Modulating the Hippocampal and Striatal Memory Networks With rTMS

June 13, 2022 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

Background:

People have 2 memory systems. One helps them learn skills and the other helps them learn facts. Repetitive transcranial magnetic stimulation (rTMS) uses electric currents to activate brain cells. This can make small changes in how brain systems operate. Researchers will use rTMS to change how memory systems work and to see if changing one system causes the other to change too. This could help find ways to improve learning and memory in people with memory disorders.

Objective:

To learn how different memory systems work with each other.

Eligibility:

Healthy adults ages 18-40 who are not pregnant

Design:

Potential participants will be screened with a neurological exam if they have not had one from NINDS in the past 2 years. They may have urine tests.

Eligible participants will have 5-10 visits at NIH. Each visit will last 1-6 hours. Visits 1-4 will each take place 1 day apart.

At visit 1, participants will have an MRI and take memory tests. For MRI, they will lie on a table that slides in and out of a cylinder that takes pictures of their brain. They will also have rTMS. For rTMS, a metal coil is held on their scalp. Brief electrical currents pass through the coil.

At visits 2 and 3, participants will have rTMS.

At visit 4, participants will have an MRI and do memory tests.

About a week later, participants will have visit 5. They will have an MRI and do memory tests. Participants may be asked to have more visits if any technical problems occur. Participant involvement will last 2 weeks.

...

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Objective

The Behavioral Neurology Unit studies the human brain systems underlying learning and adaptation with the ultimate goal of finding interventions to make these processes more efficient. We are interested in whether repetitive transcranial magnetic stimulation (rTMS) can alter functional connectivity (FC) and behavioral efficiency in two memory networks in the brain: the hippocampal network, which supports the storage and retrieval of recallable facts, concepts, and events, and the striatal network, which supports the storage and retrieval of skills and habits. Additionally, because these networks interact behaviorally and can interfere with each other, an important question is whether neuromodulation of one network changes connectivity and efficiency in the other network. Pilot data from our group suggest that exogenous stimulation of one network causes it to expand its range of FC and co-opt resources from the other, which is a potential mechanism for the observed behavioral interaction. This study is designed to test a) whether rTMS- modulates within-network FC and memory supported by that network, and b) whether this also causes FC and behavioral changes in the other network.

Study population: Healthy Volunteers

Design

This study contains four between-subjects experiments and is a mixed inter/intra subject design. Experiment 1 will use nominally excitatory stimulation targeting the hippocampal network to increase FC within the hippocampal network. We also expect to increase FC between the hippocampal and striatal networks, increased declarative memory, and a possible decrease in procedural, learning. Experiment 2 will use excitatory stimulation targeted to the striatal network. We expect this to cause stronger within- network FC in the striatal network, increased FC between the hippocampus and the striatal network and concomitant behavioral effects. Experiments 3 and 4 will be similar except that we will target nominally inhibitory stimulation to these networks and look for the inverse results. FC will be measured under resting and task-activated conditions and active rTMS will be compared to vertex sham.

Outcome measures

The primary outcome measure is the change in FC produced by rTMS within the targeted network. Between-network FC changes and corresponding memory changes will be secondary outcomes. Exploratory measures will include correlations between individual cognitive differences (questionnaires and NIH Toolbox scores), and our primary and secondary outcome measures.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
13

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

-Age 18-40 (inclusive)

EXCLUSION CRITERIA:

  • Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson disease, Alzheimer disease, schizophrenia or major depression
  • History of seizure
  • Medications acting on the central nervous system, such as those that lowers the seizure threshold such as neuroleptics, beta lactams, isoniazid, metronidazole; benzodiazepines, tricyclic or other antidepressants; or prescription stimulants.
  • Ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body
  • Implanted cardiac pacemaker or auto-defibrillator or pump
  • Non-removable body piercing
  • Claustrophobia
  • Inability to lie supine for 2 hours
  • Pregnancy, or plans to become pregnant during the study.
  • Members of the NINDS BNU
  • Subjects that received rTMS under protocol 17-N-0055 are excluded in order avoid learning effects from previously being exposed to the same behavioral tasks
  • Subjects who have contraindications to MRI (we will follow the NMR Center guidelines for MR safety). Some of the exclusions are:

  • Have non-MRI compatible metal in the body, such as a cardiac pacemaker, brain stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear implants, artificial heart valves or ferromagnetic fragments in the eye or oral cavity as these make having an MRI unsafe.

    • Unable to lie flat on the back for the expected length of the experiment (2 hours).
    • Have an abnormality on the brain imaging or neurologic examination not related to the diagnosis.
    • Non-removable body piercing or
    • Pregnancy (urine pregnancy test)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Motor Cortex rTMS
Other: RTMS
Altering the connectivity of trans-synaptic pathways
Active Comparator: PPC rTMS
Other: RTMS
Altering the connectivity of trans-synaptic pathways
Placebo Comparator: vertex rTMS
Other: RTMS
Altering the connectivity of trans-synaptic pathways

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Resting-state Functional Connectivity Between the Caudate and the Caudate Network
Time Frame: Baseline, 1 day and 14-21 days after rTMS
Participants underwent repetitive transcranial magnetic stimulation (rTMS) to the caudate network, which supports learning skills. rTMS uses electric currents to activate brain cells, which can temporarily change brain connections and memory. We measured how rTMS affects caudate network brain connectivity. These changes were observed with MRI. To measure brain connection strength, we calculated how closely neural activity correlates in the caudate network. We measured how rTMS affects connection strength before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation correlation coefficient score of 0 suggests no difference in the connections between brain areas after rTMS; a score of < 0 suggests a weakening of the connections between brain areas; and a score of > 0 suggests a strengthening of the connections between brain areas.
Baseline, 1 day and 14-21 days after rTMS
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Caudate Network
Time Frame: Baseline, one day and 14-21 days after rTMS
Participants underwent repetitive transcranial magnetic stimulation (rTMS) to the targeted memory network, i.e., caudate network. rTMS uses electric currents to activate brain cells, which can temporarily change brain connections and memory. We measured how rTMS affects caudate network brain connectivity on MRI during a Weather Prediction Task. To measure brain connection strength, we calculated how closely neural activity correlates in the caudate network. We measured how rTMS affects connection strength and skill learning by measuring them before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation score of 0 suggests no difference in the connections between brain areas; a score of < 0 suggests a weakening of the connections between brain areas; and a score of > 0 suggests a strengthening of connections between brain areas.
Baseline, one day and 14-21 days after rTMS

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Feedback Weather Prediction Task (WPT-F)
Time Frame: Changes are calculated before and one day after rTMS and before and 14-21 days after rTMS
The Feedback Weather Prediction Task (WPT-F) tests the participant's ability to learn an association by trial and error. One, two, or three-card combinations of four possible cards are presented on a computer and the subject is asked to predict the "weather;" i.e. whether it will be rainy or sunny. After each prediction, the subject receives corrective feedback. Each card is independently associated with one outcome with a fixed probability. Participants learn the probabilistic relationship between stimuli and outcomes through feedback (reward). The WPT-F was administered during the MRI session at three time periods, i.e., prior to rTMS, one day after rTMS, and 14-21 days after rTMS. The proportion of trials where the participant selected the best option, i.e., the option most tightly linked to reward, was calculated at each visit. Changes in scores between baseline and one day after and 14-21 days after rTMS were calculated.
Changes are calculated before and one day after rTMS and before and 14-21 days after rTMS
Observational Weather Prediction Task (WPT-O)
Time Frame: Changes are calculated before and one day after rTMS and before and 14-21 days after rTMS
The Observational Weather Prediction Task (WPT-O) is a paired associates test where the cue and feedback are displayed on the screen together. After all pairs are shown the cards are again shown and the participant is asked to remember which feedback outcome (sun or rain) is paired with that set of cards. Participants learn the pairing between sets of stimuli and one of two outcomes through memorization. The WPT-O was administered during the MRI session at three time periods, i.e., prior to rTMS, one day after rTMS, and 14-21 days after rTMS. The proportion of trials where the participant accurately remembered the pair, was calculated at each visit. Changes in scores between baseline and one day after and 14-21 days after rTMS will be calculated.
Changes are calculated before and one day after rTMS and before and 14-21 days after rTMS
Change From Baseline in Resting-state Functional Connectivity Between the Caudate and the Hippocampal Network
Time Frame: Baseline, one day and 14-21 days after rTMS
Participants underwent repetitive transcranial magnetic stimulation (rTMS) to the hippocampal network, which supports learning skills. rTMS uses electric currents to activate brain cells, which can temporarily change brain connections and memory. We measured how rTMS affects hippocampal network brain connectivity. These changes can be observed with MRI. To measure brain connection strength, we calculated how closely neural activity correlates in the hippocampal network. We measured how rTMS affects connection strength before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation score of 0 suggests no difference in the connections between brain areas after rTMS; a score of < 0 suggests a weakening of the connections between brain areas; and a score of > 0 suggests a strengthening of the connections between brain areas.
Baseline, one day and 14-21 days after rTMS
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Hippocampal Network
Time Frame: Baseline, one day and 14-21 days after rTMS
Participants underwent repetitive transcranial magnetic stimulation (rTMS) to the targeted memory network, i.e., hippocampal network. rTMS uses electric currents to activate brain cells, and this can temporarily change brain connections and memory. We measured how rTMS affects hippocampal network brain connectivity on MRI during a Weather Prediction Task. To measure brain connection strength, we calculated how closely neural activity correlates in the hippocampal network. We measured how rTMS affects connection strength and skill learning before and 1 day after stimulation (immediate effects), and before and 14-21 days after stimulation (long-term effects) and then calculated the change as a Z-transformation score. A change in the Fisher Z-transformation score of 0 suggests no difference in the connections between brain areas; a score of < 0 suggests a weakening of the connections between brain areas; and a score of > 0 suggests a strengthening of the connections between brain areas.
Baseline, one day and 14-21 days after rTMS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 26, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 24, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 24, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 21, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 6, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 190114
  • 19-N-0114

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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