Task-dependent Effects of TMS on the Neural Biomarkers of Episodic Memory

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 Overview

• Status: Completed
• Conditions: Normal Physiology
• Intervention / Treatment: Device: TMS

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 Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study
2. Ability of subject to understand and the willingness to sign a written informed consent document.
3. Age 18-40 (inclusive)

EXCLUSION CRITERIA

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression
2. History of seizure
3. 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.
4. Inability to provide informed consent
5. Ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body
6. Implanted cardiac pacemaker or auto-defibrillator or pump
7. Non-removable body piercing
8. Claustrophobia
9. Inability to lie supine for 1 hour
10. Pregnancy, or plans to become pregnant during the study.
11. Members of the NINDS BNU
12. Subjects who have contraindications to MRI will follow the NMR Center guidelines for MR safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Healthy Volunteer Participants; 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.

Device: TMS; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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)	During encoding (with TMS) and during retrieval (after TMS)

Collaborators and Investigators

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Eric M Wassermann, M.D., National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

General 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.
• 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.
• 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.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2021
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): February 24, 2023

Study Registration Dates

• First Submitted: January 1, 2021
• First Submitted That Met QC Criteria: January 2, 2021
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: June 20, 2025
• Last Verified: October 12, 2023

More Information

Terms related to this study

• Keywords: EEG; Memory performance; Neural Biomarkers; Noninvasive transcranial magnetic stimulation
• Other Study ID Numbers: 10000196; 000196-N

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It has not been determined if it is beneficial or feasible to share IPD. This will be decided at a later time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No