HealthyNCT00422071
Detecting a Reward Signal in the Motor Cortex
An observational study of Healthy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will use transcranial magnetic stimulation (TMS) to determine whether the activity in the brain when someone wins something affects the part of the brain that controls movement. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- How many people
- 168 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2007to 6 Mar 2014
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women, age 18-60.
Who cannot join
- Significant neurological or psychiatric history.
- History of habitual gambling, defined as either visiting casinos more than once per month or playing cards for money more than once per week or gambling over the internet more than once per month.
- Habitual consumption of more than two drinks a day, marijuana more than once a week or any other illicit drug use within the last three months.
- Use of medication affecting the DA system, such as phenothiazine antihistamines (promethazine), antiemetics or decongestants within the last month.
- Seizure History.
- Significant abnormality on neurological examination.
- Metal in the cranial cavity or eye, pacemaker, implanted pumps or stimulators.
- Subjects who have participated in experiments 1-5 in this protocol may not participate in experiment 6, or 7.
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
This study will use transcranial magnetic stimulation (TMS) to determine whether the activity in the brain when someone wins something affects the part of the brain that controls movement. Studies have shown that the brain releases signals to mark rewards for certain behavior, like the activity the brain generates when an animal receives food or drink after performing a certain action. This study will look for a way to detect this kind of signal in humans.
Healthy volunteers between 18 and 60 years of age are eligible for this study. Participants undergo TMS during two experiments slot machine stimulation and key sequence (see below). For TMS, a wire coil is held on the subject s scalp. A brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The stimulation may cause twitching in muscles of the face, arm or leg, and there may be a pulling sensation on the skin under the coil. The effect of TMS on the muscles is detected with small metal disk electrodes taped onto the skin of the arms or legs.
Read more
The stimulation strength needed to activate the hand muscles is determined at the beginning of each experiment. To do this, the subject sits with his or her arms and hand relaxed. Magnetic pulses of varying strengths are applied in order to find the right strength. Also, a series of 45 pairs of magnetic pulses is administered so close to each other that they produce only one movement. Measurements of the movements generated serve as a baseline for comparison with movements generated during the experiments.
Slot Machine Simulation
Subjects play a computer game similar to a slot machine. They press a button to start the game and watch as three barrels of the machine spin into place. Subjects can win $0.25, $1or $5 if all three barrels match when they stop spinning. If all three barrels do not match, subjects do not win any money, except in rare instances, when they are awarded money even when all three barrels do not match. In one trial in this experiment, subjects receive transcranial magnetic stimulation after they see the second barrel stop spinning. In another trial, they receive the stimulation after the third barrel stops spinning.
Key Sequence
Subjects see a letter on a computer screen and press a combination of the three keyboard keys G, H, and J. If they press the keys in the right order and under the time limit, they win $1. At some point, the letter displayed changes, and the subjects must guess a new combination to earn money. Each of the letters corresponds to its own combination of key presses. A few moments after the subjects see whether they pressed the keys in the right order, they receive TMS.
Read the detailed description
Objectvie:
The role of mesencephalic dopamine neurons in reward processing has been established in primates using electrophysiological techniques and in humans using functional neuroimaging. Their role is thought to be dual: i) they show sustained activity with the expectation of a future reward and ii) a phasic response after reward. Animal data indicate that these neurons, located in the midbrain areas A8-10, behave as a single functional unit when activated. They have rich projections to both the prefrontal and motor cortices where they synapse on interneurons and cortical pyramidal cells, producing primarily inhibition. Though their function is not fully understood, these projections clearly play an important role in motivation and learning. Since there are no electrophysiological techniques available to detect dopaminergic or inhibitory activity in the human prefrontal cortex, our objective is to develop a paradigm to detect a reward related signal in the primary motor cortex, where transcranial magnetic stimulation can be used to measure brief events.
Study Population:
The population that we will study will be healthy volunteers between the ages of 18-60, without any significant medical history, contraindication to TMS or history of addictive behavior.
Design:
Our hypothesis is that the dopamine reward-related signal will alter level of evocable inhibition in primary motor cortex. Using behavioral paradigms that deliver intermittent reward, we aim to demonstrate a difference in the amount of cortical inhibition, i) when reward is expected compared to when reward is not expected ii) after rewarded compared to unrewarded trials iii) when reward follows a variable effortful response, and iv) when there is uncertainty as to whether a reward will be administered. If we are unable to produce a signal in the motor cortex with these simple paradigms, we will look for a reward-related change in inhibition when the rewarded behavior is the associative learning of a motor sequence. We will control for effects of variations in attention related to the experimental task, but not specific for reward, with a similar behavioral paradigm that manipulates attention and expectation.
Outcome Measures:
The outcome measures will be changes in the conditioned/unconditioned MEP for each reward condition.
- Conditions
- Healthy
- Keywords
- Transcranial Magnetic Stimulation (TMS), Dopamine, Gambling, Healthy Volunteer, HV
- Medical subject headings
- Gambling
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2007 (estimated)
- Study start8 Jan 2007
- Study completion6 Mar 2014
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 HealthyStudies 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
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Eric M Wassermann, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00422071
- Sponsor's protocol ID
- 070063
- Other IDs
- 07-N-0063
- Status last verified
- 6 Mar 2014
- First submitted
- 12 Jan 2007
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Avanzi M, Uber E, Bonfa F. Pathological gambling in two patients on dopamine replacement therapy for Parkinson's disease. Neurol Sci. 2004 Jun;25(2):98-101. doi: 10.1007/s10072-004-0238-z.
PubMed 15221629Cohen MX, Young J, Baek JM, Kessler C, Ranganath C. Individual differences in extraversion and dopamine genetics predict neural reward responses. Brain Res Cogn Brain Res. 2005 Dec;25(3):851-61. doi: 10.1016/j.cogbrainres.2005.09.018. Epub 2005 Nov 11.
PubMed 16289773Strobel A, Spinath FM, Angleitner A, Riemann R, Lesch KP. Lack of association between polymorphisms of the dopamine D4 receptor gene and personality. Neuropsychobiology. 2003;47(1):52-6. doi: 10.1159/000068876.
PubMed 12606846
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detecting a Reward Signal in the Motor Cortex
- ClinicalTrials.gov ID
- NCT00422071
- Acronym / sponsor ID
- 070063
- Conditions
- Healthy
- Keywords
- Transcranial Magnetic Stimulation (TMS), Dopamine, Gambling, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 8 Jan 2007
- Study completion
- 6 Mar 2014
- First posted
- 15 Jan 2007 (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.
This study will use transcranial magnetic stimulation (TMS) to determine whether the activity in the brain when someone wins something affects the part of the brain that controls movement. Studies have shown that the brain releases signals to mark rewards for certain behavior, like the activity the brain generates when an animal receives food or drink after performing a certain action. This study will look for a way to detect this kind of signal in humans.
Healthy volunteers between 18 and 60 years of age are eligible for this study. Participants undergo TMS during two experiments slot machine stimulation and key sequence (see below). For TMS, a wire coil is held on the subject s scalp. A brief electrical current is passed through the coil, creating a magnetic pulse that stimulates the brain. The stimulation may cause twitching in muscles of the face, arm or leg, and there may be a pulling sensation on the skin under the coil. The effect of TMS on the muscles is detected with small metal disk electrodes taped onto the skin of the arms or legs.
The stimulation strength needed to activate the hand muscles is determined at the beginning of each experiment. To do this, the subject sits with his or her arms and hand relaxed. Magnetic pulses of varying strengths are applied in order to find the right strength. Also, a series of 45 pairs of magnetic pulses is administered so close to each other that they produce only one movement. Measurements of the movements generated serve as a baseline for comparison with movements generated during the experiments.
Slot Machine Simulation
Subjects play a computer game similar to a slot machine. They press a button to start the game and watch as three barrels of the machine spin into place. Subjects can win $0.25, $1or $5 if all three barrels match when they stop spinning. If all three barrels do not match, subjects do not win any money, except in rare instances, when they are awarded money even when all three barrels do not match. In one trial in this experiment, subjects receive transcranial magnetic stimulation after they see the second barrel stop spinning. In another trial, they receive the stimulation after the third barrel stops spinning.
Key Sequence
Subjects see a letter on a computer screen and press a combination of the three keyboard keys G, H, and J. If they press the keys in the right order and under the time limit, they win $1. At some point, the letter displayed changes, and the subjects must guess a new combination to earn money. Each of the letters corresponds to its own combination of key presses. A few moments after the subjects see whether they pressed the keys in the right order, they receive TMS.
Detailed description
Objectvie:
The role of mesencephalic dopamine neurons in reward processing has been established in primates using electrophysiological techniques and in humans using functional neuroimaging. Their role is thought to be dual: i) they show sustained activity with the expectation of a future reward and ii) a phasic response after reward. Animal data indicate that these neurons, located in the midbrain areas A8-10, behave as a single functional unit when activated. They have rich projections to both the prefrontal and motor cortices where they synapse on interneurons and cortical pyramidal cells, producing primarily inhibition. Though their function is not fully understood, these projections clearly play an important role in motivation and learning. Since there are no electrophysiological techniques available to detect dopaminergic or inhibitory activity in the human prefrontal cortex, our objective is to develop a paradigm to detect a reward related signal in the primary motor cortex, where transcranial magnetic stimulation can be used to measure brief events.
Study Population:
The population that we will study will be healthy volunteers between the ages of 18-60, without any significant medical history, contraindication to TMS or history of addictive behavior.
Design:
Our hypothesis is that the dopamine reward-related signal will alter level of evocable inhibition in primary motor cortex. Using behavioral paradigms that deliver intermittent reward, we aim to demonstrate a difference in the amount of cortical inhibition, i) when reward is expected compared to when reward is not expected ii) after rewarded compared to unrewarded trials iii) when reward follows a variable effortful response, and iv) when there is uncertainty as to whether a reward will be administered. If we are unable to produce a signal in the motor cortex with these simple paradigms, we will look for a reward-related change in inhibition when the rewarded behavior is the associative learning of a motor sequence. We will control for effects of variations in attention related to the experimental task, but not specific for reward, with a similar behavioral paradigm that manipulates attention and expectation.
Outcome Measures:
The outcome measures will be changes in the conditioned/unconditioned MEP for each reward condition.
Study design
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Men and women, age 18-60.
Key exclusion criteria (8 listed)
- Significant neurological or psychiatric history.
- History of habitual gambling, defined as either visiting casinos more than once per month or playing cards for money more than once per week or gambling over the internet more than once per month.
- Habitual consumption of more than two drinks a day, marijuana more than once a week or any other illicit drug use within the last three months.
- Use of medication affecting the DA system, such as phenothiazine antihistamines (promethazine), antiemetics or decongestants within the last month.
- Seizure History.
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
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 15221629Avanzi M, Uber E, Bonfa F. Pathological gambling in two patients on dopamine replacement therapy for Parkinson's disease. Neurol Sci. 2004 Jun;25(2):98-101. doi: 10.1007/s10072-004-0238-z.
- Background: PubMed 16289773Cohen MX, Young J, Baek JM, Kessler C, Ranganath C. Individual differences in extraversion and dopamine genetics predict neural reward responses. Brain Res Cogn Brain Res. 2005 Dec;25(3):851-61. doi: 10.1016/j.cogbrainres.2005.09.018. Epub 2005 Nov 11.
- Background: PubMed 12606846Strobel A, Spinath FM, Angleitner A, Riemann R, Lesch KP. Lack of association between polymorphisms of the dopamine D4 receptor gene and personality. Neuropsychobiology. 2003;47(1):52-6. doi: 10.1159/000068876.
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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?
An observational study of Healthy, 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 8 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 17 Dec 2019. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00422071, 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 17 Dec 2019.