Neuromodulation of the Fear Extinction Circuit Using Temporally and Anatomically Specific TMS in Humans

NCT ID: NCT05368987

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2027-09-30

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

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.

Conditions

PTSD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Transcranial magnetic stimulation (TMS)

Intervention Type: DEVICE

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.

Fear Conditioning and Extinction Paradigm

Intervention Type: BEHAVIORAL

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.

Interventions

Transcranial magnetic stimulation (TMS)

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.

Intervention Type: DEVICE

Fear Conditioning and Extinction Paradigm

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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Willing and able to provide informed consent.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Mohammed Milad

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mohammed Milad, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at Houston (UTHealth Houston)

Locations

UTHealth Houston

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mohammed Milad, PhD

Role: CONTACT

Mohammed.R.Milad@uth.tmc.edu

713-486-2754

Isabel Moallem, PhD

Role: CONTACT

B.Isabel.Moallem@uth.tmc.edu

Facility Contacts

Mohammed R. Milad, MD

Role: primary

Mohammed.R.Milad@uth.tmc.edu

Other Identifiers

R01MH125198

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HSC-MS-23-0426

Identifier Type: -

Identifier Source: org_study_id