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

NCT04694131 | Completed Results

• 2 other identifiers: 10000196000196-N
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Normal Physiology

Keywords

Memory performance; Neural Biomarkers; EEG; Noninvasive transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Theta/Alpha Power

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

Study Arms (1)

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.

Device: TMS

Interventions

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.

Healthy Volunteer Participants

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 32817326 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.

  PMID: 25170153 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.

  PMID: 28893648 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

Results Point of Contact

• Title: Dr. Eric Wassermann
• Organization: National Institutes of Health

wassermanne@nih.gov

301-496-0151

Study Officials

• Eric M Wassermann, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 1, 2021
• First Posted: January 5, 2021
• Study Start: July 9, 2021
• Primary Completion: February 24, 2023
• Study Completion: February 24, 2023
• Last Updated: July 4, 2025
• Results First Posted: July 4, 2025

Record last verified: 2023-10-12

Locations

US (1)