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

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Overall Status: Recruiting
• CT.gov ID: NCT04694131
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 109.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

...

Condition or Disease	Intervention/Treatment	Phase
Normal Physiology	Device: TMS	N/A

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

• Study Type: Interventional
• Anticipated Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Task-dependent Effects of TMS on the Neural Biomarkers of Episodic Memory
• Actual Study Start Date: Jul 9, 2021
• Anticipated Primary Completion Date: Aug 30, 2030
• Anticipated Study Completion Date: Aug 30, 2030

Arms and Interventions

Arm

Intervention/Treatment

Other: MS 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.

Outcome Measures

Primary Outcome Measures

1. Memory performance [1 hour]

   Accuracy: Percentage of successful (later remembered hit and correct rejection) vs unsuccessful (forgotten miss and false alarm) trials for item recognition (remember /familiar/new) and context recollection (spatial location): Analysis of hits (correctly remembered as encoded) relative to false alarms (new objects labelled as encoded) for item recognition

2. Late Positive Posterior ERP [Immediate]

   ERP amplitude 500-700 ms after trial onset (encoding and retrieval) over parietal and occipital electrodes

Secondary Outcome Measures

1. Theta/Alpha power [Immediate]

   Power in the 4-13 Hz band 0-1000 ms after trial onset (encoding and retrieval)

2. EEG functional connectivity [Immediate]

   Pearson correlation coefficients (r) between electrode time courses after trial onset (encoding and retrieval)

3. DTI structural connectivity [1-7 days before intervention]

   Fractional anisotropy (FA) at baseline between the hippocampus and cortical regions

4. fMRI functional connectivity [1-7 days before intervention]

   Resting state functional connectivity at baseline between the hippocampus and cortical regions

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

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.
• 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.
• 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.

• Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
• ClinicalTrials.gov Identifier: NCT04694131
• Other Study ID Numbers: 10000196; 000196-N
• First Posted: Jan 5, 2021
• Last Update Posted: Jul 19, 2022
• Last Verified: Jul 15, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS): Memory performance; Neural Biomarkers; EEG; Noninvasive transcranial magnetic stimulation

Study Results

No Results Posted as of Jul 19, 2022