NCT06834217

Transcranial Direct Current Stimulation and Extinction in Obsessive Compulsive Disorder

Characterization and Modulation of Functional Connectivity and Fear Extinction Abnormalities in Obsessive-Compulsive Disorder

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 180 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

Obsessive-compulsive disorder (OCD) is associated with substantial impairments in quality of life and is among the most disabling psychiatric disorders. Exposure therapy is among the first-line of treatments for obsessive-compulsive disorder (OCD) . Extinction learning is thought to be a core mechanism of therapeutic exposure. Fear and safety signal learning are traditionally associated with activity and connectivity within the canonical corticolimbic "fear circuit", which includes the amygdala, medial prefrontal cortex (mPFC), and hippocampus. Transcranial direct current stimulation (tDCS) is a neuromodulation technology that can augment brain plasticity, learning, and memory. The proposed study will test if obsessive-compulsive disorder (OCD) is associated with inhibitory safety learning deficits and if transcranial direct current stimulation (tDCS) normalizes functional connectivity and safety signal processing to recover extinction deficits in obsessive-compulsive disorder (OCD).

Detailed description

The proposed study aims to test if obsessive-compulsive disorder (OCD) is associated with dyconnectivity between the default mode network (DMN) and salience network (SN) (Aim 1), if obsessive-compulsive disorder (OCD) is associated with extinction learning deficits (Aim 2), and if front-polar transcranial direct current stimulation (tDCS) normalizes dysconnectivity and extinction learning in obsessive-compulsive disorder (OCD) (Aim 3). This study will randomize 180 adults with obsessive-compulsive disorder (OCD) (n=120) and matched non-clinical controls (n=60) for aims 1-3. After providing informed consent, baseline screening, and clinical characterization, participants would complete a three-day experiment. On day 1, all participants would complete structural and resting functional magnetic resonance imaging (fMRI) scans followed by standardized fear conditioning procedures with functional magnetic resonance imaging (fMRI) and measures of fearful responding (i.e., skin conductance response \[SCR\] and threat expectancy ratings). Participants would be conditioned to two different conditioned stimuli (CS+; CS+A and CS+B) by pairing each CS+ with an aversive shock (unconditioned stimulus \[US\]) at a 50% schedule of reinforcement. A third, neutral stimulus (CS-), would never be paired with the US. On day 2, participants would complete extinction training for the CS+A, then participants with obsessive-compulsive disorder (OCD) would be randomized (1:1, stratified, double-blind) to receive active or sham multifocal frontopolar transcranial direct current stimulation (tDCS) with resting functional magnetic resonance imaging (fMRI) before, during, and after transcranial direct current stimulation (tDCS). Blocked randomization, stratified by sex, age, and current psychiatric medication usage, would be implemented by an individual who would have no direct contact with the participants and no knowledge of the assignment to the group labels. Participants and assessors will be blind to allocation. All non-clinical controls would not receive any transcranial direct current stimulation (tDCS). Next, extinction training for the CS+B would be completed. On day 3, return of fear testing (spontaneous recovery, context renewal, and reinstatement) would be completed. Transcranial direct current stimulation (tDCS) would be administered using a battery-driven, Soterix© transcranial electric stimulator. A single anode would be placed over the frontal pole and five return electrodes would be arranged in a circumferential array. Positively charged e-fields produced by this montage would concentrate over the medial frontal pole. Participants in the active-transcranial direct current stimulation (tDCS) condition would receive 20-minutes of offline (while resting with eyes open) frontopolar transcranial direct current stimulation (tDCS) (30-seconds ramp in/out). Participants in the sham-transcranial direct current stimulation (tDCS) condition would receive 30-seconds ramp in/out followed by 20-minutes of no stimulation. Brain imaging would be performed with a Siemens MAGNETOM Prisma 3T scanner using a 64-channel phased array padded head coil. A vitamin E capsule would be secured to the outer center of the transcranial direct current stimulation (tDCS) anode to create a precise contrast in structural magnetic resonance imaging (MRI). After localization, all participants would undergo anatomical imaging for registration and normalization purposes. 6-min of rs-functional magnetic resonance imaging (fMRI) data would be collected immediately before and after frontopolar transcranial direct current stimulation (tDCS) and four \~5-min blocks rs-functional magnetic resonance imaging (fMRI) sequences would be collected during the 20-min of active- or sham-transcranial direct current stimulation (tDCS) to characterize temporal elements of dosage (e.g., linear change in rs-FC over the time course of transcranial direct current stimulation \[tDCS\] administration) in exploratory analyses.

Conditions

• Obsessive Compulsive Disorder (OCD)

Interventions

Type	Name	Description
DEVICE	Active transcranial direct current stimulation	Multifocal transcranial direct current stimulation will be delivered. The anode will be placed over the frontal pole (Fpz, 10-20 electroencephalogram \[EEG\]) and will be surrounded by 5 return electrodes (cathodes). Current will be set at 1.5mA and will be ramped in and out for 30 seconds at the beginning and end of a 20-minute stimulation period.
DEVICE	Sham transcranial direct current stimulation	Multifocal transcranial direct current stimulation will be delivered. The anode will be placed over the frontal pole (Fpz, 10-20 electroencephalogram \[EEG\]) and will be surrounded by 5 return electrodes (cathodes). Current will be set at 1.5mA and will be ramped in and out for 30 seconds at the beginning of a 20-minute period.

Timeline

• Start date: 2025-09-12
• Primary completion: 2029-04-01
• Completion: 2029-08-01
• First posted: 2025-02-19
• Last updated: 2026-02-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study