Effects of tDCS on Fear Reversal in Patients With Anxiety Disorders

A Randomized, Double-Blind, Controlled Study of Transcranial Direct Current Stimulation Intervention on Fear Reversal in Patients With Anxiety Disorders

This study evaluates the effects of single-session Transcranial Direct Current Stimulation (tDCS) on fear reversal learning in patients with anxiety disorders. Participants will be randomized into four groups to receive either active stimulation targeting specific brain regions (right DLPFC or vmPFC), an active control stimulation, or sham stimulation. The main goal is to determine if modulating these brain areas can improve the ability to update safety and threat associations.

Study Overview

• Status: Enrolling by invitation
• Conditions: Anxiety Disorders
• Intervention / Treatment: Device: Cathodal tDCS (rDLPFC); Device: Anodal tDCS (vmPFC); Device: Sham tDCS; Device: Anodal tDCS (lDLPFC)

Detailed Description

Anxiety disorders are characterized by deficits in fear regulation and cognitive flexibility, specifically the inability to inhibit fear responses when a threat becomes safe (fear reversal). Neurobiological models suggest this is linked to hyperactivity in the right dorsolateral prefrontal cortex (rDLPFC) and hypoactivity in the ventromedial prefrontal cortex (vmPFC).

This randomized, double-blind, sham-controlled study aims to verify if tDCS can improve fear reversal performance. The study involves 140 patients with anxiety disorders assigned to one of four arms:

Cathodal tDCS over the right DLPFC (inhibitory); Anodal tDCS over the vmPFC (excitatory); Sham tDCS (placebo); Anodal tDCS over the left DLPFC (active control). During the 25-minute stimulation session, participants will perform a computerized fear reversal task. Physiological data (Skin Conductance Response) and subjective anxiety ratings will be recorded simultaneously to assess the intervention's impact on cognitive and emotional regulation.

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Shenzhen Kangning Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Age between 18 and 60 years old. Right-handed. Meeting the DSM-5 diagnostic criteria for Gambling Disorder (GD). South Oaks Gambling Screen (SOGS) score ≥ 5. Normal or corrected-to-normal vision and hearing. Willingness to provide written informed consent and participate in the study.

Exclusion Criteria:

History of other severe psychiatric disorders (e.g., schizophrenia, bipolar disorder, severe depression) or neurological diseases (e.g., epilepsy, stroke, brain tumor).

History of substance abuse or dependence (excluding nicotine) in the past 6 months.

Current use of psychotropic medications that may affect cortical excitability (e.g., antidepressants, antipsychotics, anticonvulsants).

Presence of metallic implants in the head or neck area (e.g., cochlear implants, aneurysm clips) or cardiac pacemakers.

Skin lesions or sensitivity at the stimulation sites on the scalp. Pregnancy or lactation. Participation in other neuromodulation studies within the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Comparator: Cathodal rDLPFC; Participants receive inhibitory stimulation over the right dorsolateral prefrontal cortex.	Device: Cathodal tDCS (rDLPFC); Current intensity: 2.0 mA. Duration: 25 minutes. Cathode placed over F4 (10-20 system), Anode over contralateral deltoid.
Experimental: Active Comparator: Anodal vmPFC; Participants receive excitatory stimulation over the ventromedial prefrontal cortex.	Device: Anodal tDCS (vmPFC); Current intensity: 2.0 mA. Duration: 25 minutes. Anode placed over Fpz (10-20 system), Cathode over Oz.
Sham Comparator: Sham Comparator: Sham tDCS; Participants receive a pseudo-stimulation that mimics the sensation of real tDCS but delivers no therapeutic current.	Device: Sham tDCS; Current ramps up for 30 seconds and then fades to zero to mimic skin sensation, with no sustained current for the rest of the 25 minutes.
Active Comparator: Active Comparator: Anodal lDLPFC; Participants receive excitatory stimulation over the left dorsolateral prefrontal cortex (positive control).	Device: Anodal tDCS (lDLPFC); Current intensity: 2.0 mA. Duration: 25 minutes. Anode placed over F3 (10-20 system), Cathode over contralateral deltoid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Accuracy Rate in the Reversal Phase of the Fear Reversal Task	The percentage of correct responses during the reversal phase of the computerized task, where participants must inhibit previous fear associations and learn new safety signals. Higher scores indicate better cognitive flexibility.	During the intervention (Day 1, approximately 25 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaction Time in the Reversal Phase	The response time (in milliseconds) to the new CS+ (formerly CS-) and new CS- (formerly CS+) stimuli during the reversal phase.	During the intervention (Day 1, approximately 25 minutes)
Skin Conductance Response (SCR) Amplitude	The amplitude of physiological skin conductance responses to Conditioned Stimuli (CS+ and CS-), serving as an objective measure of physiological arousal and fear response.	During the intervention (Day 1, approximately 25 minutes)
Subjective Anxiety Score (VAS)	Self-reported anxiety levels measured using a Visual Analog Scale (VAS). Scores range from 0 (no anxiety) to 10 (extreme anxiety).	During the intervention (Day 1, assessed intermittently during the 25-minute task)

Collaborators and Investigators

• Sponsor: Jingchu Hu

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 5, 2026
• First Submitted That Met QC Criteria: February 5, 2026
• First Posted (Actual): February 12, 2026

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: tDCS; Anxiety; Transcranial Direct Current Stimulation; Dorsolateral Prefrontal Cortex; Cognitive Flexibility; Fear Reversal; Ventromedial Prefrontal Cortex
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: KN2025407

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No