Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans
Purpose
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
Condition
- PTSD
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Willing and able to provide informed consent. - Inclusion Criteria for PTSD Subjects - Diagnosis of current PTSD - Inclusion Criteria: Healthy Controls (HC) - no current psychiatric disorders ("Axis I" disorders)
Exclusion Criteria
- 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 - Additional exclusion criteria for Healthy controls (HC) group: Current psychiatric diagnosis ("Axis I" diagnosis)
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Basic Science
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Fear Conditioning and Extinction Paradigm, plus Transcranial Magnetic Stimulation (TMS) |
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. |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- The University of Texas Health Science Center, Houston
Detailed Description
The experiments proposed are aimed to understand how timing and location of transcranial magnetic stimulation (TMS) in humans will impact their ability to reduce conditioned fear responses and impact the activation of their brain regions involved in fear regulation. The researchers will use a novel TMS approach to vary timing and location of its delivery so that the researchers can characterize and establish best time and location to obtain optimal impact on fear inhibition, and then test these parameters in PTSD patients and see if such can rescue extinction deficits in PTSD. The anticipated impact is to enhance our understanding of the neural mechanisms of associated with TMS use and explore potential novel approaches for advancing PTSD treatment.
