Normal PhysiologyNCT01260740
The Effect of Transcranial Magnetic Stimulation on Learning With Reward in Healthy Humans
An observational study of Normal Physiology and fMRI, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Two areas on the surface of the brain, the dorsolateral prefrontal cortex (DLPFC) and motor cortex (MC), play a key role during learning. Researchers are interested in determining the effect that transcranial magnetic stimulation (TMS) on the DLPFC and MC has on participants' performance of learning tasks. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Normal Physiology, fMRI
- How many people
- 174 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2010to 23 Jun 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy
- Right-handed
- Ages 18-70 (inclusive)
- Have completed high school or college in an English speaking country.
- All participants must have had a neurological examination by a NINDS physician within the last two years.
- All participants in the fMRI experiments must also have had a clinical MRI within the last year.
Who cannot join
- Individuals with conditions that could pose a risk relating to the safety of the MRI procedure will be excluded from the protocol such as:
- Those with ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip, implanted neural stimulator, cochlear implant, ocular foreign body.
- Those with an implanted cardiac pacemaker or auto-defibrillator.
- Those with an insulin pump.
- Those with an irremovable body piercing.
- Pregnant women
Show all 16Show fewer
- Individuals with conditions that could pose a risk relating to the safety of the TMS procedure will be excluded from the protocol such as:
- Those with significant abnormality on neurological examination.
- Those with metal in the cranial cavity or eye, e.g. aneurysm clip, implanted neural stimulator, cochlear implant, ocular foreign body.
- Those with an implanted cardiac pacemaker or auto-defibrillator.
- Those with an insulin pump.
- Pregnant women
- Individuals with conditions that could compromise our interpretation of the TBS and fMRI results will be excluded such as:
- Those with significant abnormality on neurological examination.
- Those who have a significant psychiatric illness or have a history of psychiatric illness.
- Those using medication affecting the DA system, such as phenothiazine antihistamines (promethazine), antiemetics or decongestants within the last month.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Two areas on the surface of the brain, the dorsolateral prefrontal cortex (DLPFC) and motor cortex (MC), play a key role during learning. Researchers are interested in determining the effect that transcranial magnetic stimulation (TMS) on the DLPFC and MC has on participants' performance of learning tasks. By studying the effect of TMS on reaction time, learning, and memory, researchers hope to better understand how to treat conditions such as Parkinson's disease and traumatic brain injury that affect these parts of the brain.
Read more
Objectives:
- To study the effects of transcranial magnetic stimulation on the dorsolateral prefrontal cortex and motor cortex.
- To learn which areas of the brain are used to perform certain learning and memory tasks.
Eligibility:
- Healthy, right-handed individuals between 18 and 70 years of age.
Design:
- Participants will be screened with a physical and neurological examination and a medical and psychiatric history.
- Participants will be asked to take part in one of five different parts of this study. Most participants will have four 2-hour visits to the National Institutes of Health Clinical Center. Some participants (those involved in Part 5) will have only one 2-hour visit.
- Parts 1 and 2 (four visits): Participants will have TMS, and then do a learning task that may provide a small monetary reward. On the first visit, before the TMS, participants will take an intelligence test based on reading aloud the words given on a card. Participants who have not had a routine magnetic resonance imaging (MRI) scan of the brain within the past year will also have a scan.
- Parts 3 and 4 (four visits): Participants will have a functional MRI scan while doing a learning task that may provide a small monetary reward. On the first visit, before the functional MRI, participants will take an intelligence test based on reading aloud the words given on a card. Participants who have not had a routine magnetic resonance imaging (MRI) scan of the brain within the past year will also have a scan.
- Part 5 (one visit): Participants will take an intelligence test based on reading aloud the words given on a card. Then, participants will have TMS followed by a functional MRI scan. During the functional MRI, participants will do a button-pressing task that may provide a small monetary reward.
- Participants will also be asked to provide a small blood sample for genetic analysis.
Read the detailed description
Objective
Theta burst transcranial magnetic stimulation (TBS) produces functional changes in human motor cortex. Continuous inhibitory TBS, (cTBS) over the primary motor cortex (M1) produces a temporary impairment of learning in healthy individuals similar to that seen in patients with traumatic brain injury (TBI) and Parkinson disease (PD). The depression of learning by cTBS may serve as a model for learning and memory deficits in these disorders and provide a means of screening treatments for efficacy and exploring their mechanisms. Our immediate goal is to see whether manipulation of the behavioral contingencies of the task, particularly adding reward, will overcome the virtual lesion produced by cTBS.
The first aim of the project is to examine inhibitory effects of cTBS on implicit (serial reaction time /SRT) and explicit (trial-and-error) motor learning of a sequence of target locations.
The second aim of the project is to examine the effects of cTBS on non-motor implicit and explicit probabilistic classification learning using the weather prediction task (WPT). We will investigate the involvement of M1 and dorsolateral prefrontal cortex (DLPFC) in implicit and explicit learning by studying participants who will perform these tasks following cTBS over: 1) M1, 2) DLPFC and 3) sham TBS.
Our third aim is to examine the effect of manipulating reward during implicit and explicit learning following inhibitory TBS over M1 and DLPFC as it is possible that learning deficits caused by TBS can be improved by increasing the amount of reinforcement during learning.
Our fourth aim is to examine the neural networks underlying implicit and explicit learning with and without reward by studying participants who will perform these tasks during functional MRI (fMRI). Finally, we will also perform fMRI during implicit sequence learning and after cTBS over M1 to identify its effects on the neural networks involved in implicit learning.
Study population
Healthy volunteers (n = 272, aged 18 70), without any contraindication to TBS or MRI. This number includes 60 participants each for Experiments 1 and 2, 24 participants each for Experiments 3-5. In addition, 35 participants are included for piloting behavioral and imaging procedures. In order to account for potential dropouts and withdrawals (up to 20%), the total accrual ceiling includes a further 45 participants to equal 272.
Design
The study contains five, mixed or crossover design experiments with appropriate controls to eliminate order effects.
Outcome measures
We will examine the effects of reward and TBS and their interaction on measures of learning. Secondary outcome measures will be how TBS and reward interact to alter the pattern of BOLD activation on MRI and the effects of relevant genetic variation on learning variables and BOLD activation. We will examine the effects of genetic variations in relevant genes on these outcomes.
- Conditions
- Normal Physiology, fMRI
- Keywords
- Traumatic Brain Injury, Explicit Learning, Primary Motor Cortex, Dorsolateral Prefrontal Cortex, Implicit Learning, Healthy Volunteer, HV
- Medical subject headings
- Brain Injuries, Traumatic
What is being measured
The primary outcome is the main question the study is designed to answer.
We will examine the effects of reward and TBS and their interaction on measures of learning.
Measured: One hour
Secondary outcomes (1)
Secondary outcome measures will be how TBS and reward interact to alter the pattern of BOLD activation on MRI and the effects of relevant genetic variation on learning variables and BOLD activation.
Measured: One hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2010 (estimated)
- Study start7 Dec 2010
- Study completion23 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Normal PhysiologyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 174 participants (actual)
Sponsor and investigators
- 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
- NCT01260740
- Sponsor's protocol ID
- 110055
- Other IDs
- 11-N-0055
- Status last verified
- 23 Jun 2017
- First submitted
- 14 Dec 2010
- Last updated
- 6 Oct 2017
- Results posted
- No
Publications
Arancio O, Chao MV. Neurotrophins, synaptic plasticity and dementia. Curr Opin Neurobiol. 2007 Jun;17(3):325-30. doi: 10.1016/j.conb.2007.03.013. Epub 2007 Apr 6.
PubMed 17419049Aron AR, Gluck MA, Poldrack RA. Long-term test-retest reliability of functional MRI in a classification learning task. Neuroimage. 2006 Feb 1;29(3):1000-6. doi: 10.1016/j.neuroimage.2005.08.010. Epub 2005 Sep 1.
PubMed 16139527Badgaiyan RD, Fischman AJ, Alpert NM. Striatal dopamine release in sequential learning. Neuroimage. 2007 Nov 15;38(3):549-56. doi: 10.1016/j.neuroimage.2007.07.052. Epub 2007 Aug 15.
PubMed 17888684
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Transcranial Magnetic Stimulation on Learning With Reward in Healthy Humans
- ClinicalTrials.gov ID
- NCT01260740
- Acronym / sponsor ID
- 110055
- Conditions
- Normal Physiology, fMRI
- Keywords
- Traumatic Brain Injury, Explicit Learning, Primary Motor Cortex, Dorsolateral Prefrontal Cortex, Implicit Learning, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 174 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 7 Dec 2010
- Study completion
- 23 Jun 2017
- First posted
- 15 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Two areas on the surface of the brain, the dorsolateral prefrontal cortex (DLPFC) and motor cortex (MC), play a key role during learning. Researchers are interested in determining the effect that transcranial magnetic stimulation (TMS) on the DLPFC and MC has on participants' performance of learning tasks. By studying the effect of TMS on reaction time, learning, and memory, researchers hope to better understand how to treat conditions such as Parkinson's disease and traumatic brain injury that affect these parts of the brain.
Objectives:
- To study the effects of transcranial magnetic stimulation on the dorsolateral prefrontal cortex and motor cortex.
- To learn which areas of the brain are used to perform certain learning and memory tasks.
Eligibility:
- Healthy, right-handed individuals between 18 and 70 years of age.
Design:
- Participants will be screened with a physical and neurological examination and a medical and psychiatric history.
- Participants will be asked to take part in one of five different parts of this study. Most participants will have four 2-hour visits to the National Institutes of Health Clinical Center. Some participants (those involved in Part 5) will have only one 2-hour visit.
- Parts 1 and 2 (four visits): Participants will have TMS, and then do a learning task that may provide a small monetary reward. On the first visit, before the TMS, participants will take an intelligence test based on reading aloud the words given on a card. Participants who have not had a routine magnetic resonance imaging (MRI) scan of the brain within the past year will also have a scan.
- Parts 3 and 4 (four visits): Participants will have a functional MRI scan while doing a learning task that may provide a small monetary reward. On the first visit, before the functional MRI, participants will take an intelligence test based on reading aloud the words given on a card. Participants who have not had a routine magnetic resonance imaging (MRI) scan of the brain within the past year will also have a scan.
- Part 5 (one visit): Participants will take an intelligence test based on reading aloud the words given on a card. Then, participants will have TMS followed by a functional MRI scan. During the functional MRI, participants will do a button-pressing task that may provide a small monetary reward.
- Participants will also be asked to provide a small blood sample for genetic analysis.
Detailed description
Objective
Theta burst transcranial magnetic stimulation (TBS) produces functional changes in human motor cortex. Continuous inhibitory TBS, (cTBS) over the primary motor cortex (M1) produces a temporary impairment of learning in healthy individuals similar to that seen in patients with traumatic brain injury (TBI) and Parkinson disease (PD). The depression of learning by cTBS may serve as a model for learning and memory deficits in these disorders and provide a means of screening treatments for efficacy and exploring their mechanisms. Our immediate goal is to see whether manipulation of the behavioral contingencies of the task, particularly adding reward, will overcome the virtual lesion produced by cTBS.
The first aim of the project is to examine inhibitory effects of cTBS on implicit (serial reaction time /SRT) and explicit (trial-and-error) motor learning of a sequence of target locations.
The second aim of the project is to examine the effects of cTBS on non-motor implicit and explicit probabilistic classification learning using the weather prediction task (WPT). We will investigate the involvement of M1 and dorsolateral prefrontal cortex (DLPFC) in implicit and explicit learning by studying participants who will perform these tasks following cTBS over: 1) M1, 2) DLPFC and 3) sham TBS.
Our third aim is to examine the effect of manipulating reward during implicit and explicit learning following inhibitory TBS over M1 and DLPFC as it is possible that learning deficits caused by TBS can be improved by increasing the amount of reinforcement during learning.
Our fourth aim is to examine the neural networks underlying implicit and explicit learning with and without reward by studying participants who will perform these tasks during functional MRI (fMRI). Finally, we will also perform fMRI during implicit sequence learning and after cTBS over M1 to identify its effects on the neural networks involved in implicit learning.
Study population
Healthy volunteers (n = 272, aged 18 70), without any contraindication to TBS or MRI. This number includes 60 participants each for Experiments 1 and 2, 24 participants each for Experiments 3-5. In addition, 35 participants are included for piloting behavioral and imaging procedures. In order to account for potential dropouts and withdrawals (up to 20%), the total accrual ceiling includes a further 45 participants to equal 272.
Design
The study contains five, mixed or crossover design experiments with appropriate controls to eliminate order effects.
Outcome measures
We will examine the effects of reward and TBS and their interaction on measures of learning. Secondary outcome measures will be how TBS and reward interact to alter the pattern of BOLD activation on MRI and the effects of relevant genetic variation on learning variables and BOLD activation. We will examine the effects of genetic variations in relevant genes on these outcomes.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy
- Right-handed
- Ages 18-70 (inclusive)
- Have completed high school or college in an English speaking country.
- All participants must have had a neurological examination by a NINDS physician within the last two years.
Key exclusion criteria (16 listed)
- Individuals with conditions that could pose a risk relating to the safety of the MRI procedure will be excluded from the protocol such as:
- Those with ferromagnetic metal in the cranial cavity or eye, e.g. aneurysm clip, implanted neural stimulator, cochlear implant, ocular foreign body.
- Those with an implanted cardiac pacemaker or auto-defibrillator.
- Those with an insulin pump.
- Those with an irremovable body piercing.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
We will examine the effects of reward and TBS and their interaction on measures of learning.
Time frame: One hour
1 secondary outcome
Secondary outcome measures will be how TBS and reward interact to alter the pattern of BOLD activation on MRI and the effects of relevant genetic variation on learning variables and BOLD activation.
Time frame: One hour
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2017.
- Background: PubMed 17419049Arancio O, Chao MV. Neurotrophins, synaptic plasticity and dementia. Curr Opin Neurobiol. 2007 Jun;17(3):325-30. doi: 10.1016/j.conb.2007.03.013. Epub 2007 Apr 6.
- Background: PubMed 16139527Aron AR, Gluck MA, Poldrack RA. Long-term test-retest reliability of functional MRI in a classification learning task. Neuroimage. 2006 Feb 1;29(3):1000-6. doi: 10.1016/j.neuroimage.2005.08.010. Epub 2005 Sep 1.
- Background: PubMed 17888684Badgaiyan RD, Fischman AJ, Alpert NM. Striatal dopamine release in sequential learning. Neuroimage. 2007 Nov 15;38(3):549-56. doi: 10.1016/j.neuroimage.2007.07.052. Epub 2007 Aug 15.
Related trials for Normal Physiology
RecruitingEarly Phase 1
Developing Transcranial Neuromodulation Protocols for Learning and Decision-Making
Normal Physiology
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
RecruitingPhase 1
A Study to Investigate the Pharmacokinetics and Safety of PKN605 in Participants With Moderate and Severe Renal Impairment Compared to Matched Control Subjects With Normal Renal Function
Participants With Moderate and Severe Renal Impairment and Healthy Participants
Not yet recruitingPhase 2
Hyaluronidase Injections for Sclerodactyly in Patients With Scleroderma
Scleroderma, Sclerodactyly
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?
An observational study of Normal Physiology and fMRI, 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 6 inclusion and 16 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: stopped early, as of the sponsor's last update on 6 Oct 2017. 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. 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?
The study was stopped early. Results are not available in the source record.
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?
We will examine the effects of reward and TBS and their interaction on measures of learning. (time frame: One hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01260740, which also lists 3 linked publications.
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 Oct 2017.