Cerebellar Neuromodulation to Enhance Fear Extinction and Predict Response to Exposure Therapy

Emerging neuroimaging studies have shown that the cerebellum contributes to different aspects of timing, prediction, learning, and extinction of conditioned responses to aversive stimuli, factors that may be relevant to the success of exposure based behavioral therapy. Our goals are to determine the cerebellar contributions to fear extinction by attempting to modulate key pathways in this process by theta burst stimulation. The long term goal is to lay the foundation for future studies in which neuromodulation is used to augment exposure therapy.

Study Overview

• Status: Completed
• Conditions: Anxiety Disorders; Social Phobia
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation

Detailed Description

Participants in this study will undergo an assessment for past history and present symptoms of mood, anxiety, trauma, substance abuse, and eating disorders. Safety screening for functional MRI (fMRI) and repetitive transcranial magnetic stimulation (rTMS) will be performed prior to enrollment.

Phase 1 of the study involves two visits. The first visit involves undergoing an fMRI scan and a motor thresholding procedure for rTMS. A clinical assessment will be performed for the above symptoms, or a recap of symptoms if the participant had been previously assessed at our institute.

The second visit involves a fear conditioning session performed in the fMRI scanner followed by one session of rTMS over either a cerebellar or occipital lobe (control) target. This will be immediately followed by a fear extinction phase, also in the fMRI scanner. The participant will return in 24hours to determine consolidation of the fear extinction process.

Phase 2 is similar to Phase 1, except that each participant will undergo two sessions of the fear conditioning and fear extinction phases while undergoing an fMRI scan. In one session, they will receive rTMS over a cerebellar target. In the other session, they will receive rTMS over a control site. These sessions will be separated by at least 1 week.

The participants will then undergo 10 weeks of exposure therapy for social phobia. The goal is to determine whether neuroplasticity related to cerebellar stimulation can predict the response to exposure therapy.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74011
      • Laureate Institute for Brain Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Generalize Anxiety or Social Phobia with an OASIS score =>8

Exclusion Criteria:

• Safety concerns related to undergoing an fMRI scan or tDCS, such as metal in the head, history of unprovoked seizures in self or a first-degree family member, medications that reduce seizure threshold, pregnant or planning to become pregnant.
• History of Post Traumatic Stress Disorder, Obsessive Compulsive Disorder, Panic Disorder, Current Major Depressive Illness, Substance Abuse in the past 1-year, or any thought disorder such as schizophrenia or bipolar disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anodal tDCS; Anodal tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.	Device: Transcranial Direct Current Stimulation; tDCS is a non-invasive form of neuromodulation in which direct current is administered placed over a brain region of interest to induce physiological changes such as inhibition or excitation over that region.; Other Names: tDCS
Experimental: Cathodal tDCS; Cathodal tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.	Device: Transcranial Direct Current Stimulation; tDCS is a non-invasive form of neuromodulation in which direct current is administered placed over a brain region of interest to induce physiological changes such as inhibition or excitation over that region.; Other Names: tDCS
Active Comparator: Sham tDCS; Sham tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.	Device: Transcranial Direct Current Stimulation; tDCS is a non-invasive form of neuromodulation in which direct current is administered placed over a brain region of interest to induce physiological changes such as inhibition or excitation over that region.; Other Names: tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activation of ventromedial prefrontal cortex after cerebellar stimulation	Activation of vmPFC	Phase 1, Years 1-3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in resting state connectivity between vmPFC and cerebellar stimulation target	Change in resting state connectivity between vmPFC and cerebellum after cerebellar stimulation	Phase 1, Years 1-3
Baseline cerebellar-cerebral connectivity prediction of exposure therapy outcomes	Baseline cerebellar-cerebral connectivity prediction of exposure therapy outcomes	Phase 2, Years 3-5

Collaborators and Investigators

• Sponsor: Laureate Institute for Brain Research, Inc.
• Investigators: Principal Investigator: Yoon-Hee Cha, MD, Laureate Institute for Brain Research

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 5, 2017
• First Posted (Actual): September 7, 2017

Study Record Updates

• Last Update Posted (Actual): September 1, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: tDCS; Neuromodulation; Anxiety; Social Phobia; Cerebellum; Fear Extinction
• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Anxiety Disorders; Phobia, Social
• Other Study ID Numbers: 2017_001_01

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: Yes
• product manufactured in and exported from the U.S.: No