Normal PhysiologyNCT04694131
Task-dependent Effects of TMS on the Neural Biomarkers of Episodic Memory
A study testing TMS in people with Normal Physiology, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Transcranial magnetic stimulation (TMS) of the brain has been used to change the activity and connections in the brain to improve memory. Researchers are interested in how these brain changes cause memory improvements and how activity at the time of stimulation may change the effects of TMS. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Normal Physiology
- What is being tested?
- TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Jul 2021to 24 Feb 2023
- 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 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Age 18-40 (inclusive)
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression
- History of seizure
- Medications acting on the central nervous system, such as those that lowers the seizure threshold such as neuroleptics, beta lactams, isoniazid, metronidazole; benzodiazepines, tricyclic or other antidepressants; or prescription stimulants.
- Inability to provide informed consent
- Ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body
Show all 13Show fewer
- Implanted cardiac pacemaker or auto-defibrillator or pump
- Non-removable body piercing
- Claustrophobia
- Inability to lie supine for 1 hour
- Pregnancy, or plans to become pregnant during the study.
- Members of the NINDS BNU
- Subjects who have contraindications to MRI will follow the NMR Center guidelines for MR safety.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
Transcranial magnetic stimulation (TMS) of the brain has been used to change the activity and connections in the brain to improve memory. Researchers are interested in how these brain changes cause memory improvements and how activity at the time of stimulation may change the effects of TMS.
Read more
Objective:
To learn how brain stimulation can be used to improve memory.
Eligibility:
Healthy adults ages 18-40
Design:
Participants will be screened with a medical record review.
Participants will have 3 study visits.
At visit 1, participants will have a physical exam and will talk about their health. They will have magnetic resonance imaging (MRI). The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, participants will lie on a table that can slide in and out of the scanner. A coil will be placed over the head. Participants will be asked to keep their eyes focused on a small cross on a computer screen inside the scanner. The scanner makes loud noises. Participants will get earplugs.
At visits 2 and 3, participants will have TMS and perform tasks. For TMS, a wire coil encased in plastic is held on the scalp. When the coil is triggered, a brief electrical current passes through the coil and creates a magnetic pulse that stimulates the brain. During TMS, an electroencephalogram (EEG) will record brain activity. For the EEG, a cloth cap with electrodes is fitted on the participant s head. Participants will complete a memory task and a spatial processing task. They will also complete surveys about their mental state.
Participation will last 2-3 weeks.
Read the detailed description
Study Description:
The Behavioral Neurology Unit studies the human brain systems underlying learning and adaptation with the goal of finding interventions to make these processes more efficient. In this study, we are interested in examining how the task state of the episodic memory network influences the effect of faciliatory TMS on memory and its EEG neural correlates. It is hypothesized that Network-targeted parietal-TMS will improve memory performance and enhance EEG biomarkers of successful memory performance, but that these changes will be modulated by the ongoing task activity during stimulation.
Objectives:
Primary Objectives:
Investigate how TMS modulates EEG neural measures of successful memory and the association of this modulation with behavioral performance
Examine how memory task state influences susceptibility to plasticity via TMS and determine the optimal neural state for improving memory
Exploratory Objectives:
Search for MRI predictors of the effects of TMS
Endpoints:
Primary Endpoints: Memory performance, Late Positive Posterior ERP, evoked theta/alpha power (secondary), EEG functional connectivity (secondary)
Exploratory Endpoints: fMRI resting state functional connectivity, fractional anisotropy
- Conditions
- Normal Physiology
- Being tested
- TMS
- Keywords
- Memory performance, Neural Biomarkers, EEG, Noninvasive transcranial magnetic stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMSDevice
The intervention of interest will be TMS delivered to the region of the left posterior parietal cortex with the greatest connectivity with the left hippocampus derived from the baseline resting-state fMRI session. This region was chosen because of its dense connections with the hippocampus, allowing stimulation of this location to modulate function of the hippocampal-cortical network. The control intervention target will be vertex, a commonly used active control site which does not influence neural or behavioral activity.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Volunteer Participants | Other | All participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects. There will be two experiment days, during which TMS will be delivered during the behavioral tasks (spatial task trials and encoding phase of the memory task). Participants will receive TMS delivered to parietal cortex on one day and vertex stimulation on the other day. Each experiment day will include one block of TMS delivered prior to task trial onsets and one block delivered simultaneously with trial onsets. Receives: Device: TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Memory Performance
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the accuracy of memory for the item and the location (context), presented as the percentage of successful trials. Accuracy is shown for each stimulation condition (parietal or vertex location, before or during the trial)
Measured: 1 hour
Late Positive Posterior (ERP) Event Related Potential
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the neural response to trials which were later remembered relative to trials which were later forgotten. Values represent the difference in average EEG amplitude, in uV, between remembered and forgotten trials and compared across each stimulation condition (parietal or vertex location, before or during the trial)
Measured: During encoding (with TMS) and during retrieval (after TMS)
Secondary outcomes (1)
Theta/Alpha Power
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the neural response to trials which were later remembered relative to trials which were later forgotten. Values represent the difference in average task-evoked power in the theta/alpha range (4-13Hz), in uV, between remembered and forgotten trials and compared across each stimulation condition (parietal or vertex location, before or during the trial)
Measured: During encoding (with TMS) and during retrieval (after TMS)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2021
- Study start9 Jul 2021
- Primary completion24 Feb 2023
- Study completion24 Feb 2023
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Eric M Wassermann, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04694131
- Sponsor's protocol ID
- 10000196
- Other IDs
- 000196-N
- Status last verified
- 12 Oct 2023
- First submitted
- 1 Jan 2021
- Last updated
- 4 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It has not been determined if it is beneficial or feasible to share IPD. This will be decided at a later time.
Publications
Hermiller MS, Chen YF, Parrish TB, Voss JL. Evidence for Immediate Enhancement of Hippocampal Memory Encoding by Network-Targeted Theta-Burst Stimulation during Concurrent fMRI. J Neurosci. 2020 Sep 9;40(37):7155-7168. doi: 10.1523/JNEUROSCI.0486-20.2020. Epub 2020 Aug 17.
PubMed 32817326Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014 Aug 29;345(6200):1054-7. doi: 10.1126/science.1252900.
PubMed 25170153Silvanto J, Bona S, Cattaneo Z. Initial activation state, stimulation intensity and timing of stimulation interact in producing behavioral effects of TMS. Neuroscience. 2017 Nov 5;363:134-141. doi: 10.1016/j.neuroscience.2017.09.002. Epub 2017 Sep 8.
PubMed 28893648
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Task-dependent Effects of TMS on the Neural Biomarkers of Episodic Memory
- ClinicalTrials.gov ID
- NCT04694131
- Acronym / sponsor ID
- 10000196
- Conditions
- Normal Physiology
- Keywords
- Memory performance, Neural Biomarkers, EEG, Noninvasive transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 9 Jul 2021 (actual)
- Primary completion
- 24 Feb 2023 (actual)
- Study completion
- 24 Feb 2023 (actual)
- First posted
- 5 Jan 2021 (actual)
- Results
- Posted 4 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Transcranial magnetic stimulation (TMS) of the brain has been used to change the activity and connections in the brain to improve memory. Researchers are interested in how these brain changes cause memory improvements and how activity at the time of stimulation may change the effects of TMS.
Objective:
To learn how brain stimulation can be used to improve memory.
Eligibility:
Healthy adults ages 18-40
Design:
Participants will be screened with a medical record review.
Participants will have 3 study visits.
At visit 1, participants will have a physical exam and will talk about their health. They will have magnetic resonance imaging (MRI). The MRI scanner is a metal cylinder surrounded by a strong magnetic field. During the MRI, participants will lie on a table that can slide in and out of the scanner. A coil will be placed over the head. Participants will be asked to keep their eyes focused on a small cross on a computer screen inside the scanner. The scanner makes loud noises. Participants will get earplugs.
At visits 2 and 3, participants will have TMS and perform tasks. For TMS, a wire coil encased in plastic is held on the scalp. When the coil is triggered, a brief electrical current passes through the coil and creates a magnetic pulse that stimulates the brain. During TMS, an electroencephalogram (EEG) will record brain activity. For the EEG, a cloth cap with electrodes is fitted on the participant s head. Participants will complete a memory task and a spatial processing task. They will also complete surveys about their mental state.
Participation will last 2-3 weeks.
Detailed description
Study Description:
The Behavioral Neurology Unit studies the human brain systems underlying learning and adaptation with the goal of finding interventions to make these processes more efficient. In this study, we are interested in examining how the task state of the episodic memory network influences the effect of faciliatory TMS on memory and its EEG neural correlates. It is hypothesized that Network-targeted parietal-TMS will improve memory performance and enhance EEG biomarkers of successful memory performance, but that these changes will be modulated by the ongoing task activity during stimulation.
Objectives:
Primary Objectives:
Investigate how TMS modulates EEG neural measures of successful memory and the association of this modulation with behavioral performance
Examine how memory task state influences susceptibility to plasticity via TMS and determine the optimal neural state for improving memory
Exploratory Objectives:
Search for MRI predictors of the effects of TMS
Endpoints:
Primary Endpoints: Memory performance, Late Positive Posterior ERP, evoked theta/alpha power (secondary), EEG functional connectivity (secondary)
Exploratory Endpoints: fMRI resting state functional connectivity, fractional anisotropy
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteer Participants | Other | Device: TMSAll participants will receive all conditions and the order of all conditions will be counterbalanced across participants. Statistical comparisons will be within-subjects. There will be two experiment days, during which TMS will be delivered during the behavioral tasks (spatial task trials and encoding phase of the memory task). Participants will receive TMS delivered to parietal cortex on one day and vertex stimulation on the other day. Each experiment day will include one block of TMS delivered prior to task trial onsets and one block delivered simultaneously with trial onsets. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Age 18-40 (inclusive)
Key exclusion criteria (13 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression
- History of seizure
- Medications acting on the central nervous system, such as those that lowers the seizure threshold such as neuroleptics, beta lactams, isoniazid, metronidazole; benzodiazepines, tricyclic or other antidepressants; or prescription stimulants.
- Inability to provide informed consent
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 |
|---|---|---|
| TMSThe intervention of interest will be TMS delivered to the region of the left posterior parietal cortex with the greatest connectivity with the left hippocampus derived from the baseline resting-state fMRI session. This region was chosen because of its dense connections with the hippocampus, allowing stimulation of this location to modulate function of the hippocampal-cortical network. The control intervention target will be vertex, a commonly used active control site which does not influence neural or behavioral activity. | Device | Healthy Volunteer Participants |
Primary outcome
Memory Performance
Time frame: 1 hour
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the accuracy of memory for the item and the location (context), presented as the percentage of successful trials. Accuracy is shown for each stimulation condition (parietal or vertex location, before or during the trial)
Late Positive Posterior (ERP) Event Related Potential
Time frame: During encoding (with TMS) and during retrieval (after TMS)
Participants completed a memory task with simultaneous EEG acquisition and transcranial magnetic stimulation (TMS) delivered to either a memory-relevant parietal lobe target or a vertex control site. Participants were shown a series of objects in one of four quadrants on the screen, with TMS delivered either prior to or concurrent with the trial onset. They were instructed to remember the object and the location. This outcome measure examines the neural response to trials which were later remembered relative to trials which were later forgotten. Values represent the difference in average EEG amplitude, in uV, between remembered and forgotten trials and compared across each stimulation condition (parietal or vertex location, before or during the trial)
1 secondary outcome
Theta/Alpha Power
Time frame: During encoding (with TMS) and during retrieval (after TMS)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32817326Hermiller MS, Chen YF, Parrish TB, Voss JL. Evidence for Immediate Enhancement of Hippocampal Memory Encoding by Network-Targeted Theta-Burst Stimulation during Concurrent fMRI. J Neurosci. 2020 Sep 9;40(37):7155-7168. doi: 10.1523/JNEUROSCI.0486-20.2020. Epub 2020 Aug 17.
- Background: PubMed 25170153Wang JX, Rogers LM, Gross EZ, Ryals AJ, Dokucu ME, Brandstatt KL, Hermiller MS, Voss JL. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science. 2014 Aug 29;345(6200):1054-7. doi: 10.1126/science.1252900.
- Background: PubMed 28893648Silvanto J, Bona S, Cattaneo Z. Initial activation state, stimulation intensity and timing of stimulation interact in producing behavioral effects of TMS. Neuroscience. 2017 Nov 5;363:134-141. doi: 10.1016/j.neuroscience.2017.09.002. Epub 2017 Sep 8.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. It has not been determined if it is beneficial or feasible to share IPD. This will be decided at a later time.
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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. This study is not recruiting at the moment.
Eric M Wassermann, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TMS in people with Normal Physiology, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 4 inclusion and 13 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 4 Jul 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. 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 4 Jul 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?
Memory Performance (time frame: 1 hour). 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?
On the ClinicalTrials.gov record for NCT04694131, which also lists 3 linked publications.
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 4 Jul 2025.