Network Control TMS fMRI

Study Overview
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Brief Summary
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This study uses different types of functional magnetic resonance imagining (fMRI) to generate individual transcranial magnetic stimulation (TMS) targets. During the TMS/fMRI imagining sessions, the investigators stimulate a target of either high or low regional controllability during a working memory task to investigate network responses and the impact of TMS on behavior.

Detailed Description
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This study involves up to 4 visits for ADHD patients and 5 visits for non-symptomatic subjects. Visit 1 has both remote and in-person procedures. The remote part of visit 1 will consist of a consenting and extended screening visit. The in-person procedures of visit 1 will be scheduled for the same day as visit 2. Before visit 2, the investigators will demonstrate TMS to make sure participants can tolerate the stimulation. Visit 2 consists of an hour-long baseline MRI Scan along with an assessment session. The baseline MRI scan is used to find individualized TMS targets. The assessment session of visit 2 will be done over a video call. During the video call, the investigators will have the participant complete some computerized tasks and assessments. Visit 3 will be a 1-hour long TMS/fMRI session, where the participant will complete a working memory task twice while single pulse TMS is being delivered. In between the 2 rounds of the working memory task, the participant will receive 4 minutes of repetitive stimulation. Non-symptomatic subjects will have a fourth visit that mirrors visit 3. Visit 5 or Visit 4 for ADHD participants, will take place if behavioral task is available, otherwise study participation will be considered complete. During the optional visit, participants may complete behavioral tasks during an MRI scan. No TMS will be administered during the final visit. Participants will receive the compensation at the end of their participation. Payment may be given earlier if the participant withdraws from the study.

Official Title
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Network Control Transcranial Magnetic Stimulation (TMS) Functional Magnetic Resonance Imaging (fMRI)

Conditions
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Attention Deficit Hyperactivity Disorder, Attention Deficit Disorder, Working Memory

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation (TMS)
* Procedure: High controllability TMS target


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-28 years old Right-handed No history of schizophrenia or bipolar disorder No history of neurological illness Healthy participants: no history of any mental illness ADD/ADHD Participants; Diagnosed with ADD/ADHD ADD/ADHD: Ability to refrain from stimulant medication within 24 hours of study sessions For participants reporting daily use of more than 400mg caffeine/ day: willing to lower down to this level at least 1 week prior to screening visit and maintain throughout study visits Exclusion Criteria: Unable to have an MRI scan Unable to receive or tolerate TMS Pregnant, nursing, or trying to become pregnant (self-attestation alone) History of stoke, epilepsy, or brain scarring Healthy participants: psychoactive medication use Healthy participants: first degree relative with psychosis ADHD participants: inability to refrain from stimulant medication within 23 hours of study sessions Active suicidality or current suicidal risk as determined by the investigator Any medication that interferes with fMRI recordings as per PI discretion Otherwise determined by investigator to be unfit for study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 28 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: Non-Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: All healthy participants will have TMS administered to both their high and low regional controllability targets, but the order is randomized and counterbalanced. ADHD participants will have TMS administered to only their high regional controllability target.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High regional controllability TMS target in non-symptomatic participants<br>We will administer TMS to an individualized target of high regional controllability while non-symptomatic participant completes a working memory task inside the MRI scanner. | Device: Transcranial Magnetic Stimulation (TMS)<br>* Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication.<br>Procedure: High controllability TMS target<br>* Administer TMS to a brain regions with high regional controllability while the subject engages in a working memory task.<br>|
| Active Comparator: Low controllability TMS target in non-symptomatic participants<br>We will administer TMS to an individualized target of low regional controllability while non-symptomatic participant completes a working memory task inside the MRI scanner. | Device: Transcranial Magnetic Stimulation (TMS)<br>* Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication.<br>|
| Experimental: High regional controllability TMS target in ADHD participants<br>We will administer TMS to an individualized target of high regional controllability while patient completes a working memory task inside the MRI scanner. | Device: Transcranial Magnetic Stimulation (TMS)<br>* Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication.<br>Procedure: High controllability TMS target<br>* Administer TMS to a brain regions with high regional controllability while the subject engages in a working memory task.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of TMS to a high regional controllability target vs TMS to a low regional controllability target on Nback task performance | Control subjects have two visits where they complete a working memory task (Nback) while receiving TMS. The TMS target is counterbalanced across the two visits, with one administering TMS to high regional controllability target and the other to a low regional controllability target. Nback task performance will be determined for both high controllability and low regional controllability TMS targets using summary behavior measures, including percent accuracy. Higher percent accuracy indicates better task performance. | Up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Nback task performance after rTMS | Control subjects complete two trials of a working memory task (Nback) while receiving single pulses of TMS. In between the two Nback trials, subjects receive neuromodulatory repetitive TMS (rTMS). Change in the Nback task performance after rTMS will be determined for high and low regional controllability targets. Greater positive change indicates better task performance after rTMS. | Single visit ( 2 hours) | 
| Change in Nback task performance after rTMS to a high regional controllability target - ADHD/ADD patients | Patients with ADD/ADHD complete two trials of a working memory task (Nback) while receiving single pulses of TMS. In between the two Nback trials, subjects receive neuromodulatory repetitive TMS (rTMS). Change in the Nback task performance after rTMS will be determined for subjects with ADHD. Greater positive change indicates better task performance after rTMS. | Single visit ( 2 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, memory, ADHD, healthy, MRI, ADD