Individualized Closed Loop TMS for Working Memory Enhancement

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04402294
• Collaborator: (none)
• Enrollment: 38
• Location: 1
• Anticipated Duration (Months): 37.3
• Patients Per Site Per Month: 1

Study Details

Study Description

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. Next, the individualized target will be stimulated in a TMS/ fMRI imaging session to investigate working memory states and optimal stimulation frequencies.

Condition or Disease	Intervention/Treatment	Phase
Working Memory in Healthy Participants	Device: Repetitive Transcranial Magnetic Stimulation (rTMS)	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Crossover Assignment
• Intervention Model Description: 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.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.
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Basic Science
• Official Title: Individualized Closed Loop Transcranial Magnetic Stimulation (TMS) for Working Memory Enhancement
• Actual Study Start Date: Nov 24, 2021
• Anticipated Primary Completion Date: Jan 1, 2024
• Anticipated Study Completion Date: Jan 1, 2025

Outcome Measures

Primary Outcome Measures

1. fMRI Classifier Fit [Baseline]

   Using deep learning classification methods, an 'optimal' brain state will be identified from baseline task and resting fMRI. This will be the target during future interleaved TMS/fMRI brain readouts.

2. Effect of Individualized Stimulation Frequency on Working Memory [Baseline, Immediately After the Intervention]

   Overall, the investigators will be assessing whether there is a significant change in working memory performance using neuromodulation at the individual's optimal stimulation frequency versus sub-optimal frequency, as determined by performance during fMRI/ rTMS sessions and rTMS behavioral sessions.

Secondary Outcome Measures

1. Working Memory Performance in MRI Sessions [Baseline, After approx. 1 month, After approx. 2 months]

   During rounds of interleaved rTMS with fMRI recordings, participants will be engaging in a working memory task. Online block-wise performance will be evaluated for both speed and accuracy as an indicator of the effect of the neuromodulation train preceding it.

2. Working Memory Performance in Behavior Sessions [Baseline, Immediately after the Intervention]

   During each offline working memory rTMS session, participants' speed and accuracy on a working memory task will be evaluated as an indicator of the degree to which the neuromodulation is affecting performance.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 18-60 years old

• Right handed

• No current or lifetime history of any DSM-V diagnosis

• No history of neurological disorder or traumatic brain injury (other than mild)

• No current psychoactive medication use

• Normal cognition

• Female patients must attest to not being pregnant

• Capacity to give informed consent and follow study procedures

• Sufficient command of English language to understand and respond to written as well as verbal instructions

Exclusion Criteria:

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

• Implanted devices, such as an aneurysm clip or cardiac pacemaker

• History of stroke, epilepsy, or brain scarring

• Cognitive impairment

• Recent use of psychoactive medications, as determined by investigators

• People who are unwilling/unable to abstain from medications that substantially reduce the seizure threshold to TMS under PI discretion

• Otherwise determined by investigator to be unfit for study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04402294
• Other Study ID Numbers: 832891
• First Posted: May 26, 2020
• Last Update Posted: Dec 21, 2021
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by University of Pennsylvania: memory; healthy; TMS

Study Results

No Results Posted as of Dec 21, 2021