Polymorphism, Genetic Clinical Trial
Official title:
The Effect of BDNF on Motor Learning
The purpose of the study is to assess the status of brain-derived neurotrophic factor brain
(BDNF) and how the brain behaves in response to skill acquisition. Specifically we will
investigate the relationship of the status of BDNF with cortical excitability changes and
learning that occur during a motor training paradigm. We aim to 1) determine cortical
excitability changes by using transcranial magnetic stimulation (TMS) before and after
training; 2) to determine finger tracking accuracy before and after training; and 3)
determine the presence of BDNF polymorphism in each participant.
We are testing healthy adults in this study, and eventually would like to apply to persons
who have neurologic disorders such as stroke or dystonia. By applying a magnetic field to
the outside of the head, electrical currents are produced within the brain that can
stimulate brain tissue. Using TMS, the brain can be studied to gain a greater understanding
of the mechanisms associated with cortical excitability in healthy and patient populations.
There is limited knowledge of what influence genetic biomarkers such as BDNF have on
cortical excitability changes within the cortex following learning. Studies have indicated
that people without this certain gene are less likely to show changes in brain excitability
during TMS and during motor learning than people with this gene
Subjects and Design: A pretest/posttest design will be used. A convenience sample of healthy
college students will be studied and will undergo an initial screening by the PI or
Co-Investigators consisting of medical history and neurologic disorder review to assess
safety and qualifications to participate.
Inclusion/ Exclusion Criteria: Inclusion criteria include ages between 18-45 years and no
past history of psychiatric or neurologic disease. Exclusion criteria include subjects with
any neuromuscular disorder that impairs upper extremity motion or seizure history. Subjects
cannot be pregnant nor have indwelling metal or medical devices that are incompatible with
TMS testing.
With the subject seated in a supportive chair, the subject's skin will be cleaned
surrounding the first doral interoseus belly and dorsum of the hand. Next small surface
electromyographic (EMG) electrodes will be attached at the muscle belly and tendon. A ground
electrode will be placed on the dorsum of the hand or wrist.
Next, the threshold for TMS activation of the target muscle will be determined. To find the
optimal position for activating the first dorsal interosseous muscle, we will use a 70-mm
figure-eight TMS coil connected to a Magstim rapid magnetic stimulator. The coil will be
handheld on the scalp over the approximate area of the primary motor cortex (M1) in the
contralateral hemisphere to the recording electrode, and moved systematically to find the
optimal position. Single-pulse magnetic stimuli will be delivered manually at approximately
0.1 Hz starting at an intensity of 50% of the stimulator maximum. This level will be
adjusted systematically until the resting motor threshold is found, defined as the minimum
intensity required to elicit a motor evoked potential (MEP) >50 µV peak-to-peak in at least
5 of 10 trials with the target muscle at rest. Various cortical excitability measures will
be collected lasting approximately 20 minutes.
Finger tracking/training will be provided for 30 minutes under the supervision of the PI or
Co-I. Subjects will wear a finger electrogoniometer at the index finger metacarpophalangeal
(MP) joint. Subjects will use flexion/extension movements of the respective joint to track
waveforms on a computer screen. The training would consist of 30 blocks of tracking trials.
Each block will consist of 3 trials. The protocol parameters for different blocks will
differ in waveform, amplitude, frequency, trial duration, and joint position. For example, a
square wave would involve a different movement pattern execution as opposed to a triangular
wave. The waveforms may also differ on the forearm position to create "stimulus-response
compatible" or "stimulus-response incompatible" conditions. For example, a stimulus-response
incompatible joint position would involve extending and flexing the joint (finger MP or
elbow) in the horizontal plane to produce cursor movements in the vertical plane. All these
factors challenge the individual's capabilities to problem solve to achieve optimum
learning.
Following training and accuracy testing, cortical excitability measures will be collected
again lasting approximately 20 minutes. Lastly, a saliva sample will be collected for
genetic screening for brain derived neurotrophic factor (BDNF) polymorphism. We will collect
approximately 2 ml (less than one-half teaspoon) of saliva by asking the subject to spit
into a tube. It may take up to 30 minutes to provide a saliva sample, however, most people
typically require less time (approximately 5 minutes).
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