Transcranial Direct Current Stimulation and Fear Extinction
The Effects of Transcranial Direct Current Stimulation on Fear Extinction Learning and Memory Processes
2 other identifiers
interventional
67
1 country
2
Brief Summary
Psychiatric disorders characterized by pathological fear and anxiety are common and often disabling. Despite their limitations, exposure therapies are among the most efficacious treatments for these disorders. Extinction learning is thought to be a core mechanism of therapeutic exposure. Extinction learning is mediated by a well-defined circuit encompassing the medial prefrontal cortex (mPFC), amygdala, and hippocampus. This raises the exciting possibility that direct engagement of this circuitry might enhance the response to therapeutic exposure. Transcranial direct current stimulation (tDCS) is a neuromodulation technology that can augment brain plasticity, learning, and memory. The proposed study will evaluate whether tDCS can engage extinction circuitry, and improve extinction learning and memory. This study will enroll psychiatrically healthy volunteers to test whether tDCS applied to the mPFC can augment spontaneous mPFC activity, engagement of extinction circuitry during extinction learning and recall, and classically-conditioned extinction learning and memory. Healthy volunteers will complete a standardized, three-day fear conditioning and extinction learning and memory task. On day 1, participants will complete a fear conditioning task. On day 2, participants will receive sham (placebo) or active tDCS prior to completing a fear extinction learning task. On day 3, participants will complete an extinction recall task. Electrodermal activity and heart rate will be continuously monitored during the conditioning and extinction procedures to assess autonomic arousal. All procedures will be completed in a magnetic resonance imaging (MRI) scanner; imaging data will be collected before and after tDCS and during all conditioning and extinction procedures.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Apr 2019
Longer than P75 for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 1, 2019
CompletedFirst Posted
Study publicly available on registry
April 9, 2019
CompletedStudy Start
First participant enrolled
April 9, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2023
CompletedAugust 24, 2023
August 1, 2023
4.1 years
April 1, 2019
August 22, 2023
Conditions
Outcome Measures
Primary Outcomes (5)
Fractional amplitude of low frequency fluctuations (fALFF)
fALFF is a measure of resting brain activity that is derived by calculating regionally-specific fluctuations in Blood Oxygen Level-Dependent (BOLD) activation within a low-frequency band, typically while the participant is at rest.
Immediately following administration of tDCS on day 2 of the protocol.
Event related brain activation during extinction learning
Blood Oxygen Level-Dependent imaging (BOLD imaging) will be measured during extinction training.
BOLD imaging will be measured during extinction training on day 2 of the protocol.
Event related brain activation during extinction recall
Blood Oxygen Level-Dependent imaging (BOLD imaging) will be measured during extinction recall.
BOLD imaging will be measured during the test of extinction recall on day 3 of the experimental protocol.
Skin conductance response (SCR) during extinction learning
SCR will be measured by collecting electrodermal activity (EDA) on the left hand and subtracting the maximal EDA value during the presentation of the virtual context (CX) picture from the maximal EDA value during the presentation of the conditioning stimuli (CS).
SCR will be measured during extinction learning on day 2 of the experimental protocol.
Skin conductance response (SCR) during extinction recall
SCR will be measured by collecting electrodermal activity (EDA) on the left hand and subtracting the maximal EDA value during the presentation of the virtual context (CX) picture from the maximal EDA value during the presentation of the conditioning stimuli (CS).
SCR will be measured during extinction recall on day 3 of the experimental protocol.
Secondary Outcomes (3)
Functional connectivity measure of tDCS
Immediately prior to and following administration of tDCS. Change in connectivity from pre to post stimulation (delta) will be modeled and used as the dependent variable.
Functional connectivity during extinction learning
During extinction learning on day 2 of the experimental protocol.
Functional connectivity during extinction recall
During extinction recall on day 3 of the experimental protocol.
Study Arms (2)
Active tDCS
ACTIVE COMPARATORCurrent will be ramped in/out for 30 seconds at the begging and end of a 20-minute period and a constant current will be delivered for the 20-minutes between ramping.
Sham tDCS
SHAM COMPARATORCurrent will be ramped in/out for 30 seconds at the begging and end of a 20-minute period during which no stimulation will be delivered.
Interventions
Subjects will receive 20 minutes of multifocal transcranial direct current stimulation. The anode will be placed over the frontal pole (Fpz, 10-20 EEG) and will be surrounded by 5 return electrodes (cathodes). Current will be set at 1.5mA and will be ramped in/out at the begging and end of the 20-minutes of stimulation over the course of 30 seconds.
Eligibility Criteria
You may qualify if:
- Ability to provide informed consent (as established by clinical interview), and voluntary, signed informed consent prior to the performance of any study-specific procedures;
- Ability and willingness to perform study-relevant clinical assessments;
- Ability and willingness to receive transcranial direct current stimulation (tDCS);
- Ability and willingness to complete magnetic resonance imaging (MRI) scans;
- Free of current psychiatric diagnosis;
- Psychiatrically healthy;
- years of age;
- Medication free or stable (\> 4 weeks) medication(s).
You may not qualify if:
- Any unstable medical, psychiatric, or neurological condition (including active or otherwise problematic suicidality) that may necessitate urgent treatment;
- Any substance dependence or severe substance abuse within the past 6 months;
- Daily use of psychotropic medications that substantially lower seizure threshold (e.g., clozapine);
- Daily use of psychotropic drugs that may interfere with extinction learning (e.g., anxiolytics);
- Any history of a psychotic disorder or of mania;
- Current active suicidal ideation or any suicidal intent;
- Any major neurological disease or history of major head trauma, including concussion with extended loss of consciousness, or of psychosurgery;
- Any history of epilepsy;
- Pregnancy;
- Any metal in the body or other contraindication to MRI scanning or tDCS;
- Any history of adverse effects to brain stimulation;
- A current Diagnostic and Statistical Manual diagnosis in the past 6 months, as determined by clinical interview;
- History of a severe psychiatric disorder, either documented or by clinician judgment;
- Use of drugs that are known to influence hemodynamic properties, except for drugs that are used to treat hypertension;
- Severe claustrophobia, back pain, or other condition that may make an extended magnetic resonance scan difficult or lead to excessive movement during the scan.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Thomas Adamslead
- National Institute of Mental Health (NIMH)collaborator
Study Sites (2)
Yale School of Medicine
New Haven, Connecticut, 06511, United States
University of Kentucky
Lexington, Kentucky, 40506, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Thomas Adams, PhD
University of Kentucky
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Randomization will be administrated by independent research staff. Double-blind software will be used to ensure that the experimenter and subject remain blind during task administration.
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
April 1, 2019
First Posted
April 9, 2019
Study Start
April 9, 2019
Primary Completion
June 1, 2023
Study Completion
June 1, 2023
Last Updated
August 24, 2023
Record last verified: 2023-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- Data will be made available following study publication.
Raw imaging and psychophysiological data will be freely available upon study publication. Data will be stored on a yet to be determined data sharing repository supported by the National Institutes of Health.