Trial Outcomes & Findings for Network Control TMS fMRI (NCT NCT05736458)

Last Updated: 2025-02-06

Results Overview

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.

Recruitment status

TERMINATED

Study phase

Target enrollment

68 participants

Primary outcome timeframe

Up to 3 weeks

Results posted on

2025-02-06

Participant Flow

Of the 68 participants screened for the study, 45 were enrolled and 23 did not start study procedures (13 screen failed, 4 withdrew from participation, and 6 lost to follow-up)

Participant milestones

Participant milestones
Measure	Non-symptomatic Participants High Modal Controllability First, Then Low Modal Controllability Target Non-symptomatic participants will complete 2 TMS/fMRI visits, first receiving TMS to a high modal controllability target then the alternate low modal controllability target for the second TMS/fMRI. We will administer TMS to an individualized target of high \& low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.	Non-symptomatic Participants Low Modal Controllability First, Then High Modal Controllability Target Non-symptomatic participants will complete 2 TMS/fMRI visits, first receiving TMS to a low modal controllability target then the alternate high modal controllability target for the second TMS/fMRI. We will administer TMS to an individualized target of high \& low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.	High Modal 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. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.
Baseline MRI and Assessments STARTED	13	13	19
Baseline MRI and Assessments COMPLETED	11	13	15
Baseline MRI and Assessments NOT COMPLETED	2	0	4
TMS/fMRI #1 STARTED	11	13	15
TMS/fMRI #1 COMPLETED	11	13	13
TMS/fMRI #1 NOT COMPLETED	0	0	2
Washout (at Least 7 Days) STARTED	11	13	0
Washout (at Least 7 Days) COMPLETED	11	12	0
Washout (at Least 7 Days) NOT COMPLETED	0	1	0
TMS/fMRI #2 (Only for Non-symptomatic) STARTED	11	12	0
TMS/fMRI #2 (Only for Non-symptomatic) COMPLETED	11	12	0
TMS/fMRI #2 (Only for Non-symptomatic) NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Non-symptomatic Participants High Modal Controllability First, Then Low Modal Controllability Target Non-symptomatic participants will complete 2 TMS/fMRI visits, first receiving TMS to a high modal controllability target then the alternate low modal controllability target for the second TMS/fMRI. We will administer TMS to an individualized target of high \& low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.	Non-symptomatic Participants Low Modal Controllability First, Then High Modal Controllability Target Non-symptomatic participants will complete 2 TMS/fMRI visits, first receiving TMS to a low modal controllability target then the alternate high modal controllability target for the second TMS/fMRI. We will administer TMS to an individualized target of high \& low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.	High Modal 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. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.
Baseline MRI and Assessments Lost to Follow-up	0	0	4
Baseline MRI and Assessments Withdrawal by Subject	2	0	0
TMS/fMRI #1 Physician Decision	0	0	2
Washout (at Least 7 Days) Lost to Follow-up	0	1	0

Baseline Characteristics

Network Control TMS fMRI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Non-symptomatic Participants n=26 Participants Non-symptomatic participants or those without any psychiatric history complete two visits involving functional MRI (fMRI) and TMS. Each visit targets a specific brain controllability region, with one visit focusing on a high controllability region and the other on a low controllability region.	ADHD Participants n=19 Participants Participants diagnosed with ADHD or ADD complete one visit involving functional MRI (fMRI) and TMS. This visit focuses exclusively on a high controllability brain region.	Total n=45 Participants Total of all reporting groups
Age, Continuous	22.96 years STANDARD_DEVIATION 2.89 • n=5 Participants	22.68 years STANDARD_DEVIATION 1.86 • n=7 Participants	22.84 years STANDARD_DEVIATION 2.49 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	17 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	19 participants n=7 Participants	45 participants n=5 Participants
E-SWAN ADHD scale Inattentive ADHD Subscale	-1.310 units on a scale STANDARD_DEVIATION 0.730 • n=5 Participants	0.750 units on a scale STANDARD_DEVIATION 0.810 • n=7 Participants	-0.440 units on a scale STANDARD_DEVIATION 1.28 • n=5 Participants
E-SWAN ADHD scale Hyperactive/Impulsive ADHD Subscale	-1.300 units on a scale STANDARD_DEVIATION 0.940 • n=5 Participants	0.550 units on a scale STANDARD_DEVIATION 0.840 • n=7 Participants	-0.520 units on a scale STANDARD_DEVIATION 1.28 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 weeks

Population: Of the 23 participants who completed all study procedures, 2 participants were unusable for this analysis.

Outcome measures

Outcome measures
Measure	TMS to a High Controllability Target in Non-Symptomatic Participants n=21 Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a high controllability region.	TMS to a Low Controllability Target in Non-Symptomatic Participants n=22 Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a low controllability region.
Effect of Single TMS Pulses to a High vs. Low Regional Controllability Target on Working Memory Task Performance	79.71 percentage of accuracy Interval 69.96 to 89.45	78.39 percentage of accuracy Interval 70.45 to 86.33

PRIMARY outcome

Timeframe: Pre- and post-TMS at visits 3 (approximately day 7) and 4 (approximately day 14)

Population: Of the 23 participants who completed all study procedures, 2 participant's data was unusable for this analysis for the percent change comparison and high controllability group. Only 1 participant was unusable for the low controllability group.

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.

Outcome measures

Outcome measures
Measure	TMS to a High Controllability Target in Non-Symptomatic Participants n=21 Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a high controllability region.	TMS to a Low Controllability Target in Non-Symptomatic Participants n=22 Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a low controllability region.
Effect of rTMS on Working Memory Task Performance Nback results Pre-rTMS	79.71 percentage accuracy Interval 69.96 to 89.45	78.39 percentage accuracy Interval 70.45 to 86.33
Effect of rTMS on Working Memory Task Performance Nback results Post-rTMS	81.65 percentage accuracy Interval 73.4 to 89.9	84.75 percentage accuracy Interval 77.57 to 91.93

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TMS to a High Controllability Target in Non-Symptomatic Participants n=21 Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a high controllability region.	TMS to a Low Controllability Target in Non-Symptomatic Participants n=22 Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a low controllability region.
Effect of rTMS to High vs. Low Controllability Target on Working Memory Task Performance	1.94 percentage accuracy change Interval -3.11 to 6.99	6.36 percentage accuracy change Interval 0.57 to 12.16

SECONDARY outcome

Timeframe: Pre- and post-TMS at visit 3 (approximately day 7)

Population: Of the 13 participants with ADHD that completed the study, 1 participant's data was unusable for this analysis.

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.

Outcome measures

Outcome measures
Measure	TMS to a High Controllability Target in Non-Symptomatic Participants n=12 Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a high controllability region.	TMS to a Low Controllability Target in Non-Symptomatic Participants Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a low controllability region.
Effect of rTMS on Working Memory Performance in Participants With ADHD Nback results Pre-rTMS	69.64 percentage of accuracy Interval 57.21 to 82.08	—
Effect of rTMS on Working Memory Performance in Participants With ADHD Nback results Post-rTMS	81.18 percentage of accuracy Interval 70.12 to 92.25	—

Adverse Events

High & Low Modal Controllability TMS Target in Non-symptomatic Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

High Modal Controllability TMS Target in ADHD Participants

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	High & Low Modal Controllability TMS Target in Non-symptomatic Participants n=26 participants at risk Non-symptomatic participants will complete 2 TMS/fMRI visits with alternate targets for a high and low modal controllability target. We will administer TMS to an individualized target of high \& low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.	High Modal Controllability TMS Target in ADHD Participants n=19 participants at risk We will administer TMS to an individualized target of high regional controllability while patient completes a working memory task inside the MRI scanner. 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. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task.
General disorders Headache, dizziness, and nausea	0.00% 0/26 • Adverse event data was collected from study enrollment until study completion (up to 3 weeks).	5.3% 1/19 • Number of events 1 • Adverse event data was collected from study enrollment until study completion (up to 3 weeks).
General disorders Minor Discomfort	0.00% 0/26 • Adverse event data was collected from study enrollment until study completion (up to 3 weeks).	5.3% 1/19 • Number of events 1 • Adverse event data was collected from study enrollment until study completion (up to 3 weeks).

Additional Information

Dr. Desmond Oathes, Principal Investigator

University of Pennsylvania

Phone: 215-573-9390

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place