Network Control TMS fMRI

University of Pennsylvania68 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Attention Deficit Hyperactivity Disorder Attention Deficit Disorder Working Memory

Interventions

Transcranial Magnetic Stimulation (TMS)DEVICE

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.

High controllability TMS targetPROCEDURE

Administer TMS to a brain regions with high regional controllability while the subject engages in a working memory task.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 28 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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