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| ID | Type | Description | Link |
|---|---|---|---|
| 000196-N |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TMS | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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) | During encoding (with TMS) and during retrieval (after TMS) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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INCLUSION CRITERIA:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
EXCLUSION CRITERIA
An individual who meets any of the following criteria will be excluded from participation in this study:
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| Name | Affiliation | Role |
|---|---|---|
| Eric M Wassermann, M.D. | National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32817326 | Background | 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. | |
| 25170153 | Background | Wang 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. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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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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43 participants were consented to the study and 32 participants successfully completed all study requirements.
Participants were recruited from the NIH healthy volunteer database and the NIH postbac list serve, as well as individuals who self-referred. Recruitment of study participants occurred from July 2021 to February 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Participants | Healthy participants undergoing all study procedures |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Participants | Healthy participants undergoing all study procedures |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | Posted | Mean | Standard Deviation | proportion accuracy | 1 hour |
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During and Immediately after TMS session
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Participants | Healthy participants undergoing all study procedures | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Eric Wassermann | National Institutes of Health | 301-496-0151 | wassermanne@nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 15, 2022 | Jan 12, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 6, 2022 | Jan 12, 2024 | ICF_001.pdf |
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| During encoding (with TMS) and during retrieval (after TMS) |
| 28893648 | Background | Silvanto 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. |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Context |
Memory for spatial location of item |
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| Primary | 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) | Due to EEG trigger issues, only 14 subjects were able to complete the retrieval arm and have data analyzed as ERPs. | Posted | Mean | Standard Deviation | uV | During encoding (with TMS) and during retrieval (after TMS) |
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|
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| Secondary | 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) | Due to EEG trigger issues, only 14 subjects had retrieval data analyzed as task-evoked power | Posted | Mean | Standard Deviation | uV | During encoding (with TMS) and during retrieval (after TMS) |
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| 32 |
| 0 |
| 32 |
| 0 |
| 32 |
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| Vertex, before TMS |
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| Vertex, during TMS |
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| Vertex, before trial TMS |
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| Vertex, during trial TMS |
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