Laryngeal Vibration as a Non-invasive Treatment for Spasmodic Dysphonia
Phase: NA
Conditions: Spasmodic Dysphonia
Sponsor: University of Minnesota

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 1 of 27 
Revised: 9/28/2017 
PROTOCOL TITLE: 
Effect of Short-term Laryngeal Vibration on Voice Quality Grant title: Feasibility 
of laryngeal vibration as a treatment for spasmodic dysphonia 
 
PRINCIPAL INVESTIGATOR or FACULTY ADVISOR: 
Jürgen Konczak 
612-624-4370 
jkonczak@umn.edu 
 
STUDENT INVESTIGATOR: 
 
VERSION NUMBER/DATE: 
2 – 14 October 2020 
 
 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 2 of 27 
Revised: 9/28/2017 
REVISION HISTORY 
 
Revision # 
Version Date Summary of Changes 
Consent Change? 
1.2 
31 January 
2020 
Amended the title to include 
“Short-term” 
No 
2 
14 August 
2020 
1- Substituted the original 
stationary, wired laryngeal 
vibration device with a wearable, 
wireless device. 
2- Shortened the procedure. Instead 
of 3x17 min vibration, participants 
will only receive 2x20 min vibro-
tactile stimulation. 
3- An option for remote testing was 
added to the protocol. 
Yes 
3 
24 August 
2020 
Responded  
 
4 
14 October 
2020 
Responded 
Remote testing 
consent added. 
5 
31 January 
2021 
1- Added usability testing 
questionnaire to the 
protocol 
Yes 
 
 
 
 
 
 
 
 
 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 3 of 27 
Revised: 9/28/2017 
Table of Contents 
 
1.0 
Objectives ................................................................................................................ 6 
2.0 
Background .............................................................................................................. 6 
3.0 
Study Endpoints/Events/Outcomes .......................................................................... 9 
4.0 
Study Intervention(s)/Investigational Agent(s) ........................................................ 9 
5.0 
Procedures Involved ............................................................................................... 12 
6.0 
Data and Specimen Banking .................................................................................. 16 
7.0 
Sharing of Results with Participants ...................................................................... 16 
8.0 
Study Population .................................................................................................... 16 
9.0 
Vulnerable Populations .......................................................................................... 17 
10.0 Local Number of Participants ................................................................................ 17 
11.0 Local Recruitment Methods ................................................................................... 17 
12.0 Withdrawal of Participants .................................................................................... 18 
13.0 Risks to Participants ............................................................................................... 19 
14.0 Potential Benefits to Participants ........................................................................... 19 
15.0 Statistical Considerations ....................................................................................... 20 
16.0 Confidentiality ....................................................................................................... 21 
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants .................... 21 
18.0 Provisions to Protect the Privacy Interests of Participants .................................... 22 
19.0 Compensation for Research-Related Injury ........................................................... 22 
20.0 Consent Process ..................................................................................................... 22 
21.0 Setting .................................................................................................................... 23 
22.0 Multi-Site Research ............................................................................................... 24 
23.0 Resources Available ............................................................................................... 24 
24.0 References .............................................................................................................. 24 
 
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PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 4 of 27 
Revised: 9/28/2017 
ABBREVIATIONS/DEFINITIONS 
• 
EEG:  
Electroencephalogram 
• 
FD  
Focal dystonia 
• 
SD:  
Spasmodic dysphonia 
• 
VTS:  
Vibro-tactile stimulation 
 
 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 5 of 27 
Revised: 9/28/2017 
STUDY SUMMARY 
 
Study Title 
Effect of Laryngeal Vibration on Voice Quality  
Study Design 
Single-intervention, pre- posttest design. Subjects 
perform voice production tasks before, during and 
after vibration. 
Primary Objective 
The purpose of this research is to examine the 
effects of laryngeal vibration on objective markers 
of speech quality in healthy human volunteers and 
people with spasmodic dysphonia, a voice disorder 
affecting the laryngeal muscles. 
Secondary Objective(s) 
Obtain preliminary data in a limited sample of SD 
patients that show the potential effectiveness of the 
approach after a single application of vibro-tactile 
stimulation (VTS) of the larynx. 
Research 
Intervention(s)/Investigational 
Agents 
Vibro-tactile stimulation of the superficial skin 
surface above the larynx (human voice box) 
Scientific Assessment 
Nationally based non-federal funding organizations-
National Spasmodic Dysphonia Association 
IND/IDE # (if applicable) 
NSR IDE 
IND/IDE Holder 
N/A 
Investigational Drug Services 
# (if applicable) 
N/A 
Study Population 
People diagnosed with spasmodic dysphonia and 
healthy adult volunteers without a voice disorder 
Local Sample Size (number of 
participants recruited locally) 
We have recruited 17 – 9 females, 6 males (as of 
6/5/2018) 
 
 
 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 6 of 27 
Revised: 9/28/2017 
1.0 
Objectives 
1.1 Purpose:  
The general aim of the research is to provide scientific evidence that VTS 
represents a non-invasive form of neuromodulation that can induce 
measurable improvements in the speech of SD patients. This research 
addresses a clinical need to develop alternative or auxiliary treatments for a 
rare voice disorder with limited treatment options. A successful completion 
of the proposed work will be an important step in advancing laryngeal VTS 
as a therapeutic intervention for improving the voice symptoms in SD. 
Specifically, the scientific yield by achieving the specific aims is threefold: 
First, it will elucidate the unknown neurophysiological mechanism behind 
laryngeal VTS by documenting the neural changes associated with VTS. 
Second, it will establish that VTS can improve voice quality in SD. Third, 
by documenting that laryngeal VTS yields long-term benefits on voice 
quality in SD patients, it would provide a solid basis for a clinical trial that 
needs to address open questions on optimal dosage and duration of VTS-
based voice therapy, the magnitude of the therapeutic effect across adductor 
and abductor SD and its long term efficacy. 
2.0 
Background 
2.1 
Significance of Research Question/Purpose:  
The general aim of the study is to provide preliminary scientific evidence 
that VTS represents a non-invasive form of neuromodulation that can 
induce measurable improvements in the speech of SD patients. This work 
addresses a clinical need to develop alternative or auxiliary treatments for a 
rare voice disorder with very limited treatment options. A successful 
completion of the proposed work will be an important step in advancing 
laryngeal VTS as a therapeutic intervention for improving the voice 
symptoms in SD. 
2.2 Preliminary Data:  
We conducted a series of preliminary investigations to assess the feasibility 
of applying VTS to the human larynx. First, we searched for suitable 
vibrators that could be applied to the skin above the voice box and provide 
the necessary amplitude to penetrate sufficiently the thyroid cartilage and to 
stimulate the underlying mucosal mechanoreceptors and/or proprioceptors 
of extrinsic laryngeal muscles. Second, we recorded the acoustic signals 
during vocalization with and without VTS to determine its effect on voice 
production. Third, we measured the EEG responses to laryngeal vibration to 
understand the cortical responses to laryngeal VTS. 
Selecting and piloting appropriate vibrators. We systematically tested a 
range of commercially available, small precision vibrators that delivered 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 7 of 27 
Revised: 9/28/2017 
amplitudes between 1.7-14.3 G (based on 100g inertial load testing). 
Vibrators were attached to the skin above the larynx of healthy volunteers 
and tested under varying voltage inputs. During testing subjects repeatedly 
vocalized vowel tones for 6-second intervals that were recorded for later 
acoustic frequency analysis. It became clear that vibrators with amplitudes 
above 6G are unsuitable (e.g. induced a gag reflex at higher voltage; 
uncomfortable to wear for prolonged periods of time (> 10 min). We 
systematically narrowed the selection to a encapsulated cylinder vibrator 
(Fig. 1) that has a maximum amplitude < 6G and produced clearly 
detectable periodic signals in the acoustic data at frequencies that were 
within the frequency range known to stimulate laryngeal mechanoreceptors 
[1].  
Existing Literature:  
SD is a characterized by involuntary, random movement of laryngeal 
muscles causing disruption of fluent speech with strained-strangled voice 
quality. SD is more prevalent in women [2, 3]. Onset is typically in midlife. 
There are two types of SD: (a) adductor (AD) typified by uncontrolled vocal 
fold closure, and (b) abductor (AB) characterized by uncontrolled vocal fold 
opening. The AD form is more common and typically occurs during the 
voiced components of speech. SD symptoms are task specific, occurring 
during speech but not during other phonatory (e.g., prolonging vowels) or 
non-phonatory tasks (e.g., breathing). SD shares several abnormal 
neurologic signs with FD of the head, neck and hand. For example, 
abnormal blink reflexes were observed in SD, torticollis, and blepharospasm 
[4-7] and abnormal long-latency responses to peripheral nerve stimulation 
have been observed in SD [8], in blepharospasm and oromandibular 
dystonia [9]. Recent evidence from our group and the work of others 
strongly indicate that basal ganglia-related diseases such as Parkinson’s 
disease or certain forms of dystonia are associated with somatosensory and 
specifically proprioceptive abnormalities that are closely linked to the 
observed motor deficits [10-21] (for reviews see: [22, 23]). Finally, our own 
work confirmed that SD as a voice disorder is associated with a deficit in 
arm kinaesthesia [24] – a finding consistent with results from patients with 
FD of the head and neck [21].  
Neurophysiology behind VTS. It has long been established that VTS can 
stimulate muscle spindles [25-27] and mechanoreceptors [28] affecting 
motor behavior and inducing changes in kinaesthesia [29-31]. In general, 
vibrating the skin at amplitudes of ≤ 15 µm is sufficient to activate Ia 
muscle spindle aﬀerents of superficial muscles, which evokes a contractile 
response called the Tonic Vibration Reflex [26, 27]. To elicit kinaesthetic 
illusions, vibration must typically range between 40-100 Hz [32, 33]. Brief 
vibration to a relaxed muscle typically leads to an increase in muscle tone 
that can easily be overcome by voluntary phasic innervation [34], while 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 8 of 27 
Revised: 9/28/2017 
excitatory input to spinal α-motor neurons is depressed when vibration is 
applied for prolonged periods [35]. At the cortical level it has been shown 
that prolonged muscle tendon vibration of wrist flexors (30 min) induced an 
increase in corticospinal excitability of the antagonistic wrist extensors 
lasting up to 60 min after vibration indicating that VTS can induce 
measurable changes in short-term cortical plasticity [36, 37].  
Somatosensory deficits and VTS in FD. Numerous research reports 
documented somatosensory deficits in FD (for review see [38]). For 
example, proprioceptive-based finger position sense thresholds and the 
perception of arm motion are abnormal in patients with cervical dystonia or 
blepharospasm [21, 39]. The abnormalities in tactile and proprioceptive 
processing are not restricted to the affected dystonic musculature, but were 
also documented in non-affected body regions [21, 40, 41] indicating a 
generalized somatosensory deficit in FD. Recording of somatosensory 
evoked potentials (SEPs) and TMS data document that abnormal processing 
of somatosensory information in FD is associated with abnormally enhanced 
cortical excitability and decreased intracortical inhibition [42, 43], which 
also has been confirmed for SD [44]. The susceptibility of FD to 
somatosensory stimulation has long been known, because patients with task-
specific dystonia may use sensory tricks (geste antagoniste) to temporarily 
alleviate dystonic symptoms by touching or pressing areas of or near the 
dystonic musculature [45, 46]. Research on cervical dystonia documented 
that effective sensory tricks are associated with pallidal and motor cortical 
desynchronization at low frequencies (6-8Hz) [47]. It has further been 
shown that FD responds to VTS. Vibrating dystonic neck muscles of 
patients with torticollis, who exhibit abnormally tilted head postures, 
induced head righting and nearly restored normal head posture [48]. 
Vibrating non-dystonic arm muscles in patients with cervical dystonia and 
blepharospasm skewed arm position sense to a greater extent than healthy 
controls [39]. In summary, there is overwhelming evidence that 
somatosensory processing is affected in many forms of FD (for reviews see 
[22, 38]). VTS has been shown to influence somatosensory perception and 
may reduce the severity of dystonic postures [13, 39, 45, 48]. 
One challenge in applying VTS to the speech motor system is that intrinsic 
laryngeal muscles and the mucosa of the epiglottis are shielded by thyroid 
cartilage. While proprioceptors of limb muscles can be stimulated by 
placing vibrators on the skin above them, this is not possible for laryngeal 
muscles. That is, non-invasive vibrators are needed that can be easily 
attached to the skin above the larynx and vibrate with sufficient amplitude to 
induce responses in laryngeal mechanoreceptors. Many of the vibrators that 
have been used in the past to investigate vibration responses in limb muscles 
are not suitable due to size, weight and voltage requirements. Fortunately, 
recent advancements in vibrator technology (largely driven by cell phone 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 9 of 27 
Revised: 9/28/2017 
engineering) have produced small, low voltage, yet powerful vibrators that, 
for the first time, make it feasible to wear and operate vibrators at the neck 
for a prolonged time without restricting a person’s movement. 
3.0 
Study Endpoints/Events/Outcomes 
3.1 Primary Endpoint/Event/Outcome:  
If successful, the work under this protocol would lay the scientific 
foundation for a clinical trial to examine the usefulness of the approach in a 
larger patent sample. It would document the sensorimotor cortical activation 
patterns associated with SD and the cortical responses to VTS. It would 
promote development of wearable, user-programmable medical devices that 
could apply VTS while monitoring its effect on voice production in real-
time. Ultimately, VTS would enlarge the available therapeutic arsenal by 
either augmenting existing Botox therapy or becoming an alternative 
intervention option for patients who do not tolerate Botox injections. 
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 
Description:  
The participants will wear a light-weight, wearable collar (See figure 1) 
that can be removed as easy as a bracelet. The complete system consists of 
two components: 1) a flexible enclosure that houses the electronics, 2) a 
collar made of soft, wear-resistive, and washable textile materials. The 
collar has a pouch, in which the electronics enclosure can be inserted. The 
enclosure can be removed from the textile collar for separate cleaning of 
the collar after prolonged wear, which is every single testing session. 
The output of the microphone or accelerometer embedded in the device 
will be stored locally in the wearable device for automatic internal 
processing in the wearable device to activate the vibrators or calculate the 
threshold using the developed algorithms. The stored data will be 
automatically removed every 60 s and data will be never transferred out of 
the wearable device. In the control mode, either the voice or the 
accelerometer data will be used by the device to activate the vibrators when 
the user vocalizes or speaks. We have implemented a detection algorithm 
that uses either the accelerometer signal or the acoustic signal from the 
microphone to turn the vibrators on and off. 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 10 of 27 
Revised: 9/28/2017 
 
Figure 1: Schematic illustration of a laryngeal vibration device having vibrators carried by 
a collar. 
 
Figure 2. 
Vibratory motor used for this study (Precision Microdrives Ltd., London, UK, Model 307 
– 100) Length: 25 mm. Diameter: 9 mm.  
The device applies vibration to the to the skin above the larynx using two vibratory 
motors. The vibratory motors (Precision MicrodrivesTM, Model 307 – 100) used are 
low-voltage (~1V) and non-invasive. For this protocol, they vibrate at frequencies 
between 30 - 100 Hz (i.e. 100 times per second). The small electric motors are 
encapsulated (see Fig. 2). There are no moving parts that can come in contact with 
the skin. At a stimulation frequency of 100Hz, the inertial load is approximately 
2.7G, which translates to a vibration amplitude well below the threshold that may 
induce a swallowing reflex (> 6G). The vibrators embedded in the device are 
movable, thus we are able to position them around the larynx of every participant. 
The microphone embedded in the device is positioned in front of the larynx. Prior to 
testing, the microphone of the wearable device will record the audio signal for 1 
minute. During this time the participant will be silent. The recorded audio signal 
used to determine a signal power threshold to adjust the signal-to-noise ratio of the 
voice signal. These recorded data will not be transferred from the wearable device, 
but are deleted from device memory as soon as the threshold calculation is 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 11 of 27 
Revised: 9/28/2017 
completed. The process of calculating threshold is automatic and does not require 
interaction by the user or the experimenter. 
Using the calculated threshold, the speech detection algorithm will turn on the 
vibrators. To ensure consistency across all participants, the vibration frequency will 
be held constant at 100Hz for all participants. 
The rotating mass of each vibrator in of the device is encapsulated. It does not come 
in direct contact with the skin. The position of vibrators relative to the voice box can 
be adjusted. The vibrators need to be placed around the larynx (Figure 3). For in-
person testing, the study personnel will manually adjust the location of the device 
vibrators according to the width of the larynx of the participant. For remote session 
testing, the participant will measure the width of his/her larynx during the video call 
with study personnel. Next, the participant will be instructed to move the vibrators 
and place them apart to the value of measured larynx width from the previous step. 
Finally, the participant will wear the wearable device in front of the camera. The 
study personnel via video call will check and make sure the placement is consistent 
with the study protocol.  
 
The device has a physical on/off switch that the user controls. No tablet or computer 
is necessary for operation. Participants will download an app to their smart phones. 
That app will allow users 1) to turn the vibratory motors on or off remotely (i.e. 
without the use of the physical switch), 2) to change to mode of operation to 
continuous vibration for a specified time between 1-20 min, ), or 3) to turn on the 
voice detection mode, during which VTS will only be turned on during detected 
speech. The vibration frequency cannot be altered by the user. A resistor embedded 
in the electronics controls the output voltage to 1.1 V, which corresponds to a 100Hz 
vibration. 
 
4.2 Drug/Device Handling:  
The strength of the vibration is similar to the vibration experienced from 
vibrating cell phones or gaming joysticks. Vibro-tactile stimulation at the 
applied frequency and amplitude is not known to cause pain or tissue 
damage. The participant may feel a mild tingling or vibrating sensation. 
Preliminary testing on healthy human subjects showed that at the given 
vibration parameters (see 4.1) no adverse reactions occur.  

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 12 of 27 
Revised: 9/28/2017 
 
Figure 3. 
Demonstrating the placement of vibratory motors on the larynx. During this study, the 
vibrators are embedded in the wearable collar. 
5.0 
Procedures Involved 
5.1 Study Design: 
Subjects will perform voice production tasks before, during and after 
vibration. The subject will wear the collar around their neck. Two light-
weight, low voltage, non-invasive surface electrical vibratory motors that 
are embedded in the wearable collar will be positioned on the skin of the 
anterior portion of the neck adjacent to the voice box to vibrate the larynx 
(see Fig. 3 for demonstrating the location of vibrators). Voice production 
before, during, and after the vibration will be recorded via a microphone for 
subsequent acoustic analysis on voice quality by speech analysis experts. In 
addition, during voice production, electroencephalography (EEG) will be 
recorded with a 64-channel system (Active 2 BioSemi B.V., Amsterdam, 
The Netherlands or the mobile ANT Neuro EEGO EEG System, Hengelo, 
The Netherlands) at a sampling frequency of 512 Hz. Subjects will wear a 
regular head cap arranged in the standard 10-20 configuration (see Figure 
1). Four additional external electrodes will be used. Two electrodes will be 
placed above and below the left eye to detect eye movements. Another two 
electrodes will be attached on bilateral mastoid processes to serve as 
reference electrodes. A water-based conductive gel is applied between the 
electrodes and the skin, which can be cleaned easily with water. 
Deleted: Figure 1

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 13 of 27 
Revised: 9/28/2017 
 
Figure 1. 
 EEG cap with 10-20 electrode configuration 
5.2 Study Procedures:  
Voice assessment. To assess voice quality, participants will perform two 
voice production tasks. First, they will vocalize the vowels ‘ahh’ and ‘ee’. 
They will perform each task three times per assessment. Second, they read 
aloud twenty test sentences. They will repeat these assessments several 
times during testing (see Fig. 4). The sentence reading task consists of a set 
of test sentences based on a 20-sentence inventory described by Ludlow et 
al. as being sensitive to the voice symptoms experienced in SD [2]. 
Participants will read the sentences at their own comfortable pace and 
loudness. In addition, participants will rate their perceived effort level of 
vocalization on an ordinal scale of 0 to 10 (0 being with no effort and 10 
being with maximal effort).  
Application of laryngeal vibration. Each VTS trial begins with a 10-second 
rest period, followed by 4 seconds of vocalization. After 2 seconds of 
vocalization, vibration will set in while the subject continues to vocalize. 
Thus, each trial has a rest, a vocalization only, and a vocalization + 
vibration period. Each participant performs 50 trials per set.  
The timeline of the complete protocol is illustrated in Figure 4. Testing will 
begin with a pretest voice assessment, followed by two sets comprising the 
vibration only and vocalization + vibration conditions. The order of the 
conditions will be counter-balanced between subjects to account for possible 
order effects. During the vibration only condition, subjects will be silent and 
are allowed to read for diversion. After each set a 5-min break will be given 
and fluids will be offered. Voice assessment batteries will be administered 
after each set. After completion of two sets and final voice assessments are 
immediately after treatment (Post 2 OFF), and 20 min and 60 min after VTS 
has stopped (Post 20, Post 60).  
 
Deleted: 4

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
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Revised: 9/28/2017 
 
Figure 2. 
 Experimental design for in-person testing. 
Usability questionnaire: The last section of study is to ask participants to fill 
out a questionnaire about the usability of the wearable collar. 
 
Optional remote testing 
In case a laboratory visits is not feasible, testing will be conducted remotely. 
Testing consists of a single session and will be conducted via a video call. A 
high-quality microphone, a voice recorder, the wearable collar, and study 
and device instruction will be provided to the participant prior to the video 
call. In addition, participants will download the smartphone application for 
controlling the device before the video call. The smartphone application is 
developed for main operating systems which are Android and iOS (for 
iPhone) and the phone only requires to have Android version 7 or higher, or 
iOS version 11 or higher for iPhone. 
There is no EEG and eye movement recording during the remote testing, 
and only voice will be recorded using the microphone and the voice recorder 
that has been shipped to the participant. 
At the beginning of the remote session the participant will be instructed to 
measure the width of their larynx during the video call with study personnel. 
The study personnel will make sure the measurement in done correctly. 
Next, the participant will be instructed to move the vibrators and place them 
apart to the value of measured larynx width from the previous step. Finally, 
the participant will wear the wearable device in front of the camera. The 
study personnel via video call will check and make sure the placement is 
consistent with the study protocol. 
The remote testing session will only involve voice recording using the 
provided microphone and voice recorder. The instruction for using devices 
is in the package that the participant received before the video call. A study 
personnel who conducts the study will walk the participant through the 
instruction and assures that the devices are properly set up before starting 
the remote testing. The testing follows the following procedure (See Figure 
6): 
For the baseline assessment, participants will vocalize the vowels ‘ahh’ and 
‘ee’ each five times and read aloud the 20 test sentences from Appendix A 
of Ludlow et al. [2]. Participants will read the sentences at their own 
comfortable pace and loudness. In addition, participants will rate their 
perceived effort level of vocalization on an ordinal scale of 0 to 10 (0 being 
5 min 
5 min 
10 min 
VTS Set 1 
VTS Set 2 
20 
min 
Voice 
Assess. 
Pretest 
Vocal. 
+ Vibr. 
Vibr. 
Only 
Voice 
Assess. 
Post 1 
OFF 
Vocal. 
+ Vibr. 
Vibr. 
Only 
Voice 
Assess. 
Post 2 
OFF 
40 
min
Voice 
Assess.  
Post 20 
Voice 
Assess. 
Post 60 
Retention 
5 min 
Deleted: 5

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
VERSION DATE:  
01/31/2021 
 
 
Page 15 of 27 
Revised: 9/28/2017 
with no effort and 10 being with maximal effort). This concludes the pretest 
voice assessment (see Fig. 6). Subsequently, participants will apply the 
laryngeal vibration on themselves as instructed for a period of 10 minutes. A 
study personnel will instruct the participant for each step of the testing. The 
voice assessment will be repeated after each set of VTS and twice during the 
retention period (see Fig. 6) The procedure for remote testing is identical to 
the in-laboratory visit except it does not include EEG and eye movement 
recording.  
 
 
 
 
Figure 6. 
 Experimental design for remote testing. 
 
The recorded voice data will be stored on the voice recorder that was sent to 
the participant. The voice data are already deidentified. The audio file 
names do not contain any HIPPA incompliant information. The files names 
comprise only the subject ID and the session number (i.e prestest, set 1, 
etc.). Upon completion of the remote testing session, the participant will 
receive a prepaid shipping label via email. The participant will print the 
label and send the equipment back to the laboratory, thus there is no 
shipping cost for the participant 
The stored deidentified voice data will be then removed from the voice 
recorder and will stored separately on a password protected University of 
Minnesota HIPAA compliant server where in-laboratory testing data is also 
located. 
Usability questionnaire: The last section of study is to ask participants to fill 
out a questionnaire about the usability of the wearable collar.  
 
5.3 Study Duration:  
The study consists of a single session. Total exposure time to vibration will 
be approximately 30 minutes. Each VTS set will last 20 minutes. There will 
be 5 minutes breaks between sets. The interspersed, repeated voice 
assessment will allow to document time-dependent changes in voice quality 
and cortical activation due to laryngeal vibration up to 60 minutes past VTS 
application. Total duration of the study will be 115 minutes. 
 
5.4 Individually Identifiable Health Information: 
20 
min 
Voice 
Assess. 
Pretest 
Vocal. 
+ Vibr. 
Vibr. 
Only 
Voice 
Assess. 
Post 1 
OFF 
Vocal. 
+ Vibr. 
Vibr. 
Only 
Voice 
Assess. 
Post 2 
OFF 
40 
min
Voice 
Assess.  
Post 20 
Voice 
Assess. 
Post 60 
5 min 
5 min 
10 min 
VTS Set 1 
VTS Set 2 
Retention 
5 min 

PROTOCOL TITLE: Effect of Short-term Laryngeal Vibration on Voice Quality. Grant 
title: Feasibility of laryngeal vibration as a treatment for 
spasmodic dysphonia 
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For SD participants, we collect health information concerning disease 
duration, and any possible treatment (Botox injection) that they receive and 
when the last Botox injection had occurred prior to testing. For healthy 
control participants we only collect initial contact information, but no PHI. 
The respective HIPAA Agreement Template Form has been uploaded to 
ETHOS. The PI and his study team have no direct access to any other 
medical records.  
6.0 
Data and Specimen Banking 
N/A. 
7.0 
Sharing of Results with Participants 
N/A 
8.0 
Study Population 
8.1 Inclusion Criteria:  
8.1.1 Patients: 
Diagnosis of spasmodic dysphonia made through a voice disorder specialist. 
 
8.1.2 Controls: 
Healthy adults, aged 18-75 years with no known neurological or orthopedic 
deficits that may affect speech motor functions. 
8.2 Exclusion Criteria:  
8.2.1 Patients: 
- 
Regular intake of benzodiazepines 
- 
Cognitive impairment: score < 27 on Mini-mental state examination; 
score > 19 on Beck depression inventory 
- 
Identifies with a neurological or musculoskeletal impairment affecting 
speech motor function. These impairments may include a form of: 
Dyskinesia, Dystonia, Essential Tremor, Huntington’s Disease, Multiple 
System Atrophy, Muscle Tension Dysphonia, Parkinsonism, Progressive 
Supranuclear Palsy, Spasticity, Intracranial Neoplasm (brain tumor), 
Spinal Neoplasm, Cerebrovascular Accident (Stroke), Mild Traumatic 
Brain Injury, Intracranial Hemorrhage, Multiple Sclerosis 
8.2.2 Controls: 
- 
History of impairments affecting speech function. 
- 
Regular intake of benzodiazepines. 
- 
Cognitive impairment: score < 27 on Mini-mental state examination; 
score > 19 on Beck depression inventory. 
8.3 Screening:  

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SD participants will be screened by Dr. George Goding at the Fairview 
Lion’s Voice Clinic or Dr. Kari Urberg at the Park Nicollet Voice Clinic, St. 
Louis Park, MN. All SD subjects will be assessed by the clinicians using an 
established protocol [2]. The clinical assessment consists of a questionnaire 
(CAPE V) [49], clinical speech evaluation and a nasoendoscopic exam. 
These clinical assessments are part of the routine exam that patients receive 
for diagnostic purposes. They are not an explicit part of this study.  
9.0 
Vulnerable Populations 
9.1 Vulnerable Populations:  
☐ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ Adults lacking capacity to consent and/or adults with diminished 
capacity to consent, including, but not limited to, those with acute 
medical conditions, psychiatric disorders, neurologic disorders, 
developmental disorders, and behavioral disorders 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☒ None of the above 
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented:  
Number of patients with spasmodic dysphonia (SD) will be 20 and number 
of healthy control subjects (CTL) are 20.  
11.0 Local Recruitment Methods 

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11.1 Recruitment Process:  
Voice-disordered subjects (SD) will be recruited through our own SD 
patient database, through Dr. George Goding at the Fairview Lion’s Voice 
Clinic, or through Dr. Kari Urberg at the Park Nicollet Voice Clinic, St. 
Louis Park, MN. Control subjects will be recruited from the community via 
flyer and will be matched for gender and age to the SD participants.  
11.2 Identification of Potential Participants:  
SD patients are seen regularly by Drs. Goding and Urberg as part of their 
clinical routine. Dr. Goding sees approximately 30-40 patients a month and 
administers Botox injections as medically indicated. Both clinicians will 
identify potential participants and inform them about the study possibility. 
The initial contact to potential participants is made by either Dr. Goding or 
Dr. Urberg at their respective clinics. We will not access patient databases 
in either clinic to identify potential participants through the study 
coordinator. Note that potential participants are regularly seen by Drs. 
Goding/Urberg as part of the ongoing patient treatment (e.g. Botox 
injections). At these scheduled visits Drs. Goding/Urberg will share the 
study information flyer (see ETHOS section: Recruitment Materials) with 
potential participants and explain to them the scope of the study. If patients 
are interested in participating, the contact information of the study 
coordinator will be shared with the patient, who can then contact the study 
team. Once the study coordinator is contacted by a potential participant, he 
will explain the study procedure in detail and will invite participation. If 
agreeable, a date for obtaining informed consent and data collection is set. 
Prior to study begin, investigators will obtain and document informed 
consent from each participant according to21 CFR 50, Protection of Human 
Subjects (see also section 20.0).  
Both Drs. Goding and Urberg have legitimate access to patient PHI as part 
of their clinical work. Relevant PHI (type of diagnosis, disease duration, 
frequency of Botox injections) will not be shared with the study team of the 
PI before consent has been obtained and the participant has signed the 
appropriate HIPAA form. 
11.3   Recruitment Materials:  
Healthy and SD participants will be invited to the study via flyers that 
summarize the study and its goals. 
11.4 Payment:  
Study participants will be reimbursed $100 for one time in-lab study visit. 
Study participants will be reimbursed $50 for remote study.  
12.0 Withdrawal of Participants 
12.1 Withdrawal Circumstances:  

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Participants may opt to take a break or withdraw at any time during the 
study, if they experience discomfort or become fatigued. 
Although our preliminary investigation showed that the applied vibration 
frequency and amplitude is not sufficient to induce a swallowing or gag 
reflex, we will stop the procedure, if such incidence is observed. Elicitation 
of a swallowing reflex is not harmful, but its repeated non-volitional 
elicitation may cause discomfort.  
12.2 Withdrawal Procedures:  
If such event would occur, we would give the participant the option to adjust 
the vibration parameters or to completely withdraw from the study. Any 
data collected up to that point would be destroyed and not used in further 
analysis. 
12.3 Termination Procedures:   
Upon reaching the limit of the proposed study population, recruitment will 
stop and only data analysis will continue. Once the analysis is completed, 
the de-identified data sets will remain on UMN HIPAA compliant servers. 
They will form the basis for any scientific publication resulting from the 
study. We will then orderly terminate the study following the procedures 
required by IRB. 
13.0 Risks to Participants 
13.1 Foreseeable Risks: 
Vibration Risks. The risks in this study are minimal other than the 
possibility of skin redness over the skin or feelings mimicking numbness 
over the neck area during trials. These discomforts, if any occurs, usually 
disappear within minutes after vibration is removed. 
EEG Risks. There is no particular risk associated with EEG recordings. The 
procedure is non-invasive and no energy is imposed by the system to the 
participant. Participants may opt to take a break or stop/withdraw at any 
time, if they experience any discomfort due the wearing of the EEG cap. 
Wearable Collar Risks: This risk of using the collar with respect to 
irritation/rubbing is minimal. Because the textile is chosen from 
biocompatible material and the collar is not moving during the testing, there 
is minimal risk associated with it. In addition, because the electronics do not 
have any contact with the tissue and are enclosed in a housing, the risk of 
the electronics being affected by moisture/sweat is minimal. 
14.0 Potential Benefits to Participants 
14.1 Potential Benefits: 

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There is no direct benefit to participating in this study. At this point, there 
are no known data that provide conclusive evidence for the effectiveness of 
laryngeal vibration in reducing voice disorder symptoms. 
15.0 Statistical Considerations 
15.1 Data Analysis Plan:  
Analysis of voice data. Acoustic analysis will follow the methodology 
described by [50]. Waveform and wide-band spectrograms will be used to 
identify and measure the duration of the variables. The acoustic signal will 
be examined for the presence of phonatory breaks and aperiodic breaks. 
Phonatory breaks are defined as any voiced phonemic segment without 
sound that is greater than 50ms; the duration of phonatory breaks will be 
measured. Aperiodic segments will be identified as any voiced phonemic 
segment that contains non-repetitive cycles that are greater than 50ms; and 
the duration of the break will be measured. To standardize the duration 
measures for both phonatory and aperiodic breaks, the sum of the duration 
of breaks will be divided by the sum of the duration of all voiced segments 
for each subject. Inter-rater reliability will be measured using Cohen’s alpha 
and intra-rater reliability will use Pearson’s r correlation (expected to range 
between r=.89 to r= .98 according to [50]). For both break types, the 
absence of phonation or the presence of aperiodicity at the boundary of a 
syllable or the beginning of a word will not be considered. We will perform 
a MANCOVA procedure employing all acoustic variables with pre-
/posttests as independent factors. If the MANCOVA is significant, separate 
univariate ANOVAs will be performed on each acoustic variable 
(dependent) and assessment conditions as a repeated measure (independent) 
[50]. Appropriate Bonferroni adjustments will account for multiple testing. 
Analysis of EEG data. EEG recordings during speech are known to be 
susceptible to noise from the multiple muscles in and near the head that are 
involved in speech production. We have been cognizant to this fact and a) 
designed a simple vocalization task that does not involve complex patterns 
of muscle activation and b) use modern noise removal techniques that have 
been successfully applied for the analysis of voice related EEG. Dr. Yang is 
an expert in the analysis of speech-related EEG and will lend his expertise 
for EEG data analysis, which is based on the widely utilized MATLAB 
EEGlab toolbox [51]. Space limitation does not permit to describe all 
processing steps in detail. However, here we outline its major approach. 
First, to remove motion and electromyographic artifacts, all channels will be 
filtered (0.5 Hz high-pass and 20 Hz low-pass FIR filter). Second, target 
events will be extracted and trials containing non-physiological signal 
amplitudes will be rejected (typically outside [-100 μv 100 μv]). Third, for 
further objective noise removal the ADJUST algorithm (Automatic EEG 
artifact Detector based on the Joint Use of Spatial and Temporal features) 

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will be utilized - algorithm also included in the NIH Neuroimaging Tools 
and Resources Platform. Finally, an Independent Component Analysis 
(ICA) will be applied [52]. The ICA statistically decomposes all 64 channels 
into 64 independent sources of information (components) whose weighted 
sum is assumed to result in the formation of the recorded data. After this 
step, the pruned components are combined, generating a cleaner data set. 
After the ICA weights have been computed, the ADJUST will be employed 
to detect those independent components, which based on the statistical 
criteria of the algorithm, were the potential sources of stereotyped artifacts 
(eye blinks, vertical eye movement, horizontal eye movement, generic 
discontinuity i.e. inappropriate signals due to noisy channels or muscle 
activation) [53]. The statistical criteria for removing noise components 
include temporal kurtosis and spatial average difference [SAD] (from eye 
blinking), the maximum epoch variance [MEV] and SAD (from vertical eye 
movements), the MEV and spatial eye difference [SED] (from horizontal 
eye movements), and MEV and the generic discontinuity spatial feature 
[GDSF] (from bad channels and muscle activation). After the removal of 
noise components, a time-frequency analysis will be carried out on all 
channels of the pruned dataset. The analysis will yield the mean event-
related changes in the spectral power “ERSP” (from pre-stimulus baseline) 
for the different frequency ranges at each time instance of all epochs. 
16.0 Confidentiality 
16.1 Data Security:  
All private information will be stored in a secured location and all recorded 
and derived data from either in-laboratory testing or remote testing will be 
de-identified and stored separately on a password protected University of 
Minnesota HIPAA compliant server. In any publications or presentations, 
we will not include any information that will make it possible to identify 
you as a subject. However, your record for the study may be reviewed by 
departments at the University with appropriate regulatory oversight. 
17.0 Provisions to Monitor the Data to Ensure the Safety of 
Participants 
17.1 Data Integrity Monitoring.  
The PI and study coordinator oversee the progress of the study and to ensure 
that it is conducted, recorded, and reported in accordance with the protocol, 
standard operating procedures, and applicable regulatory requirements. This 
study does not constitute a clinical trial at this point. Neither CITI, nor IRB 
have requested additional intramural or extramural monitors. Consequently, 
no independent monitoring reports. This study is currently not listed with 
clinicaltrails.gov.  
17.2 Data Safety Monitoring.  

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Protection of subject confidentiality will be strictly monitored. All records 
will be kept confidential and without identifying the subjects in published 
materials. Only authorized personnel directly associated with the study will 
have access to digital files or paper data sheets with original data sets that 
may contain information about subject identity. The paper files will be kept 
in locked file cabinets in the laboratory of the PI, to which only authorized 
personnel has access. The files containing the subject identifying codes will 
be destroyed after 10 years. All digital data will be stored on a secure, 
HIPAA compliant server maintained by the University of Minnesota Office 
of Information Technology and/or using “Box” as the HIPAA compliant 
tool (see https://it.umn.edu/center-excellence-hipaa-data). All research 
personnel completed the required data and safety monitoring courses (e.g., 
responsible conduct of research, HIPAA, etc.). 
18.0 Provisions to Protect the Privacy Interests of Participants 
18.1 Protecting Privacy: As described in section 11, participants will only contact 
information as it is needed to interact with them prior or after testing. The 
collected PHI is very limited and will only be used in de-identified form 
during analysis and in any possible scientific publications. During the 
consent process, we explicitly tell the participant what PHI if any will be 
collected and how long we will store it. We also describe the study 
procedure in detail and emphasize that the procedure is not invasive and 
carries no known health risk. 
18.2 Access to Participants:  
Only the study coordinator has access to PHI or address information about 
the participants. The other members of the study team only have access to 
de-identfied data.  
19.0 Compensation for Research-Related Injury 
19.1 Compensation for Research-Related Injury:  
In the unlikely event that this research activity results in an injury, treatment 
will be available, including first aid, emergency treatment and follow-up 
care as needed. Care for such injuries will be billed in the ordinary manner 
to subjects or their insurance company.  
20.0 Consent Process 
20.1 Consent Process (when consent will be obtained):  
• 
For in-laboratory testing: 
o Consent will take place either in the laboratory prior to testing by 
signing the consent document in person or digitally through REDCap 
via a tablet provided to the participant or a link to the eConsent that 
has been shared with the participant before the laboratory visit. 

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Investigators will obtain and document informed consent from each 
participant according to 21 CFR 50, Protection of Human Subjects. 
o There are, at minimum, several days and often weeks between 
informing the prospective participants and obtaining the consent. This 
study requires that patients are seen towards the end of their Botox 
cycle. Once a potential study participant contacts the study 
coordinator, has received the relevant study information, and has 
agreed to participate, the coordinator and the participant agree on a 
date suggested by the participant. The patients know best when they 
become symptomatic and the effect of the Botox injection is wearing 
off.  
o The referring clinician determines that a potential participant 
understands the information.  
o Copy of the consent form for the in-laboratory testing has been 
uploaded to ETHOS. 
• 
For remote testing: 
o Consent will take place prior to testing digitally through REDCap via 
a link to the eConsent that has been shared with the participant prior 
to the remote testing and video call. Investigators will obtain and 
document informed consent from each participant according to 21 
CFR 50, Protection of Human Subjects. 
o There are, at minimum, several days and often weeks between 
informing the prospective participants and obtaining the consent. This 
study requires that patients are seen towards the end of their Botox 
cycle. Once a potential study participant contacts the study 
coordinator, has received the relevant study information, and has 
agreed to participate, the coordinator and the participant agree on a 
date suggested by the participant. The patients know best when they 
become symptomatic and the effect of the Botox injection is wearing 
off.  
o The referring clinician determines that a potential participant 
understands the information.  
o Copy of the consent form for the remote testing has been uploaded to 
ETHOS. 
21.0 Setting 
21.1 Research Sites:  
Locations where participant will be recruited. Healthy participants will be 
invited to the study via flyers, and SD individuals will be invited through 

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Dr. George Goding at the Fairview Lion’s Voice Clinic, or Dr. Kari Urberg 
at the Park Nicollet Voice Clinic, St. Louis Park, MN. 
Locations where the research will be conducted: Multiple Sensory 
Perception Laboratory, Elliott Hall, University of Minnesota 
22.0 Multi-Site Research 
N/A 
23.0 Resources Available 
23.1 Resources Available:  
• 
We have been collaborating with Drs. Goding and Urberg for several 
years. We are recruiting patients with voice disorders since 2012 and 
have not had difficulties meeting our recruitment goals.  
• 
As of June 2018 this protocol has been in place for four years. We 
anticipate to finish work under this current protocol by the end of this 
year.  
• 
The in-person testing will take place in the Multisensory Perception 
Laboratory (MSP Lab) in Elliott Hall, University of Minnesota 
campus. This is a core research facility of the Center for Translational 
Sensory Science (CATSS). The MSP Lab consists of two rooms, each 
with a large sound-attenuating chamber for participant testing, and 
many specialized pieces of equipment (see below). The MSP Lab is a 
shared research space and is available to groups throughout the 
University of Minnesota community, as well as industry groups 
associated with CATSS. 
• 
The MSP Lab is not a clinical entity. No physicians or licensed 
psychologists are on staff. If participants require medical help because 
of an anticipated or unanticipated event during participation, 
investigators will have to notify emergency services through a 911 
call. 
• 
All study personnel has been trained to perform their respective 
function according to the protocol. They are aware of their duties for 
informing participants and for obtaining consent. They all have 
received the necessary human subject protection training as required 
by University policies. 
24.0 References 
 
1. 
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2. 
Ludlow, C.L., et al., Research priorities in spasmodic dysphonia. Otolaryngology 
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3. 
Soland, V.L., K.P. Bhatia, and C.D. Marsden, Sex prevalence of focal dystonias. J 
Neurol Neurosurg Psychiatry, 1996. 60(2): p. 204-5. 

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Cohen, L.G., et al., Blink reflex excitability recovery curves in patients with 
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Tolosa, E., L. Montserrat, and A. Bayes, Blink reflex studies in focal dystonias: 
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Topka, H. and M. Hallett, Perioral reflexes in orofacial dyskinesia and spasmodic 
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8. 
Ludlow, C.L., et al., Abnormalities in long latency responses to superior 
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Berardelli, A., et al., Pathophysiology of blepharospasm and oromandibular 
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Adamovich, S.V., et al., The interaction of visual and proprioceptive inputs in 
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Demirci, M., et al., A mismatch between kinesthetic and visual perception in 
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21. 
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Goodwin, G.M., D.I. McCloskey, and P.B. Matthews, The contribution of muscle 
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Roll, J.P. and J.P. Vedel, Kinaesthetic role of muscle afferents in man, studied by 
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Cordo, P., et al., Proprioceptive consequences of tendon vibration during 
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Cordo, P.J., et al., Effect of slow, small movement on the vibration-evoked 
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De Gail, P., J.W. Lance, and P.D. Neilson, Differential effects on tonic and phasic 
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35. 
Shinohara, M., Effects of prolonged vibration on motor unit activity and motor 
performance. Med Sci Sports Exerc, 2005. 37(12): p. 2120-5. 
36. 
Steyvers, M., et al., Frequency-dependent effects of muscle tendon vibration on 
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37. 
Forner-Cordero, A., et al., Changes in corticomotor excitability following 
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38. 
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pathophysiological implications. Brain, 2012. 135(Pt 6): p. 1668-81. 
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Grünewald, R.A., et al., Idiopathic focal dystonia: a disorder of muscle spindle 
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Fiorio, M., et al., Tactile temporal discrimination in patients with blepharospasm. 
J Neurol Neurosurg Psychiatry, 2008. 79(7): p. 796-8. 

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41. 
Molloy, F.M., et al., Abnormalities of spatial discrimination in focal and 
generalized dystonia. Brain, 2003. 126(Pt 10): p. 2175-82. 
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