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

The University of Texas Health Science Center, Houston250 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

250

Conditions

PTSD

Interventions

Transcranial magnetic stimulation (TMS)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 ParadigmBEHAVIORAL

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

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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.

Time frame: Experimental Day 1

Skin Conductance Response (SCR)

Time frame: 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.

Time frame: Experimental Day 1

Functional MRI (fMRI) blood-oxygen-level-dependent (BOLD) responses

Time frame: Experimental Day 3

Secondary Outcomes

Score on State-Trait Anxiety Inventory (STAI) - Form Y1

STAI - Form Y1 is a commonly used measure of trait and state anxiety that consists of 20 statements that describe oneself. Each statement is scored from 1 (Not at all) to 4 (very much so). The total score range is 20-80. STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).

Time frame: Experimental Day 1

Score on State-Trait Anxiety Inventory (STAI) - Form Y1

Time frame: Experimental Day 3

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts