Brain ConnectivityNCT05322239
Resting State Changes Following Theta Burst Stimulation
A study testing Intermittent Theta Burst Stimulation and Continuous Theta Burst Stimulation in people with Brain Connectivity, run by Nicholas Balderston, PhD at 1 site in United States.
Trial summary
Transcranial magnetic stimulation (TMS) is increasingly being applied to effectively treat mental illness, however efforts to quantify the effects of TMS on the network architecture of the brain have largely been limited in scope and tied to specific neurologic and psychiatric disorders. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Brain Connectivity
- What is being tested?
- Intermittent Theta Burst Stimulation and Continuous Theta Burst Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2022to 1 Aug 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Able to give their consent
- Right-handed
Who cannot join
- Non-english speaking
- Any significant medical 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
Show all 14Show fewer
- History of seizure
- History of epilepsy or other neurological problems
- Increased risk of seizure for any reason
- Pregnancy
- 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
- Claustrophobia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Nicholas l Balderston, PhD, 215-746-3058, nicholas.balderston@pennmedicine.upenn.edu
About this study
Official title: Novel Electric-field Modelling Approach to Quantify Changes in Resting State Functional Connectivity Following Theta Burst Stimulation
Transcranial magnetic stimulation (TMS) is increasingly being applied to effectively treat mental illness, however efforts to quantify the effects of TMS on the network architecture of the brain have largely been limited in scope and tied to specific neurologic and psychiatric disorders. The objective of the current work is to build and validate a whole-brain, domain-general model of brain connectivity changes following TMS, based on physical models of the current distribution at the cortex. PUBLIC HEALTH RELEVANCE: This work is relevant to public health because it will provide direct evidence that brain connectivity changes following neuromodulatory TMS vary as a function of the current density at the cortex, which can be used to predict psychiatric symptom change following neuromodulatory TMS.
Read the detailed description
Transcranial magnetic stimulation (TMS) is currently approved by the FDA for the treatment of depression, obsessive compulsive disorder, and smoking cessation. Despite evidence that TMS improves symptoms by modulating brain connectivity, the few published studies that have measured brain connectivity before and after neuromodulatory TMS have been population-, dose-, and pattern-specific, with connectivity effects that are limited in scope to a handful a priori regions of interest. Accordingly, there is a critical need for generalized, comprehensive model that explains how functional brain connectivity changes at the whole-brain level following neuromodulatory TMS. Therefore, the objectives of this grant are to 1) develop a model using whole-brain estimates of the TMS-induced electric (e)-field to predict changes in resting state functional connectivity following neuromodulatory TMS, and 2) validate this model in a large cohort of healthy volunteers receiving multiple doses of either intermittent or continuous theta burst stimulation (iTBS and cTBS, respectively). Our central hypothesis is that changes in functional connectivity will vary systematically with the current density at the cortex, operationally defined using e-field modelling. Investigators have pilot data suggesting that the variability in pre-post rsFC changes following TMS can be predicted using estimates of the current density at the cortex with a medium to large effect size. Our approach will be to measure rsFC in healthy volunteers before and after each of 3 doses (5 sessions/dose; 600 pulses/session) of iTBS or cTBS. Stimulation will be delivered to the left dlPFC, and targeting will be individualized based on fMRI data collected during the Sternberg working memory paradigm. Our primary outcome measure will be the percent of variability in pre-post rsFC accounted for by our model. Our rationale for this approach is that by collecting resting state data pre and post these doses of iTBS and cTBS, investigators will be able to quantify the effect of pattern (i.e. cTBS vs. iTBS) and dose (i.e. number of pulses) on functional connectivity changes. This work is innovative because it uses a novel application of e-field modelling to predict changes in rsFC data following TMS administration. PUBLIC HEALTH RELEVANCE: This work is relevant to public health because it will provide direct evidence that functional connectivity changes following neuromodulatory TMS vary as a function of the current density at the cortex. The empirical support for this model gained from this current work will set the stage for the use of this model for individualized targeting in subsequent clinical trials. Importantly, because of the domain-general nature of this approach its application is not limited to any specific disorder. Likewise, because our approach is not tied to any specific functional connectivity feature, it can be applied to regions outside those currently under investigation, which could facilitate target discovery in understudied disorders.
- Conditions
- Brain Connectivity
- Being tested
- Intermittent Theta Burst Stimulation, Continuous Theta Burst Stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent Theta Burst StimulationDevice
iTBS parameters. A series of 20, 10 s trains will be presented over the course of the ~3.5 min session. Each train will consist of 2 s of stimulation with an 8 s ITI. During the 2 s of stimulation, 10, 50 Hz bursts will be repeated at intervals of 200 ms (5 Hz).
Continuous Theta Burst StimulationDevice
cTBS parameters. A single 600 pulse cTBS train will be delivered during each stimulation session. The train will consist of 50 Hz bursts, repeated at intervals of 200 ms (5 Hz) for 40 sec.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent Theta Burst Stimulation | Experimental | TBS. A Magventure MagPro 100X stimulator with a B65 figure-8 coil will be used for the TBS sessions. On each of the 3 stimulation days, 5 iTBS sessions will be administered at 30 min intervals. Receives: Device: Intermittent Theta Burst Stimulation |
| Continuous Theta Burst Stimulation | Experimental | TBS. A Magventure MagPro 100X stimulator with a B65 figure-8 coil will be used for the TBS sessions. On each of the 3 stimulation days, 5 cTBS sessions will be administered at 30 min intervals. Receives: Device: Continuous Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting state - dose 1
Investigators will measure resting state functional connectivity 24 hours after first dose of continuous or intermittent theta burst stimulation.
Measured: 24 hours
Resting state - dose 2
Investigators will measure resting state functional connectivity 24 hours after second dose of continuous or intermittent theta burst stimulation.
Measured: 24 hours
Resting state - dose 3
Investigators will measure resting state functional connectivity 24 hours after third dose of continuous or intermittent theta burst stimulation.
Measured: 24 hours
Working memory - dose 1
Investigators will measure reaction time during the Sternberg Working memory paradigm 24 hours after first dose of continuous or intermittent theta burst stimulation.
Measured: 24 hours
Working memory - dose 2
Investigators will measure reaction time during the Sternberg Working memory paradigm 24 hours after second dose of continuous or intermittent theta burst stimulation.
Measured: 24 hours
Working memory - dose 3
Investigators will measure reaction time during the Sternberg Working memory paradigm 24 hours after third dose of continuous or intermittent theta burst stimulation.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2022
- Study start17 Nov 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion1 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain ConnectivityStudies of the same condition, open and under way.
- 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
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Therefore, the proposed approach will be to measure the cumulative effect of TBS on resting state functional connectivity in healthy volunteers before and 24 hours after each of 3 identical doses (5 sessions/dose; 600 pulses/session) of cTBS or iTBS. Stimulation will be delivered to the left dlPFC; targeting will be individualized based on fMRI data collected during the Sternberg Working Memory (WM) paradigm.
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nicholas Balderston, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nicholas Balderston, PhD, University of Pennsylvania
- Investigators
- Nicholas L Balderston, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05322239
- Sponsor's protocol ID
- 851028
- Status last verified
- Jan 2026
- First submitted
- 24 Mar 2022
- Last updated
- 7 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Repositories receiving data and/or samples from this protocol may be open-access or restricted access. Samples and data will be stripped of identifiers and may be coded ("de-identified") or unlinked from an identifying code ("anonymized"). When coded data is shared, the key to the code will not be provided to collaborators, but will remain with the PI.
Publications
Balderston NL, Beer JC, Seok D, Makhoul W, Deng ZD, Girelli T, Teferi M, Smyk N, Jaskir M, Oathes DJ, Sheline YI. Proof of concept study to develop a novel connectivity-based electric-field modelling approach for individualized targeting of transcranial magnetic stimulation treatment. Neuropsychopharmacology. 2022 Jan;47(2):588-598. doi: 10.1038/s41386-021-01110-6. Epub 2021 Jul 28.
PubMed 34321597
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Electric-field Modelling Approach to Quantify Changes in Resting State Functional Connectivity Following Theta Burst Stimulation
- ClinicalTrials.gov ID
- NCT05322239
- Acronym / sponsor ID
- 851028
- Conditions
- Brain Connectivity
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Nicholas Balderston, PhDUniversity, hospital or other
- Study start
- 17 Nov 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 1 Aug 2027 (estimated)
- First posted
- 11 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Transcranial magnetic stimulation (TMS) is increasingly being applied to effectively treat mental illness, however efforts to quantify the effects of TMS on the network architecture of the brain have largely been limited in scope and tied to specific neurologic and psychiatric disorders. The objective of the current work is to build and validate a whole-brain, domain-general model of brain connectivity changes following TMS, based on physical models of the current distribution at the cortex. PUBLIC HEALTH RELEVANCE: This work is relevant to public health because it will provide direct evidence that brain connectivity changes following neuromodulatory TMS vary as a function of the current density at the cortex, which can be used to predict psychiatric symptom change following neuromodulatory TMS.
Detailed description
Transcranial magnetic stimulation (TMS) is currently approved by the FDA for the treatment of depression, obsessive compulsive disorder, and smoking cessation. Despite evidence that TMS improves symptoms by modulating brain connectivity, the few published studies that have measured brain connectivity before and after neuromodulatory TMS have been population-, dose-, and pattern-specific, with connectivity effects that are limited in scope to a handful a priori regions of interest. Accordingly, there is a critical need for generalized, comprehensive model that explains how functional brain connectivity changes at the whole-brain level following neuromodulatory TMS. Therefore, the objectives of this grant are to 1) develop a model using whole-brain estimates of the TMS-induced electric (e)-field to predict changes in resting state functional connectivity following neuromodulatory TMS, and 2) validate this model in a large cohort of healthy volunteers receiving multiple doses of either intermittent or continuous theta burst stimulation (iTBS and cTBS, respectively). Our central hypothesis is that changes in functional connectivity will vary systematically with the current density at the cortex, operationally defined using e-field modelling. Investigators have pilot data suggesting that the variability in pre-post rsFC changes following TMS can be predicted using estimates of the current density at the cortex with a medium to large effect size. Our approach will be to measure rsFC in healthy volunteers before and after each of 3 doses (5 sessions/dose; 600 pulses/session) of iTBS or cTBS. Stimulation will be delivered to the left dlPFC, and targeting will be individualized based on fMRI data collected during the Sternberg working memory paradigm. Our primary outcome measure will be the percent of variability in pre-post rsFC accounted for by our model. Our rationale for this approach is that by collecting resting state data pre and post these doses of iTBS and cTBS, investigators will be able to quantify the effect of pattern (i.e. cTBS vs. iTBS) and dose (i.e. number of pulses) on functional connectivity changes. This work is innovative because it uses a novel application of e-field modelling to predict changes in rsFC data following TMS administration. PUBLIC HEALTH RELEVANCE: This work is relevant to public health because it will provide direct evidence that functional connectivity changes following neuromodulatory TMS vary as a function of the current density at the cortex. The empirical support for this model gained from this current work will set the stage for the use of this model for individualized targeting in subsequent clinical trials. Importantly, because of the domain-general nature of this approach its application is not limited to any specific disorder. Likewise, because our approach is not tied to any specific functional connectivity feature, it can be applied to regions outside those currently under investigation, which could facilitate target discovery in understudied disorders.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Therefore, the proposed approach will be to measure the cumulative effect of TBS on resting state functional connectivity in healthy volunteers before and 24 hours after each of 3 identical doses (5 sessions/dose; 600 pulses/session) of cTBS or iTBS. Stimulation will be delivered to the left dlPFC; targeting will be individualized based on fMRI data collected during the Sternberg Working Memory (WM) paradigm.
| Arm | Type | Receives |
|---|---|---|
| Intermittent Theta Burst Stimulation | Experimental | Device: Intermittent Theta Burst StimulationTBS. A Magventure MagPro 100X stimulator with a B65 figure-8 coil will be used for the TBS sessions. On each of the 3 stimulation days, 5 iTBS sessions will be administered at 30 min intervals. |
| Continuous Theta Burst Stimulation | Experimental | Device: Continuous Theta Burst StimulationTBS. A Magventure MagPro 100X stimulator with a B65 figure-8 coil will be used for the TBS sessions. On each of the 3 stimulation days, 5 cTBS sessions will be administered at 30 min intervals. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Able to give their consent
- Right-handed
Key exclusion criteria (14 listed)
- Non-english speaking
- Any significant medical 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
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 |
|---|---|---|
| Intermittent Theta Burst StimulationiTBS parameters. A series of 20, 10 s trains will be presented over the course of the ~3.5 min session. Each train will consist of 2 s of stimulation with an 8 s ITI. During the 2 s of stimulation, 10, 50 Hz bursts will be repeated at intervals of 200 ms (5 Hz). | Device | Intermittent Theta Burst Stimulation |
| Continuous Theta Burst StimulationcTBS parameters. A single 600 pulse cTBS train will be delivered during each stimulation session. The train will consist of 50 Hz bursts, repeated at intervals of 200 ms (5 Hz) for 40 sec. | Device | Continuous Theta Burst Stimulation |
Primary outcome
Resting state - dose 1
Time frame: 24 hours
Investigators will measure resting state functional connectivity 24 hours after first dose of continuous or intermittent theta burst stimulation.
Resting state - dose 2
Time frame: 24 hours
Investigators will measure resting state functional connectivity 24 hours after second dose of continuous or intermittent theta burst stimulation.
Resting state - dose 3
Time frame: 24 hours
Investigators will measure resting state functional connectivity 24 hours after third dose of continuous or intermittent theta burst stimulation.
Working memory - dose 1
Time frame: 24 hours
Investigators will measure reaction time during the Sternberg Working memory paradigm 24 hours after first dose of continuous or intermittent theta burst stimulation.
Working memory - dose 2
Time frame: 24 hours
Investigators will measure reaction time during the Sternberg Working memory paradigm 24 hours after second dose of continuous or intermittent theta burst stimulation.
Working memory - dose 3
Time frame: 24 hours
Investigators will measure reaction time during the Sternberg Working memory paradigm 24 hours after third dose of continuous or intermittent theta burst stimulation.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2026.
- Results publication: PubMed 34321597Balderston NL, Beer JC, Seok D, Makhoul W, Deng ZD, Girelli T, Teferi M, Smyk N, Jaskir M, Oathes DJ, Sheline YI. Proof of concept study to develop a novel connectivity-based electric-field modelling approach for individualized targeting of transcranial magnetic stimulation treatment. Neuropsychopharmacology. 2022 Jan;47(2):588-598. doi: 10.1038/s41386-021-01110-6. Epub 2021 Jul 28.
- Individual participant dataSharing planned: Yes. Repositories receiving data and/or samples from this protocol may be open-access or restricted access. Samples and data will be stripped of identifiers and may be coded ("de-identified") or unlinked from an identifying code ("anonymized"). When coded data is shared, the key to the code will not be provided to collaborators, but will remain with the PI.
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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.
Nicholas L Balderston principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent Theta Burst Stimulation and Continuous Theta Burst Stimulation in people with Brain Connectivity, run by Nicholas Balderston, PhD 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 2 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 7 Jan 2026. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicholas L Balderston (2157463058, nicholas.balderston@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting state - dose 1 (time frame: 24 hours). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05322239, which also lists 1 linked publication.
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 7 Jan 2026.