Task Augmentation of Transcranial Magnetic Stimulation (TMS) (TaskTMS)

University of Pennsylvania

Status: Completed

Conditions: Healthy

Treatments: Behavioral: IASP Task; Behavioral: SST Task; Device: sham TMS; Device: active TMS; Other: MRI

Study type: Interventional

Funder types: Other

Identifiers

NCT04586205

832232

Details and patient eligibility

About

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.

Full 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.

Enrollment: 17 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

17 participants in 2 patient groups

Active rTMS + IASP

Active Comparator group

Description:

Participants perform the IASP emotional task Receive active rTMS

Treatment:

Other: MRI

Behavioral: SST Task

Behavioral: IASP Task

Device: active TMS

Sham rTMS + IASP

Sham Comparator group

Description:

Participants perform the IASP emotional task Receive Sham rTMS

Treatment:

Device: sham TMS

Other: MRI

Behavioral: SST Task

Behavioral: IASP Task