Individualized Closed Loop TMS for Working Memory Enhancement

NCT04402294 | Completed Results FDA Device

• 2 other identifiers: 832891R01MH120811-05
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The study is investigating working memory brain states by using transcranial magnetic stimulation (TMS) in combination with functional magnetic resonance imaging (fMRI). The study uses a novel, individualized targeting approach for TMS based on each subject's individual multi-modal fMRI data. The individualized target will be stimulated in a TMS/ fMRI imaging session to investigate working memory states and optimal stimulation frequencies.

Conditions

Memory

Keywords

memory; healthy; TMS; MRI

Outcome Measures

Primary Outcomes (4)

• Reaction Time Changes During N-Back Task in Responses to Different TMS Frequencies

  During the TMS/fMRI scan, participants perform a working memory task (N-back). To evaluate how different repetitive TMS frequencies (5, 10, and 20 Hz) impact reaction time during N-back task, each rTMS train is followed by a block of the N-back task. A decoder identifies one frequency as optimal frequency and another as suboptimal frequency. Reaction Time during optimal, suboptimal, and no stimulation condition is assessed by taking average of reaction time on accurate trials with faster reaction times indicating better performance.

  Single visit (~2 hours)

• Accuracy Changes During N-Back Task in Responses to Different TMS Frequencies

  During the TMS/fMRI scan, participants perform a working memory task (N-back). To evaluate how different repetitive TMS frequencies (5, 10, and 20 Hz) impact accuracy during N-back task, each rTMS train is followed by a block of the N-back task. A decoder identifies one frequency as optimal frequency and another as suboptimal frequency. Accuracy during optimal, suboptimal, and no stimulation condition is assessed by taking average of all the trials with better accuracy indicating better performance.

  Single visit (~2 hours)

• Reaction Time Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation

  Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a working memory task (Delayed Match to Sample). The delay period reflects how long participants can retain the information in working memory. Common delay periods used in research, including our study, are 0 seconds, 4 seconds, and 12 seconds.The outcome measure shows the reaction time for each of these variables.

  Up to 1 month

• Accuracy Changes in the Delayed Matching to Sample Task Following Optimal vs. Suboptimal rTMS Stimulation

  Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'suboptimal' rTMS frequency, as determined by their TMS/fMRI visit. After each neuromodulation session, subjects complete a working memory task (Delayed Match to Sample). The delay period reflects how long participants can retain the information in working memory. Common delay periods used in research, including our study, are 0 seconds, 4 seconds, and 12 seconds.The outcome measure shows the accuracy for each of these variables.

  Up to 1 month

Secondary Outcomes (2)

• Reaction Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation

  Up to 1 month

• Movement Time Changes in the Reaction Time Index Task Following Optimal vs. Suboptimal rTMS Stimulation

  Up to 1 month

Study Arms (2)

Optimized TMS frequency, Then Sub-Optimal TMS Frequency

EXPERIMENTAL

In the first neuromodulation session, participants will receive rTMS using their optimal TMS frequency. After washout period of 1 week (minimum), the participants will start their second neuromodulation session using their sub-optimal TMS frequency instead.

Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI); Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Sub-Optimal TMS Frequency, Then Optimized TMS frequency

EXPERIMENTAL

In the first neuromodulation session, participants will receive rTMS using their sub-optimal TMS frequency. After washout period of 1 week (minimum), the participants will start their second neuromodulation session using their optimal TMS frequency instead.

Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI); Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Interventions

Functional Magnetic Resonance Imaging (fMRI) DIAGNOSTIC_TEST

Participants undergo resting-state and task-based fMRI to identify individualized transcranial magnetic stimulation (TMS) targets and determine optimal and sub-optimal stimulation frequencies. Additional fMRI scans are performed after each neuromodulation phase to assess changes following three days of stimulation at the optimal and sub-optimal frequencies.

Optimized TMS frequency, Then Sub-Optimal TMS Frequency; Sub-Optimal TMS Frequency, Then Optimized TMS frequency

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

Participants first receive multiple rTMS frequencies during an fMRI scan to assess brain responses and determine individualized optimal and sub-optimal stimulation frequencies. They then complete two neuromodulation intervention periods, receiving rTMS at the identified optimal and sub-optimal frequencies. Each frequency is administered over three consecutive days, with the order of conditions randomized and counterbalanced.

Optimized TMS frequency, Then Sub-Optimal TMS Frequency; Sub-Optimal TMS Frequency, Then Optimized TMS frequency

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• )18-60 years old 2) Right handed 3) No psychiatric history as diagnosed by the SCID-V 4) Normal cognition 5) Capacity to give informed consent and follow study procedures 6) Sufficient command of English language to understand and respond to written as well as verbal instructions

You may not qualify if:

• History of neurological disorder or traumatic brain injury (other than mild)
• Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data
• Unable to receive TMS
• Implanted devices, such as an aneurysm clip or cardiac pacemaker
• History of stroke, epilepsy, or brain scarring
• Recent use of psychoactive medications, as determined by investigators
• Pregnant, nursing, or trying to become pregnant (self-attestation alone)
• Color blindness
• Otherwise determined by investigator to be unfit for study

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

Magnetic Resonance Imaging; Transcranial Magnetic Stimulation

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Magnetic Field Therapy; Therapeutics

Limitations and Caveats

Enrollment goals were not met due to delays caused by COVID-19. Of the 23 subjects who completed the study, data from only 19 were analyzed. Technical issues with the remaining 4 subjects resulted in uninterpretable data.

Results Point of Contact

• Title: Dr. Desmond Oathes, Principal Investigator
• Organization: University of Pennsylvania

oathes@pennmedicine.upenn.edu

215-573-9390

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: Task and resting fMRI will be used to determine an individualized brain target for each participant. In a subsequent session, participants will complete a task fMRI with repetitive TMS neuromodulation; during this session, various stimulation protocols will be interleaved with working memory task blocks to result in online brain readouts of the degree in which modulation affected the brain state in regards to working memory performance. Based on this testing, an optimal and sub-optimal TMS stimulation frequency will be determined for each individual participant. Each frequency will be administered separately across three stimulation days using a crossover design, with the order of frequencies being randomized and counterbalanced. Therefore, each subject will receive six days of TMS stimulation: three using the optimal frequency, and three using the sub-optimal frequency. The initial TMS/ task fMRI testing session will be completed at the midpoint and end of the study.

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 26, 2020
• Study Start: November 24, 2021
• Primary Completion: June 13, 2024
• Study Completion: June 13, 2024
• Last Updated: July 17, 2025
• Results First Posted: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)