The Effect of Transcranial Magnetic Stimulation on Learning With Reward in Healthy Humans
The Effect of Transcranial Magnetic Stimulation on Learning With Reward in Healthy Humans
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.
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.
-  Participants will be 272 healthy volunteers drawn from the population in the NIH
 clinical research volunteer program.

 INCLUSION CRITERIA:

 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.

 EXCLUSION CRITERIA:

 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

 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.