Cathodal tDCS in obsessive-compulsive disorder: cognitive and neurophysiological outcomes in a double-blind sham-controlled trial

Abstract

Objective

This preliminary study examined the efficacy of cathodal transcranial direct current stimulation (tDCS) targeting the medial prefrontal cortex (mPFC) in reducing symptom severity, enhancing cognitive flexibility, and modulating brain-derived neurotrophic factor (BDNF) levels in individuals with obsessive-compulsive disorder (OCD).

Methods

A double-blind, randomized, sham-controlled trial was conducted with 20 patients meeting DSM-V criteria for OCD, of whom 15 completed the intervention and were included in the final analysis. Participants received cathodal mPFC-tDCS (2 mA, 20 min, 10 sessions) or sham stimulation. Symptom severity (Y-BOCS), cognitive flexibility (task-switching), salivary BDNF, and frontal alpha activity (qEEG at Fz) were measured at baseline, post-treatment, and follow-up.

Results

The tDCS group exhibited greater reductions in Y-BOCS scores over time (F(2, 26) = 12.562, p < 0.001, partial η² = 0.425). Task-switching performance improved in the experimental group compared with controls (F(2, 26) = 20.351, p < 0.001, partial η² = 0.531). Salivary BDNF levels increased significantly in the tDCS group at follow-up (F(2, 16) = 6.086, p = 0.01, partial η² = 0.432). Trends toward normalization of frontal alpha activity were observed, but did not reach statistical significance.

Conclusions

Cathodal mPFC-tDCS was associated with reduced OCD symptom severity, improved cognitive flexibility, and increased salivary BDNF. These preliminary findings warrant replication in larger controlled samples.

Significance

This study extends previous tDCS research in OCD by integrating clinical outcomes with cognitive performance and a peripheral marker of neuroplasticity. It provides preliminary support for mPFC-targeted tDCS as a potential intervention for OCD.

Highlights

• •Cathodal tDCS reduced obsessive-compulsive symptom severity.
• •Cathodal tDCS improved cognitive flexibility following treatment.
• •Salivary brain-derived neurotrophic factor increased at follow-up after tDCS.

1. Introduction

Obsessive-compulsive disorder (OCD) is characterized by obsessions (e.g., intrusive thoughts) that raise anxiety and compulsions (e.g., repetitive behaviors) (Seibell and Hollander, 2014). OCD is exhausting and causes significant personal distress, with approximately 20–25% of patients are resistant to standard pharmacological and psychological interventions (Roh et al., 2023).

Dysfunctions in brain-derived neurotrophic factor (BDNF), a protein involved in nerve cell growth, have been associated with OCD (Wang et al., 2019; Hao et al., 2022). BDNF levels in OCD patients vary based on symptom dimensions (dos Santos et al., 2011), and lower levels are linked to cognitive impairments such as reduced inhibition and cognitive flexibility (Penadés et al., 2007; Shin et al., 2013). Impaired cognitive flexibility exacerbates obsessive behavior patterns by hindering adaptation to new rules (Gruner and Pittenger, 2017; Liu et al., 2023).

An example of impaired cognitive flexibility in OCD is reflected in task-switching paradigms. Studies have shown that patients with OCD exhibit increased switch costs—namely, longer reaction times and higher error rates—when compared to healthy controls. This suggests a deficit in the ability to shift attention and strategies flexibly, potentially due to dysfunction in the fronto-parietal network and altered activation of brain regions such as the superior parietal lobule and prefrontal cortex (Stein et al., 2019).

The prefrontal cortex (PFC) plays a critical role in executive functions, including inhibition and cognitive flexibility, and is implicated in OCD pathology (Carmi et al., 2018; Ahmari and Rauch, 2022). The medial PFC (mPFC) is hyperactive in OCD patients during cognitive conflict detection (Yazdi-Ravandi et al., 2018) and is associated with increased theta and decreased alpha power, serving as potential markers of symptom severity (Karadag et al., 2003).

Transcranial direct current stimulation (tDCS) modulates brain activity by delivering low electrical currents via scalp electrodes (Filmer et al., 2014). Anodal stimulation enhances brain activity, while cathodal stimulation decreases it, addressing disorders involving hyperactivity, such as OCD (Allman et al., 2016; Palm et al., 2016). Evidence suggests tDCS benefits OCD patients, reducing symptoms as measured by the Yale-Brown Obsessive Compulsive Scale (YBOCS) (Brunelin et al., 2018; Gowda et al., 2019). Additionally, cathodal stimulation over the mPFC decreases anxiety induced by obsessions in refractory OCD patients (Todder et al., 2018).

Despite the established clinical benefits of tDCS, research has predominantly focused on emotional well-being, neglecting cognitive performance. This study aims to evaluate the efficacy of cathodal tDCS in improving both neurocognitive functioning and BDNF-related symptom dimensions in OCD patients.

2. Material and methods

2.1. Participants

Twenty adult patients (13 men, 7 women; mean age = 29.07 years, SD = 9.74) diagnosed with OCD according to DSM-V criteria were recruited from the Anxiety Clinic at the Beer Sheba Mental Health Center. All participants had been on stable pharmacological treatment for at least three months prior to enrollment and were required to maintain their medication regimen unchanged throughout the study period .Exclusion criteria included neurological disorders, seizures, pacemakers or defibrillators, substance abuse, or any additional Axis I disorder. All procedures were conducted in compliance with relevant laws and institutional guidelines. The study was approved by the institutional ethics committee in accordance with Ministry of Health regulations (approval number: 0011–23-MHC; approval date: January 2023). The trial was registered in the Israeli Ministry of Health Clinical Trials Registry (registration number: MOH_2023-03-30_012488). All participants provided written informed consent prior to participation, and their privacy rights were fully respected throughout the study. A total of five participants dropped out before completing the intervention, resulting in a final completer sample of 15 participants. The sample size was determined by feasibility, given the preliminary nature of the study.

2.2. Tools

2.2.1. Transcranial direct current stimulation (tDCS)

We used the Soterix Medical 1 × 1 transcranial direct current low-intensity stimulator (Model 1300 A; Soterix Medical Inc., Woodbridge, NJ, USA as the tDCS device. This battery-operated unit delivers a stable, direct current as a medical intervention. The current is administered through a pair of saline- soaked (0.9% NaCl) sponge electrodes, each measuring 35 cm² (7 cm × 5 cm).

2.3. Brain activity

To measure brain activity, EEG was recorded using the TruScan EEG system (Dymed Diagnostics) with 19 scalp electrodes positioned according to the international 10–20 electrode placement system. Resting-state EEG was recorded for 5 min with eyes closed, at a sampling rate of 750 Hz, using linked ears as the reference. A 0.5–45 Hz band-pass filter and a 50 Hz notch filter were applied to remove line noise. EEG signals were visually inspected, and segments containing ocular, movement, or muscle artifacts were manually rejected by a trained EEG technician before qEEG analysis. Quantitative EEG (qEEG) analyses were performed using NeuroGuide software (Applied Neuroscience Inc.), which generated measures of absolute and relative power. EEG was recorded from multiple scalp electrodes; however, the present neurophysiological analysis focused specifically on absolute alpha power at the Fz electrode as the frontal region-of-interest measure.

2.3.1. Brain-derived neurotrophic factor (BDNF) determination

Saliva samples were collected from each participant via passive expectoration into sterile collection tubes. Salivary BDNF was assessed as a non-invasive peripheral marker of neurotrophic activity, an approach indirectly supported by evidence linking circulating BDNF with central BDNF-related processes (Klein et al., 2011; Pan et al., 1998). BDNF concentrations were determined using a commercial human BDNF ELISA kit (Cat. No. K12–1303, KINESISDx, Krishgen Biosystems, Los Angeles, CA, USA), following the manufacturer's protocol. All samples were analyzed in duplicate by a technician who was blinded to the treatment condition.

2.3.2. Cognitive performance

Cognitive performance was assessed using a task-switching paradigm. In each trial, participants viewed a single word displayed in either green or red font. When the font was green, they were instructed to indicate the word's length. When the font was red, they were asked to identify the second-to-last letter.

Words ranged from 4 to 5 letters and consisted of commonly used Hebrew words, categorized as neutral (e.g., “table”), positive (e.g., “happy”), or negative (e.g., “pain”). Font color, which determined the task, was randomized across trials. In 50% of the trials, the font color remained consistent (“same” rule), and in the other 50%, it alternated (“different” rule), allowing assessment of cognitive flexibility under task-switching demands.

2.3.3. OCD symptoms

The Yale–Brown Obsessive–Compulsive Scale (Y-BOCS), developed by Goodman et al. (1989), is the gold standard for assessing the severity of OCD symptoms. It comprises a Symptom Checklist and a Severity Scale, evaluating obsessions and compulsions separately across five dimensions: time spent, interference, distress, resistance, and control. The total score ranges from 0 to 40, with higher scores indicating greater severity (Goodman et al., 1989). In the current study, Y-BOCS scores were used to determine baseline symptom severity, treatment response, and follow-up changes.

2.4. Procedures

The study employed a double-blind, sham-controlled, between-subjects design. Participants were assigned in a 1:1 ratio to the experimental or control group using a random number generator to ensure equal allocation. Participants, tDCS operators, clinical outcome assessors, and laboratory technicians were blinded to group allocation throughout the study. Blinding effectiveness was not formally assessed. The experimental group received cathodal tDCS at 2 mA for 20 min, applied to the medial prefrontal cortex (mPFC) at FPz (based on the international 10–20 EEG system), with the anodal electrode placed on the wrist. This montage was selected based on prior work using cathodal tDCS over the mPFC to reduce obsession-induced anxiety in patients with refractory OCD (Todder et al., 2018).

The control group received sham stimulation with identical electrode placement, but current was delivered only during the first 30 s. Both groups completed 10 sessions of tDCS across two blocks of five consecutive daily sessions.

Assessments— including Y-BOCS ratings administered by psychiatry residents and psychiatrists, quantitative EEG (qEEG), and cognitive tasks—were administered at three time points: before the first session (T1), after the tenth session (T2), and at follow-up (T3), conducted 30–40 days post-intervention. This window was allowed to accommodate participant scheduling constraints. Exact follow-up timing by participant was not available for analysis. Saliva samples were collected at each time point to assess BDNF levels and evaluate the immediate and long-term effects of tDCS on neural plasticity.

2.5. Statistical analysis

All statistical analyses were performed using JASP (version 0.19.1). Unless otherwise specified, all tests were two-tailed. Effect sizes were calculated and reported alongside p-values to provide context for the magnitude of observed effects. Baseline characteristics of the experimental and sham-control groups were compared using independent-samples t-tests for continuous variables and chi-square tests for categorical variables. Assumptions of normality and homogeneity of variance were verified using the Shapiro-Wilk and Levene's tests, respectively, as implemented in JASP.

2.5.1. Primary outcome analysis

Changes in Y-BOCS scores were evaluated using repeated-measures Analysis of variance (ANOVA), with time (baseline, post-treatment, and follow-up) as a within-subjects factor and group (experimental vs. sham control) as a between-subjects factor. Greenhouse-Geisser corrections were applied when sphericity assumptions were violated. Post hoc pairwise comparisons with Bonferroni corrections were performed to adjust for control for multiple comparisons.

2.5.2. Secondary outcome analyses

Frontal Neural Activity (frontal alpha activity at the Fz electrode site), cognitive performance (task-switching test outcomes, including reaction times and accuracy), and salivary BDNF levels were evaluated using repeated-measures ANOVA, with time (baseline vs. post-treatment) as a within-subject factor and group as a between-subject factor. Bonferroni corrections were applied to post hoc comparisons to control for Type I errors.

2.5.3. Missing data

In the middle of the study, the qEEG amplifier used for data collection broke down. Replacing the equipment required significant time due to logistical challenges during the ongoing war in Israel. As a result, some participants could not complete the qEEG assessments, leading to missing data. Despite this, analyses were conducted on the available data to assess the z-scores of absolute alpha power at Fz.

3. Results

The final analytic sample included 15 participants, with eight in the cathodal tDCS group and seven in the sham-control group. All discontinuations were due to participants' inability or reluctance to attend in-person treatment sessions during a period of heightened security instability in Israel. Participant flow from randomization through allocation, discontinuation, and analysis is presented in the CONSORT flow diagram (see Fig. 1).

Fig. 1.

CONSORT flow diagram of participant randomization, allocation, discontinuation, and analysis.

The groups did not differ significantly on any demographic variables (e.g., age, sex, education) or clinical characteristics, including Y-BOCS symptom severity, baseline salivary BDNF levels and z-scores of absolute alpha power recorded at the Fz electrode (see Table 1).

Table 1.

Baseline demographic and clinical characteristics.

Demographic	TreatmentN = 8a	ControlN = 7a	Pbb
Age	28.25 (10.98)a	30.00 (9.73)	0.862
Sex			0.999
Male	4 (50%)	4 (57%)
Female	4 (50%)	3 (43%)
Education (years)	13.11 (1.26)	12.99 (1.50)	0.770
YBOCS	31 (11.29)	30.1 (7.87)	0.902
BDNF	0.118 (0.11)	0.158 (0.08)	0.139
Fz Alpha Power	0.92 (1.41)	1.26 (0.82)	0.063

Note. Values represent mean (SD) for continuous variables and % for categorical variables.

YBOCS = Yale-Brown Obsessive Compulsive Scale; BDNF = Brain-Derived Neurotrophic Factor; Fz Alpha Power = z-scores of absolute alpha activity recorded at the Fz electrode using qEEG.

p-values are based on Wilcoxon rank-sum test (continuous) and Fisher's exact test (categorical).

^aMean (SD); (%).

^bWilcoxon rank sum test; Fisher's exact test.

3.1. Symptom severity: Y-BOCS

At baseline (T1), the mean score for the experimental group was 31.0 (SD = 11.29), and for the control group, it was 30.1 (SD = 7.87). After the final session (T2), the experimental group had a mean score decreased to 23.78 (SD = 12.56), while the control group's mean score was 30.8 (SD = 9.46). At follow-up (T3), the experimental group's mean score further decreased to 22.89 (SD = 10.57), while the control group's mean score was 29.8 (SD = 8.15).

A repeated-measures ANOVA was conducted to examine the effects of time (baseline [T1], post-treatment [T2], and follow-up [T3]) and group (experimental vs. control) on symptom severity. The analysis revealed significant main effects for time (F(2, 26) = 11.858, p < 0.001, partial η² = 0.411) and a significant time × group interaction (F(2, 26) = 12.562, p < 0.001, partial η² = 0.425), indicating that changes in symptom severity differed between groups across the three time points (see Fig. 2(. No significant main effect was found for group (F(1,13) = 0.936, p = 0.347).

Fig. 2.

Clinical effect of the treatment Across Time by Group.

Note. Mean YBOCS scores for the treatment and control groups at three time points: baseline (T1), post-treatment (T2), and follow-up (T3). Error bars represent standard errors.

Pairwise comparisons were conducted to further explore the significant time × group interaction: For the experimental group, symptom severity decreased significantly from T1 to T2 (t = 5.493, p < 0.001, Cohen's d = 0.72) and from T1 to T3 (t = 6.169, p < 0.001, Cohen's d = 0.808). No significant changes were observed across time points for the control group (p > 0.05). Between-group comparisons at each time point revealed no significant differences in symptom severity (p > 0.05).

Simple main effects analysis indicated that changes over time were significant in the experimental group (F(2, 14) = 17.836, p < 0.001), while no significant changes were observed in the control group (F(2,12) = 0.453, p = 0.643).

3.2. Neurophysiological changes: frontal neural activity

A repeated-measures ANOVA was conducted to examine the effects of time (T1: baseline, T2: post-treatment, T3: follow-up) and group (experimental vs. control) on the z-scores of absolute alpha power at the Fz electrode, as measured by qEEG.

There was no significant main effect of time on the z-scores of absolute alpha power (F(2, 14) = 2.386, p = 0.128, partial η² = 0.254). However, a significant time × group interaction was observed (F(2, 14) = 3.8, p = 0.048, partial η² = 0.352), indicating that changes in alpha power over time differed between the experimental and control groups (see Fig. 3). The Greenhouse-Geisser correction for sphericity was applied (Mauchly's W = 0.319, p = 0.033), yielding an adjusted interaction effect (F(1.19, 8.331) = 3.8, p = 0.081), which approached significance.

Fig. 3.

Frontal Neural Activity Across Time by Group

Note. Z-scores reflect absolute alpha power values recorded at the Fz electrode during resting-state EEG. Values represent group means across three time points: baseline (T1), post-treatment (T2), and follow-up (T3). Error bars represent standard errors.

The between-subjects effect of group on alpha power was not significant (F(1, 7) = 0.001, p = 0.973, partial η² = 0.000).

At T1 (baseline), the experimental group had a mean z-score of 0.921 (SD = 1.413), while the control group had a mean of −1.257 (SD = 0.821). At T2 (post-treatment), the experimental group's mean z-score was 0.062 (SD = 3.016), while the control group's mean increased to 3.25 (SD = 3.662). At T3 (follow-up), the experimental group's mean z-score was 0.094 (SD = 1.966), while the control group's mean decreased to −0.797 (SD = 2.589). Mauchly's test indicated that the assumption of sphericity was violated (p = 0.033). The Greenhouse-Geisser correction (ε = 0.595) was applied. Equality of Variances: Levene's test confirmed equal variances across groups for all time points (p > 0.05).

Custom contrasts for the time × group interaction indicated that none of the comparisons reached significance after Bonferroni correction (p > 0.05).

3.3. Cognitive task-switching

A repeated-measures ANOVA was conducted to examine the effects of time (baseline, end of treatment, follow-up), trial type (same vs. different), word type (negative, positive, neutral), and group (experimental vs. control) on reaction times. Descriptively, the experimental group demonstrated longer reaction times across conditions at baseline compared to the control group. At follow-up, the experimental group showed greater reductions in reaction times, particularly in the neutral and positive word conditions. The analysis revealed a significant time × group interaction (F(2, 26) = 20.351, p < 0.001, partial η² = 0.531), indicating that changes in reaction times over time differed between the experimental and control groups (see fig. 4). Reaction times in the control group varied significantly across time points (F(2, 12) = 5.752, p = 0.015), with the most substantial changes observed at follow-up. In contrast, the experimental group demonstrated a more pronounced reduction in reaction times across time points (F(2, 14) = 22.573, p < 0.001).

Fig. 4.

Reaction Times Across Time Points by Group, Task Type, and Emotion.

Note. Values represent mean reaction times (in milliseconds) across three time points (T1 = baseline, T2 = post-treatment, T3 = follow-up), separately for same-task and different-task conditions and for each emotional valence (positive [POS], neutral [NEU], negative [NEG]). Error bars represent standard errors.

The trial type × group interaction was also significant (F(1, 13) = 7.202, p = 0.015, partial η² = 0.286), showing that differences between same and different trials varied by group. However, no significant main effect of word type or its interaction with group was found (F(2, 26) = 1.044, p = 0.362, partial η² = 0.055).

The main effect of group was not significant (F(1, 13) = 0.068, p = 0.797), suggesting times. Deviation contrasts revealed significant group differences between baseline and end of treatment (t(18) = 2.482, p = 0.023, Cohen's d = 0.454). No other contrasts no overall differences between the experimental and control groups in reaction were statistically significant.

3.4. Salivary BDNF concentrations

At baseline, the mean BDNF level in the treatment group was 0.118 (SD = 0.118), compared to 0.158 (SD = 0.085) in the sham group. By the end of treatment, the treatment group's BDNF levels increased to 0.143 (SD = 0.153), while the sham group's levels were 0.138 (SD = 0.113). At follow-up, the treatment group exhibited a substantial increase in BDNF levels to 0.43 (SD = 0.351), whereas the sham group showed a smaller increase to 0.208 (SD = 0.16).

There was a significant main effect of time on BDNF levels (F(2, 26) = 3.851, p = 0.034, partial η² = 0.229), indicating that BDNF levels varied across time points (see fig. 5). However, the time × group interaction was not significant (F(2, 26) = 1.745, p = 0.195, partial η² = 0.118), suggesting that changes over time were similar across groups.

Fig. 5.

Mean Salivary BDNF Levels Over Time by Group.

Note. Mean salivary BDNF concentrations for the treatment and control groups across three time points: baseline (T1), post-treatment (T2), and follow-up (T3). Error bars represent standard errors.

No significant main effect of group was observed (F(1, 13) = 0.766, p = 0.397, partial η² = 0.056), indicating that overall BDNF levels did not differ significantly between the treatment and sham groups.

Pairwise comparisons showed a significant increase in BDNF levels from baseline to follow-up within the treatment group (F(2, 16) = 6.086, p = 0.01, partial η² = 0.432). No significant changes across time were observed in the sham group (F(2,10) = 0.636, p = 0.554, partial η² = 0.113). The between-group difference at follow-up approached significance, with the treatment group demonstrating higher BDNF levels compared to the sham group (mean difference = 0.222, t(13) = 1.325, p = 0.088, Cohen's d = 1.085).

4. Discussion

This preliminary study investigated the therapeutic potential of cathodal transcranial direct current stimulation (tDCS) over the medial prefrontal cortex (mPFC) in obsessive-compulsive disorder (OCD). The findings demonstrate that cathodal tDCS can significantly reduce OCD symptoms, improve cognitive flexibility, and influence brain-derived neurotrophic factor (BDNF) levels, highlighting its multifaceted benefits.

4.1. Symptom reduction

Cathodal tDCS significantly reduced symptom severity in the experimental group, with sustained improvements observed at follow-up. This aligns with prior studies that have demonstrated the efficacy of tDCS in modulating hyperactive cortical regions associated with OCD, such as the mPFC (Brunelin et al., 2018; Carmi et al., 2018). Hyperactivity in the mPFC has been linked to heightened conflict monitoring and intrusive thoughts in OCD patients (Yazdi-Ravandi et al., 2018). Recent reviews have highlighted the potential of tDCS as an adjunctive treatment for OCD, particularly in treatment-resistant populations (Brunelin et al., 2018; Gowda et al., 2019).

4.2. Cognitive flexibility

Improvements in task-switching performance in the experimental group suggest that tDCS enhances cognitive flexibility, a core deficit in OCD (Gruner and Pittenger, 2017). Cognitive flexibility is essential for adapting to changing environmental demands, and its impairment exacerbates obsessive and compulsive behaviors) Penadés et al., 2007(. Previous research has shown that cathodal tDCS over the prefrontal cortex can modulate executive functions and improve cognitive processes impaired in OCD (Filmer et al., 2014; Liu et al., 2023). These findings support the hypothesis that tDCS enhances the brain's capacity to adapt to novel contexts by reducing hyperactivity in the mPFC.

4.3. Neurophysiological findings

Although no significant main effect of time on frontal alpha activity was observed, the time × group interaction suggests a differential pattern of change between groups. Specifically, frontal alpha activity remained relatively stable in the cathodal tDCS group, whereas the control group showed a transient increase at post-treatment. This pattern does not indicate a uniform reduction in alpha power following cathodal tDCS, but may suggest greater stability of frontal alpha activity over time. Reduced frontal alpha activity has been associated with cognitive control deficits in OCD (Karadag et al., 2003). Our findings are consistent with prior research demonstrating that tDCS can modulate abnormal cortical activity, promoting better cognitive and emotional regulation (Allman et al., 2016(. However, the variability in outcomes across studies suggests that further research is needed to refine stimulation protocols and identify patient-specific factors influencing responsiveness.

4.4. BDNF modulation

The increase in salivary brain-derived neurotrophic factor (BDNF) levels in the treatment group at follow-up highlights the potential neuroplasticity-enhancing effects of tDCS. BDNF is critical for neuronal growth, synaptic plasticity, and learning, and its dysregulation has been implicated in OCD pathology (Wang et al., 2019; Hao et al., 2022). Previous studies have shown that reduced BDNF levels correlate with cognitive deficits and symptom severity in OCD (dos Santos et al., 2011). Neuromodulation techniques, including tDCS, may enhance BDNF expression, contributing to symptom alleviation and cognitive improvements (Palm et al., 2016; Brunelin et al., 2018).

The delayed elevation of salivary BDNF following tDCS may reflect sustained neuroplastic adaptations within central stress-regulatory neural circuits. This delayed pattern is consistent with evidence from preclinical tDCS studies, in which BDNF upregulation was reported 24 h and up to one week after stimulation (Podda et al., 2016). These neurobiological changes likely underpin tDCS-induced improvements in cognitive and affective processing, potentially mediated through strengthened connectivity in cortico-limbic networks, including the prefrontal cortex and amygdala. The temporal delay in BDNF upregulation, observed approximately two weeks post-treatment, suggests a cascade of molecular and cellular events, such as activation of neurotrophic signaling pathways (e.g., TrkB receptor signaling) and epigenetic modifications, which support long-term neural plasticity and resilience against stress-related dysfunction. These findings underscore the importance of integrating neurobiological markers into studies evaluating the therapeutic effects of tDCS.

4.5. Clinical implications

This study suggests that cathodal tDCS could serve as a promising intervention for OCD, addressing both emotional and cognitive dimensions. However, the present findings should be interpreted within the broader context of prior tDCS studies in OCD, which have yielded mixed findings that may partly reflect differences in stimulation protocols. Several studies have reported symptom reduction following active stimulation, including cathodal stimulation over medial prefrontal regions, similar to the present study, and stimulation targeting the pre-supplementary motor area (Todder et al., 2018; Gowda et al., 2019). At the same time, systematic reviews and meta-analytic work have noted heterogeneity in clinical efficacy findings, which may reflect, at least in part, variability in stimulation protocols, including stimulation target, montage configuration, polarity, stimulation dose, and number of sessions (Brunelin et al., 2018; Pinto et al., 2023). More recently, Chu et al. (2025) compared different cathodal tDCS montages in treatment-resistant OCD and identified dual-site orbitofrontal cortex–pre-supplementary motor area stimulation as the most promising montage in their sample. Taken together, these findings suggest that variability between the present findings and prior studies may reflect protocol-level and sample-related differences rather than a uniform effect of tDCS across all stimulation approaches. Within this context, the present findings add to the emerging literature suggesting that cathodal tDCS may have clinical and cognitive benefits in OCD, while also underscoring the need to refine stimulation parameters. The observed cognitive improvements suggest that tDCS may complement behavioral interventions by supporting cognitive flexibility and patients' ability to adapt to changing contexts, processes that are often impaired in OCD.

4.6. Limitations

Several limitations should be acknowledged. The study's limited sample size constrains the generalizability of the findings. Direct comparison of the present partial η² values with previous tDCS trials in OCD was limited by differences in reported effect-size metrics and stimulation protocols. Therefore, the large effect sizes observed in the present study should be interpreted cautiously, particularly given the small sample size. Furthermore, logistical challenges due to the ongoing conflict in Israel resulted in participant attrition and missing data, particularly for neurophysiological assessments. Future research should employ larger samples, rigorous sham-controlled designs, and standardized tDCS protocols to validate these findings and explore long-term effects.

5. Conclusion

Cathodal tDCS targeting the mPFC significantly reduces OCD symptoms, improves cognitive flexibility, and enhances neurobiological markers such as BDNF. These findings contribute to the growing evidence supporting tDCS as a promising adjunctive treatment for OCD. However, further research is essential to establish standardized protocols, explore patient-specific factors influencing responsiveness, and confirm the efficacy of tDCS in larger, diverse populations.

Author Note

The authors declare no conflicts of interest. This study was conducted independently and was not supported by any commercial interests or external funding sources. The study was approved by an institutional ethics committee adhering to the principles outlined in the Declaration of Helsinki.

CRediT authorship contribution statement

Rut Zaks-Ohayon: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Software, Writing – original draft. Talia Beit-On Hakmon: Data curation, Visualization, Writing – review & editing. Hagit Cohen: Writing – review & editing. Itay Besser: Supervision. Zippi Frenkel: Writing – original draft. Jonathan Guez: Supervision. Doron Todder: Conceptualization, Supervision.

Declaration of generative AI and AI-assisted Technologies in the Writing Process

During the preparation of this work, the authors used [OpenAI/ChatGPT] to improve wording in some sections. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Funding

This work was supported by internal resources of the Beer-Sheva Mental Health Center, Ministry of Health, Israel. No external funding was received for this study.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.