Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle

April 27, 2022 updated by: National Institute of Mental Health (NIMH)

The Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle

Background:

Researchers want to better understand brain processes related to fear and anxiety. They want to find out if transcranial magnetic stimulation (TMS), a type of brain stimulation, can reduce anxiety.

Objective:

To see how TMS affects fear and anxiety through memory and attention tasks.

Eligibility:

Healthy people ages 18-50 who are right-handed

Design:

Participants will be screened through another protocol.

Participants in the pilot study will have 1 visit. This includes:

Urine tests

Questionnaires about mood and thinking

Shock and startle workup: Electrodes are taped to the wrists or fingers. Participants will be shocked to find out what level of shock is uncomfortable but tolerable. They will hear loud, sudden noises through headphones.

TMS: A coil is held on the scalp. A magnetic field stimulates the brain. Sometimes they might receive fake TMS. This feels the same as real TMS. They will perform simple tasks. Participants in the main study will have 2 visits within 2 weeks.

The first visit includes:

Urine tests

Questionnaires about mood and thinking

MRI: Participants lie on a table that slides into a scanner. They will be in the scanner about 1 hour. A computer screen in the scanner will tell them to perform simple tasks.

The second visit includes:

Shock and startle workup

TMS

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Objective: To determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects. Toward this aim we will test the effect of transcranial magnetic stimulation (TMS) on two outcome measures: 1) Fear and anxiety during the threat of predictable and unpredictable shock (NPU threat test; Substudies 1 and 3), and 2) Working memory (WM) related anxiety downregulation while performing the Sternberg WM task under threat of shock (Substudy 2).

Study population: The study population will consist of up to 184 healthy volunteers between the ages of 18-50.

Design: This study will consists of two (sub-studies 1 and 2) or three (sub-study 3) outpatient visits (1 MRI, 1 or 2 TMS visits [2 for sub-study 3]). In this protocol we will explore the effect of TMS in three sub-studies in the TMS study visit. The sub-studies will contain either the NPU or the Sternberg task during the TMS visits. The first visit (MRI) will consist of the same procedures for all sub-studies. Each subject will be assigned to only one of the sub-studies.

Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock.

NPU Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the NPU threat test. Subjects will be exposed to blocks in which they are either 1) safe from shock (neutral), 2) at risk of shock delivered only during a cue (predictable), or 3) at risk of shock presented randomly (unpredictable).

Outcome measures: In both studies the primary outcome measure will be anxiety-potentiated startle (APS), which is the increase in startle magnitude during periods of threat compared to periods of safety. We expect active, but not sham TMS to increase activity in the dlPFC, and therefore reduce APS in both studies

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
61

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:
  • Ages 18-50
  • Subjects able to give their consent
  • Right handed

EXCLUSION CRITERIA:

  • Non-English speaking individual
  • Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurological illness, seizure, etc.)
  • Current or past Axis I psychiatric disorder(s) as identified with the Structured Clinical Interview for DSM-IV, non-patient edition (SCID-np)
  • Active or history of active suicidal ideation.
  • Evidence of a first-degree relative with history of psychosis or bipolar disorder; specifically, participant will know diagnosis or treatment in order to confirm presence of disorder.
  • Alcohol/drug problems in the past year or lifetime alcohol or drug dependence according to the Structured Clinical Interview for DSM-IV.
  • Current use of medications that act on histamine (i.e. diphenhydramine), dopamine (methylphenidate), norepinephrine (buproprion), serotonin (sertraline), or acetylcholine (amitryptiline) receptors. Subjects will be excluded on this basis if they either 1) take these medications on a chronic basis, or 2) if they have taken the drug within 5 half-lives of the drug metabolism, determined by the medical professional at the time of screening.
  • History of seizure (childhood febrile seizures are acceptable and these subjects may be included in the study),
  • History of epilepsy in self or first degree relatives, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion.
  • Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold (table below).
  • Pregnancy, or positive pregnancy test.
  • Neurological syndrome of the arm (e.g., carpal tunnel syndrome, cubital tunnel syndrome, etc.)
  • Positive urine toxicology screen during the screening visit.
  • IQ <80
  • Employee or staff of NIMH or are an immediate family member of a NIMH employee, staff, or NIMH contractors.
  • Allergy to lidocaine or topical anesthetics (participants in sub-study 3 only).

  • Any medical condition that increases risk for fMRI or TMS:

    • Any metal in their body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or if you were a welder or metal worker, since you may small metal fragments in the eye.
    • Participants who are uncomfortable in small closed spaces (have claustrophobia) and would feel uncomfortable in the MRI machine
    • Patients who have difficulty lying flat on their back for up to 60 min in the scanner
    • History of hearing loss

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Substudy 1 Active and Sham
HVs that receive TMS over the right dlPFC
Drug: Transcranial Magnetic Stimulation Sham
TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Device: Transcranial Magnetic Stimulation
TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Experimental: Substudy 2 Active and Sham
HVs that receive TMS over the right dlFPC
Drug: Transcranial Magnetic Stimulation Sham
TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Device: Transcranial Magnetic Stimulation
TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Experimental: Substudy 3 Active and Sham
HVs will receive offline TMS to the lest IPS (FPN)
Drug: Transcranial Magnetic Stimulation Sham
TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Device: Transcranial Magnetic Stimulation
TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Anxiety-potentiated Startle
Time Frame: Pre and post stimulation

Electromyography Facial electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle at 2000 Hz using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm hydrogel coated vinyl electrodes (Rhythmlink #DECUS10026; Columbia, SC).

Startle EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = [Zx × 10] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD > 2x run SD) were excluded, and "no blink" (peak < baseline range) trials were coded as 0. To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI.
Pre and post stimulation
Working Memory (WM) Related Anxiety Downregulation While Performing the Sternberg WM Task Under Threat of Shock.
Time Frame: Pre and post stimulation

Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock.

Electromyography Facial electromyography (EMG) startle responses are recorded from the left orbicularis oculi muscle at 2000 Hz.

Startle EMG is bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses are scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores (tx = [Zx × 10] + 50). Noisy trials (baseline SD > 2x run SD) are excluded, and "no blink" (peak < baseline range) trials are coded as 0. These t scores are then averaged across trials within each condition, and threat-safe contrasts are calculated independently for each level of load (low vs. high) and timing (maintenance vs. ITI).
Pre and post stimulation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Mental Health (NIMH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Christian Grillon, Ph.D., National Institute of Mental Health (NIMH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 23, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 19, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 29, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 23, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 17, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 170042
  • 17-M-0042

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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