Transcranial direct current stimulation targeting the medial prefrontal cortex modulates functional connectivity and enhances safety learning in obsessive-compulsive disorder: Results from two pilot studies

Abstract

Background: Exposed-based psychotherapy is a mainstay of treatment for obsessive-compulsive disorder (OCD) and anxious psychopathology. The medial prefrontal cortex (mPFC) and the default mode network (DMN), which is anchored by the mPFC, promote safety learning. Neuromodulation targeting the mPFC might augment therapeutic safety learning and enhance response to exposure-based therapies.

Methods: To characterize the effects of mPFC neuromodulation on functional connectivity, 17 community volunteers completed resting-state functional magnetic resonance imaging scans before and after 20 min of frontopolar anodal multifocal transcranial direct current stimulation (tDCS). To examine the effects of tDCS on therapeutic safety learning, 24 patients with OCD completed a pilot randomized clinical trial; they were randomly assigned (double-blind, 50:50) to receive active or sham frontopolar tDCS before completing an in vivo exposure and response prevention (ERP) challenge. Changes in subjective emotional distress during the ERP challenge were used to index therapeutic safety learning.

Results: In community volunteers, frontal pole functional connectivity with the middle and superior frontal gyri increased, while connectivity with the anterior insula and basal ganglia decreased (ps < .001, corrected) after tDCS; functional connectivity between DMN and salience network also decreased after tDCS (ps < .001, corrected). OCD patients who received active tDCS exhibited more rapid therapeutic safety learning (ps < .05) during the ERP challenge than patients who received sham tDCS.

Conclusions: Frontopolar tDCS may modulate mPFC and DMN functional connectivity and can accelerate therapeutic safety learning. Though limited by small samples, these findings motivate further exploration of the effects of frontopolar tDCS on neural and behavioral targets associated with exposure-based psychotherapies.

Trial registration: ClinicalTrials.gov NCT03572543.

Keywords: TMS/DBS/VNS; behavior therapy; brain stimulation; cognitive behavior therapy (CBT); obsessive-compulsive disorder (OCD).

© 2021 Wiley Periodicals LLC.

Figures

Figure 1.

1.5 mA multifocal tDCS was administered using a Starstim transcranial electric stimulator, with a 1 cm2 anode over Fpz (10-20 EEG) surrounded by five cathodes in a circumferential array (AF3, AF4, F3, FZ, and F4). Simulation of the electrical fields produced by this montage was performed using Stimweaver and showed enhance electrical field potentials throughout the mPFC, particularly the frontopolar cortex and adjacent cortices, with limited effects on surrounding grey matter, including in brain tissue beneath the cathodes.

Figure 2.

(A) Seed-based functional connectivity analyses with stringent cluster correction (p < .001, cluster sizes > 31 voxels) before and after administration of tDCS identified reduced negative functional connectivity between the frontopolar (FP) seed (red) and the right anterior insula / putamen (AI/Put; green) and pallidum / caudate (Pal/Cau; orange) and increased functional connectivity between the FP and the right superior and middle frontal gryi ([sFG] blue and [mFG] yellow). (B) Mean connectivity between FP and each of these clusters before and after tDCS.

Figure 2.

(A) Seed-based functional connectivity analyses with stringent cluster correction (p < .001, cluster sizes > 31 voxels) before and after administration of tDCS identified reduced negative functional connectivity between the frontopolar (FP) seed (red) and the right anterior insula / putamen (AI/Put; green) and pallidum / caudate (Pal/Cau; orange) and increased functional connectivity between the FP and the right superior and middle frontal gryi ([sFG] blue and [mFG] yellow). (B) Mean connectivity between FP and each of these clusters before and after tDCS.

Figure 3.

Inter-network connectivity between the salience network (SN) and subnetworks of the default mode network ([DMN] ventral, posterior, and medial) significantly (ps < .005, significant after Bonferroni correction) decreased following administration of frontopolar tDCS.

Figure 4.

Despite nearly identical SUDS ratings at the beginning of the ERP Challenge (min. 1 of trial 1), OCD patients who received active tDCS reported significantly greater within-trial (solid lines, p ≤ .05) and between-trial (dashed lines, p ≤ .01) therapeutic extinction learning than those who received sham stimulation. Note. SUDS = Subjective Units of Distress (0-100)