Project Title
Student1, major; Student2, major; Mentor1, department; Mentor2, department
Background
Brain damage, such as that due to neurological diseases or stroke, often impairs the functioning of speechrelated areas of the brain. In some cases, notably that of Parkinson’s disease (PD), this causes difficulties in
controlling voice pitch (intonation) during speech and this is manifested as voice tremors. This difficulty in
communicating can have a strong negative impact on quality of life, emphasizing the importance of
understanding how vocal pitch is controlled by speech-related areas in the brain.
High-Definition transcranial Direct Current Stimulation (HD-tDCS) is a technique which stimulates brain
cells, or neurons, to increase or decrease their excitability. Findings in previous studies have shown that HDtDCS affects functional behavior and the brain’s ability to form new connections (neural plasticity) (Kuo et al.,
2013; Monti et al., 2013; Malyutina & Den Ouden, 2014), which suggests that it may be effective for improving
vocal pitch motor control. Evidence from earlier functional magnetic resonance imaging (fMRI) studies has
shown that ventral motor cortex, an area of the brain that controls the movement of speech production
muscles, is strongly activated when humans control their voice pitch (Parkinson et al., 2012). Therefore, in this
project we aim to study how HD-tDCS of ventral motor cortex can modulate pitch motor control during vocal
production.
The control of voice pitch is partly dependent on auditory feedback. In everyday life, this is the sound
of one’s own voice, but in a lab setting this feedback can be modulated if the speaker wears headphones
through which their speech is played back simultaneously. Studies have shown that if the auditory feedback
from a speech task is altered by shifting the pitch of the speaker’s voice up or down, there will be a
compensatory vocal response in the opposite direction (e.g. if the pitch of the voice feedback is lowered, the
participants will automatically raise the pitch they are producing) (Behroozmand et al., 2012; Chen et al., 2007;
Larson, 1998). The speed (reaction time) with which this occurs and the extent to which the speakers
compensate (compensation magnitude) are measures of vocal pitch motor control. By measuring the speed
and magnitude of the vocal responses and comparing them before and after the application of HD-tDCS, it will
be possible to validate the role of ventral motor cortex in pitch control and to determine whether it may be
possible to improve its function.
EEG (electroencephalography) is a method to study the neural mechanisms of brain functions through
recording of neural activity using electrodes placed on the surface of the scalp. Previous studies have used
EEG recordings to study neural mechanisms of vocal pitch motor control in humans (Behroozmand et al.,
2009, 2014). Findings of these studies have demonstrated that specific EEG signals, primarily in the left
hemisphere, are modulated as a result of systematic manipulation of pitch alteration in voice feedback, and
have been shown to be larger in specific groups, such as musicians with absolute pitch ability. These findings
suggest that combining EEG recordings with auditory feedback alteration is a promising method that allows us
to study behavioral and brain correlates of vocal pitch motor control simultaneously. In this project, we propose
to use these techniques to identify possible changes to the behavioral and neural measures of vocal pitch
motor control after brain stimulation with HD-tDCS.
Research Question
The proposed study aims to answer the following questions:
1) To what extent does HD-tDCS neurostimulation on the ventral motor cortex affect the ability to
modulate pitch control in response to altered auditory feedback?
2) What changes in brain activity correlate with changes in vocal pitch motor control after brain
stimulation, as measured with EEG?
Project Goals and Objectives
This study is part of a broader program studying the relationships between communication disorders and the
brain. The goal of this specific project is to investigate whether pitch control can be affected by neural
stimulation, providing information that will facilitate the diagnosis and treatment of neurological diseases
resulting in speech motor disorders in patients, such as persons with Parkinson’s disease. At the same time,
this study will be used to assess the application of the auditory feedback alteration technique to validate the
effectiveness of neurostimulation on behavioral and neural measures of speech motor control.
Project Significance
While previous studies have investigated the neural correlates associated with vocal pitch motor control using
EEG, there have been no studies combining HD-tDCS and EEG. This project will not only provide insight into
the possibility of enhancing pitch motor control through brain stimulation, but also looks into the neural effects
of the relatively new HD-tDCS technique. The findings of this research project will increase our understanding
of the mechanisms underlying vocal pitch motor control, which will pave the way toward developing treatments
for improving speech communication in patients with neurological diseases.
Project Design
In this group project, [Student1] will be primarily responsible for research question 1, and [Student2] will be
primarily responsible for research question 2. Prior to and in the initial stages of this project, [Student1] will be
trained in the use of HD-tDCS by [Mentor1], and [Student2] will be trained by [Mentor2] to use EEG recordings
to measure neural activity. With the help of our mentors, we will submit to the Institutional Review Board for
human subject approval and will comply with all rules, regulations, and training requirements throughout the
testing (HD-tDCS and EEG are both noninvasive and have been consistently approved in the past).
For data collection, we will recruit 30 college-age participant volunteers through word-of-mouth and
flyers. Their testing will take place in two sessions. During the first session, subjects will be administered a
series of preliminary tests. These will include a hearing test, a short survey identifying past hearing/speech
impairment and musical/vocal training, and a pretest to measure their behavioral vocal responses to pitch
shifts in the auditory feedback. For this test, participants will be asked to produce a steady vowel sound while
receiving auditory feedback of their voice over headphones. The pitch they are receiving will then be altered in
either an upward or downward direction, and the subjects’ vocal response to this alteration of the feedback will
be recorded. This procedure will be repeated for approximately 200 vocalization trials (100 upward and 100
downward pitch shifts) in each participant, with each vocalization lasting about 2-3 seconds and with brief
breaks (1-2 seconds) between each. Due to the variability in individuals’ vocal responses to pitch shift stimuli,
these results will be used to match subjects as evenly as possible into three experimental groups. EEG
recordings will also be performed during the pre-testing session to obtain a baseline measure of neural activity
for vocal pitch control. EEG signals will be recorded by placing a cap with 64 electrodes on the participant’s
head. To ensure high-quality EEG recording, the impedance between subject’s scalp and electrodes will be
kept below 5 KΩ through injecting conductive gel in the space between scalp and each electrode. Each
pretesting session will last a duration of close to an hour and a half, with maximally one hour for preparation of
the test and EEG electrodes followed by a 30-minute recording of neural and behavioral responses to
feedback alteration during vocal pitch motor control.
After this first session, the results will be analyzed and the subjects will be pseudo-randomized into
three groups in order to balance their distribution based on age, gender and behavioral measures of vocal
responses to pitch shift stimuli. Of the three experimental groups, one is to receive anodal HD-tDCS
stimulation, one to receive cathodal stimulation, and one to receive “sham” (placebo) stimulation. Anodal, or
positive electrical current stimulation generally increases neuron excitability, while cathodal (negative)
stimulation reduces excitability (inhibiting neural activation). The sham group will go through a procedure that
mimics the sensation produced by stimulation, but without actual neural stimulation.
During the second session, subjects will receive 20 minutes of HD-tDCS neurostimulation (or the sham
counterpart) to the ventral motor cortex, without being told which type they are receiving. Five electrodes will
be placed in an EEG cap, configured to induce focal stimulation of ventral motor cortex. The electrode holders
are filled with a saline gel to improve conduction. A total current of 2 mA will be passed through the electrodes,
meeting safety standards for this technique. Afterwards, participants will again be tested with the pitch-shift
procedure while their EEGs are recorded, following the same procedures as in the first session. This second
session will take roughly two hours, due to both the EEG testing and HD-tDCS stimulation. Measures of vocal
responses (e.g. compensation speed and magnitude) and EEG will be analyzed and compared before and
after HD-tDCS of ventral motor cortex to determine changes in behavioral and neural correlates of vocal pitch
motor control following neurostimulation.
We will conduct the trials for each session, with [Student1] administering all of the HD-tDCS stimulation
for the project, and with [Student2] administering all of the EEG testing for the project. [Mentor1], [Mentor2],
and graduate students from both labs will be available for assistance and instruction on how to use these
techniques. We will both be responsible for the analysis of results and will collaborate on the writeup of a paper
for publication in a peer-reviewed journal.
Nov
Dec
X
Oct
X
X
X
Sept
X
X
May
X
X
X
Apr
X
Mar
Feb
Preparation (training, submission to IRB)
Recruitment
Session 1
Preliminary Data Analysis and Preparation
Discovery Day (submission, prep., presentation)
Session 2
Data Analysis
Write-up of Report
Jan
Project Timeline
X
X
X
X
X
*There will be a gap between the spring and fall semesters, indicated by a bold line, as we will not be working over the summer.
Anticipated Results and Dissemination
It is expected that anodal HD-tDCS to the ventral motor cortex will result in improved reaction times for pitch
control and a gain in the magnitude of correction, and that cathodal stimulation will have a negative effect on
reaction times and the magnitude of speakers’ pitch corrections. It is further expected that EEG testing will
reveal enhanced brain activity during pitch-shift stimulation in specific parts of the brain, particularly in the left
hemisphere areas involved in speech production and motor control.
The results of the first session of the study will be presented on Discovery Day, April 24, 2015, and the
final results will be presented the following year. We will also collaborate with our mentors, [Mentor1] and [Mentor2],
to write up a report for publication in a peer-reviewed journal, such as Brain Stimulation,
Neuromodulation or Brain & Language.
Personal Statement—
Beginning in middle school with participation in the National Spelling Bee, I have always had a fascination with
the inner mechanisms of language. My interests began with the history and etymology of words, but over time
have progressed to the structure of language and how it is processed. I am currently pursuing a degree in
linguistics through the BARSC program, and since this allows me to design my own program of study, I have
the option of further specializing my degree in a subfield of linguistics. Over the past few weeks, I have had
the opportunity to assist with several projects in mentor’s lab by inputting data and helping to pilot
experiments. From what I have seen within this short time, I would like to delve further into research within this
field. The proposed study not only allows me to begin research in phonetics, which I am currently planning to
focus my degree program around, but to also gain hands-on experience with neurolinguistics and to discover
whether this is an area which I would also enjoy studying in depth. Through this project, I hope to be exposed
to some of the questions that are currently at the forefront of linguistics study, and to develop the skills
necessary for further research in any discipline, both as an undergraduate and in a future graduate program.
Personal Statement—
I became deeply interested in and involved with Parkinson’s disease at a young age. Growing up with a
grandmother who had the disease, I witnessed and experienced how the disease affected different aspects of
her health, particularly her speech. She became incapable of controlling the steadiness and tone of her voice
during conversations, and this behavior heightened my curiosity about details of the disease. I approached
[Mentor2] after reading about his research within speech motor control and Parkinson’s disease, and after
meeting with him and learning more about his research I immediately knew I was dedicated to and passionate
towards his study. This proposed study would allow me to further enhance my knowledge about speech motor
control through the use of EEG and the brain activity involved with pitch modulation. This study would ignite
any future research and understanding towards the development of diagnostic and therapeutic techniques for
patients who have difficulty controlling their speech, such as Parkinson’s patients. Additionally, this study would
help to determine whether a minor in neuroscience is an area I would enjoy studying, and possibly focus on in
a future medical career.
References
Behroozmand, R., Ibrahim, N., Korzyukov, O., Robin, D. a, & Larson, C. R. (2014). Left-hemisphere activation
is associated with enhanced vocal pitch error detection in musicians with absolute pitch. Brain and
Cognition, 84(1), 97–108.
Behroozmand, R., Karvelis, L., Liu, H., & Larson, C. R. (2009). Vocalization-induced enhancement of the
auditory cortex responsiveness during voice F0 feedback perturbation. Clinical Neurophysiology, 120(7),
1303–1312.
Behroozmand, R., Korzyukov, O., Sattler, L., & Larson, C. R. (2012). Opposing and following vocal responses
to pitch-shifted auditory feedback: evidence for different mechanisms of voice pitch control. The Journal of
the Acoustical Society of America, 132(4), 2468–77.
Chen, S. H., Liu, H., Xu, Y., & Larson, C. R. (2007). Voice F[sub 0] responses to pitch-shifted voice feedback
during English speech. The Journal of the Acoustical Society of America, 121(2), 1157.
Kuo, H. I., Bikson, M., Datta, A., Minhas, P., Paulus, W., Kuo, M. F., & Nitsche, M. A. (2013). Comparing
cortical plasticity induced by conventional and high-definition 4 x 1 ring tDCS: a neurophysiological study.
Brain stimulation, 6(4), 644-648.
Larson, C. R. (1998). Cross-modality influences in speech motor control: the use of pitch shifting for the study
of F0 control. Journal of Communication Disorders, 31(6), 489–502; quiz 502–3; 553.
Malyutina, S. & Den Ouden, D.B. (2014). High-definition transcranial direct current stimulation of single word
processing [poster], Annual Meeting of the Society for the Neurobiology of Language 2014, Amsterdam,
The Netherlands, August 27-29.
Monti, A., Ferrucci, R., Fumagalli, M., Mameli, F., Cogiamanian, F., Ardolino, G., & Priori, A. (2013).
Transcranial direct current stimulation (tDCS) and language. Journal of Neurology, Neurosurgery, and
Psychiatry, 84(8), 832-842.
Parkinson, A. L., Flagmeier, S. G., Manes, J. L., Larson, C. R., Rogers, B., & Robin, D. a. (2012).
Understanding the neural mechanisms involved in sensory control of voice production. NeuroImage,
61(1), 314–22.
Magellan Scholar BUDGET FORM 1
Student’s Name:
Double-click on table to enter data
Hours
Rate
Estimated number of hours
student will work
Enter the hourly wage
Research hours during semesters
when enrolled in classes
224
$10.00
$2,240.00
Research hours during semesters
when NOT enrolled in classes
0
$0.00
$0.00
Student salary
Subtotal
Fringe: Student salary * student fringe rate (What is fringe? See budget instructions or guidebook)
Enrolled in classes
$2,240.00
0.55%
NOT enrolled in classes
$0.00
8.29%
Materials/Supplies
Enter sub-total from below:
Travel
Enter sub-total from below:
$12.32
$0.00
$745.00
TOTAL:
$2,997.32
Amount requested for MGS award:
$2,997.32
Budget Justification/Description
Student Salary: Indicate estimated number of student research hours per week and hourly rate separated by semesters when student is enrolled in
classes or not enrolled in classes (generally fall or spring vs summer semesters).
While enrolled in classes: 7 hours/week for 16 weeks during spring semester at $10/hour, 7 hours/week for 16
weeks during fall semester at $10/hour
Materials/Supplies: Indicate items, quantity, and estimated price. Be sure to include taxes on all purchases.
10 Sintered Ag/AgCl electrodes for HD-tDCS, at $26 +
8% sales/use tax + shipping at $25:
1 box of (50) syringes + 8% sales/use tax:
2 tubes of Signa Electrode Gel, at $8 + 8% sales/use tax:
Discovery Day poster (24" X 36"):
Participant incentives: 12 participants, at $30:
$306
$32
$17
$30
$360
Total:
$745
Travel: Indicate location, purpose of travel, estimate itemized costs (transportation, lodging, registration, etc).
I will not be traveling for this project. All research for this project will be conducted in the Institute for Mind
and Brain and labs at USC.
Magellan Scholar BUDGET FORM 2
Student’s Name:
Double-click on table to enter data
Hours
Rate
Estimated number of hours
student will work
Enter the hourly wage
Research hours during semesters
when enrolled in classes
224
$10.00
$2,240.00
Research hours during semesters
when NOT enrolled in classes
0
$0.00
$0.00
Student salary
Subtotal
Fringe: Student salary * student fringe rate (What is fringe? See budget instructions or guidebook)
Enrolled in classes
$2,240.00
0.55%
NOT enrolled in classes
$0.00
8.29%
Materials/Supplies
Enter sub-total from below:
Travel
Enter sub-total from below:
$12.32
$0.00
$743.00
TOTAL:
$2,995.32
Amount requested for MGS award:
$2,995.32
Budget Justification/Description
Student Salary: Indicate estimated number of student research hours per week and hourly rate separated by semesters when student is enrolled in
classes or not enrolled in classes (generally fall or spring vs summer semesters).
While enrolled in classes: 7 hours/week for 16 weeks during spring semester at $10/hour, 7 hours/week for 16
weeks during fall semester at $10/hour
Materials/Supplies: Indicate items, quantity, and estimated price. Be sure to include taxes on all purchases.
2 Jars of EEG electrode gel, at $80 + 8% sales/use tax:
Discovery Day poster (24" X 36"):
Participant incentives: 18 participants, at $30:
$173
$30
$540
Total:
$743
Travel: Indicate location, purpose of travel, estimate itemized costs (transportation, lodging, registration, etc).
I will not be traveling for this project. All research for this project will be conducted in the Institute for Mind
and Brain and labs at USC.