Task Augmentation of Transcranial Magnetic Stimulation (TMS)

NCT ID: NCT04586205

Last Updated: 2025-05-31

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-07

Study Completion Date

2024-03-11

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This pilot, within-subjects, randomized proof-of-concept study investigates the effects of activating the DLPFC promotion system on TMS treatment outcomes. Twenty-five healthy volunteers will participate in four sessions involving either active or sham repetitive transcranial magnetic stimulation (rTMS). Using anatomically guided TMS paired with cognitive tasks, the study tests the hypothesis that cognitive paired associative stimulation enhances cortical responses. For this pilot study, we are focusing only on the augmentation of TMS with the IASP task.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The standard clinical use of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) has shown limited efficacy. One contributing factor may be the common use of scalp-based targeting rather than neuronavigation techniques using functional MRI (fMRI), which enable more precise, individualized targeting of functional brain networks. Image-guided TMS can account for anatomical variability and may enhance treatment outcomes.

Another promising approach is combining TMS with concurrent cognitive activation of the dorsolateral prefrontal cortex (DLPFC). This concept, known as cognitive paired associative stimulation, builds on traditional paired associative stimulation (PAS), where coordinated stimulation enhances cortical response. In this framework, delivering TMS to the DLPFC while participants engage in a DLPFC-activating cognitive task could produce greater neural activation than either stimulus alone. Prior research suggests that the brain's cognitive or emotional state during stimulation can significantly modulate TMS effects, though it's unclear whether this enhancement depends on the type of cognitive task or the magnitude of neural activation.

Study Design and Procedure This within-subjects, mechanism-focused pilot study builds on the Research Domain Criteria (RDoC) framework for cognitive control. The primary goal is to examine how pairing rTMS with specific task conditions affects DLPFC activation and connectivity.

Participants (ages 18-60, healthy volunteers) will undergo the following:

Screening Visit (2 hours): Consent and eligibility. Visit 1 - Baseline MRI (1 hour): Participants undergo structural and functional MRI to localize the "Fitzgerald target" in the DLPFC. Data will be analyzed using FSL and neuronavigated using BrainSight.

Visit 2 - Task-Only fMRI Session (2 hours): Participants complete both the SST (cognitive task) and the IASP (emotional task) in the scanner. Each task contains high- and low-load trials, and participants complete both tasks (they are not assigned to one or the other).

Visits 3 \& 4 - TMS Sessions (2 hours each): In a randomized crossover design, participants complete the IASP task while receiving either:

Active rTMS Sham rTMS These sessions test whether pairing emotional cognitive activation with TMS enhances cortical response. Note: TMS was never delivered alone-participants always performed the IASP task during stimulation.

2-Week Break Visits 5 \& 6 - Follow-Up TMS Sessions (2 hours each): Participants repeat the IASP task with the alternate stimulation condition (sham or active). fMRI data is again collected to assess DLPFC activation and connectivity post-stimulation.

Each TMS session uses:

Stimulation Parameters: 120% resting motor threshold (RMT), triplet 50 Hz bursts at 5 Hz, 2s on / 8s off, 600 pulses per session (\~3 min 9 sec total).

Probe Scans: Single-pulse TMS (120% RMT; 77 pulses/session) inside the scanner to measure cortical reactivity.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Healthy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

A within-subjects design was used. Healthy participants between the ages of 18 and 60 who met basic eligibility criteria were invited to participate.

In the first phase, all participants completed both the Sternberg task (SST) and the International Affective Picture System (IASP) task, each containing high- and low-load trials.

In the second phase, participants completed the IASP task during two separate TMS sessions: one with active rTMS and one with sham rTMS, in a randomized crossover design. No TMS-alone condition was included. All TMS sessions were conducted in the MRI scanner, allowing investigators to collect both brain activation to single-pulse TMS probes and connectivity data.

Participants were randomized to receive either active or sham rTMS during the first session, and then crossed over to the alternate condition after a two-week break. This design allowed for within-subject comparison of cortical response during the same task across both stimulation conditions.
Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Active rTMS + IASP

Participants perform the IASP emotional task Receive active rTMS

Group Type ACTIVE_COMPARATOR

active TMS

Intervention Type DEVICE

Participants receive active repetitive transcranial magnetic stimulation (rTMS) while performing the International Affective Picture System (IASP). Stimulation is delivered at 120% of resting motor threshold (RMT), in triplet 50 Hz bursts, repeated at 5 Hz (2s on, 8s off), totaling 600 pulses per session.

IASP Task

Intervention Type BEHAVIORAL

Participants complete the IASP (emotional image viewing) task during each TMS session (active and sham). The task includes both high- and low-load trials, designed to activate the dorsolateral prefrontal cortex (DLPFC). Task order and load levels are consistent across both stimulation sessions.

SST Task

Intervention Type BEHAVIORAL

In a separate MRI session prior to TMS sessions, participants complete the SST which includes both high-load and low-load trials. This cognitive task is used to examine baseline DLPFC activation and to contrast cognitive vs. emotional activation profiles.

MRI

Intervention Type OTHER

Participants undergo MRI sessions to measure DLPFC cortical reactivity and connectivity.

Sham rTMS + IASP

Participants perform the IASP emotional task Receive Sham rTMS

Group Type SHAM_COMPARATOR

sham TMS

Intervention Type DEVICE

Participants receive sham rTMS while performing the IASP task. Stimulation is mimicked without actual neural activation using the same schedule and coil placement as the active condition.

IASP Task

Intervention Type BEHAVIORAL

Participants complete the IASP (emotional image viewing) task during each TMS session (active and sham). The task includes both high- and low-load trials, designed to activate the dorsolateral prefrontal cortex (DLPFC). Task order and load levels are consistent across both stimulation sessions.

SST Task

Intervention Type BEHAVIORAL

In a separate MRI session prior to TMS sessions, participants complete the SST which includes both high-load and low-load trials. This cognitive task is used to examine baseline DLPFC activation and to contrast cognitive vs. emotional activation profiles.

MRI

Intervention Type OTHER

Participants undergo MRI sessions to measure DLPFC cortical reactivity and connectivity.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

active TMS

Participants receive active repetitive transcranial magnetic stimulation (rTMS) while performing the International Affective Picture System (IASP). Stimulation is delivered at 120% of resting motor threshold (RMT), in triplet 50 Hz bursts, repeated at 5 Hz (2s on, 8s off), totaling 600 pulses per session.

Intervention Type DEVICE

sham TMS

Participants receive sham rTMS while performing the IASP task. Stimulation is mimicked without actual neural activation using the same schedule and coil placement as the active condition.

Intervention Type DEVICE

IASP Task

Participants complete the IASP (emotional image viewing) task during each TMS session (active and sham). The task includes both high- and low-load trials, designed to activate the dorsolateral prefrontal cortex (DLPFC). Task order and load levels are consistent across both stimulation sessions.

Intervention Type BEHAVIORAL

SST Task

In a separate MRI session prior to TMS sessions, participants complete the SST which includes both high-load and low-load trials. This cognitive task is used to examine baseline DLPFC activation and to contrast cognitive vs. emotional activation profiles.

Intervention Type BEHAVIORAL

MRI

Participants undergo MRI sessions to measure DLPFC cortical reactivity and connectivity.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Gender, inclusive
* 18 60 years of age
* Right-handed
* No history of meeting Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for any diagnosis
* Normal cognition
* Patients must be able to read and understand English
* Participants must be able to provide consent

Exclusion Criteria

* Pregnancy (Female participants)
* Outside age range
* Meets DSM criteria for any diagnosis
* Unable to have an MRI scan
* Medical condition that interferes with the collection or interpretation of MRI data
* Implanted devices such as: aneurysm clip or cardiac pacemaker
* History of stroke, epilepsy, or brain scarring
* Cognitive impairment
* Recent use of psychoactive medications, as determined by investigators
* Otherwise determined by investigator to be unfit for participation
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Yvette Sheline

Director, Center for Neuromodulation in Depression and Stress (CNDS)

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Center for Neuromodulation in Depression and Stress

Philadelphia, Pennsylvania, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

832232

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Effect of TMS on PTSD Biomarkers
NCT04563078 COMPLETED NA
rTMS in First Episode Psychosis
NCT02131129 COMPLETED NA
In-patient SCC TMS
NCT05645575 RECRUITING NA
rTMS for Relieving Chronic OA Pain
NCT05097729 WITHDRAWN NA