Network Control TMS fMRI

Network Control and Functional Context: Mechanisms for TMS Response

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.

Study Overview

• Status: Terminated
• Conditions: Attention Deficit Hyperactivity Disorder; Attention Deficit Disorder; Working Memory
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation (TMS); Procedure: High controllability TMS target

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.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 28 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High regional controllability TMS target in non-symptomatic participants; 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); 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.; Procedure: High controllability TMS target; Administer TMS to a brain regions with high regional controllability while the subject engages in a working memory task.
Active Comparator: Low controllability TMS target in non-symptomatic participants; 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); 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.
Experimental: High regional controllability TMS target in ADHD participants; 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); 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.; Procedure: High controllability TMS target; Administer TMS to a brain regions with high regional controllability while the subject engages in a working memory task.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Single TMS Pulses to a High vs. Low Regional Controllability Target on Working Memory Task Performance	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.	Up to 3 weeks
Effect of rTMS on Working Memory Task Performance	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.	Pre- and post-TMS at visits 3 (approximately day 7) and 4 (approximately day 14)
Effect of rTMS to High vs. Low Controllability Target on Working Memory Task Performance	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.	Up to 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of rTMS on Working Memory Performance in Participants With ADHD	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.	Pre- and post-TMS at visit 3 (approximately day 7)

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute of Mental Health (NIMH); National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2019
• Primary Completion (Actual): July 30, 2023
• Study Completion (Actual): July 30, 2023

Study Registration Dates

• First Submitted: January 19, 2023
• First Submitted That Met QC Criteria: February 10, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: MRI; memory; ADHD; healthy; TMS; ADD
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity
• Other Study ID Numbers: 830174; RF1MH116920 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes