Effect of cTBS on Startle and TMS-evoked BOLD

NCT07415772 | Not Yet Recruiting DMC FDA Device

• 1 other identifier: 860105
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anxiety

Keywords

anxiety; transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (2)

• TMS-evoked BOLD responses

  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

  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.

Study Arms (1)

Transcranial Magnetic Stimulation

OTHER

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; Device: Sham TMS

Interventions

Active TMS DEVICE

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.

Transcranial Magnetic Stimulation

Sham TMS DEVICE

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.

Transcranial Magnetic Stimulation

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-6013, United States

Location

MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Nicholas Balderston, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas Balderston, PhD

CONTACT

12157463058; nicholas.balderston@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: Subjects will be blinded to the condition received at each study visit.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2026
• First Posted: February 17, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 30, 2031
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)