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

Thomas G. Adams, Josh M. Cisler, Benjamin Kelmendi, Jamilah R. George, Stephen A. Kichuk, Christopher L. Averill, Alan Anticevic, Chadi G. Abdallah, Christopher Pittenger

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)37-48
Number of pages12
JournalDepression and Anxiety
Volume39
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
We would like to thank Eileen Billingslea, MA, and Suzanne Wasylink, RN‐C, for their assistance with IRB and clinical trial compliance, subject recruitment and screening, and budget management. Portions of these data were presented at annual conferences for the American College of Neuropsychopharmacology (ACNP) and Anxiety and Depression Association of America (ADAA). Dr. Adams and the reported studies were supported by the National Institute of Mental Health (NIMH; K23MH111977, T32MH062994, and L30MH111037). Study 1 was also supported, in part, by the Clinical Neurosciences Division of the National Center for PTSD and the Department of Veteran Affairs. Brain stimulation equipment was loaned by Starstim® to support study pilots and was purchased using funds from the Detre Foundation (R13306). Study 2 was supported, in part, by an International Obsessive‐Compulsive Disorder Foundation (IOCDF) Young Investigator Award and an American Psychiatric Association (APA) Psychiatric Fellowship Award (R12965). These studies were also supported by the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center. Dr. Anticevic is supported by the NIMH (R01MH108590). Dr. Abdallah is supported by the Beth K. and Stuart Yudofsky Chair in the Neuropsychiatry of Military Post Traumatic Stress Syndrome. Dr. Pittenger is supported by the Taylor Family Foundation and the NIMH (R01MH116038 and K24MH121571). The views in this article are those of the authors, not of the State of Connecticut or of other funders.

Funding Information:
We would like to thank Eileen Billingslea, MA, and Suzanne Wasylink, RN-C, for their assistance with IRB and clinical trial compliance, subject recruitment and screening, and budget management. Portions of these data were presented at annual conferences for the American College of Neuropsychopharmacology (ACNP) and Anxiety and Depression Association of America (ADAA). Dr. Adams and the reported studies were supported by the National Institute of Mental Health (NIMH; K23MH111977, T32MH062994, and L30MH111037). Study 1 was also supported, in part, by the Clinical Neurosciences Division of the National Center for PTSD and the Department of Veteran Affairs. Brain stimulation equipment was loaned by Starstim? to support study pilots and was purchased using funds from the Detre Foundation (R13306). Study 2 was supported, in part, by an International Obsessive-Compulsive Disorder Foundation (IOCDF) Young Investigator Award and an American Psychiatric Association (APA) Psychiatric Fellowship Award (R12965). These studies were also supported by the State of Connecticut through its support of the Ribicoff Research Facilities at the Connecticut Mental Health Center. Dr. Anticevic is supported by the NIMH (R01MH108590). Dr. Abdallah is supported by the Beth K. and Stuart Yudofsky Chair in the Neuropsychiatry of Military Post Traumatic Stress Syndrome. Dr. Pittenger is supported by the Taylor Family Foundation and the NIMH (R01MH116038 and K24MH121571). The views in this article are those of the authors, not of the State of Connecticut or of other funders.

Publisher Copyright:
© 2021 Wiley Periodicals LLC

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

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