Network Control TMS fMRI

Not Applicable

Terminated

Conditions: Working Memory
Attention Deficit Hyperactivity Disorder
Attention Deficit Disorder

Interventions: Device: Transcranial Magnetic Stimulation (TMS)
Procedure: High controllability TMS target

Registration Number: NCT05736458

Lead Sponsor: University of Pennsylvania

Brief Summary: 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: This study involves up to 4 visits for patients with Attention Deficit Hyperactivity Disorder (ADHD) 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 68

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
High regional controllability TMS target in ADHD participants	Transcranial Magnetic Stimulation (TMS)	We will administer TMS to an individualized target of high regional controllability while patient completes a working memory task inside the MRI scanner.
Low controllability TMS target in non-symptomatic participants	Transcranial Magnetic Stimulation (TMS)	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.
High regional controllability TMS target in ADHD participants	High controllability TMS target	We will administer TMS to an individualized target of high regional controllability while patient completes a working memory task inside the MRI scanner.
High regional controllability TMS target in non-symptomatic participants	Transcranial Magnetic Stimulation (TMS)	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.
High regional controllability TMS target in non-symptomatic participants	High controllability TMS target	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.

Primary Outcome Measures

Name	Time	Method
Effect of Single TMS Pulses to a High vs. Low Regional Controllability Target on Working Memory Task Performance	Up to 3 weeks	Control participants complete two visits in which they undergo functional MRI interleaved with TMS targeting a specific controllability region. Each visit involves administering single pulses of TMS while participants perform a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while completing the N-back task. The targeted brain region is counterbalanced across visits, with one visit stimulating a high regional controllability target and the other stimulating a low regional controllability target. The effect of single-pulse TMS on N-back task performance will be assessed before rTMS administration using percent accuracy scores. Percent accuracy reflects the percentage of correct trials out of the total Nback trials, with higher scores indicating better task performance.
Effect of rTMS on Working Memory Task Performance	Pre- and post-TMS at visits 3 (approximately day 7) and 4 (approximately day 14)	Control participants complete two visits with functional MRI interleaved with TMS targeting a specific controllability region. Each visit includes single pulses of TMS during a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while performing the N-back task. The targeted controllability region is counterbalanced, with one visit stimulating a high controllability target and the other a low controllability target. The effect of rTMS on N-back task performance will be assessed by comparing participants' percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS. Percent accuracy, indicating the percentage of correct trials, will be analyzed for both high and low regional controllability targets across the visits.
Effect of rTMS to High vs. Low Controllability Target on Working Memory Task Performance	Up to 3 weeks	Control participants complete two visits where they undergo functional MRI interleaved with TMS targeting specific brain controllability regions. Each visit includes single pulses of TMS during a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while performing the N-back task. The targeted brain region is counterbalanced across visits, with one visit stimulating a high controllability target and the other a low controllability target. In order to compare the effect of rTMS to high versus low controllability targets on working memory performance, we will assess the change in N-back task percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS to both regions. A greater percent change (positive value) means improved task performance following rTMS.

Secondary Outcome Measures

Name	Time	Method
Effect of rTMS on Working Memory Performance in Participants With ADHD	Pre- and post-TMS at visit 3 (approximately day 7)	Participants with ADHD complete a single visit where they undergo functional MRI interleaved with TMS to a high controllability region. During the visit, participants receive single pulses of TMS while performing the working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while completing the N-back task. The effect of rTMS on N-back task performance is assessed by comparing participants' percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS. Percent accuracy reflects the percentage of correct trials out of the total number of N-back trials, with higher percent accuracy indicating better performance.