Modulation of the Parieto-frontal Communication

Study Overview
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Brief Summary
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Background: Research shows that the parietal and prefrontal areas of the brain are involved in short-term memory. Researchers want to look at the effects of transcranial magnetic stimulation (TMS) of these areas on short-term memory and brain activity. They will use functional magnetic resonance imaging (fMRI) to look at brain activity. Objective: To look at the effects of TMS on brain pathways involved in memory. Eligibility: Healthy, right-handed adults ages 18-50 Design: Participants will have 3 or 4 visits at least 1 week apart. They cannot drink alcohol for at least 48 hours before each visit. The screening visit lasts about 1 (Omega) hours. It can be combined with the first testing visit. Screening includes: Medical history Physical exam Neurological exam Urine tests Questionnaires about being left or right handed and about their ability to imagine physical activities. The first testing visit lasts about 1 (Omega) hours and includes an MRI. For the MRI, participants lie on a table that slides into a machine. They will lie still or perform simple memory tasks on a computer screen. The second and third testing visits last about 3 hours. Participants will have: 2 MRIs TMS: A wire coil is held to the scalp. A brief electrical current passes through the coil to create a magnetic pulse that affects brain activity. They will perform simple memory tasks. EMG: Small electrodes are taped to the skin to record muscle activity while they rest. After the study, participants will complete a questionnaire about any discomfort they experienced during the study. ...

Detailed Description
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Objective: This study aims to identify whether repetitive dual-site transcranial magnetic stimulation (TMS) can modulate the functional connectivity between the parietal and dorso-lateral prefrontal cortices. Study population: The study involves 26 healthy volunteers. Design: This controlled study comprises 3 main visits for each subject: (1) a baseline, evaluation visit during which fMRI will be acquired during a visual short memory task along with diffusion tensor imaging and structural MRI; (2) a visit during which resting state fMRI (rsfMRI) will be acquired, followed by paired-associative stimulation (PAS) with pulses delivered over the parietal and then over the dorso-lateral prefrontal cortex, in order to induce a temporary plastic change in the interaction between the parietal and prefrontal cortices; the PAS will be followed by another rsfMRI and task fMRI; (3) a visit identical to #2 during which the PAS will be delivered with pulses in reverse order of previous visit. Outcome measures: The effects of PAS will be quantified with rsfMRI and a short working memory task, considered as a proxy for complex motor and cognitive control. The primary outcome will be to investigate the resting state functional connectivity changes induced by each PAS intervention The secondary outcome #1 will be to evaluate the difference in visual angle error between sessions 2 and 3 in a working memory task during which the subjects will be asked to remember the position of a bar presented on the screen at different time intervals before the inquiry. The secondary outcome #2 will be to build an fMRI-DTI analysis pipeline for generation of TMS targets individually customized for each subject and a given task.

Official Title
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Modulation of the Parieto-frontal Communication

Conditions
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Normal Physiology

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation (TMS)
* Behavioral: Working Memory Task


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Age between 18-50 years. Right-handed (handedness questionnaire will be part of the initial evaluation) Able to give informed consent. Have a normal neurological exam within the last year and MoCA>27 Willing and able to abstain from alcohol for at least 48 hours prior to the study. Willing to not participate in other rTMS studies in the week preceding visits for the current protocol. EXCLUSION CRITERIA: -All participants must be able to undergo MRI and TMS, for which the MRI- and TMS-safety checklists will be part of the initial evaluation, and reconfirmed at the beginning of every visit. It will constitute as exclusion criteria if the participant: has metal in his/her body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or if he/she was a welder or metal worker, since small metal fragments may be found in the eyes. is uncomfortable in small closed spaces (claustrophobia) so that he/she would feel uncomfortable in the MRI machine. is not able to lie comfortably on the back for up to 2 hours has hearing loss. --is pregnant. Self-reported consumption of >14 alcoholic drinks/week for a man and >7 alcoholic drinks/week for a woman. History of or current brain tumor, stroke, head trauma with loss of consciousness, epilepsy or seizures. Taking medications that act directly on the central nervous system such as anti-epileptics, anti-histamines, anti-parkinsonian medication, medication for insomnia, anti-depressants, anti-anxiety medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PPC-DLPFC<br>In this arm, the TMS paired-pulses will be first delivered over the posterior parietal cortex (PPC) and then over the dorsolateral prefrontal cortex (DLPFC) | Device: Transcranial Magnetic Stimulation (TMS)<br>* Description: This will comprise single and repeated paired-pulses delivered over motor and non-motor areas.<br>Behavioral: Working Memory Task<br>* This will consist in remembering an item presented 1 to 5 steps before the inquiry. This task will span the whole duration of the functional MRI acquisition.<br>|
| Active Comparator: DLPFC-PPC<br>Arm Description: In this arm, the TMS paired-pulses will be first delivered over the over the dorsolateral prefrontal cortex (DLPFC) and then posterior parietal cortex (PPC) | Device: Transcranial Magnetic Stimulation (TMS)<br>* Description: This will comprise single and repeated paired-pulses delivered over motor and non-motor areas.<br>Behavioral: Working Memory Task<br>* This will consist in remembering an item presented 1 to 5 steps before the inquiry. This task will span the whole duration of the functional MRI acquisition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resting state functional connectivity change induced by the paired associative stimulation |  | Study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the visual angle error of a working memory task between the DLPFC-PCC and PPC-DLPFC paired associative stimulation |  | Study completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paired Associative Stimulation (PAS), Functional Magnetic Resonance Imaging (fMRI), Electrical Field Modeling, Working Memory