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

Study Overview
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Brief Summary
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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. ...

Detailed Description
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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

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

Conditions
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Normal Physiology

Intervention / Treatment
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* Device: TMS


Participation Criteria
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Eligibility Criteria
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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: 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) EXCLUSION CRITERIA 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: MS<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Memory performance | 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 | 1 hour | 
| Late Positive Posterior ERP | ERP amplitude 500-700 ms after trial onset (encoding and retrieval) over parietal and occipital electrodes | Immediate | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Theta/Alpha power | Power in the 4-13 Hz band 0-1000 ms after trial onset (encoding and retrieval) | Immediate | 
| EEG functional connectivity | Pearson correlation coefficients (r) between electrode time courses after trial onset (encoding and retrieval) | Immediate | 
| DTI structural connectivity | Fractional anisotropy (FA) at baseline between the hippocampus and cortical regions | 1-7 days before intervention | 
| fMRI functional connectivity | Resting state functional connectivity at baseline between the hippocampus and cortical regions | 1-7 days before intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EEG, Memory performance, Neural Biomarkers, Noninvasive transcranial magnetic stimulation