimulation, both interventions produced a positive effect on memory symptoms in AD patients. Finally, the safety of both techniques was observed in the AD population after the reporting of almost no serious events.

Correction: The psychological impact of the COVID-19 pandemic in Portugal: The role of personality traits and emotion regulation strategies.

[This corrects the article DOI: 10.1371/journal.pone.0269496.].

Non-pharmacological treatment-related changes of molecular biomarkers in major depressive disorder: A systematic review and meta-analysis.

Background: Major depressive disorder (MDD) is a serious mood disorder and leading cause of disability. Despite treatment advances, approximately 30% of individuals with MDD do not achieve adequate clinical response. Better understanding the biological mechanism(s) underlying clinical response to specific psychopharmacological interventions may help fine tune treatments in order to further modulate their underlying mechanisms of action. However, little is known regarding the effect of non-pharmacological treatments (NPTs) on candidate molecular biomarker levels in MDD. This review aims to identify molecular biomarkers that may elucidate NPT response for MDD. Methods: We performed a systematic review and a multilevel linear mixed-effects meta-analyses, and a meta-regression. Searches were performed in PubMed, Scopus, and PsycINFO in October 2020 and July 2021. Results: From 1387 retrieved articles, 17 and six studies were included in the systematic review and meta-analyses, respectively. Although there was little consensus associating molecular biomarker levels with symptomology and/or treatment response, brain metabolites accessed via molecular biomarker-focused neuroimaging techniques may provide promising information on whether an individual with MDD would respond positively to NPTs. Furthermore, non-invasive brain stimulation interventions significantly increased the expression of neurotrophic factors (NTFs) compared to sham/placebo, regardless of add-on pharmacological treatment. Conclusions: NTFs are candidate biomarkers to fine-tune NIBS for MDD treatment.

The Emotional Movie Database (EMDB): a self-report and psychophysiological study.

Film clips are an important tool for evoking emotional responses in the laboratory. When compared with other emotionally potent visual stimuli (e.g., pictures), film clips seem to be more effective in eliciting emotions for longer periods of time at both the subjective and physiological levels. The main objective of the present study was to develop a new database of affective film clips without auditory content, based on a dimensional approach to emotional stimuli (valence, arousal and dominance). The study had three different phases: (1) the pre-selection and editing of 52 film clips (2) the self-report rating of these film clips by a sample of 113 participants and (3) psychophysiological assessment [skin conductance level (SCL) and the heart rate (HR)] on 32 volunteers. Film clips from different categories were selected to elicit emotional states from different quadrants of affective space. The results also showed that sustained exposure to the affective film clips resulted in a pattern of a SCL increase and HR deceleration in high arousal conditions (i.e., horror and erotic conditions). The resulting emotional movie database can reliably be used in research requiring the presentation of non-auditory film clips with different ratings of valence, arousal and dominance.

Speed of Processing (SoP) Training Plus α-tACS in People With Mild Cognitive Impairment: A Double Blind, Parallel, Placebo Controlled Trial Study Protocol.

Several cognitive training programs, alone or in combination with non-invasive brain stimulation have been tested in order to ameliorate age-related cognitive impairments, such as the ones found in Mild Cognitive Impairment (MCI). However, the effects of Cognitive Training (CT)-combined or not-with several forms of non-invasive brain stimulation have been modest at most. We aim to assess if Speed of Processing (SoP) training combined with alpha transcranial alternating current stimulation (α-tACS) is able to increase speed of processing as assessed by the Useful Field of View (UFOV), when comparing to SoP training or active α-tACS alone. Moreover, we want to assess if those changes in speed of processing transfer to other cognitive domains, such as memory, language and executive functioning by using the NIH EXAMINER. We also want to test the mechanisms underlying these interventions, namely brain connectivity and coherence as assessed by electroencephalography (EEG). To that purpose, our proposal is to enroll 327 elders diagnosed with MCI in a double-blinded, parallel randomized clinical trial assessing the effects of combining SoP with alpha endogenous tACS (either active or sham) in people with MCI. Participants will perform an intervention that will last for 15 sessions. For the first 3 weeks, participants will receive nine sessions of the intervention, and then will receive two sessions per week (i.e., booster) for the following 3 weeks. They will then be assessed at 1, 3, and 6 months after the intervention has ended. This will allow us to detect the immediate, and long-term effects of the interventions, as well as to probe the mechanisms underlying its effects. Clinical Trial Registration: Clinicaltrials.gov, Identifier: NCT05198726.

The Acute Impact of the Early Stages of COVID-19 Pandemic in People with Pre-Existing Psychiatric Disorders: A Systematic Review.

People with pre-pandemic health conditions are more vulnerable and more likely to suffer greater psychosocial impact due to the current COVID-19 pandemic and the lockdown measures. Thus, the objective of this work was to systematically review the impact of the early stages COVID-19 pandemic on people with pre-existing psychiatric disorders. The search was performed between 23 January and 2 September 2021 in PubMed, PsycINFO, and EMBASE. A total of 4167 published results were identified; however, only 49 were included in this review. Results show that there was considerable heterogeneity among studies, which resulted in a low consensus. However, it seems that the impact of the first stage of the COVID-19 pandemic on psychiatric disorders was two-fold: (1) an overall effect, in which people suffering from psychiatric disorders in general experienced more psychological distress and anxiety when compared to people who had no psychiatric diagnosis, and (2) a condition-specific effect, namely in people suffering from eating disorders and obsessive compulsive disorders. Moreover, the current work highlights that there were also some external factors that were related to worsening symptoms. For instance, unemployment or experiencing work and financial difficulties can be a trigger for greater distress during the pandemic for people with mood disorders, and being alone and in social isolation during the COVID-19 pandemic may actually increase substance use and relapse rates. Further studies are needed to prospectively investigate the long-term effects of the current COVID-19 pandemic on people with (pre)-existing psychiatric conditions and on the onset or deterioration of psychiatric-related symptoms in a larger number of participants, as well as exploring the long-term effects of the current pandemic on mental health.

The psychological impact of the COVID-19 pandemic in Portugal: The role of personality traits and emotion regulation strategies.

Recent evidence suggests that both personality traits (PT) and emotion regulation (ER) strategies play an important role in the way people cope with the COVID-19 pandemic. The aim of this study was two folded. First, to longitudinally investigate the psychological distress (depression, anxiety, and stress levels) taking in consideration PT and ER strategies in 3 different moments: during the first lockdown period (April/20), at the first deconfinement (May/20) and 1-month after the first deconfinement (Jun/20)-Experiment I. Second, to cross-sectionally evaluate the impact of the pandemic in psychological distress and the correlates with PT and ER 6-months after the first deconfinement November/20 to February/21 -Experiment II. A total of 722 volunteers (Experiment I = 180; Experiment II = 542) aged 18 years or older participated in this online survey. The findings from Experiment I show that psychological distress decreased after the lockdown period, however, neuroticism traits predicted higher levels of depression, anxiety and stress symptoms, while difficulties in ER strategies were identified as a risk factor for depression and stress. For experiment II, neuroticism traits and being infected with COVID-19 were associated to higher levels of symptomatology, while unemployment and the use of emotional suppression strategies to cope with emotional situations were associated to depressive and anxiety symptoms. Although the psychological impact of the COVID-19 outbreak decreased over time in our sample, the current findings suggest that difficulties in emotional regulation and high levels of neuroticism traits might be potential risk factors for psychiatric symptomatology during the COVID-19 pandemic. Thus, people with difficulties in ER and neuroticism traits would benefit from psychological interventions that provide personality-appropriate support and promote emotion regulation skills during stressful events, such as the case of the global pandemic.

Working Memory Training Coupled With Transcranial Direct Current Stimulation in Older Adults: A Randomized Controlled Experiment.

Background: Transcranial direct current stimulation (tDCS) has been employed to boost working memory training (WMT) effects. Nevertheless, there is limited evidence on the efficacy of this combination in older adults. The present study is aimed to assess the delayed transfer effects of tDCS coupled with WMT in older adults in a 15-day follow-up. We explored if general cognitive ability, age, and educational level predicted the effects. Methods: In this single-center, double-blind randomized sham-controlled experiment, 54 older adults were randomized into three groups: anodal-tDCS (atDCS)+WMT, sham-tDCS (stDCS)+WMT, and double-sham. Five sessions of tDCS (2 mA) were applied over the left dorsolateral prefrontal cortex (DLPFC). Far transfer was measured by Raven's Advanced Progressive Matrices (RAPM), while the near transfer effects were assessed through Digit Span. A frequentist linear mixed model (LMM) was complemented by a Bayesian approach in data analysis. Results: Working memory training improved dual n-back performance in both groups submitted to this intervention but only the group that received atDCS+WMT displayed a significant improvement from pretest to follow-up in transfer measures of reasoning (RAPM) and short-term memory (forward Digit Span). Near transfer improvements predicted gains in far transfer, demonstrating that the far transfer is due to an improvement in the trained construct of working memory. Age, formal education, and vocabulary score seem to predict the gains in reasoning. However, Bayesian results do not provide substantial evidence to support this claim. Conclusion: This study will help to consolidate the incipient but auspicious field of cognitive training coupled with tDCS in healthy older adults. Our findings demonstrated that atDCS may potentialize WMT by promoting transfer effects in short-term memory and reasoning in older adults, which are observed especially at follow-up.

Modulation of the cognitive event-related potential P3 by transcranial direct current stimulation: Systematic review and meta-analysis.

Transcranial direct current stimulation (tDCS) has been widely used to modulate cognition and behavior. However, only a few studies have been probing the brain mechanism underlying the effects of tDCS on cognitive processing, especially throughout electrophysiological markers, such as the P3. This meta-analysis assessed the effects of tDCS in P3 amplitude and latency during an oddball, n-back, and Go/No-Go tasks, as well as during emotional processing. A total of 36 studies were identified, but only 23 were included in the quantitative analysis. The results show that the parietal P3 amplitude increased during oddball and n-back tasks, mostly after anodal stimulation over the left dorsolateral prefrontal cortex (p = 0.018, SMD = 0.4) and right inferior frontal gyrus (p < 0.001, SMD = 0.669) respectively. These findings suggest the potential usefulness of the parietal P3 ERP as a marker of tDCS-induced effects during task performance. Nonetheless, this study had a low number of studies and the presence of considerable risk of bias, highlighting issues to be addressed in the future.

Digitalized transcranial electrical stimulation: A consensus statement.

OBJECTIVE: Although relatively costly and non-scalable, non-invasive neuromodulation interventions are treatment alternatives for neuropsychiatric disorders. The recent developments of highly-deployable transcranial electric stimulation (tES) systems, combined with mobile-Health technologies, could be incorporated in digital trials to overcome methodological barriers and increase equity of access. The study aims are to discuss the implementation of tES digital trials by performing a systematic scoping review and strategic process mapping, evaluate methodological aspects of tES digital trial designs, and provide Delphi-based recommendations for implementing digital trials using tES. METHODS: We convened 61 highly-productive specialists and contacted 8 tES companies to assess 71 issues related to tES digitalization readiness, and processes, barriers, advantages, and opportunities for implementing tES digital trials. Delphi-based recommendations (>60% agreement) were provided. RESULTS: The main strengths/opportunities of tES were: (i) non-pharmacological nature (92% of agreement), safety of these techniques (80%), affordability (88%), and potential scalability (78%). As for weaknesses/threats, we listed insufficient supervision (76%) and unclear regulatory status (69%). Many issues related to methodological biases did not reach consensus. Device appraisal showed moderate digitalization readiness, with high safety and potential for trial implementation, but low connectivity. CONCLUSIONS: Panelists recognized the potential of tES for scalability, generalizability, and leverage of digital trials processes; with no consensus about aspects regarding methodological biases. SIGNIFICANCE: We further propose and discuss a conceptual framework for exploiting shared aspects between mobile-Health tES technologies with digital trials methodology to drive future efforts for digitizing tES trials.