This study investigates the effects of transcranial direct current stimulation (tDCS) on brain network connectivity in individuals with obsessive-compulsive disorder (OCD).

In a randomized, double-blind, sham-controlled experimental design anodal tDCS (vs. sham) was applied in a total of 43 right-handed patients with OCD, targeting the right pre-supplementary motor area (pre-SMA). Cathodal reference electrode was put on the left pre-SMA. The current was set as 2 mA, with a stimulation duration of either 30 s (sham) or 1200 s. Concurrent resting-state functional MRI data were collected following tDCS (or sham) stimulation. We employed regression dynamic causal modelling (rDCM) to extract whole brain effective connectivity (EC) matrices subsequently analyzing these matrices through graph theory approaches to examine changes in brain activity across different network scales.

We found that tDCS compared to sham caused significant changes in local effective connectivity. Increased recruitment level was detectable in the sensorimotor network (SMN), indicating enhanced intra-network connectivity after active tDCS. Clustering coefficient and local efficiency were also found to be increased in the same area. No significant changes were detectable with regard to global network connectivity.

Current findings indicate that single-session tDCS can effectively alter local effective connectivities within the SMN in OCD patients. Given the relevance of the SMN and connected regions for the pathophysiology of OCD we believe that tDCS targeting these areas might constitute an effective intervention to normalize altered network connectivity in the disorder of OCD.

We used a single tDCS session, which may not reflect long-term effects.

Efficacy and safety of transcranial direct current stimulation (tDCS) in the treatment of obsessive-compulsive disorder (OCD) were explored by meta-analysis.

Four electronic databases (Cochrane, PubMed, Embase, Web of Science) were retrieved at 25/06/23. From our inclusion criteria, seven studies (N = 201 patients) were included, and we performed a meta-analysis using Stata15.0.

Results suggested that the total Y-BOCS (Yale-Brown obsessive com-pulsive scale) scale was significantly lower in patients with OCD after tDCS treatment [SMD= -0.46, 95%CI (-0.84, -0.07), I2=39%, p = 0.02, Grade: high]. Subgroup analysis showed statistically significant results when treatment duration ≤ 20 days [SMD= -0.95, 95%CI (-1.80, -0.10), p = 0.03]. Moreover, tDCS and sham tDCS-treated OCD patients showed neither significantly different depressive symptoms nor significantly different adverse events [RR= -0.21, 95%CI (-0.58, 0.15), p = 0.25, Grade: moderate] and [RR = 3.98, 95%CI (0.04, 374.99), p = 0.55, Grade: very low], respectively.

tDCS maybe reduce the Y-BOCS total scores in OCD patients and depressive symptoms, but for adverse reactions. the results are inconclusive.

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation for treatment-resistant obsessive compulsive disorder (OCD). We aim to compare the treatment outcomes of a newly developed dual-site cathodal tDCS method over the orbitofrontal cortex (OFC) and pre-supplementary motor area (pre-SMA) and two previously reported montages (cerebellum-OFC and pre-SMA) in patients with treatment-resistant OCD. Methods: Eighteen OCD patients were randomly assigned to receive twice-daily 2 mA/20 min sessions for 10 consecutive weekdays, with the active cathode placed on the cerebellum-OFC, bilateral pre-SMA, or OFC-pre-SMA tDCS. The primary outcome was the change in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The resting electroencephalogram (EEG) was recorded to obtain the default mode network (DMN) via low-resolution electromagnetic tomography. Each patient received one-week and one-month follow-ups after two weeks of stimulation. Results: At the end of the stimulation, the Y-BOCS scores in the cerebellum-OFC, pre-SMA, and OFC-pre-SMA tDCS groups (n = 6 in each group) were decreased by 14.15 ± 13.31, 7.4 ± 9.59, and 20.75 ± 8.70%, respectively, but no significant differences were found among the groups. In the OFC-pre-SMA tDCS group, OC symptoms significantly decreased by a mean of -20.75% immediately after the 20th tDCS session, and the improvement remained at 1 week and 1 month after tDCS. EEG source functional connectivity analyses revealed increased functional connectivity within the frontal network after OFC-pre-SMA tDCS, whereas decreased functional connectivity within the DMN was observed after cerebellum-OFC tDCS. Conclusions: Dual-site cathodal tDCS over the OFC and pre-SMA might be considered a potential montage to treat patients with treatment-resistant OCD. Future studies using randomized sham-controlled designs are needed.

This systematic review was prospectively registered with PROSPERO (CRD42023426005) and the data collected in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of reporting of included studies was evaluated in accordance with the CONSORT statement.

Eleven randomized controlled trials were identified. Evaluation of the reviewed studies revealed low levels of overall compliance with the CONSORT statement highlighting the need for improved reporting. Key areas included insufficient information about - the intervention (for replicability), participant flow, recruitment, and treatment effect sizes. Study discussions did not fully consider limitations and generalizability, and the discussion/interpretation of the findings were often incongruent with the results and therefore misleading. Only two studies reported a significant difference between sham and active tDCS for OCD outcomes, with small effect sizes noted.

The variability in protocols, lack of consistency in procedures, combined with limited significant findings, makes it difficult to draw any meaningful conclusions about the effectiveness of tDCS for OCD. Future studies need to be appropriately powered, empirically driven, randomized sham-controlled clinical trials.

Characterized by its disabling nature, obsessive compulsive disorder (OCD) affects individuals profoundly, with nearly 40% of patients showing resistance to initial treatment methods. Despite being safe and easily accessible, transcranial direct current stimulation (tDCS) lacks extensive substantiation supporting its efficacy in treating OCD. The objective of this study was to evaluate how cathodal high-definition transcranial direct current stimulation (HD-tDCS) applied to the right orbitofrontal cortex affected patients with OCD in terms of efficacy.

47 patients with OCD were enrolled. They were randomly allocated to active or sham stimulation groups, and underwent HD-tDCS stimulation treatment for 2 weeks. The central electrode located in the right orbitofrontal cortex region was cathodic. The severity of the patients' obsessive-compulsive symptoms, depression and anxiety were assessed before and after treatment.

Out of the total, 44 patients concluded the treatment, comprising 23 participants from the active stimulation group and 21 from the sham stimulation group. Notably, substantial reductions in symptoms related to OCD, depression, and anxiety were exhibited in both groups. With a response rate of 26.1% in the active stimulation group and 23.8% in the sham stimulation group, there was no significant difference in efficacy observed. Furthermore, the reduction in depression and anxiety symptoms at the conclusion of the treatment was not notably superior in the active stimulation group.

This study provided evidence for the acceptability and safety of HD-tDCS. Nevertheless, the study did not reveal notable clinical effectiveness of tDCS in addressing moderate to severe OCD in comparison to the sham stimulation group.

Obsessive-compulsive disorder (OCD) is a prevalent mental condition characterized by recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions), significantly disrupting daily functioning and social interactions. Transcranial direct current stimulation (tDCS) presents a promising non-invasive treatment modality aimed at alleviating symptoms. However, the evidence regarding its effectiveness remains inconclusive. This study seeks to address this gap by conducting a systematic review and meta-analysis of clinical trials, offering improved guidance for clinical intervention. A comprehensive search strategy was implemented across multiple databases, including PubMed, Cochrane CENTRAL, Embase, Scopus, and Web of Science. This search focused strictly on randomized controlled trials (RCTs) involving 147 patients. These trials evaluated the efficacy of tDCS in OCD patients. Subsequent data extraction, risk of bias assessment, and statistical analysis using Review Manager software revealed the potential efficacy of tDCS in reducing OCD symptoms. The meta-analysis not only fails to demonstrate significant superiority of active tDCS over sham tDCS but also suggests that sham tDCS may be more effective than active tDCS in reducing OCD symptoms. This finding diminishes the promise of tDCS as an effective treatment for OCD. Larger trials are warranted to further elucidate these findings.

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive thoughts and repetitive behaviors, with associated brain abnormalities in various regions. This study explores the correlation between neural biomarkers and the response to transcranial Direct Current Stimulation (tDCS) in OCD patients. Using structural MRI data from two tDCS trials involving 55 OCD patients and 28 controls, cortical thickness, and gray matter morphometry was analyzed. Findings revealed thicker precentral and paracentral areas in OCD patients, compared to control (p < 0.001). Correlations between cortical thickness and treatment response indicated a significant association between a thinner precentral area and reduced Yale-Brown Obsessive Compulsive Scale (YBOCS) scores (p = 0.02). While results highlight the complexity of treatment response predictors, this study sheds light on potential neural markers for tDCS response in OCD patients. Further investigations with larger datasets are warranted to better understand the underpinnings of these biomarkers and their implications for personalized treatment approaches.

Currently, there is still debate over the effectiveness of transcranial direct current stimulation (tDCS) in treating obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD) and anxiety disorders (ADs). To investigate the immediate and long-term effectiveness of tDCS in these diseases, we conducted a systematic review and quantitative analysis of existing literature on the treatment of OCD, PTSD, and ADs with tDCS. Following the PRISMA guidelines, we searched seven electronic databases and systematically retrieved articles published from May 2012 to June 2024 that compared the effects of active tDCS with sham stimulation in the treatment of these disorders. We included primary outcome measures such as the change scores in disorder-specific and general anxiety symptoms before and after treatment, as well as secondary outcomes such as changes in disorder-specific and general anxiety symptoms at follow-up. We also assessed the impact of tDCS on depressive symptoms. Fifteen papers met the eligibility criteria. Overall, the results of meta-analysis indicated that tDCS had a high effect in improving specific symptoms (SMD = -0.73, 95% CI: -1.09 to -0.37) and general anxiety symptoms (SMD = -0.75; 95% CI: -1.23 to -0.26) in OCD, PTSD and ADs, with effects lasting up to 1 month and showing a moderate effect size. Furthermore, tDCS demonstrated immediate and significant alleviation of depressive symptoms in these diseases. This study concludes that tDCS can serve as a non-invasive brain stimulation technology for treating these disorders, and the therapeutic effects can be maintained for a period of time.

Transcranial direct current stimulation (tDCS) is a safe, accessible, and promising therapeutic approach for obsessive-compulsive disorder (OCD).

This study aimed to evaluate the effect of tDCS on electroencephalography (EEG) microstates and identify potential biomarkers to predict efficacy.

A total of 24 individuals diagnosed with OCD underwent ten sessions of tDCS targeting the orbitofrontal cortex, while 27 healthy individuals were included as controls. Microstates A, B, C, and D were extracted before and after tDCS. A comparative analysis of microstate metrics was performed between the OCD and the healthy control groups, as well as within the OCD group before and after tDCS. Multiple linear regression analysis was performed to identify potential biomarkers of tDCS.

Comparison to healthy controls, the OCD group exhibited a significantly reduced duration of microstate A and increased occurrence of microstate D. The transition between microstates A and C was significantly different between patients with OCD and healthy controls and was no longer observed following tDCS. Multiple linear regression analysis revealed that the duration of microstate C was associated with an improvement OCD symptom after tDCS.

The results revealed an aberrant large-scale EEG brain network that could be modulated by tDCS. In particular, the duration of EEG microstate C may be a neurophysiological characteristic associated with the therapeutic effects of tDCS on OCD.

Transcranial direct current stimulation (tDCS) is proven to be safe in treating various neurological conditions in children and adolescents. It is also an effective method in the treatment of OCD in adults.

To assess the safety and efficacy of tDCS as an add-on therapy in drug-naive adolescents with OCD.

We studied drug-naïve adolescents with OCD, using a Children's Yale-Brown obsessive-compulsive scale (CY-BOCS) scale to assess their condition. Both active and sham groups were given fluoxetine, and we applied cathode and anode over the supplementary motor area and deltoid for 20 min in 10 sessions. Reassessment occurred at 2, 6, and 12 wk using CY-BOCS.

Eighteen adolescents completed the study (10-active, 8-sham group). CY-BOCS scores from baseline to 12 wk reduced significantly in both groups but change at baseline to 2 wk was significant in the active group only. The mean change at 2 wk was more in the active group (11.8 ± 7.77 vs 5.25 ± 2.22, P = 0.056). Adverse effects between the groups were comparable.

tDCS is safe and well tolerated for the treatment of OCD in adolescents. However, there is a need for further studies with a larger sample population to confirm the effectiveness of tDCS as early augmentation in OCD in this population.

The present study evaluated the therapeutic efficacy and tolerability of 10 transcranial direct current stimulation (tDCS) sessions in treatment-resistance obsessive-compulsive disorder (OCD) patients using a multisite double-blind sham-controlled design.

Eighty treatment-resistance outpatients suffering from obsessive-compulsive disorder were randomized to receive either active or sham transcranial direct current stimulation. The cathode was positioned over the supplementary motor area and the anode over the right supraorbital area. Patients were evaluated at baseline, end of treatment (day 14), one-month follow-up (day 45), and three-month follow-up (day 105) on the Yale-Brown Obsessive Compulsive Scale.

Although a significant interaction between time and treatment was observed, the primary endpoint-measuring the change in Yale-Brown obsessive compulsive scale scores after two weeks-was not achieved. Conversely, the secondary endpoint, which concerned the change in Yale-Brown obsessive compulsive scale scores after three months, was successfully met. It is important to note, however, that there were no significant differences in the percentage of responders and remitters at any of the post-treatment assessments. This suggests that the treatment may not have had a clinically relevant impact. Patients well received the transcranial direct current stimulation treatment, indicating its good tolerability.

This is the largest controlled trial using transcranial direct current stimulation in treatment-resistance obsessive-compulsive disorder patients. Our results indicate the importance of studying the placebo effect in transcranial direct current stimulation and the necessity to consider a long follow-up time to best evaluate the effects of the intervention.

ClinicalTrials.gov, identifier NCT03304600.

Repetitive transcranial magnetic stimulation (rTMS) has been found to be helpful for the treatment of obsessive-compulsive disorder (OCD). However, the relative efficacy of different rTMS protocols is unclear.

To conduct a systematic review and network meta-analysis (NMA) of published literature to compare the relative efficacy of different rTMS protocols for decreasing Yale-Brown Obsessive Compulsive Severity (Y-BOCS) scores in patients with OCD.

Relevant articles published between 1985 to September 2023 were searched from the Cochrane Central Register of Controlled Trials, PubMed and PsycInfo. Double or single-blinded randomized controlled studies conducted on patients with OCD comparing an active rTMS protocol with either another active or sham rTMS protocol were included. Network meta-analysis (NMA) was conducted using a frequentist approach. Standardized mean difference (SMD) of change in Y-BOCS scores was calculated employing Hedge's g. Pairwise meta-analysis using random effects model was conducted which was extended to the NMA using restricted maximum likelihood estimation procedure. Surface under the cumulative ranking (SUCRA) probabilities were used to rank the interventions.

Excitatory rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC), inhibitory rTMS of right DLPFC, inhibitory as well as excitatory rTMS of bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and inhibitory rTMS of bilateral supplementary motor area (SMA) were superior to sham stimulation. The DLPFC and mPFC/ACC protocols had a higher probability of being among the top-ranked interventions. The majority of studies had a modest sample size and at least some concerns in the risk of bias assessment.

rTMS targeting either the medial or lateral prefrontal cortices is a promising intervention for resistant OCD. There is a need to confirm these findings in large systematic studies.

Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation technique that is portable and easy to use. Long-term, home-based treatments with tSMS of the supplementary motor area (SMA) are promising for movement disorders and other brain diseases. The aim of the present work was to investigate the potential of SMA-tSMS for reducing corticospinal excitability. We completed an open pilot study in which twenty right-handed healthy subjects (8 females; age: 31.3 ± 5.4 years) completed two 30-min sessions (at least one week apart) of SMA-tSMS. We assessed corticospinal excitability by applying transcranial magnetic stimulation (TMS) over the primary motor cortex, recording 30 motor evoked potentials (MEPs) from either the left or right first dorsal interosseous (FDI, 'hotspot' muscle) and extensor carpi radialis (ECR, 'offspot' muscle) in each session before and after (up to 30 min) tSMS. We observed moderate-to-extreme level of Bayesian evidence for a reduction of MEP amplitude after 30 min of tSMS over SMA compared to baseline. Thus, tSMS applied over SMA may reduce corticospinal excitability. These findings, if confirmed with double-blind, placebo-controlled experiments, support the potential of targeting the SMA for neuromodulating a large motor network in future therapeutic applications of tSMS.

Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects about 2%-3% of the global population. Despite the availability of several treatments, many patients with OCD do not respond adequately, highlighting the need for new therapeutic approaches. Recent studies have associated various inflammatory processes with the pathogenesis of OCD, including alterations in peripheral immune cells, alterations in cytokine levels, and neuroinflammation. These findings suggest that inflammation could be a promising target for intervention. Transcranial photobiomodulation (t-PBM) with near-infrared light is a noninvasive neuromodulation technique that has shown potential for several neuropsychiatric disorders. However, its efficacy in OCD remains to be fully explored. This study aimed to review the literature on inflammation in OCD, detailing associations with T-cell populations, monocytes, NLRP3 inflammasome components, microglial activation, and elevated proinflammatory cytokines such as TNF-α, CRP, IL-1β, and IL-6. We also examined the hypothesis-based potential of t-PBM in targeting these inflammatory pathways of OCD, focusing on mechanisms such as modulation of oxidative stress, regulation of immune cell function, reduction of proinflammatory cytokine levels, deactivation of neurotoxic microglia, and upregulation of BDNF gene expression. Our review suggests that t-PBM could be a promising, noninvasive intervention for OCD, with the potential to modulate underlying inflammatory processes. Future research should focus on randomized clinical trials to assess t-PBM's efficacy and optimal treatment parameters in OCD. Biomarker analyses and neuroimaging studies will be important in understanding the relationship between inflammatory modulation and OCD symptom improvement following t-PBM sessions.

Trichotillomania (or hair pulling disorder) is a habitual condition in which patients constantly pull their hair. Although psychotherapies such as behavioral therapy and pharmacotherapy have shown relative effectiveness for trichotillomania, some patients fail to respond to these interventions or show only partial responses. Recently, noninvasive brain stimulation techniques such as transcranial direct current stimulation have shown promise in the treatment of psychiatric disorders. We designed a new protocol that included intensified and repeated during 16 sessions, every other day, 2 sessions one day, current intensity of 2 mA for 20 minutes, which regions dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA): Anodal (F3) and cathodal (SMA) were selected as stimulation target areas. The results showed that after the electrical stimulation intervention and also in the follow-up phase, there was a significant improvement in hair pulling behavior and psychiatric evaluations such as depression and anxiety. Therefore, there are many hopes in the effectiveness of the protocol used (intensified and repeated DLPFC and SMA areas) in the treatment of trichotillomania disorder, although there is a need for a future experimental study with a larger group of patients.

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.

Non-invasive brain stimulation (NIBS) techniques have a rich historical background, yet their utilization has witnessed significant growth only recently. These techniques encompass transcranial electrical stimulation and transcranial magnetic stimulation, which were initially employed in neuroscience to explore the intricate relationship between the brain and behaviour. However, they are increasingly finding application in research contexts as a means to address various neurological, psychiatric, and neurodegenerative disorders. This article aims to fulfill two primary objectives. Firstly, it seeks to showcase the current state of the art in the clinical application of NIBS, highlighting how it can improve and complement existing treatments. Secondly, it provides a comprehensive overview of the utilization of NIBS in augmenting the brain function of healthy individuals, thereby enhancing their performance. Furthermore, the article delves into the points of convergence and divergence between these two techniques. It also addresses the existing challenges and future prospects associated with NIBS from ethical and research standpoints.

Compulsive checking, a common symptom of obsessive-compulsive disorder (OCD), has been difficult to capture experimentally. Therefore, determination of its neural basis remains challenging despite some evidence suggesting that it is linked to dysfunction of cingulostriatal systems. This study introduces a novel experimental paradigm to measure excessive checking and its neurochemical correlates.

Thirty-one patients with OCD and 29 healthy volunteers performed a decision-making task requiring them to decide whether 2 perceptually similar visual representations were the same or different under a high-uncertainty condition without feedback. Both groups underwent 7T magnetic resonance spectroscopy scans on the same day. Correlations between out-of-scanner experimental measures of checking and the glutamate/GABA (gamma-aminobutyric acid) ratio in the anterior cingulate cortex, supplementary motor area, and occipital cortex were assessed. Their relationship with subjective ratings of doubt, anxiety, and confidence was also investigated.

Patients with OCD exhibited excessive and dysfunctional checking, which was significantly correlated with changes in the glutamate/GABA ratio within the anterior cingulate cortex. No behavioral/neurochemical relationships were evident for either the supplementary motor area or occipital cortex. The excessive checking observed in patients was negatively correlated with their confidence levels and positively related to doubt, anxiety, and compulsivity traits.

We conclude that experimental measures of excessive and dysfunctional checking in OCD, which have been linked to increased doubt, anxiety, and lack of confidence, are related to an imbalance between excitatory and inhibitory neural activity within the anterior cingulate cortex. This study adds to our understanding of the role of this region in OCD by providing a laboratory model of the possible development of compulsive checking.

Deficits in response inhibition are associated with numerous psychiatric disorders. Previous studies have revealed the crucial role of the right inferior frontal gyrus (rIFG), pre-supplementary motor area (preSMA), and beta activity in these brain regions in response inhibition. Multi-channel transcranial alternating current stimulation (tACS) has garnered significant attention for its ability to modulate neural oscillations in brain networks. In this study, we employed multi-channel tACS targeting rIFG-preSMA network to investigate its impact on response inhibition in healthy adults.

In Experiment 1, 70 healthy participants were randomly assigned to receive 20 Hz in-phase, anti-phase, or sham stimulation over rIFG-preSMA network. Response inhibition was assessed using the stop-signal task during and after stimulation, and impulsiveness was measured via the Barratt Impulsiveness Scale. Additionally, 25 participants received stimulation at the left supraorbital area to account for potential effects of the "return" electrode. Experiment 2, consisting of 25 participants, was conducted to validate the primary findings of Experiment 1, including both in-phase and sham stimulation conditions, based on prior estimations derived from the results of Experiment 1.

In Experiment 1, we found that in-phase stimulation significantly improved response inhibition compared with sham stimulation, whereas anti-phase stimulation did not. These findings were consistently replicated in Experiment 2. We also conducted an exploratory analysis of the multi-channel tACS impact, revealing that its effects primarily emerged during the post-stimulation phase. Furthermore, individuals with higher baseline attentional impulsiveness showed greater improvements in the in-phase stimulation group.

These results demonstrate that in-phase beta-tACS over rIFG-preSMA network can effectively improve response inhibition in healthy adults and provides a new potential treatment for patients with deficits in response inhibition.

Compulsivity is considered a transdiagnostic dimension in obsessive-compulsive and related disorders, characterized by heterogeneous cognitive and behavioral phenotypes associated with abnormalities in cortico-striatal-thalamic-cortical circuitry. The present study investigated the structural morphology of white and gray matter in rats selected for low- (LD) and high- (HD) compulsive drinking behavior on a schedule-induced polydipsia (SIP) task. Regional brain morphology was assessed using ex-vivo high-resolution magnetic resonance imaging (MRI). Voxel-based morphometry of segmented MRI images revealed larger white matter volumes in anterior commissure and corpus callosum of HD rats compared with LD rats. HD rats also showed significantly larger regional volumes of dorsolateral orbitofrontal cortex, striatum, amygdala, hippocampus, midbrain, sub-thalamic nucleus, and cerebellum. By contrast, the medial prefrontal cortex was significantly smaller in HD rats compared with LD rats with no significant group differences in whole brain, ventricular, or cerebrospinal fluid volumes. These findings show that limbic cortico-basal ganglia structures implicated in impulse control disorders are distinct in rats that are vulnerable to develop compulsive behavior. Such abnormalities may be relevant to the etiology of compulsive disorders in humans.

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (¹H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.

Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect.

FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages.

Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation.

tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step.

ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Even though obsessive compulsive disorder (OCD) is one of the ten most disabling diseases according to the WHO, only 30-40% of patients suffering from OCD seek specialized treatment. The currently available psychotherapeutic and pharmacological approaches, when properly applied, prove ineffective in about 10% of cases. The use of neuromodulation techniques, especially Deep Brain Stimulation, is highly promising for these clinical pictures and knowledge in this domain is constantly evolving. The aim of this paper is to provide a summary of the current knowledge about OCD treatment, while also discussing the more recent proposals for defining resistance.

Transcranial direct current stimulation (tDCS) has been showing promising effects for the treatment of obsessive-compulsive disorder (OCD), but there is still no conclusion on its efficacy for this disorder. We performed a systematic review and meta-analysis of trials using tDCS for OCD and a computer modeling analysis to evaluate the electric field (EF) strengths of different electrode assemblies in brain regions of interest (ROIs) (PROSPERO-42021262465). PubMed/MEDLINE, Embase, Cochrane Library and Web of Science databases were searched from inception to 25 September 2022. Randomized controlled trials (RCTs) and open-label studies were included. The primary aim was the effect size (Hedges' g) of continuous outcomes and potential moderators of response. For EF modeling, SimNIBS software was used. Four RCTs and four open-label trials were included (n = 241). Results revealed a large effect of tDCS in the endpoint, but no significant effect between active and sham protocols. No predictor of response was found. EF analysis revealed that montages using the main electrode over the (pre)supplementary motor area with an extracephalic reference electrode might lead to stronger EFs in the predefined ROIs. Our results revealed that tDCS might be a promising intervention to treat OCD; however, larger studies are warranted.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that affects up to 2.8% of the adult population. Albeit pharmacological and behavioral therapies alleviate some core symptoms of ADHD, they do not avail cognitive dysfunction adequately. Executive dysfunction has been considered to have a principal role in ADHD and has previously been linked to activity alterations in the prefrontal cortex. Transcranial Direct Current Stimulation (tDCS) is a noninvasive brain stimulation technique that may modulate prefrontal cortex activity and induce neuroplasticity, with preliminary results in ADHD. The aim of the present study is to assess the effect of repeated tDCS on measures of executive functions in adults with ADHD.

In this randomized double-blind sham-controlled study, 22 adults with ADHD were allocated into two groups and were administered five consecutive sessions of 2 mA active/sham tDCS over the dorsolateral prefrontal cortex (right anodal/left cathodal). A neuropsychological test battery was administered before the first session and immediately after the last session.

The maximum number of digits and the total number of correct trials in the Digit Span Backward test increased in the active group (p = 0.017). The total move score in the Tower of London test decreased (p = 0.033), suggesting better planning ability. However, no significant differences were observed on Stroop Test and Trail Making Test after tDCS.

The present study corroborates the modulating effects of tDCS on planning and working memory in a small group of adults with ADHD. Our results highlighted that cognitive functions are modulable using tDCS in adults with ADHD.

Early research into neural correlates of obsessive compulsive disorder (OCD) has focused on individual components, several network-based models have emerged from more recent data on dysfunction within brain networks, including the the lateral orbitofrontal cortex (lOFC)-ventromedial caudate, limbic, salience, and default mode networks. Moreover, the interplay between multiple brain networks has been increasingly recognized. As the understanding of the neural circuitry underlying the pathophysiology of OCD continues to evolve, so will too our ability to specifically target these networks using invasive and noninvasive methods. This review discusses the rationale for and theory behind neuromodulation in the treatment of OCD.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder, with 30−40% of OCD patients being unresponsive to adequate trials of anti-OCD drugs and cognitive behavior therapy. The aim of this paper is to investigate the efficacy of non-invasive brain stimulation (NIBS) on treating refractory OCD. With PubMed, Embase, PsycInfo, and Cochrane Library used on 15 February 2022, 24 randomized controlled trials involving 663 patients were included. According to this analysis, NIBS including repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcranial direct current stimulation (tDCS), had a moderate effect on the reduction of Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (SMD = 0.54, 95% CI: 0.26−0.81; p < 0.01). In the subgroup analysis, rTMS seemed to produce a better therapeutic effect (SMD = 0.73, 95% CI: 0.38−1.08; p < 0.01). Moreover, excitatory (SMD = 1.13, 95% CI: 0.24−2.01; p = 0.01) and inhibitory (SMD = 0.81, 95% CI: 0.26−1.36; p < 0.01) stimulation of the dorsolateral prefrontal cortex (DLPFC) both alleviated OCD symptoms. In the secondary outcome of clinical response rates, NIBS treatment led to an increase in response rates (RR = 2.26, 95% CI: 1.57−3.25; p < 0.01).

Repetitive transcranial magnetic stimulation (rTMS) is used as a therapeutic option for obsessive-compulsive disorder (OCD) in both clinical and research settings. There has been no consensus with regard to target area and other parameters, although 1-Hz rTMS over the supplementary motor area (SMA) is found to be promising. Priming stimulation, which involves high-frequency followed by low-frequency rTMS, has been shown to enhance neural response to low-frequency rTMS. Hence, this study was conducted to investigate the effect of adjunctive priming rTMS over the SMA in treatment-resistant OCD.

Thirty patients with OCD who were symptomatic after an adequate selective serotonin reuptake inhibitor trial were randomized into 2 groups: one group receiving active priming stimulation (6-Hz rTMS at 80% resting motor threshold) followed by 1-Hz rTMS (priming rTMS group) and the other receiving sham stimulation followed by 1-Hz rTMS (rTMS-only group). Both groups received 10 sessions of such interventions for 2 weeks. Both the rater and patients were blind to the treatment allocation. Assessments were done using the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Clinical Global Impression-Improvement scale at baseline, 2 weeks, and 4 weeks.

Both groups showed a significant improvement in all domains of psychopathology over time. The priming rTMS group was better than the rTMS-only group in reducing the Yale-Brown Obsessive Compulsive Scale compulsion score (P < 0.023) as well as scores of the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression-Improvement scale. None developed any adverse effects requiring medical attention.

Priming rTMS over the SMA is safe and has favorable effects in OCD. It seems to have a predominant effect on the reduction of compulsions, presumably rectifying the impaired response inhibition in patients with OCD.

Obsessive-compulsive disorder (OCD) is a disabling condition for which approximately 40% of patients do not respond to first-line treatment. Transcranial direct current stimulation (tDCS) is a safe and accessible technique that modulates cortical excitability and inhibition, but evidence of its efficacy for OCD is insufficient.

To investigate the efficacy of tDCS for OCD and alterations of cortical excitability and inhibition after treatment measured by concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG).

Twenty-four OCD patients underwent 10 20-min sessions of 1.5 mA high-definition tDCS with a cathode placed over the right orbitofrontal cortex (OFC) and anode electrodes set around the cathodal electrode. TMS-EEG was performed before and after tDCS treatment. OCD symptom severitys was assessed using Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the Beck Depression Inventory-Ⅱ (BDI-Ⅱ), and Beck Anxiety Inventory (BAI) were used to assess the severity of depression and anxiety symptoms. Twenty-seven healthy controls were recruited with TMS-EEG recorded.

Following tDCS, the Y-BOCS, BDI-Ⅱ, and BAI scores decreased significantly (all p = 0.000). TMS-evoked N100 amplitude, thought to be related to GABA_B receptor function, was significantly reduced after tDCS (Z = -2.143, p = 0.032) which was higher in OCD patients than in healthy controls at baseline (Z = -2.151, p = 0.031).

Pharmacotherapy during tDCS treatment may influence the effect of tDCS and EEG.

Cathodal high-definition tDCS applied over the OFC could improve OCD, depression, and anxiety symptoms along with alleviation of GABA_B receptor function.

Transcranial electrical stimulation (tES) comprises noninvasive neuromodulation techniques that deliver low-amplitude electrical currents to targeted brain regions with the goal of modifying neural activities. Expanding evidence from the past decade, specifically using transcranial direct current simulation and transcranial alternating current stimulation, presents promising applications of tES as a treatment for psychiatric disorders. In this review, the authors discuss the basic technical aspects and mechanisms of action of tES in the context of clinical research and practice and review available evidence for its clinical use, efficacy, and safety. They also review recent advancements in use of tES for the treatment of depressive disorders, schizophrenia, substance use disorders, and obsessive-compulsive disorder. Findings largely support growing evidence for the safety and efficacy of tES in the treatment of patients with resistance to existing treatment options, particularly demonstrating promising treatment outcomes for depressive disorders. Future directions of tES research for optimal application in clinical settings are discussed, including the growing home-based, patient-friendly methods and the potential pairing with existing pharmacological or psychotherapeutic treatments for enhanced outcomes. Finally, neuroimaging advancements may provide more specific mapping of brain networks, aiming at more precise tES therapeutic targeting in the treatment of psychiatric disorders.

Exposed-based psychotherapy is a mainstay of treatment for obsessive-compulsive disorder (OCD) and anxious psychopathology. The medial prefrontal cortex (mPFC) and the default mode network (DMN), which is anchored by the mPFC, promote safety learning. Neuromodulation targeting the mPFC might augment therapeutic safety learning and enhance response to exposure-based therapies.

To characterize the effects of mPFC neuromodulation on functional connectivity, 17 community volunteers completed resting-state functional magnetic resonance imaging scans before and after 20 min of frontopolar anodal multifocal transcranial direct current stimulation (tDCS). To examine the effects of tDCS on therapeutic safety learning, 24 patients with OCD completed a pilot randomized clinical trial; they were randomly assigned (double-blind, 50:50) to receive active or sham frontopolar tDCS before completing an in vivo exposure and response prevention (ERP) challenge. Changes in subjective emotional distress during the ERP challenge were used to index therapeutic safety learning.

In community volunteers, frontal pole functional connectivity with the middle and superior frontal gyri increased, while connectivity with the anterior insula and basal ganglia decreased (ps < .001, corrected) after tDCS; functional connectivity between DMN and salience network also decreased after tDCS (ps < .001, corrected). OCD patients who received active tDCS exhibited more rapid therapeutic safety learning (ps < .05) during the ERP challenge than patients who received sham tDCS.

Frontopolar tDCS may modulate mPFC and DMN functional connectivity and can accelerate therapeutic safety learning. Though limited by small samples, these findings motivate further exploration of the effects of frontopolar tDCS on neural and behavioral targets associated with exposure-based psychotherapies.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder which often proves refractory to current treatment approaches. Transcranial direct current stimulation (tDCS), a noninvasive form of neurostimulation, with potential for development as a self-administered intervention, has shown potential as a safe and efficacious treatment for OCD in a small number of trials. The two most promising stimulation sites are located above the orbitofrontal cortex (OFC) and the supplementary motor area (SMA).

The aim of this feasibility study is to inform the development of a definitive trial, focussing on the acceptability, safety of the intervention, feasibility of recruitment, adherence and tolerability to tDCS and study assessments and the size of the treatment effect. To this end, we will deliver a double-blind, sham-controlled, crossover randomised multicentre study in 25 adults with OCD. Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated and given in counterbalanced order. Each course comprises four 20-min stimulations, delivered over two consecutive days, separated by at least 4 weeks' washout period. We will collect information about recruitment, study conduct and tDCS delivery. Blinded raters will assess clinical outcomes before, during and up to 4 weeks after stimulation using validated scales. We will include relevant objective neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning.

We will analyse the magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure, to estimate effect size and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Additionally, qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, as well as the impact on their overall quality of life. These clinical outcomes will enable the project team to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the treatment in a full-scale trial.

ISRCTN17937049 . (date applied 08/07/2019). Recruitment (ongoing) began 23rd July 2019 and is anticipated to complete 30th April 2021.

Non-invasive brain stimulation techniques such as conventional transcranial direct current stimulation (tDCS) and high definition tDCS (HD-tDCS) are increasingly being used as add-on treatment options in schizophrenia and obsessive-compulsive disorder (OCD). This is reporting of the use of a novel accelerated, symptom-specific, add-on tDCS (combining conventional and high definition) protocol in a patient with both schizophrenia and OCD. The intervention showed clinical utility by reducing both schizophrenia and OCD symptoms.

Previous studies have examined the effect of transcranial direct current stimulation (tDCS) on the in-vivo concentrations of neuro-metabolites assessed through magnetic resonance spectroscopy (MRS) in neurological and psychiatry disorders. This review aims to systematically evaluate the data on the effect of tDCS on MRS findings and thereby attempt to understand the potential mechanism of tDCS on neuro-metabolites.

The relevant literature was obtained through PubMed and cross-reference (search till June 2020). Thirty-four studies were reviewed, of which 22 reported results from healthy controls and 12 were from patients with neurological and psychiatric disorders.

The evidence converges to highlight that tDCS modulates the neuro-metabolite levels at the site of stimulation, which, in turn, translates into alterations in the behavioural outcome. It also shows that the baseline level of these neuro-metabolites can, to a certain extent, predict the outcome after tDCS. However, even though tDCS has shown promising effects in alleviating symptoms of various psychiatric disorders, there are limited studies that have reported the effect of tDCS on neuro-metabolite levels.

There is a compelling need for more systematic studies examining patients with psychiatric/neurological disorders with larger samples and harmonised tDCS protocols. More studies will potentially help us to understand the tDCS mechanism of action pertinent to neuro-metabolite levels modulation. Further, studies should be conducted in psychiatric patients to understand the neurological changes in this population and potentially unravel the neuro-metabolite × tDCS interaction effect that can be translated into individualised treatment.

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research.

Invasive and noninvasive neurostimulation therapies for obsessive-compulsive and related disorders (OCRD) were systematically reviewed with the aim of assessing clinical characteristics, methodologies, neuroanatomical substrates, and varied stimulation parameters. Previous reviews have focused on a narrow scope, statistical rather than clinical significance, grouped together heterogenous protocols, and proposed inconclusive outcomes and directions. Herein, a comprehensive and transdiagnostic evaluation of all clinically relevant determinants is presented with translational clinical recommendations and novel response rates. Electroconvulsive therapy (ECT) studies were limited in number and quality but demonstrated greater efficacy than previously identified. Targeting the pre-SMA/SMA is recommended for transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). TMS yielded superior outcomes, although polarity findings were conflicting, and refinement of frontal/cognitive control protocols may optimize outcomes. For both techniques, standardization of polarity, more treatment sessions (>20), and targeting multiple structures are encouraged. A deep brain stimulation (DBS) 'sweet spot' of the striatum for OCD was proposed, and CBT is strongly encouraged. Tourette's patients showed less variance and reliance on treatment optimization. Several DBS targets achieved consistent, rapid, and sustained clinical response. Analysis of fiber connectivity, as opposed to precise neural regions, should be implemented for target selection. Standardization of protocols is necessary to achieve translational outcomes.