Normal Behavioral PatternsNCT03994120
Modulating the Hippocampal and Striatal Memory Networks With rTMS
A study testing RTMS in people with Normal Behavioral Patterns, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Behavioral Patterns
- What is being tested?
- RTMS
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2019to 24 Mar 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- -Age 18-40 (inclusive)
Who cannot join
- 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
Show all 17Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
...
Read the 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.
- Conditions
- Normal Behavioral Patterns
- Being tested
- RTMS
- Keywords
- Memory Systems, Repetitive Transcranial Magnetic Stimulation, Behavioral Efficiency, Hippocampal and Striatal Memory Networks
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RTMSOther
Altering the connectivity of trans-synaptic pathways
| Study group | Role | What they receive |
|---|---|---|
| Motor Cortex rTMS | Active comparator | Motor Cortex rTMS Receives: Other: RTMS |
| PPC rTMS | Active comparator | PPC rTMS Receives: Other: RTMS |
| vertex rTMS | Placebo comparator | vertex rTMS Receives: Other: RTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Resting-state Functional Connectivity Between the Caudate and the Caudate Network
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.
Measured: Baseline, 1 day and 14-21 days after rTMS
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Caudate Network
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.
Measured: Baseline, one day and 14-21 days after rTMS
Secondary outcomes (4)
Feedback Weather Prediction Task (WPT-F)
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.
Measured: Changes are calculated before and one day after rTMS and before and 14-21 days after rTMS
Observational Weather Prediction Task (WPT-O)
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.
Measured: 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
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.
Measured: Baseline, one day and 14-21 days after rTMS
Change From Baseline in Task-based Functional Connectivity Between the Caudate and the Hippocampal Network
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.
Measured: Baseline, one day and 14-21 days after rTMS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2019
- Study start26 Sep 2019
- Primary completion24 Mar 2021
- Study completion24 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Normal Behavioral PatternsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Eric M Wassermann, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03994120
- Sponsor's protocol ID
- 190114
- Other IDs
- 19-N-0114
- Status last verified
- May 2021
- First submitted
- 20 Jun 2019
- Last updated
- 6 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulating the Hippocampal and Striatal Memory Networks With rTMS
- ClinicalTrials.gov ID
- NCT03994120
- Acronym / sponsor ID
- 190114
- Conditions
- Normal Behavioral Patterns
- Keywords
- Memory Systems, Repetitive Transcranial Magnetic Stimulation, Behavioral Efficiency, Hippocampal and Striatal Memory Networks
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 24 Mar 2021 (actual)
- Study completion
- 24 Mar 2021 (actual)
- First posted
- 21 Jun 2019 (actual)
- Results
- Posted 14 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Motor Cortex rTMS | Active comparator | Other: RTMSMotor Cortex rTMS |
| PPC rTMS | Active comparator | Other: RTMSPPC rTMS |
| vertex rTMS | Placebo comparator | Other: RTMSvertex rTMS |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- -Age 18-40 (inclusive)
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RTMSAltering the connectivity of trans-synaptic pathways | Other | Motor Cortex rTMS, PPC rTMS, vertex rTMS |
Primary outcome
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.
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.
4 secondary outcomes
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric M Wassermann, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing RTMS in people with Normal Behavioral Patterns, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2022.