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Updated: Oct 11, 2026
High-definition Transcranial Direct Current Stimulation over Right Dorsolateral Prefrontal Cortex to Enhance Metacognitive Sensitivity
Published on: September 26, 2025
High-definition transcranial direct current stimulation (HD-tDCS) modulates neural response for face-emotion
Paloma Pfeiffer1, Artemis Zavaliangos-Petropulu1, Brandon Taraku1
1Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, United States.
Background:
Transcranial direct current stimulation (tDCS) may alleviate depressive symptoms. Using a face-emotion recognition fMRI task, we investigated whether left dorsolateral prefrontal cortex (DLPFC) high-definition (HD)-tDCS modulates neural circuitry associated with affective processing biases in major depressive disorder (MDD).
Methods:
As part of an exploratory clinical trial, MDD patients were randomized to receive 12-daily 20-minute sessions of 2 mA active (n=37, age: 35.0±8.8years, 59%F) or sham (n=29, age: 33.0±10.5 years, 65%F) HD-tDCS. Clinical and task-fMRI data were collected pre- and post-treatment. Analyses compared blood-oxygen-level-dependent (BOLD) response over time between active and sham groups for processing of happy, fearful, and neutral face stimuli versus objects at the whole-brain level and within hippocampal and amygdala regions-of-interest (ROIs).
Results:
Whole-brain analysis showed significant group-by-time interactions for fearful faces versus objects in right fronto-parietal regions (FWE, p<0.05), with the active and sham groups exhibiting increased and decreased activation, respectively. Increased right-hippocampal BOLD response for happy or fearful faces, and all faces versus objects occurred for active HD-tDCS, but not for sham (FWE, p<0.05). Left-hippocampal activity decreased for happy faces versus objects in the sham group (p<0.05). Increased right-hippocampal activity for fearful versus objects correlated with improved anxiety in the active group (p<0.05).
Conclusions:
Left DLPFC HD-tDCS modulated distributed cortical and hippocampal circuitry involved in emotional face processing. The association between right hippocampal activation and anxiety improvement suggests a potential role for hippocampal function in treatment response and warrants further investigation as a candidate neuroimaging biomarker.
