Individualized Closed Loop TMS for Working Memory Enhancement

Memory Clinical Trial

Official title:

Individualized Closed Loop Transcranial Magnetic Stimulation (TMS) for Working Memory Enhancement

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04402294
• Other study ID #: 832891
• Secondary ID: R01MH120811-05
• Status: Recruiting
• Phase: N/A
• Start date: November 24, 2021
• Est. completion date: January 31, 2025

Study information

• Verified date: February 2024
• Source: University of Pennsylvania
• Contact: Almaris Figueroa-Gonzalez
• Phone: 215-746-6751
• Email: almaris.figueroa-gonzalez[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: January 31, 2025
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Memory

Intervention

Device:
• Repetitive Transcranial Magnetic Stimulation (rTMS)
The investigators will create individualized TMS targets using deep learning methods on task and resting fMRI data to target working memory augmentation. The individualized target will be stimulated in a subsequent fMRI scan involving working memory task performance interleaved with repetitive TMS (rTMS) delivered at a variety of stimulation frequencies. Based on activation readouts in response to rTMS, an optimal and sub-optimal brain state frequency to impact working memory performance will be selected for each participant. Participants will receive rTMS at each frequency separately for three days (six days total), with the order of frequency randomly assigned and counterbalanced. Following each three day protocol, another fMRI working memory readout will be conducted to support the targeting and frequency selection algorithms.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of different TMS frequencies on N-back performance	During the TMS/fMRI scan, subjects complete working memory task (N-back). To assess the effect of different repetitive TMS frequencies (5-20hz) on N-back performance, each rTMS train is followed by a block of the N-back task. Performance will be measured using percent accuracy for each Nback block. Higher percent accuracy indicates better task performance.	Single visit (~2 hours)
Primary	Effect 'Optimal' vs 'Least-Optimal' rTMS frequency on the Delayed Match to Sample Task	Each subject completes two 3-day neuromodulation sessions, one using their 'optimal' rTMS frequency, and the other using their 'least-optimal' rTMS frequency, as determined by ther TMS/fMRI Visit. After each neuromodulation session, subjects complete a working memory task (Delayed Match to Sample).; To assess the effect of each rTMS frequency on the Delayed Match to Sample task performance, percent accuracy will be measured. Higher percent accuracy indicates better task performance.	Up to 1 month