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Effectiveness of Focal High-Definition Transcranial Direct Current Stimulation Targeting the Left Dorsolateral Prefrontal Cortex on Executive Control and Depressive Symptoms in Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Trial
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1
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| Subject:
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Personalized Interventions and Diagnosis of Complex Neurological Disorders
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Presenter Author:
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| Name:
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Mojtaba Ahmadi
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Author:
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Mojtaba Ahmadi - Presenter
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| Affiliation 1:
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PhD Student in Cognitive Psychology, Department of Psychology, Azarbaijan Shahid Madani University, Tabriz, Iran. mojtaba.ahmadi@azaruniv.ac.ir
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Kian Sabokbari
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PhD Student in Cognitive Psychology, Department of Psychology, Azarbaijan Shahid Madani University, Tabriz, Iran. kian.sabokbari@azaruniv.ac.ir
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Gholamreza Chalabianloo - Corresponding
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Associate Professor in Neuroscience, Department of Psychology, Azarbaijan Shahid Madani University, Tabriz, Iran. Chalabianloo@azaruniv.ac.ir
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Abstract
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Original Research
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introduction :
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Major depressive disorder (MDD) is associated with impairments in executive control, including inhibitory control, working memory, and cognitive flexibility. Although transcranial direct current stimulation (tDCS) has emerged as a promising non-invasive neuromodulatory intervention for MDD, evidence regarding its effects on executive functioning remains limited and heterogeneous. High-definition tDCS (HD-tDCS) enables more focal cortical stimulation and may provide a targeted approach to modulating prefrontal circuits involved in executive control. This study examined the effects of focal HD-tDCS targeting the left dorsolateral prefrontal cortex (left DLPFC) on executive control and depressive symptom severity in adults with MDD.
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Methods:
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This randomized, double-blind, sham-controlled, parallel-group trial included 60 adults with MDD aged 20–40 years recruited from psychiatric clinics and specialized mental health centers in Tehran, Iran, during the first six months of 2026. Participants were initially recruited using convenience sampling and subsequently randomly allocated in a 1:1 ratio to active HD-tDCS or sham stimulation, with 30 participants per group. MDD was confirmed using the Structured Clinical Interview for DSM-5 Disorders (SCID-5), and depressive symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAM-D-17). Active stimulation was delivered using a 4 × 1 HD-tDCS montage targeting the left DLPFC, with the central anode positioned at F3 and four return electrodes at AF3, FC1, F7, and FC5. Stimulation was administered at 2.0 mA for 20 min per session over 12 sessions across two weeks. Executive control was assessed using the Stroop Color–Word Test, a 2-back working-memory task, and a task-switching paradigm. Stroop interference was the primary cognitive outcome. Post-intervention between-group differences were examined using analysis of covariance (ANCOVA), adjusting for baseline scores.
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Results:
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Fifty-eight participants completed the post-intervention assessment. Compared with sham stimulation, active HD-tDCS significantly reduced Stroop interference (adjusted mean difference = −7.84, p < .001, Hedges’ g = 0.78) and Stroop errors (adjusted mean difference = −2.31, p = .002, g = 0.69). Active HD-tDCS also improved 2-back accuracy (adjusted mean difference = 6.47 percentage points, p = .004, g = 0.63) and reduced task-switching cost (adjusted mean difference = −54.62 ms, p = .005, g = 0.61). Depressive symptom severity decreased significantly more in the active group than in the sham group (adjusted mean difference = −4.26, p = .001, g = 0.72). Exploratory analyses indicated that cognitive improvements were not fully explained by reductions in depressive symptoms.
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Conclusion:
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A two-week course of focal HD-tDCS targeting the left DLPFC was associated with improvements in inhibitory control, working memory, and cognitive flexibility, as well as reduced depressive symptom severity in adults with MDD. These findings provide preliminary evidence that focal prefrontal neuromodulation may represent a promising adjunctive approach for addressing cognitive dysfunction in MDD. Larger randomized controlled trials with longer follow-up and neurophysiological assessments are warranted to establish the durability and underlying neural mechanisms of these effects.
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| Attachment:
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| Keywords:
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Major depressive disorder; high-definition transcranial direct current stimulation; executive control; inhibitory control; working memory; dorsolateral prefrontal cortex
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| Key message:
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