Effect of rTMS on Anxiety

NCT03993509 | Completed Results FDA Device

• 1 other identifier: 833320
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Given the overall lack of treatment adherence/efficacy, side effects of drugs, and the substantial burden of anxiety disorders on the individual and on the national healthcare system, there is a critical need for mechanistic research into the CNS mechanisms that underlie these disorders. Accordingly, the objective of this grant is to use noninvasive neuromodulation to causally identify the key neural mechanisms that mediate the cognitive symptoms of anxiety. This project is relevant to public health because it has the potential to lead to novel repetitive transcranial magnetic stimulation treatments for pathological anxiety.

Conditions

Anxiety; Fear; Anxiety and Fear

Outcome Measures

Primary Outcomes (4)

• Anxiety Potentiated Startle

  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 24-hours post stimulation

• Fear Potentiated Startle

  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 fear, 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 FPS, we subtracted the response during the predictable ITI from the response during the predictable Cue.

  Pre and 24 hours post stimulation

• Sternberg WM Accuracy

  Sternberg task: On each WM trial, subjects will see a series of 4 letters presented singularly (encoding period) that will be followed by a brief interval where subjects are required to maintain these letters (maintenance period). At the end of the maintenance period, subjects will be prompted to make a response based on the task instructions (response period). The response prompt will consist of a letter and a number. The letter will be chosen from the study series, and the number will correspond to a position in the series. The subjects will indicate whether the position of the letter in the series matches the number.

  Pre and 24 hours post stimulation

• TMS-evoked BOLD Responses

  As with Experiment 1, subjects will have Neutral, Predictable, and Unpredictable periods. During the neutral periods, they will be safe from shocks. During the predictable periods, they can receive shocks but only when there is a cue present. During the unpredictable periods, they are at risk for shock during the entire duration of the block. Rather than probing their ongoing anxiety with the startle probes, we replaced the startle probes with single TMS pulses to the right dlPFC. This allowed us to causally examine the effect of right dlPFC activity (induced by the TMS pulse) on the neural activity. BOLD responses are collapsed across regions and conditions to examine right dlPFC BOLD down regulation.

  Responses are measured within the TMS/fMRI session in response to each TMS pulse and collapsed across trials. There is no sham condition. This session was typically conducted during the washout period, but varied depending upon participant schedule.

Study Arms (2)

1 Hz Arm

EXPERIMENTAL

Subjects will receive a continuous train of 1 Hz stimulation until all 3000 pulses are delivered. Consistent with the 10 Hz condition, TMS will occur during the Sternberg WM paradigm.

Device: rTMS to the right dlPFC

10 Hz Arm

EXPERIMENTAL

Subjects will receive 75, 4 second trains at 10 Hz, separated by a 36 second ITI. Stimulation will occur while subjects are doing the Sternberg WM paradigm. The timing of the Sternberg task will be jittered so that each rTMS train will be administered during the maintenance interval of a WM trial.

Device: rTMS to the right dlPFC

Interventions

rTMS to the right dlPFC DEVICE

A Magventure MagPro 100X stimulator with a B65 active/placebo figure-8 coil will be used. The TMS coil will be placed on the head over the target. rTMS intensity will be 100% of the motor threshold (MT), adjusted for field strength difference at motor cortex and target cortex using the individual E-field model. Subjects will receive 3000 pulses/session.

1 Hz Arm; 10 Hz Arm

Eligibility Criteria

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

You may qualify if:

• Subjects must be 18-50 years old
• Able to give their consent
• Right-handed

You may not qualify if:

• Non-english speaking
• Any significant medical or neurological problems
• Current or past Axis I psychiatric disorder(s), 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
• IQ \<80
• 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

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Results Point of Contact

• Title: Nicholas Balderston
• Organization: University of Pennsylvania

nicholas.balderston@pennmedicine.upenn.edu

2157463058

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both the subject and the TMS operator will be blinded as to the study condition (active vs. sham)
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Aims 1 and 2 will be tested using a between-subjects design where 1 group of healthy volunteers will receive 4-day courses of active and sham 1 Hz stimulation to the right dlPFC, while the other group will receive 4-day courses of active and sham 10 Hz stimulation to the right dlPFC. Aim 1, will test the effects of this stimulation on anxiety during the NPU threat task. Aim 2, will test the effects of this stimulation on anxiety-related working memory (WM) deficits using the Sternberg WM paradigm. Aim 3 will be tested using a within-subjects design where this same group of subjects will receive single-pulse active and sham stimulation to the right dlPFC during the Neutral, Predictable, and Unpredictable (NPU) threat task while in the MRI scanner. BOLD activity to the TMS pulses will be the primary outcome measure.

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: October 30, 2019
• Primary Completion: November 23, 2022
• Study Completion: November 23, 2022
• Last Updated: January 23, 2025
• Results First Posted: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)