Individualized Closed Loop TMS for Working Memory Enhancement

NCT ID: NCT04402294

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-24
• Study Completion Date: 2024-06-13

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.

Detailed Description

Prior to any study visits, all subjects will be pre-screened through a REDCap online self-report screening REDCap. The study involves 11 study visits.

The first study visit will consist of a consenting and extended screening visit. All participants will have the opportunity to ask questions before signing the electronic consent form. We will complete a semi-structured clinical interview and will demonstrate TMS to ensure the participant is comfortable with all study procedures. This visit will be completed both remote and in-person.

The second study visit will involve a 1-hour MRI scan. During the scan, the participant will complete multiple computerized tasks. The MRI scan will include both structural and functional scans, and those scans will be used to localize the stimulation target for the subsequent sessions.

The third study visit will be a 2-hour TMS/fMRI session, and the participant will engage in behavioral tasks while interleaved rTMS rounds are delivered at different excitatory frequencies (frequency range:

2Hz-20Hz). This scan will be used to determine the optimal stimulation frequency for the individual participant.

The fourth, fifth, and sixth study visits will involve neuromodulation with either the optimized frequency or the frequency least successful in moving a participants brain state, as determined from the third study visit. Each subject will receive ~3000 pulses in each session, including the pulses from the motor threshold determination. We will determine the stimulation amplitude by using the Stokes equation, which accounts for differences in cortical distance from the site relative to motor cortex (where the motor threshold is found).

The seventh study visit will involve a 1-hour TMS/fMRI session while the participant is engaging in a behavioral task. This visit is designed to examine brain and behavioral changes after the first round of neuromodulation.

The seventh and the eighth visit will be scheduled at least one week apart.

The eighth, ninth, and tenth study visits will mirror the fourth, fifth, and sixth study visits and will involve neuromodulation with either the optimized or least-optimized individual frequency. The order of optimized and least-optimized frequencies will be counterbalanced across participants between Visit 4-6 and Visit 8-10 (i.e., half of the participants will receive stimulations of the two frequencies in one order, and the other half will receive stimulations of the two frequencies in the reverse order). The eleventh visit will mirror the seventh visit and will examine brain and behavioral changes after the second round of neuromodulation.

Conditions

Memory

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Optimized TMS frequency, Then Sub-Optimal TMS Frequency

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.

Group Type: EXPERIMENTAL

Functional Magnetic Resonance Imaging (fMRI)

Intervention Type: 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.

Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type: 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.

Sub-Optimal TMS Frequency, Then Optimized TMS frequency

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.

Group Type: EXPERIMENTAL

Functional Magnetic Resonance Imaging (fMRI)

Intervention Type: 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.

Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Type: 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.

Interventions

Functional Magnetic Resonance Imaging (fMRI)

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.

Intervention Type: DIAGNOSTIC_TEST

Repetitive Transcranial Magnetic Stimulation (rTMS)

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.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1)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

Exclusion Criteria

1. History of neurological disorder or traumatic brain injury (other than mild)

2. Unable to have an MRI scan, or current or prior medical condition that could interfere with the collection or interpretation of MRI data

3. Unable to receive TMS

4. Implanted devices, such as an aneurysm clip or cardiac pacemaker

5. History of stroke, epilepsy, or brain scarring

6. Recent use of psychoactive medications, as determined by investigators

7. Pregnant, nursing, or trying to become pregnant (self-attestation alone)

8. Color blindness

9. Otherwise determined by investigator to be unfit for study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Desmond Oathes

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01MH120811-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

832891

Identifier Type: -

Identifier Source: org_study_id