Comparable Efficacy of Repeated Transcranial Direct Current Stimulation, Cognitive Behavioral Therapy, and Their Combination in Improvement of Cold and Hot Cognitive Functions and Amelioration of Depressive Symptoms.

ABSTRACT: This study aimed to evaluate the effectiveness of repeated transcranial direct current stimulation (rtDCS), cognitive behavioral therapy (CBT), and their combination (rtDCS-CBT) in the treatment of cognitive dysfunction, social cognition, and depressive symptoms in women diagnosed with major depressive disorder (MDD). A total of 40 female participants with MDD were randomly assigned to one of four groups: rtDCS, CBT, rtDCS-CBT, and a control group. The participants' depressive symptoms, executive functions, and social cognition were assessed at baseline, preintervention, postintervention, and during a 1-month follow-up. The rtDCS group received 10 sessions of anodal dorsolateral and cathodal ventromedial prefrontal cortex (2 mA for 20 minutes). The CBT group received 10 sessions of traditional CBT, whereas the combined group received CBT after the tDCS sessions. The results of the analysis of variance indicated that all intervention groups demonstrated significant improvements in depressive symptoms, cognitive dysfunction, and social cognition compared with the control group (all p < 0.001). Furthermore, the rtDCS-CBT group exhibited significantly greater reductions in depressive symptoms when compared with each intervention alone (all p < 0.001). Notably, working memory improvements were observed only in the rtDCS group ( p < 0.001). In conclusion, this study suggests that both CBT and tDCS, either individually or in combination, have a positive therapeutic impact on enhancing executive functions, theory of mind, and depressive symptoms in women with MDD.

NMDA receptor-related mechanisms of dopaminergic modulation of tDCS-induced neuroplasticity.

Dopamine is a key neuromodulator of neuroplasticity and an important neuronal substrate of learning, and memory formation, which critically involves glutamatergic N-methyl-D-aspartate (NMDA) receptors. Dopamine modulates NMDA receptor activity via dopamine D1 and D2 receptor subtypes. It is hypothesized that dopamine focuses on long-term potentiation (LTP)-like plasticity, i.e. reduces diffuse widespread but enhances locally restricted plasticity via a D2 receptor-dependent NMDA receptor activity reduction. Here, we explored NMDA receptor-dependent mechanisms underlying dopaminergic modulation of LTP-like plasticity induced by transcranial direct current stimulation (tDCS). Eleven healthy, right-handed volunteers received anodal tDCS (1 mA, 13 min) over the left motor cortex combined with dopaminergic agents (the D2 receptor agonist bromocriptine, levodopa for general dopamine enhancement, or placebo) and the partial NMDA receptor agonist D-cycloserine (dosages of 50, 100, and 200 mg, or placebo). Cortical excitability was monitored by transcranial magnetic stimulation-induced motor-evoked potentials. We found that LTP-like plasticity was abolished or converted into LTD-like plasticity via dopaminergic activation, but reestablished under medium-dose D-cycloserine. These results suggest that diffuse LTP-like plasticity is counteracted upon via D2 receptor-dependent reduction of NMDA receptor activity.

Consolidation of motor sequence learning eliminates susceptibility of SMAproper to TMS: a combined rTMS and cTBS study.

Earlier research suggested that after 210 practice trials, the supplementary motor area (SMA) is involved in executing all responses of familiar 6-key sequences in a discrete sequence production (DSP) task (Verwey, Lammens, and van Honk, 2002). This was indicated by slowing of each response 20 and 25 min after the SMA had been stimulated for 20 min using repetitive transcranial magnetic stimulation (rTMS). The present study used a similar approach to assess the effects of TMS to the more posterior SMAproper at the end of practice and also 24 h later. As expected stimulation of SMAproper with 20 min of 1 Hz rTMS and 40 s of continuous theta burst stimulation (cTBS) immediately after practice slowed sequence execution relative to a sham TMS condition, but stimulation on the day following practice did not cause slowing. This indicates that offline consolidation makes learning robust against stimulation of SMAproper. Execution of all responses in the sequence was disrupted 0, 20, and 40 min after rTMS, but after cTBS, this occurred only after 40 min. The results suggest that it is implicit sequence knowledge that is processed by the SMAproper and that consolidates.

Combined Yoga and Transcranial Direct Current Stimulation Increase Functional Connectivity and Synchronization in the Frontal Areas.

Transcranial direct current stimulation (tDCS) is a non-invasive neuro-stimulation technique that can modulate cortical excitability. Similarly, yoga is shown to affect the brain's neural activity and networks. Here, we aimed to investigate the effect of combined yoga and tDCS on brain oscillations and networks using resting-state electroencephalography recordings. In a randomized, cross-over, double-blind design, twenty-two healthy subjects participated in a yoga/active tDCS session (2 mA; 20 min; anode-F3, cathode F4) or yoga/sham tDCS on 2 separate days. Resting-state EEG data were collected before and after each intervention. Power spectral density (PSD) and functional connectivity, measured by a synchronization measure, phase-locking value, were computed for each condition. There were no significant differences in PSD values among the two interventions. The network-based statistic method was employed for detecting functional connectivity differences between yoga/active and yoga/sham tDCS interventions. Results show that the addition of active tDCS to yoga is associated with increased functional connectivity of the scalp and source EEG data in the frontal area. The changes were widespread, intra-hemispheric, and inter-hemispheric connections, which were mainly between the frontal area to other regions. At the source level, most of the connectivity changes were found in the fronto-parietal network. These findings suggest that combining yoga with tDCS might lead to brain network changes related to the executive and attentional functions.

Nutrient intake, dietary patterns, and anthropometric variables of children with ADHD in comparison to healthy controls: a case-control study.

BACKGROUND: Poor health behaviors and variables are recently more documented in attention-deficit hyperactivity disorder (ADHD) lifestyle which might be relevant to the pathophysiology of this disorder. The objective of this case-control study was to assess the nutrient intake, dietary patterns, and anthropometric variables in children with ADHD compared to normal peers. METHOD: One hundred children diagnosed with ADHD were included and compared to 100 healthy, sex-matched normal children as the control group. Anthropometric indices, macronutrients, and micronutrients were measured and compared in both groups. RESULTS: ADHD children were significantly consuming more simple sugars, tea, ready-made meals but less protein, vitamin B1, vitamin B2, vitamin C, zinc and calcium compared to the control group. The body mass index (BMI) and waist circumference of children with ADHD were significantly higher and were related to the severity and type of the disease. CONCLUSION: Unhealthy eating behavior is more frequent in children with ADHD, compared to normal children which might warrant lifestyle intervention in this disorder.

Effect of combined yoga and transcranial direct current stimulation intervention on working memory and mindfulness.

Transcranial direct stimulation, a non-invasive neurostimulation technique for modulating cortical excitability, and yoga have both respectively been shown to positively affect cognition. While preliminary research has shown that combined transcranial direct stimulation and meditation may have synergistic effects on mood and cognition, this was the first study to explore the combination of transcranial direct stimulation and yoga. Twenty-two healthy volunteers with a regular yoga practice were randomized to receive either active transcranial direct stimulation (anodal left, cathodal right dorsolateral prefrontal cortex) followed by yoga intervention or sham transcranial direct stimulation followed by yoga intervention a double-blind, cross-over design over two separate intervention days. Outcome measures included working memory performance, measured with the n-back task and mindfulness state, measured with the Toronto Mindfulness Scale, and were conducted offline, with pre-post assessments. Twenty participants completed both days of the intervention. Active transcranial direct stimulation did not have a significant effect on working memory or levels of mindfulness. There was a significant placebo effect, with better performance on day 1 of the intervention, irrespective of whether participants received active or sham transcranial direct stimulation. There was no significant difference between active versus sham transcranial direct stimulation concerning working memory performance and mindfulness, which may be accounted by the small sample size, the transient nature of the intervention, the fact that yoga and transcranial direct stimulation concerning were not conducted simultaneously, and the specific site of stimulation.

ADHD subtype-specific cognitive correlates and association with self-esteem: a quantitative difference.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a major neurodevelopmental disorder with heterogeneous symptoms, subtypes, and cognitive deficits. Cognitive deficits are central to ADHD pathophysiology and one potential source of heterogeneity in ADHD. Subtype-specific cognitive correlates are not, however, well-studied. We explored cognitive correlates of ADHD subtypes based on the Wechsler Intelligence Scale for Children (WISC-IV) scores. We also assessed subtype-specific self-esteem rating in ADHD subtypes and explored its association with cognitive correlates. METHODS: One hundred thirty-nine children with ADHD (80.6% boy, 19.4% girl) were categorized into the predominantly "hyperactive (ADHD-H)", "inattentive (ADHD-I)" and "combined (ADHD-C)" subtype based on their symptoms and scores on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) and Conners Parent-Rating Scale (CPRS-RS). They were then individually administrated the WISC-IV and completed a self-esteem inventory. Group differences in the WISC-IV indices and their predictability in discriminating ADHD subtypes were analyzed. RESULTS: We found a quantitative differentiation of cognitive abilities among ADHD subtypes with "working memory" as the most compromised cognitive domain. ADHD-I had the poorest cognitive profile while ADHD-H scored highest in all cognitive domains. Importantly, cognitive abilities were negatively correlated with inattention and positively correlated with hyperactive symptoms. Moreover, self-esteem ratings were positively correlated with the cognitive domains and were rated differently based on the subtypes. ADHD-H, with the highest cognitive strength, reported the highest level of self-esteem among all subtypes. CONCLUSIONS: ADHD subtype-specific symptoms, cognitive deficits, and self-esteem problems should be considered for precise diagnosis and effective and personalized treatment in ADHD in light of further supporting evidence and assessments. Cognitive interventions might be more compatible with and effective in inattentive and combined subtypes of ADHD. Working memory improving-based interventions can benefit all ADHD subtypes. A supportive educational system in school and providing adjunct supportive interventions should be considered for children with ADHD as well.

Efficacy and clinical predictors of response to rTMS treatment in pharmacoresistant obsessive-compulsive disorder (OCD): a retrospective study.

BACKGROUND: Application of repetitive transcranial magnetic stimulation (rTMS) for treating obsessive-compulsive disorder (OCD) has been promising and approved by the Food and Drug Administration in 2018, but effects differ between patients. Knowledge about clinical predictors of rTMS response may help to increase clinical efficacy but is not available so far. METHODS: In a retrospective study, we investigated the efficacy of rTMS over the dorsolateral prefrontal cortex (DLPFC) or supplementary motor area (SMA) in 65 pharmaco-resistant OCD outpatients recruited for rTMS treatment from July 2015 to May 2017. Patients received either SMA rTMS (n = 38) or bilateral DLPFC rTMS (n = 27) in case of reporting higher affective and depressive symptoms in addition to the primary OCD symptoms. OCD symptoms and depression/anxiety states were measured at baseline (before the 1st session) and after the 20th session of rTMS. Additionally, we performed a binary logistic regression analysis on the demographic and clinical variables based on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) 3-factor and 2-factor models and individual items to investigate potential predictors of rTMS response. RESULTS: Patients' scores in Y-BOCS and Beck anxiety/depression inventories were significantly decreased following rTMS treatment. 46.2% of all patients responded to rTMS, based on the criterion of at least a 30% reduction in Y-BOCS scores. There was no significant difference between response rates of patients in DLPFC and SMA groups. No significant demographic predictors of rTMS efficacy were identified. The factors "obsession severity", "resistance" and "disturbance" and the "interference due to obsessions" and "resistance against compulsions" items of the Y-BOCS significantly predicted response to rTMS. CONCLUSIONS: In patients with less intrusive/interfering thoughts, and low scores in the "obsession severity", "disturbance", and "resistance" factors, rTMS might have superior effects. Identifying clinical and non-clinical predictors of response is relevant to personalize and adapt rTMS protocols in pharmaco-resistant OCD patients. Interpretation of rTMS efficacy should be done with caution due to the lack of a sham intervention condition.

Sleep-deprivation and autobiographical memory: evidence from sleep-deprived nurses.

Negative effects of sleep deprivation on different types of memory are well documented, but the specific effects on autobiographical memory performance are not well studied. In this study, we investigated performance on the autobiographical memory test in a group of sleep-deprived and well-rested nurses. One-hundred participants divided into sleep-deprived (N = 50, 25 females) and well-rested (N = 50, 25 females) groups took part in the study. The sleep-deprived group included night-shift nurses with 8-12 hr sleep deprivation, while the well-rested group had the usual night sleep before performance assessment. All participants were matched for gender, age, education and employment status. They completed depression and anxiety inventories, and underwent the autobiographical memory test, which included 18 cue words with positive, negative and neutral valence. The sleep-deprived group scored significantly higher in depression scores. Analysis of covariance (ANCOVA) results showed that sleep-deprived participants had a significantly poorer autobiographical memory compared with the well-rested group. Additionally, specific memories were significantly declined in the sleep-deprived group. This group remembered significantly less positive and more negative memories. Findings implicate that sleep deprivation has detrimental effects on autobiographical memory specificity and valence, and is associated with mood dysregulation.

Impaired working memory updating affects memory for emotional and non-emotional materials the same way: evidence from post-traumatic stress disorder (PTSD).

Due to the limited capacity of working memory (WM), efficient suppression of no longer relevant memory contents (inhibition) and revising the current contents of the memory (updating) are crucial factors in memorizing. However, not every individual is able to do so; among them are post-traumatic stress disorder (PTSD) patients who seem to have trouble forgetting trauma-related materials, making their memory overloaded with irrelevant information. The present study assumes that the inability to forget in PTSD patients is due to the impaired updating function of WM and, therefore, suggests that these individuals have inferior WM function for both emotional and unemotional materials. A sample of 30 male veterans with PTSD and 30 healthy individuals (mean age = 46.62, SD = 5.23) participated in the study completing PTSD Checklist, Digit Span Task, and a computerized n-back task. Results revealed that although PTSD subjects showed a generally inferior WM compared with normal individuals; however, their WM performance for emotional and non-emotional stimuli was not significantly different. Supporting the main hypothesis of the study, the findings suggest that a dysfunctional updating function of WM underlies both forgetting and memorizing which affects memory for both emotional and non-emotional material similarly.

Safety of noninvasive brain stimulation in children.

PURPOSE OF REVIEW: Noninvasive brain stimulation (NIBS) is a promising method for altering cortical excitability with clinical implications. It has been increasingly used in children, especially in neurodevelopmental disorders. Yet, its safety and applications in the developing brain require further investigation. This review aims to provide an overview of the safety of commonly used NIBS techniques in children, including transcranial electrical stimulation (tES) and transcranial magnetic stimulation (TMS). Safety data for other NIBS methods is not reported in this review. RECENT FINDINGS: In line with studies from the last decade, findings in the last 2 years (2022-2023) support the safety of NIBS in children and adolescents within the currently applied protocols. Both tES and TMS are well tolerated, if safety rules, including exclusion criteria, are applied. SUMMARY: We briefly discussed developmental aspects of stimulation parameters that need to be considered in the developing brain and provided an up-to-date overview of tES/TMS applications in children and adolescents. Overall, the safety profile of tES/TMS in children is good. For both the tES and TMS applications, epilepsy and active seizure disorder should be exclusion criteria to prevent potential seizures. Using child-sized earplugs is required for TMS applications. We lack large randomized double-blind trialsand longitudinal studies to establish the safety of NIBS in children. VIDEO ABSTRACT: http://links.lww.com/YCO/A78 .

Adjunctive transcranial direct current stimulation to improve swallowing functions in Parkinson's disease.

Swallowing problems are frequent in Parkinson's disease (PD). The aim of this study was to determine the effectiveness of combined transcranial Direct Current Stimulation (tDCS) and Conventional Dysphagia Therapy (CDT) on dysphagia in PD patients. Twenty PD patients with dysphagia were randomized into two groups: combination therapy (anodal tDCS plus CDT) and sham tDCS combined with CDT. Anodal or sham tDCS, bilaterally over the pharyngeal motor cortex, was applied with one mA during the first 20 min (real) or 30 s (sham) of CDT, which was delivered for 30 min. Both groups received twice-daily treatment sessions within two weeks. Swallowing functions were evaluated before, immediately, and one month after the intervention via the Penetration-Aspiration Scale (PAS), and the Swallowing Disorder Questionnaire (SDQ) as the primary outcome measures, and the Dysphagia Handicap Index (DHI) as the secondary outcome measure. The results showed a significant improvement of PAS scores from baseline to post-intervention and baseline to follow-up in both groups without significant differences between groups (t=0.03, p=0.973, and t=1.27, p=0.22 for post-intervention and follow-up time points, respectively). The results showed a significant reduction of SDQ and DHI scores in both groups after the intervention, but the magnitude of the change was significantly larger in the anodal tDCS group at the post-intervention (ta=2.58, pa=0.019 and tb=2.96, pb=0.008) and follow-up (ta=2.65, pa=0.016 and tb=2.97, pb=0.008) time points. This study provides preliminary evidence that bi-hemispheric anodal tDCS combined with CDT enhances swallowing functions in patients with Parkinson's disease more than CDT alone.

Neurocognitive effects of 3 mA prefrontal electrical stimulation in schizophrenia: A randomized sham-controlled tDCS-fMRI study protocol.

BACKGROUND: Schizophrenia (SCZ) is characterized by cognitive deficits that are linked to prefrontal cortex dysfunction. While transcranial direct current stimulation (tDCS) shows promise for improving cognition, the effects of intensified 3mA tDCS protocols on brain physiology are unknown. This project aims to elucidate the neurophysiological and cognitive effects of an intensified prefrontal tDCS protocol in SCZ. METHODS: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, trial. Forty-eight participants with SCZ and cognitive impairment (measured via a set of executive functions tests) will be randomly allocated to receive either a single session of active (n = 24) or sham (n = 24) tDCS (20-min, 3-mA). The anodal and cathodal electrodes are positioned over the left and right DLPFC respectively. The stimulation occurs concurrently with the working memory task, which is initiated precisely 5 minutes after the onset of tDCS. Structural and resting-state (rs-fMRI) scans are conducted immediately before and after both active and sham tDCS using a 3 Tesla scanner (Siemens Prisma model) equipped with a 64-channel head coil. The primary outcome will be changes in brain activation (measures vis BOLD response) and working memory performance (accuracy, reaction time). DISCUSSION: The results of this study are helpful in optimizing tDCS protocols in SCZ and inform us of neurocognitive mechanisms underlying 3 mA stimulation. This study will additionally provide initial safety and efficacy data on a 3 mA tDCS protocol to support larger clinical trials. Positive results could lead to rapid and broader testing of a promising tool for debilitating symptoms that affect the majority of patients with SCZ. The results will be made available through publications in peer-reviewed journals and presentations at national and international conferences.

Targeting the prefrontal-supplementary motor network in obsessive-compulsive disorder with intensified electrical stimulation in two dosages: a randomized, controlled trial.

Obsessive-compulsive disorder (OCD) is associated with a high disease burden, and treatment options are limited. We used intensified electrical stimulation in two dosages to target a main circuitry associated with the pathophysiology of OCD, left dorsolateral prefrontal cortex (l-DLPFC), and pre-supplementary motor area (pre-SMA) and assessed clinical outcomes, neuropsychological performance, and brain physiology. In a double-blind, randomized controlled trial, thirty-nine patients with OCD were randomly assigned to three groups of sham, 2-mA, or 1-mA transcranial direct current stimulation (tDCS) targeting the l-DLPFC (F3) and pre-SMA (FC2) with anodal and cathodal stimulation respectively. The treatment included 10 sessions of 20-minute stimulation delivered twice per day with 20-min between-session intervals. Outcome measures were reduction in OCD symptoms, anxiety, and depressive states, performance on a neuropsychological test battery (response inhibition, working memory, attention), oscillatory brain activities, and functional connectivity. All outcome measures except EEG were examined at pre-intervention, post-intervention, and 1-month follow-up times. The 2-mA protocol significantly reduced OCD symptoms, anxiety, and depression states and improved quality of life after the intervention up to 1-month follow-up compared to the sham group, while the 1-mA protocol reduced OCD symptoms only in the follow-up and depressive state immediately after and 1-month following the intervention. Both protocols partially improved response inhibition, and the 2-mA protocol reduced attention bias to OCD-related stimuli and improved reaction time in working memory performance. Both protocols increased alpha oscillatory power, and the 2-mA protocol decreased delta power as well. Both protocols increased connectivity in higher frequency bands at frontal-central areas compared to the sham. Modulation of the prefrontal-supplementary motor network with intensified tDCS ameliorates OCD clinical symptoms and results in beneficial cognitive effects. The 2-mA intensified stimulation resulted in larger symptom reduction and improved more converging outcome variables related to therapeutic efficacy. These results support applying the intensified prefrontal-SMA tDCS in larger trials.

Efficacy of Transcranial Direct Current Stimulation on Pain Level and Disability of Patients with Fibromyalgia: A Systematic Review of Randomized Controlled Trials with Parallel-Group Design.

Transcranial direct current stimulation (tDCS) has been increasingly applied in fibromyalgia (FM) to reduce pain and fatigue. While results are promising, observed effects are variable, and there are questions about optimal stimulation parameters such as target region (e.g., motor vs. prefrontal cortices). This systematic review aimed to provide the latest update on published randomized controlled trials with a parallel-group design to examine the specific effects of active tDCS in reducing pain and disability in FM patients. Using the PRISMA approach, a literature search identified 14 randomized controlled trials investigating the effects of tDCS on pain and fatigue in patients with FM. Assessment of biases shows an overall low-to-moderate risk of bias. tDCS was found effective in all included studies conducted in patients with FM, except one study, in which the improving effects of tDCS were due to placebo. We recommended tDCS over the motor and prefrontal cortices as "effective" and "probably effective" respectively, and also safe for reducing pain perception and fatigue in patients with FM, according to evidence-based guidelines. Stimulation polarity was anodal in all studies, and one single-session study also examined cathodal polarity. The stimulation intensity ranged from 1-mA (7.14% of studies) to 1.5-mA (7.14% of studies) and 2-mA (85.7% of studies). In all of the included studies, a significant improvement in at least one outcome variable (pain or fatigue reduction) was observed. Moreover, 92.8% (13 of 14) applied multi-session tDCS protocols in FM treatment and reported significant improvement in their outcome variables. While tDCS is therapeutically effective for FM, titration studies that systematically evaluate different stimulation intensities, durations, and electrode placement are needed.

The impact of bilateral anodal transcranial direct current stimulation of the premotor and cerebellar cortices on physiological and performance parameters of gymnastic athletes: a randomized, cross-over, sham-controlled study.

Professional sports performance relies critically on the interaction between the brain and muscles during movement. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique which modulates cortical excitability and can be used to improve motor performance in athletes. The present study aimed to investigate the effect of bilateral anodal tDCS (2 mA, 20 min) over the premotor cortex or cerebellum on motor and physiological functions and peak performance of professional gymnastics athletes. Seventeen professional gymnastics athletes participated in a randomized, sham-controlled, crossover study. In this study, we assessed the efficacy of two anodal tDCS protocols (2 mA, 20 min) with stimulation over the bilateral premotor cortex or cerebellum with the return electrodes placed over the opposite supraorbital areas. Power speed, strength coordination, endurance, static and dynamic strength, static and dynamic flexibility, and rating of perceived exertion were measured before and immediately after tDCS interventions (bilateral anodal tDCS over premotor cortices, anodal tDCS over the cerebellum, and sham tDCS). Additionally, physiological muscle performance parameters, including maximum voluntary isometric contraction (MVIC) of upper body muscles, were assessed during tDCS. Bilateral anodal tDCS over the premotor cortex, compared to anodal tDCS over the cerebellum and sham tDCS conditions, significantly improved power speed, strength coordination, and static and dynamic strength variables of professional gymnastics athletes. Furthermore, bilateral anodal tDCS over the cerebellum, compared to sham tDCS, significantly improved strength coordination. Moreover, bilateral premotor anodal tDCS significantly increased MVIC of all upper body muscles during stimulation, while anodal tDCS over the cerebellum increased MVIC in only some muscles. Bilateral anodal tDCS over the premotor cortex, and to a minor degree over the cerebellum, might be suited to improve some aspects of motor and physiological functions and peak performance levels of professional gymnastics athletes.Clinical Trial Registration ID: IRCT20180724040579N2.

Time-course of the tDCS antidepressant effect: An individual participant data meta-analysis.

INTRODUCTION: Prefrontal transcranial direct current stimulation (tDCS) shows promise as an effective treatment for depression. However, factors influencing treatment and the time-course of symptom improvements remain to be elucidated. METHODS: Individual participant data was collected from ten randomised controlled trials of tDCS in depression. Depressive symptom scores were converted to a common scale, and a linear mixed effects individual growth curve model was fit to the data using k-fold cross-validation to prevent overfitting. RESULTS: Data from 576 participants were analysed (tDCS: n = 311; sham: n = 265), of which 468 were unipolar and 108 had bipolar disorder. tDCS effect sizes reached a peak at approximately 6 weeks, and continued to diverge from sham up to 10 weeks. Significant predictors associated with worse response included higher baseline depression severity, treatment resistance, and those associated with better response included bipolar disorder and anxiety disorder. CONCLUSIONS: Our findings suggest that longer treatment courses, lasting at least 6 weeks in duration, may be indicated. Further, our results show that tDCS is effective for depressive symptoms in bipolar disorder. Compared to unipolar depression, participants with bipolar disorder may require additional maintenance sessions to prevent rapid relapse.

The Impact of Bilateral Anodal tDCS over Left and Right DLPFC on Executive Functions in Children with ADHD.

Transcranial direct current stimulation (tDCS) is increasingly used for therapeutic purposes in attention-deficit hyperactivity disorder (ADHD). The dorsolateral prefrontal cortex (DLPFC) is the most targeted region of tDCS studies in ADHD. There is limited knowledge and mixed results about the relevance of left or right DLPFCs in ADHD's cognitive deficits. No study so far has investigated the impact of the increased excitability of both left and right DLPFC with anodal tDCS on cognitive deficits in ADHD. Here, we explored the impact of online bilateral anodal left and right DLPFC tDCS on executive dysfunction in children with ADHD. Twenty-two children with ADHD (mean age ± SD =8.86 ± 1.80) received bilateral anodal online tDCS over the left and right DLPFC (1.5 mA, 15 min) in two separate sessions in active and sham states. They underwent a battery of four neuropsychological tasks of executive functions during stimulation that measured working memory, cognitive flexibility, response inhibition, and executive control. Bilateral anodal left and right DLPFC tDCS did not improve performance on working memory, cognitive flexibility, and response inhibition. Executive control was, however, partially improved for those who received active tDCS first. The upregulation of bilateral DLPFC tDCS with anodal polarity does not improve executive dysfunction in children with ADHD. The unilateral modulation of DLPFC with anodal tDCS may be more beneficial to cognitive deficits in ADHD in light of previous works targeting only left and/or right DLPFC.

The impact of prefrontal transcranial direct current stimulation (tDCS) on theory of mind, emotion regulation and emotional-behavioral functions in children with autism disorder: A randomized, sham-controlled, and parallel-group study.

Advances in our knowledge about the neuropsychological mechanisms underlying core deficits in autism spectrum disorder (ASD) have produced several novel treatment modalities. One of these approaches is modulation of activity of the brain regions involved in ASD symptoms. This study examined the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) on autism symptom severity, theory of mind, emotion regulation strategies, and emotional-behavioral functions in children with ASD. Thirty-two children (Mage  = 10.16, SD = 1.93, range 7-12 years) diagnosed with ASD were randomly assigned to active (N = 17) or sham stimulation (N = 15) groups in a randomized, sham-controlled, parallel-group design. Participants underwent 10 sessions of active (1.5 mA, 15 min, bilateral left anodal/right cathodal DLPFC, 2 sessions per week) or sham tDCS. Autism symptom severity, theory of mind, emotion regulation strategies, and emotional-behavioral functioning of the patients were assessed at baseline, immediately after the intervention, and 1 month after the intervention. A significant improvement of autism symptom severity (i.e., communication), theory of mind (i.e., ToM 3), and emotion regulation strategies was observed for the active as compared to the sham stimulation group at the end of the intervention, and these effects were maintained at the one-month follow-up. The results suggest that repeated tDCS with anodal stimulation of left and cathodal stimulation of right DLPFC improves autism symptom severity as well as social cognition and emotion regulation in ASD. LAY SUMMARY: Previous research has suggested that targeting core mechanisms underlying cognitive-emotional and behavioral deficits of autistic children might improve symptoms of ASD. Deficient social and behavioral functioning, impaired theory of mind, and emotional regulation deficits have been identified as core treatment targets for this group. Specific subregions of the prefrontal cortex are involved in these deficits, including hypoactivity of the dorsolateral prefrontal cortex (DLPFC). Upregulation of this area with non-invasive brain stimulation, namely anodal transcranial direct current stimulation (tDCS), results in improved social and behavioral functioning in children with ASD. Very few studies have however examined the effects of this intervention on theory of mind, emotional regulation, and emotional-behavioral problems. We examined the effects of anodal tDCS over the left DLPFC (F3), combined with cathodal tDCS over the right DLPFC (F4) on autism symptom severity as well as theory of mind, emotional regulation, and emotional-behavioral problems of children with ASD. This intervention improved autism symptom severity, specific domains of theory of mind, and emotion regulation. These findings have clinical implications for the treatment of ASD and suggest that targeting core mechanisms underlying socio-cognitive-emotional deficits of autistic children using tDCS might improve symptoms of ASD.