Effect of cTBS on Startle and TMS-evoked BOLD

February 9, 2026 updated by: University of Pennsylvania

The Effect of Right dlPFC cTBS on Acute Measures of Anxiety, Functional Connectivity, and TMS-evoked BOLD Responses.

The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression; however, there is little mechanistic evidence supporting an optimized treatment protocol. Thus, the objective of the current project is to develop an interleaved TMS/fMRI that can assess the effect of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to anxiety expression. PUBLIC HEALTH RELEVANCE: These results will yield direct evidence that 1 Hz and cTBS modulate brain activity associated with anxiety expression and regulation, thus informing novel TMS based anxiety treatments.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

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

The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression in anxiety disorders, depression, and posttraumatic stress disorder (PTSD). However, we lack the basic evidence to determine critical details regarding the optimal stimulation parameters including the dose, target, and protocol. In addition, there is little mechanistic evidence for why any particular right dlPFC target/dose/protocol should be effective for a given set of patients. Indeed, there is little consensus as to whether such mechanistic evidence should generalize across disorders. Accordingly, there is a critical need to understand the mechanisms of action underlying neuromodulatory right dlPFC TMS protocols, yet there is not a standardized protocol to yield such evidence. Without a reliable approach to approach to generate such information, it will be difficult or impossible to develop and optimize novel TMS treatments for disorders like PTSD and anxiety. The objective of the current project is to develop a protocol using interleaved TMS/fMRI that can assess the effect of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to anxiety expression. Our central hypothesis is that inhibition of the right dlPFC via cTBS will also inhibit activity throughout its downstream targets, resulting in reduced anxiety, connectivity, and TMS-evoked responses among these downstream circuits during threat. Accordingly, our approach will be to measure anxious arousal, resting state functional connectivity, and TMS evoked BOLD responses before and immediately after 600 pulses of cTBS or sham stimulation in 100 high anxious individuals using a within-subjects crossover design. For anxious arousal, our primary outcome will be anxiety potentiated startle (APS) recorded with electromyography during the neutral, predictable, and unpredictable (NPU) threat paradigm administered in the lab before and after the scanning session. For the interleaved TMS/fMRI runs, our primary outcome will be TMS-evoked BOLD responses in these same downstream regions. This study is innovative because it is the first to combine these technologies to study the effect of neuromodulatory TMS on threat-related TMS-evoked BOLD responses. This project is significant because it will provide future researchers with an systematic approach for evaluating the effectiveness of neuromodulatory TMS protocols on several neural and behavioral indices of anxiety expression. It will also yield direct evidence that cTBS modulate brain activity associated with anxiety expression and regulation.

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 (Estimated)

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.
140

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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Able to give their consent
  • Right-handed
  • Individuals receiving therapy for anxiety must be stable on their regimen for at least 4 weeks prior to study enrollment.

Exclusion Criteria:

  • Non-english speaking
  • Any significant medical or neurological problems
  • Current or past non-anxiety-related psychiatric comorbidity, active or history of active suicidal ideation
  • Alcohol/drug problems in the past year or lifetime alcohol or drug dependence
  • Medications that act on the central nervous system
  • History of seizure
  • History of epilepsy
  • Increased risk of seizure for any reason
  • Pregnancy, or positive pregnancy test
  • Any medical condition that increases risk for fMRI or TMS
  • Any metal in their body which would make having an MRI scan unsafe
  • Any sort of medical implants
  • Hearing loss
  • Claustrophobia
  • orthostatic hypotension

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: Basic Science
  • Allocation: N/A
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

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.
Other: Transcranial Magnetic Stimulation
A MagVenture MagPro 100X stimulator with a B91 figure-8 coil will be used for the TMS/fMRI rTMS sessions. Motor threshold testing will be done outside of the scanner using a separate MagVenture MagPro 100X with a separate B65 coil.
Device: Active TMS
Subjects will receive a continuous 1800 pulse cTBS train to the right dlPFC at 100% of motor threshold. The train will consist of 50 Hz bursts, repeated at intervals of 200 ms (5 Hz) for 40 sec.
Device: Sham TMS
Subjects will receive a series of 100 single pulses to the right dlPFC at 100% of motor threshold. Pulses will be randomly jittered and have an average interpulse interval of 6 ± 4 seconds. Single pulses delivered in such a fashion have been shown to have little or no neuromodulatory effect on subsequent cortical excitability.

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
TMS-evoked BOLD responses
Time Frame: Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), TMS-evoked BOLD responses will be recorded immediately (within 5 minutes) before and after the intervention.
Subjects will complete 16 minutes of high-resolution multi-band, multi-echo interleaved TMS/fMRI before and after the TMS. During these runs, subjects will receive periodic single pulses of TMS delivered to the right dlPFC. TMS-evoked BOLD responses to these pulses will be the primary outcome measure
Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), TMS-evoked BOLD responses will be recorded immediately (within 5 minutes) before and after the intervention.
Anxiety Potentiated Startle
Time Frame: Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), Anxiety Potentiated Startle will be recorded immediately (within 15 minutes) before and after the intervention.
Subjects will complete the NPU threat task. The primary outcome, APS, will be calculated by subtracting the blink magnitude during the neutral ITI from the unpredictable ITI. We hypothesize that cTBS will reduce APS compared to sham TMS.
Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), Anxiety Potentiated Startle will be recorded immediately (within 15 minutes) before and after the intervention.

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.
University of Pennsylvania

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: Nicholas Balderston, PhD, University of Pennsylvania

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 (Estimated)

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.
July 1, 2026

Primary Completion (Estimated)

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.
June 1, 2031

Study Completion (Estimated)

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 30, 2031

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 16, 2026

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.
February 9, 2026

First Posted (Actual)

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.
February 17, 2026

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.
February 17, 2026

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.
February 9, 2026

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.
February 1, 2026

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.
  • 860105

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

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.

Clinical Trials on Anxiety

Clinical Trials on Active TMS

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings