Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans
2 other identifiers
interventional
250
1 country
1
Brief Summary
This study aims to explore the mechanisms of how transcranial magnetic stimulation (TMS) impacts fear circuits. The overarching objectives are to understand how varying TMS parameters affect targeted brain regions in order to optimize its impact on enhancing fear extinction memory consolidation in a population with known fear extinction deficiencies: post-traumatic stress disorder (PTSD). 250 subjects will take part in this research study across UTHealth Houston. The study will include preliminary screenings, baseline visits, and experimental visits across four days
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Feb 2022
Longer than P75 for not_applicable
1 active site
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
Study Start
First participant enrolled
February 1, 2022
CompletedFirst Submitted
Initial submission to the registry
May 5, 2022
CompletedFirst Posted
Study publicly available on registry
May 10, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2028
May 5, 2026
April 1, 2026
6.7 years
May 5, 2022
April 30, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Skin Conductance Response (SCR)
Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.
Experimental Day 1
Skin Conductance Response (SCR)
Conductance is measured by placing two electrodes next to the skin and passing a tiny electric charge between the two points. SCR is proportionally related to the number of sweat glands that are activated, meaning in essence that the more emotionally aroused an individual is, the more the SCR amount is increased.
Experimental Day 3
Functional MRI (fMRI) blood-oxygen-level-dependent (BOLD) responses
fMRI data, including blood-oxygen-level-dependent (BOLD) responses, is used in neuroimaging studies assess neural correlate activations and observe the increase/decrease in activation of a particular brain area in response to a specific cue. When these cells are active, there is an increase in blood oxygen in the surrounding area.
Experimental Day 1
Functional MRI (fMRI) blood-oxygen-level-dependent (BOLD) responses
fMRI data, including blood-oxygen-level-dependent (BOLD) responses, is used in neuroimaging studies assess neural correlate activations and observe the increase/decrease in activation of a particular brain area in response to a specific cue. When these cells are active, there is an increase in blood oxygen in the surrounding area.
Experimental Day 3
Secondary Outcomes (2)
Score on State-Trait Anxiety Inventory (STAI) - Form Y1
Experimental Day 1
Score on State-Trait Anxiety Inventory (STAI) - Form Y1
Experimental Day 3
Study Arms (1)
Fear Conditioning and Extinction Paradigm, plus Transcranial Magnetic Stimulation (TMS)
EXPERIMENTALParticipants will undergo a 3-day experimental paradigm. On day 1, participants will undergo a resting-state and structural scans in the fMRI scanner. The data from this scan will be used to determine the specific location of the TMS target for each participant. And participants will be aversively conditioned to two cues in the fMRI scanner. Task based and resting-state scans will occur on this day. On day 2, subjects will undergo extinction training outside of the scanner where one of the conditioned cues will be paired with TMS in a temporally and anatomically specific manner. A resting-state scan will occur before and after inside the scanner. On day 3, conditioned cues will be presented during the extinction recall phase of the study. This phase will be conducted in the fMRI scanner. Task-based and resting-state scans will occur on this day.
Interventions
Research subjects will undergo non-invasive TMS, with a frequency of 20Hz and intensity of 120% of their resting motor threshold (rMT) at varying time points and locations.
Participants will undergo a 3-day experimental paradigm. On day 1, participants will undergo a resting-state and structural scans in the fMRI scanner. The data from this scan will be used to determine the specific location of the TMS target for each participant. And participants will be aversively conditioned to two cues in the fMRI scanner. Task based and resting-state scans will occur on this day. On day 2, subjects will undergo extinction training outside of the scanner where one of the conditioned cues will be paired with TMS in a temporally and anatomically specific manner. A resting-state scan will occur before and after inside the scanner. On day 3, conditioned cues will be presented during the extinction recall phase of the study. This phase will be conducted in the fMRI scanner. Task-based and resting-state scans will occur on this day.
Eligibility Criteria
You may qualify if:
- Willing and able to provide informed consent.
You may not qualify if:
- Lifetime history of seizure or significant head trauma or other significant neurologic disease (e.g., tic disorder)
- History of serious/significant psychiatric diagnoses ("Axis I" diagnoses)
- Current significant suicidal ideation, plan or intent or suicidal behavior in past 6 months based on CSSRS and clinical judgment or Self-injurious behavior that involves suicidal intent, requires medical attention, or occurs daily
- Use of neuroleptics within one year prior to study
- Current substance use
- Pregnancy (to be ruled out by urine β-HCG).
- Metallic implants or devices contraindicating magnetic resonance imaging.
- Currently taking medications that lower the seizure threshold. These include antipsychotics, high dose theophylline or stimulants such as methylphenidate. Patients taking bupropion must be on a stable dose (\*last 3 months) and take less than or equal to 300 mg/day.
- Implanted devices in subject's head (shunts, cochlear implants); metal in subject's head (other than dental implants).
- High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
UTHealth Houston
Houston, Texas, 77054, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mohammed Milad, PhD
The University of Texas Health Science Center at Houston (UTHealth Houston)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
May 5, 2022
First Posted
May 10, 2022
Study Start
February 1, 2022
Primary Completion (Estimated)
September 30, 2028
Study Completion (Estimated)
September 30, 2028
Last Updated
May 5, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
- Access Criteria
- The investigator who proposed to use the data.Upon reasonable request. Requests should be directed to Mohammed.R.Milad@uth.tmc.edu. To gain access, data requestors will need to sign a data access agreement.
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).