Ignite Creation Date:
2025-12-25 @ 3:30 AM
Ignite Modification Date:
2025-12-26 @ 2:12 AM
Study NCT ID:
NCT04586205
Status:
COMPLETED
Last Update Posted:
2025-05-31
First Post:
2020-10-05
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Task Augmentation of Transcranial Magnetic Stimulation (TMS)
Sponsor:
University of Pennsylvania
Organization:
Study Overview
Official Title:
A Pilot Proof of Concept, Within Subjects, Randomized Study of the Effects of Activation of the DLPFC Promotion System on TMS Treatment
Status:
COMPLETED
Status Verified Date:
2025-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TaskTMS
Brief Summary:
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:
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.
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.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
True
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: