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Modulating the Hippocampal and Striatal Memory Networks With rTMS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03994120
Recruitment Status : Recruiting
First Posted : June 21, 2019
Last Update Posted : September 13, 2019
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:


People have 2 memory systems. One helps them learn skills and the other helps them learn facts. Repetitive transcranial magnetic stimulation (rTMS) uses electronic 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.


To learn how different memory systems work with each other.


Healthy adults ages 18-40 who are not pregnant


Potential participants will be screened with a neurological exam if they haven t 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. Participants involvement will last 2 weeks.


Condition or disease Intervention/treatment Phase
Normal Behavioral Patterns Other: RTMS Not Applicable

Detailed Description:


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


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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Modulating the Hoppocampal and Striatal Memory Networks With rTMS
Estimated Study Start Date : September 18, 2019
Estimated Primary Completion Date : March 31, 2029
Estimated Study Completion Date : March 31, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory

Arm Intervention/treatment
Active Comparator: Motor Cortex rTMS
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
vertex rTMS
Other: RTMS
Altering the connectivity of trans-synaptic pathways

Primary Outcome Measures :
  1. Functional Connectivity [ Time Frame: 24 hrs. ]
    Pre-to-Post rTMS differences in rsFC and tbFC within the targeted memory network

Secondary Outcome Measures :
  1. Memory Task Scores [ Time Frame: 24 hours ]
    Outcomes include percentage of correct/optimal responses and reaction time.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
  • Age 18-40 (inclusive)


  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03994120

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Contact: Cynthia M Fioriti (301) 496-0220

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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Eric M Wassermann, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Additional Information:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS) Identifier: NCT03994120     History of Changes
Other Study ID Numbers: 190114
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: July 19, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Memory Systems
Repetitive Transcranial Magnetic Stimulation
Behavioral Efficiency
Hippocampal and Striatal Memory Networks