HealthyTaskTMSNCT04586205
Task Augmentation of Transcranial Magnetic Stimulation (TMS)
A study testing active TMS, IASP Task and SST Task in people with Healthy, run by University of Pennsylvania at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- active TMS, IASP Task and SST Task
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Apr 2019to 11 Mar 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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 locations and contacts
1 site in 1 country.
United States1 site
Center for Neuromodulation in Depression and Stress
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Pilot Proof of Concept, Within Subjects, Randomized Study of the Effects of Activation of the DLPFC Promotion System on TMS Treatment
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.
Read the 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.
- Conditions
- Healthy
- Being tested
- active TMS, sham TMS, IASP Task, SST Task, MRI
- Keywords
- TMS, fMRI, dlPFC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
active TMSDevice
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.
sham TMSDevice
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 TaskBehavioural
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 TaskBehavioural
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.
MRIOther
Participants undergo MRI sessions to measure DLPFC cortical reactivity and connectivity.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS + IASP | Active comparator | Participants perform the IASP emotional task Receive active rTMS Receives: Device: active TMS; Behavioral: IASP Task; Behavioral: SST Task; Other: MRI |
| Sham rTMS + IASP | Sham comparator | Participants perform the IASP emotional task Receive Sham rTMS Receives: Device: sham TMS; Behavioral: IASP Task; Behavioral: SST Task; Other: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sternberg Sorting Task (SST) at Baseline
This Sternberg Sorting Task (SST) task is designed to assess how individuals store and retrieve random information from short-term memory. This task was administered to all participants before they were randomized into one of two groups (active TMS first then sham TMS or sham TMS first then active TMS). 0's were recorded for incorrect responses and 1's were recorded for correct responses. Therefore, the mean represents the accuracy percentage for each group.
Measured: Baseline (Visit 1)
International Affective Picture System (IAPS)
International Affective Picture System (IAPS): an emotional task using IAPS picture that will also compare low load and high load conditions. The number of images will vary by condition load, but for both the high-load \& low-load conditions, participants will look at IAPS pictures and answer questions about the images. Further, jittered within this design will be both neutral and negative blocks of IAPS pictures: Baseline measurement before randomizing participants into Active or Sham groups. 0's were recorded for incorrect responses and 1's were recorded for correct responses. Therefore, the mean represents the accuracy percentage for each group.
Measured: Baseline
Secondary outcomes (2)
International Affective Picture System (IAPS) at Post-intervention (Active/Sham)
These measurements were taken at the final visits. For example, the "Active then Sham TMS" group received sham TMS during this outcome measure, and the opposite for "Sham then Active TMS." International Affective Picture System (IAPS): an emotional task using IAPS picture that will also compare low load and high load conditions. The number of images will vary by condition load, but for both the high-load \& low-load conditions, participants will look at IAPS pictures and answer questions about the images. Further, jittered within this design will be both neutral and negative blocks of IAPS pictures. The mean represents the number of correct responses from each group. Values can range from 0-299 for the High-Load IAPS (0 meaning no answers correct, and 299 meaning all answers correct). Values can range from 0-326 for the Low-Load IAPS (0 meaning no answers correct, and 326 meaning all answers correct).
Measured: post-intervention (Active/Sham) (Week 6 Final Visit)
Comparing the Impact of Sternberg Sort Task (SST), the Working Memory Task and International Affective Picture System (IAPS) Emotional Task on TMS-Induced DLPFC Activation; Post-intervention (Active/Sham)
In the final visit, we recorded these following tasks in an MRI, in both the group that received active then sham TMS and the group that received sham then active TMS. We are comparing the effects of two distinct cognitive tasks on augmenting the impact of TMS on dorsolateral prefrontal cortex (DLPFC) activity. The first task is the Sternberg task (SST), a working memory task designed to engage cognitive processes by requiring participants to retain and recall information. The second is the International Affective Picture System (IAPS) task, which presents emotionally evocative images to elicit emotional responses. Our goal is to determine which task-cognitive or emotional-more effectively enhances TMS-induced DLPFC activation. Brain activity and connectivity can be quantified on a normalized scale ranging from 0 to 1, where 0 indicates no detectable activity or connectivity, and 1 represents the highest level of activity or connectivity within the measured range.
Measured: post-intervention (Active/Sham) (Week 6 Final Visit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start7 Apr 2019
- Primary completion4 Mar 2020
- Study completion11 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yvette Sheline, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04586205
- Sponsor's protocol ID
- 832232
- Acronym
- TaskTMS
- Status last verified
- May 2025
- First submitted
- 5 Oct 2020
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Proof of Concept, Within Subjects, Randomized Study of the Effects of Activation of the DLPFC Promotion System on TMS Treatment
- ClinicalTrials.gov ID
- NCT04586205
- Acronym / sponsor ID
- TaskTMS / 832232
- Conditions
- Healthy
- Keywords
- TMS, fMRI, dlPFC
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 7 Apr 2019 (actual)
- Primary completion
- 4 Mar 2020 (actual)
- Study completion
- 11 Mar 2024 (actual)
- First posted
- 14 Oct 2020 (actual)
- Results
- Posted 31 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active rTMS + IASP | Active comparator | Device: active TMS, Behavioral: IASP Task, Behavioral: SST Task, Other: MRIParticipants perform the IASP emotional task Receive active rTMS |
| Sham rTMS + IASP | Sham comparator | Device: sham TMS, Behavioral: IASP Task, Behavioral: SST Task, Other: MRIParticipants perform the IASP emotional task Receive Sham rTMS |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| active TMSParticipants 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. | Device | Active rTMS + IASP |
| sham TMSParticipants 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. | Device | Sham rTMS + IASP |
| IASP TaskParticipants 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. | Behavioural | Active rTMS + IASP, Sham rTMS + IASP |
| SST TaskIn 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. | Behavioural | Active rTMS + IASP, Sham rTMS + IASP |
| MRIParticipants undergo MRI sessions to measure DLPFC cortical reactivity and connectivity. | Other | Active rTMS + IASP, Sham rTMS + IASP |
Primary outcome
Sternberg Sorting Task (SST) at Baseline
Time frame: Baseline (Visit 1)
This Sternberg Sorting Task (SST) task is designed to assess how individuals store and retrieve random information from short-term memory. This task was administered to all participants before they were randomized into one of two groups (active TMS first then sham TMS or sham TMS first then active TMS). 0's were recorded for incorrect responses and 1's were recorded for correct responses. Therefore, the mean represents the accuracy percentage for each group.
International Affective Picture System (IAPS)
Time frame: Baseline
International Affective Picture System (IAPS): an emotional task using IAPS picture that will also compare low load and high load conditions. The number of images will vary by condition load, but for both the high-load \& low-load conditions, participants will look at IAPS pictures and answer questions about the images. Further, jittered within this design will be both neutral and negative blocks of IAPS pictures: Baseline measurement before randomizing participants into Active or Sham groups. 0's were recorded for incorrect responses and 1's were recorded for correct responses. Therefore, the mean represents the accuracy percentage for each group.
2 secondary outcomes
International Affective Picture System (IAPS) at Post-intervention (Active/Sham)
Time frame: post-intervention (Active/Sham) (Week 6 Final Visit)
Comparing the Impact of Sternberg Sort Task (SST), the Working Memory Task and International Affective Picture System (IAPS) Emotional Task on TMS-Induced DLPFC Activation; Post-intervention (Active/Sham)
Time frame: post-intervention (Active/Sham) (Week 6 Final Visit)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Healthy
Not yet recruitingPhase 1
Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast
Healthy Volunteers
RecruitingObservational study
Survey to Determine Incarcerated Persons' Views on Surrogate Decision Making
Healthy Volunteers
Active, not recruitingPhase 1
A Study to Learn How Different Amounts of the Study Medicine Called PF-07985631 Are Tolerated and Act in the Body of Healthy Adults
Healthy
Not yet recruitingObservational study
Collection and Distribution of Blood Components From Healthy Donors for In Vitro Research Use
Blood Donors, Apheresis
Recruiting
Metabolic Impact of VLCPUFA-Rich Fish Oil: A Clinical Study on Omega-3 Index Enhancement in Healthy Individuals
Fatty Acids, Omega-3, Fish Oils
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing active TMS, IASP Task and SST Task in people with Healthy, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sternberg Sorting Task (SST) at Baseline (time frame: Baseline (Visit 1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2025.