Contribution of the Somatosensory System to Speech Perceptual Processing Aim 3
Phase: NA
Conditions: Speech, Consolidation
Sponsor: Yale University

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HRP-503B – BIOMEDICAL RESEARCH PROTOCOL  
(2017-1) 
 
 
 
 
Protocol Title: Sensory Basis of Speech Motor Learning (R01) 
 
 
Principal Investigator: David Ostry 
 
 
Version Date: April 15, 2019 
 
 
(If applicable) Clinicaltrials.gov Registration #: Click or tap here to enter text. 
 
 
 
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SECTION I: RESEARCH PLAN 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.  
 
The studies in Aim 1 will be conducted at McGill University, Montreal and will be reviewed by the Faculty of 
Medicine IRB at McGill. The studies in Aim 2 and Aim 3 will be conducted at Haskins Laboratories and the Yale 
University Magnetic Resonance Research Center. 
 
Aim 1 : To identify brain structures involved in the consolidation of speech motor learning.  
 
Continuous theta-burst transcranial magnetic stimulation (cTBS) will be used to selectively suppress frontal 
motor areas and, separately, somatosensory and auditory cortex following speech motor learning to test their 
causal role in motor memory consolidation. In preliminary studies, we find that cTBS to somatosensory cortex 
following learning interferes with retention whereas sham cTBS and cTBS to primary motor cortex do not. 
This suggests that it is somatosensory cortex rather than motor cortex that participates in the consolidation of 
motor memory. 
 
Aim 2: These studies test the hypothesis that working memory circuits involving prefrontal cortex contribute 
to speech motor learning.  
 
Although memory for articulator configurations is presumably needed for learning, to enable the repetition of 
correct movements and the avoidance of errors, its contribution to speech motor learning is largely unknown. 
The proposed studies focus on memory for speech movements and sounds and its relation to learning. Using 
cTBS, we will suppress activity in a regions of pre-frontal cortex associated with somatic and auditory working 
memory (Brodmann area 46v) to test their involvement in learning. Preliminary data suggest that suppression 
of area 46v interferes both with learning and working memory, consistent with its involvement in each. 
 
Aim 3: To test the hypothesis that somatosensory inputs similar to those normally associated with speech 
production alter the perception of speech sounds and reveal the presence of a somatic cortical network that 
participates in speech perception. 
 
The involvement of the somatosensory system in speech perception presumably arises during speech motor 
learning as auditory and somatosensory inputs are repeatedly paired. We have created a model of this 
process to test the idea that the pairing of somatosensory inputs with speech sounds results in experience 
dependent changes to the perceptual classification of speech. We have developed an MR compatible robot 
that delivers speech-like patterns of facial skin deformation as participants listen to speech sounds in the 
scanner. We will use this technique to test the idea that repeated pairing of auditory and somatosensory 
inputs, as occurs in speech motor learning, engages somatosensory areas in speech perception. 
 
 
2. Probable Duration of Project: State the expected duration of the project, including all follow-up and data 
analysis activities.   
 
July 1, 2019—June 30, 2023 
 
3. Background: Describe the background information that led to the plan for this project. Provide references to 
support the expectation of obtaining useful scientific data. 

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Brain structures in speech motor memory consolidation. The consolidation of motor memory makes possible 
the retention of newly learned movements. The behavioral characteristics of motor memory consolidation 
are well documented in work on upper limb movement, but the neural circuits which enable maintenance 
and consolidation of motor memories are less certain. There has been little work on the factors and 
associated brain structures that determine motor memory consolidation in speech. For a convincing 
demonstration of the involvement of a brain structure in memory consolidation it is necessary to rule out any 
possible interference by the experimental manipulation with the learning process itself. However, it is difficult 
to rule out this possibility when, as in previous studies, stimulation is delivered prior to or during training. An 
alternative approach which we pursue in Aim 1 to assess motor memory consolidation in speech, is to disrupt 
candidate structures following the completion of training (to block consolidation) and then, following a delay 
which would normally permit consolidation, assess whether there is an impairment in retention. A small 
number of arm movement studies have taken this approach. rTMS to M1 following motor learning is found to 
disrupt retention of a simple ballistic movement task but does not alter retention of a more complex motor 
task involving altered dynamics. Apart from simple repetitive movements, it is not presently known which 
areas of the brain are involved in the consolidation of motor memory neither in arm movement nor in 
speech. It is known that changes to sensory systems occur broadly in association with motor learning, speech 
motor learning included. Accordingly, changes to sensory systems could possibly play a role in speech motor 
memory consolidation. If this were the case, then the transient suppression or disruption activity in 
somatosensory and / or auditory cortex following learning, with the goal of blocking the storage of new 
sensory targets, should adversely affect the retention of speech motor memory.  
 
Role of sensory working memory in speech motor learning. The need to retain information about prior 
movements and states is central to motor skill acquisition. This need is particularly clear in speech motor 
learning which occurs without visual guidance and hence is likely reliant on both auditory and somatosensory 
working memory. However, apart from a small set of studies on working memory in visuomotor adaptation 
and sequence learning  and our own recent work on reinforcement learning, there has been little work on 
sensory working memory in the context of motor learning and none that we are aware of in relation to 
speech motor learning per se.  
 
We expect parts of prefrontal cortex to contribute both to sensory working memory and learning. Prefrontal 
cortex in general is interconnected anatomically with frontal motor areas and also with areas of the 
cerebellum and basal ganglia. However, apart from Broca’s area in the inferior frontal gyrus, little is known 
about its role either in movement control or in speech motor learning. Areas within prefrontal cortex have 
been implicated in somatosensory and auditory working memory, specifically, ventrolateral prefrontal cortex 
(area 46v). This area is part of a network that receives both auditory and somatosensory inputs and 
accordingly, we expect that suppression of activity in 46v should adversely affect both sensory working 
memory and speech motor learning. 
 
Contribution of the somatosensory system to speech perceptual processing. Somatosensory function in 
speech is normally associated with motor function. However, one intriguing aspect of somatosensory function 
is that it affects speech perception even in the absence of movement. There are several examples in which 
somatosensory stimulation affects the auditory perception of speech sounds. Notably, somatosensory inputs 
due to speech-like skin stretch and orofacial airpuffs both result in changes to the auditory classification of 
speech. While speech processing is clearly auditory in nature, these studies suggest that the somatosensory 
system contributes not only to speech motor control, but also to the perceptual processing of speech sounds. 
Indeed, it raises the possibility that a somatosensory cortical network may participate in the perception of 
speech. 

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The participation of the somatosensory system in speech perceptual processing likely arises over the course 
of speech motor learning during which auditory and somatosensory inputs are repeatedly paired. We have 
designed a new experimental model of this process to test the idea that the pairing of somatosensory inputs 
with speech sounds results in experience dependent plasticity in auditory and somatosensory cortex, which in 
turn changes the perceptual classification of speech. The idea is that paired sensory experience over the 
course of speech motor learning results in a paired sensory contribution to speech perception.  
 
4. Research Plan: Summarize the study design and research procedures using non-technical language that can 
be readily understood by someone outside the discipline. Be sure to distinguish between standard of care vs. 
research procedures when applicable, and include any flowcharts of visits specifying their individual times 
and lengths. Describe the setting in which the research will take place. 
 
Experimental Participants: Different groups of subjects will be tested in each study of each specific aim. 
Unless otherwise indicated, subjects will each participate in only one experimental condition. The number of 
participants per condition is 20 for tests involving behavioral manipulations and 25 for testing involving fMRI. 
Subjects are randomly assigned to treatment conditions.  
 
Aim 1: To test the idea that both somatosensory and auditory cortex contribute to the consolidation of 
speech motor memory. Note that work on this Aim is to be conducted entirely at McGill University in 
Montreal.  The Methods and Expectations which are given below are provided for completeness. 
 
Methods: Subjects will train using either altered somatosensory feedback or altered auditory feedback 
(different groups of subjects). Immediately following adaptation, cTBS will be applied to either auditory or 
somatosensory or motor cortex with the goal of blocking consolidation of motor memory. Stimulation sites 
we be identified from fMRI behavioral localizer scans run on a separate day. The logic of applying cTBS to 
both sensory areas is to test the hypothesis that both areas are involved in motor memory consolidation 
regardless of whether adaptation to altered auditory or altered somatosensory feedback is tested. Subjects 
leave the laboratory following cTBS and return 24 hours later to assess retention of learning. In retention 
tests related to somatosensory feedback, subjects will be connected to the robot and required to read words 
aloud one at a time that are displayed on a computer screen. To test for retention of altered auditory 
feedback, subjects also read words aloud one at a time but are not connected to the robot. After-effect trials 
under null conditions followed by re-learning trials will be tested in each case. 
 
As a control, we will test for the possibility that any observed effects of cTBS on retention are due to current 
leakage from sensory cortices into motor cortex. Subjects in a further control group will undergo the same 
procedures using sham TMS in which the stimulating coil over somatosensory or auditory cortex is turned 
sideways. These subjects will also return 24 hours later to test for retention of learning. In preliminary data 
cTBS to M1 did not interfere with the consolidation of motor memory. Assuming this is replicated in the 
proposed studies, it would rule out the possibility of a non-specific effect of cTBS. However, if necessary we 
will add another control group, in which cTBS is applied to visual cortex. 
 
Note that sham TMS is used to assess the possibility of placebo effects of TMS stimulation. Participants are 
not informed of this deception as knowledge of potential sham stimulation may introduce cognitive factors 
into subjects’ performance, for example, if participants believe they are possibly being tricked, this could bias 
how they perform the task and make the basic sensorimotor effects under study difficult to interpret. The 
specific information that is withheld in the sham TMS procedure is that fact that the stimulating coil is turned 
sideways so that while the subjects feels vibration on the scalp, the brain is not being magnetically stimulated. 

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Participants in the sham TMS condition will be debriefed after participation, in which an explanation of the 
sham TMS procedure will be given and the reason for deception will be explained. During the debriefing 
session, subjects will have the opportunity to ask questions and they will be given the opportunity to 
withdraw from the study or have their data removed.   
 
Expectations and Interpretations. We expect that cTBS to S1 (and also to A1) will block consolidation of 
learning as assessed in after-effect and re-learning trials 24 hours after initial training. We do not expect that 
cTBS to M1 will interfere with retention, nor will sham TMS. If obtained, these results would be consistent 
with the idea that auditory and somatosensory cortex contribute to the consolidation of speech motor 
memory. 
 
Aim 2.1: To test the hypothesis that individual differences in auditory and somatosensory working memory 
predict speech motor adaptation. 
 
Methods: We will assess the relationship between sensory working memory and speech motor adaptation 
using a between subjects design. Participants will be assigned to one of two groups. Each group will undergo 
both auditory and somatosensory working memory tests as well as a test for digit span memory. One group 
will adapt to altered auditory feedback and the other group will adapt to altered somatosensory feedback. 
Memory testing and adaptation tests will be balanced for order, with half of the subjects doing the memory 
tests first and the other half doing the adaptation first. 
 
Adaptation to Altered Somatosensory Feedback. These studies will involve the application of mechanical 
loads to the jaw using a Phantom robot (Figure 1). The robot is connected to an acrylic and metal dental 
appliance that is attached to the mandibular teeth with a dental 
adhesive. The connector together with the robot permit 
completely unrestricted jaw motion in 3D when forces are not 
being applied.  
 
A computer monitor positioned in front of the subject will 
display stimulus items in random order. Subjects are instructed 
to read aloud the words that are presented on the screen. The 
subjects’ task is to produce the words “head”, "ted", "said", 
"bed". These same stimuli are used in tests of adaptation to 
altered auditory feedback. Subjects will be tested both in the 
absence of load (null condition, 200 trials) and with forces 
applied in the protrusion direction (200 trials). The strength of 
the force-field will be incremented gradually over the course of 
training to minimize subject awareness of the perturbation and the involvement of cognitive strategies in 
adaptation.  
 
Adaptation to Altered Auditory Feedback. These studies involve the alteration of auditory feedback in real-
time during speech production. A computer monitor displays the stimulus items and subjects are instructed 
to read each word aloud when it is presented. We use the Audapter software to selectively alter the first 
formant frequency of vowels within the stimulus words. We increase the volume of the signal that is played 
back to subjects. The volume change, along with masking noise, help to minimize any airborne or bone-
conducted unaltered feedback the subject might receive other than through the earphones. Subjects will be 
tested both with unaltered feedback (null condition, 200 trials) and with gradually introduced frequency shifts 
Figure 1 Adaptation to altered somatosensory 
feedback. 

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(200 trials) to minimize cognitive strategies in correcting for the perturbation. As in other work, the shift 
magnitude will be between 20 and 25% of the F1 value.  
 
Sensory Working Memory. We will test both 
somatosensory and auditory working 
memory. In the somatosensory working 
memory test, small plastic tabs will be 
attached to the lower lip using two-sided 
tape and connected with thin wire to a 
robotic device (a variant of the setup shown 
in Figure 2). On each trial, the robot will 
apply small (<1 N) loads to the lips in each 
of six different outward directions (memory 
set, Figure 3, panel a) followed by a test 
trial which half of the time corresponds to a 
direction in the memory set and half of the 
time is a lure. The subject is required to 
make a yes/no response on a keyboard to indicate whether the test 
direction was in the memory set or not. Items in the memory set will 
spaced at approximately 30 degree intervals and individually jittered on a 
trial by trial basis to introduce variability in direction for the items in the 
memory set. Subject responses will be classified, as a function of lag 
between the item in the memory set and the test movement, as hits, 
misses, correct rejections and false alarms. A test of auditory working 
memory will be conducted in the same fashion, with movements produced 
by the robot replaced by the sounds that are composed of three pure 
tones (Figure 3, panel b). Subjects are not connected to the robot for this 
test. The pure tone combinations are presented through headphones and 
as can be seen in Figure 3b, the stimuli have the basic structure of vowels. 
As in the somatosensory tests, subjects are presented with a memory set of six items followed by a test item 
which is an item in the memory set 50% of the time. Subjects will be required to indicate on a keyboard 
whether the test sound was in the memory set or not. We will use total proportion of hits summed over all 
lags minus the proportion of false alarms as an aggregate dependent measure of sensory working memory for 
both auditory and somatosensory stimuli. As a control, we will conduct tests of verbal working memory using 
a standard digit span task (memory for a sequence of digits) to address the possibility that the auditory and 
somatosensory memory tests described above involve a cognitive strategy in which subjects use a non-
sensory working memory to perform the memory task. In these tests subjects will be presented individual 
digits visually as memory set items, followed by a test digit which is in the memory set 50% of the time.  
 
Expectations and Interpretations. As in work on human arm movement, we expect that individual differences 
in sensory working memory will predict differences in speech motor adaptation. We expect, based on 
previous evidence of sensory preference in speech motor adaptation, that the benefits of sensory working 
memory will be selective. Specifically, we expect that subjects that show greater auditory working memory 
performance will also display greater amounts of adaptation to altered auditory feedback. In contrast, we 
expect that differences in somatosensory working memory will not predict differences in altered auditory 
feedback adaptation. Similarly, we expect that differences in somatosensory working memory (and not 
auditory working memory) will predict adaptation to altered somatosensory feedback. We do not expect 
measures of digit span memory to correlate with auditory or somatosensory measures of memory or with 
Figure 3. Stimuli for somatosensory 
(panel a) and auditory (panel b) 
working memory tests. 
 
Figure 2 Facial skin stretch. 

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either adaptation measure. If obtained, the results would point to the involvement of sensory working 
memory in speech motor adaptation and would likewise provide a measure of the specificity of the working 
memory contribution to adaptation. 
 
Aim 2.2: To test the participation of ventrolateral prefrontal cortex in speech motor learning. 
 
Methods: Other than for Broca’s area, little is known about the role of prefrontal cortex in human motor 
learning. We have chosen to focus on it here because of its known involvement in working memory and its 
anatomical connectivity with frontal motor regions. We will focus specifically on ventrolateral prefrontal 
cortex (area 46v) as it has been implicated in somatosensory working memory and also auditory working 
memory and is hence a likely candidate for involvement in speech motor adaptation. Using different groups of 
subjects (one for adaptation to altered auditory feedback and one for adaptation to altered somatosensory 
feedback), we will use cTBS to disrupt neural activity in this area to test its involvement in adaptation. One set 
of tests will focus on the effects of cTBS on both auditory and somatosensory working memory (all subjects 
will do both tests of sensory working memory). A second set of tests will focus on the effects of cTBS on 
speech motor adaptation, testing the effects on adaptation to altered auditory feedback and altered 
somatosensory feedback in different groups of subjects. Although it would be preferable to conduct both 
working memory and adaptation tests with the same subjects during the same test session, the duration of 
theta-burst suppression (60 to 90 minutes) is unlikely to permit this. Accordingly, two sessions per subject 
balanced for order will be required, one to test for the effects of 46v suppression on working memory and a 
second to test for the effects of 46v suppression on adaptation. In the working memory tests, the 
experimental sequence will be: working memory test I, cTBS, working memory test II. In the motor learning 
test, the sequence is: baseline utterances, cTBS, adaptation testing, baseline utterances. For each of the 
behavioral manipulations, groups of control subjects will be tested using sham TMS with the coil turned 
sideways (sham cTBS + working memory and sham cTBS + adaptation).  
 
Continuous Theta-Burst Stimulation. cTBS will be delivered using the BrainSight neuronavigation system to 
register the position of the stimulating coil to participant’s brain. cTBS is delivered using a Magstim 70 mm 
coil that produces highly focal stimulation. We will use two variants of this sequence—3 pulses at 50 Hz 
delivered five times a second, or 3 pulses at 30 Hz delivered 6 times a second, in each case for a total of 600 
pulses. We will adopt Ridding’s procedure in which the cTBS sequence is applied twice with a 10-minute 
intervening delay. The stimulation intensity for cTBS will be 70% of the resting motor threshold for the lip 
muscle orbicularis oris (Figure 4). The stimulation procedure takes 11 and a half minutes in total, including the 
10-minute delay between the two 40 second cTBS sequences.  
 
We will determine the motor threshold for orbicularis oris using 
single-pulse TMS. Single pulse TMS will be delivered to the left side 
of the scalp using BrainSight for registration. A resting motor 
threshold is determined by finding the stimulation intensity that 5 
times out of 10 gives a peak to peak MEP of 50 µV. Figure 4 shows 
MEPs recorded from orbicularis oris superior and inferior. The 
latency of the evoked response is 6 ms. 
 
We will apply cTBS to ventrolateral prefrontal cortex (Brodmann 
area 46v) which will be identified using a high-resolution 
anatomical scan. Area 46v is in the middle frontal gyrus, above the 
ascending sulcus that separates pars opercularis and pars 
triangularis (areas 44 and 45). In preliminary tests, we are readily able to localize 46v directly from anatomical 
Figure 4 Orbicularis oris superior (blue) and 
inferior (red) MEPs. 

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scans. A T1 weighted structural image (MPRAGE, 1 mm slice thickness, 192 slices, 2300 ms TR, 2.98 ms TE, 9 
deg flip angle, iPAT GRAPPA x2 acceleration) will be obtained with a 3 Tesla Siemens Prisma scanner with a 
32-channel head coil. A member of the research team will accompany the participant to the MRRC and 
remain there for the duration of this phase of the experiment.  
 
Expectations and Interpretations: As in preliminary data, we expect cTBS to 46v to lead to decreases in 
working memory and, also to decreases in adaptation. This would support the idea that these somatic and 
auditory regions in prefrontal cortex, which support sensory working memory, are also involved in speech 
motor adaptation. The magnitude of the performance reduction will provide a measure of the relative 
involvement of 46v in both kinds of adaptation and working memory. Given the extensive connectivity of 46v 
to other somatic regions of the brain, we predict that the impairment in both somatosensory working 
memory and somatosensory adaptation will be greater. 
  
Aim 3.1: To test the hypothesis that the repeated pairing of somatosensory inputs with speech sounds, such 
as occurs during speech motor learning, results in changes to the perceptual classification of speech sounds.  
 
Methods: We will assess changes to the perceptual classification of speech sounds that are related to 
repeated pairing of somatosensory and auditory inputs (as would occur during speech motor learning). Paired 
auditory-somatosensory stimulation will be divided into 4 blocks of 100 stimulus pairs each. The auditory 
stimulus will be the word “head”. Somatosensory stimuli (facial skin stretch), matched on timing and duration 
will be presented as in Figure 2 with the auditory stimulus. Before and after the training, base-line and post-
training auditory perceptual performance will be examined in the absence of somatosensory stimulation, in 
order to evaluate the effects of the pairing on speech perception. Follow-up perceptual tests will be 
conducted 24 hours and 7 days later to assess the persistence of the perceptual change. In the baseline 
perceptual tests, auditory stimuli, on a continuum between “head” and “had”, will be presented one at a time 
in random order. Subjects will be assigned to one of three experimental groups, in which the somatosensory 
stimulation in the pairing task is in either the upward, downward or backward direction. A control group will 
follow the same testing sequence without somatosensory stimulation during the training session. 
 
Expectations and Interpretations: Based on pilot data, we expect that repeated pairing of auditory and 
somatosensory stimuli will alter the offline perceptual classification of speech sounds when somatosensory 
stimulation occurs in speech relevant directions (for these sounds) but not when the skin stretch direction is 
inconsistent with that experienced during normal speech production (backward). As in work on human arm 
movement, we expect the perceptual effects to be retained at later re-test. Retention of the perceptual 
change would suggest consolidation of perceptual learning following auditory-somatosensory pairing. Altered 
perceptual classification would be consistent with the idea that the repeated pairing of auditory and 
somatosensory inputs during speech motor learning results in persistent changes to the perceptual 
classification of speech sounds that are mediated by the somatosensory system. 
 
Aim 3.2: To test the idea that somatosensory cortical areas participate in speech perception.  
 
Methods: We will use task-based fMRI scans involving both auditory and somatosensory stimulation to test 
for somatosensory involvement in speech perception. A second experiment will use resting state fMRI to 
identify areas whose functional connectivity is strengthened off-line as a result of paired auditory-
somatosensory stimulation such as that which normally accompanies speech motor learning. A member of 
the research team will accompany the participant to the MRRC and remain there for the duration of the 
experiment.  
 

Page 9 of 24 
 
The task-based scan will use both speech and non-
speech stimuli. In the speech condition, the word, 
“head” will be used in combination with downward 
facial skin stretch. In a non-speech condition sets of 
pure tones, matched in loudness and duration to the 
speech condition, will be paired with somatosensory 
stimuli. In total, there will be two auditory-
somatosensory conditions [Multi: M-1(speech vs 
soma) and M-2 (non-speech vs soma)], two auditory 
alone conditions [Aud: A-1(speech) and A-2(non-
speech)], and one somatosensory alone condition (Soma). The five stimulus conditions along with a rest 
condition will be tested in a randomized block design (Figure 5). Subjects are instructed to attend to the 
stimuli. 
  
A second imaging study focusing on resting-state connectivity will be conducted using only the multisensory 
condition from Aim 3.1. The experimental sequence is [Resting State Scan 1] → [Task-based scan during 
paired auditory-somatosensory stimulation, three 10-minute scans] → [Resting State Scan 2]. Skin stretch will 
be restricted to the downward direction. In a control condition, there will be two resting state scans, but in 
place of the paired stimulation, the subject will rest quietly while being scanned but there will be no task. A 
task-based scan, in which participants repeat aloud words presented auditorily, will be run at the end of the 
session. This will be used to obtain seed-regions to assess changes in functional connectivity associated with 
paired somatosensory auditory stimulation.  
 
Somatosensory stimulation in the scanner will involve the use an MR-compatible ultrasonic motor 
manufactured by Shinsei Co USR60-E3N (see Figure 6). A product description can be found at 
http://www.shinsei-motor.com/English/product/nonmagnetic.html. The actuator is connected to 2 cm x 3 cm 
plastic tabs which are attached 
bilaterally to subject’s face using double-
sided tape. fMRI data will be acquired 
using a 3 Tesla Siemens Prisma scanner 
with a 32-channel head coil. Both 
resting-state data and task based 
localizers will be acquired using a T2*-
weighted multi-band EPI sequence with 
x6 acceleration (2 mm isotropic voxels, 
72 slices, 950 ms TR, 30 ms TE, 60 deg 
flip angle, iPAT off). The functional 
images will be superimposed on a T1 
weighted anatomical image (1 mm slice 
thickness, other parameters as given 
above). Gradient field-maps will be collected to correct for B0 field inhomogeneity.  
 
In a preliminary study, we verified the practical feasibility of using the ultrasonic motor in the MR scanner 
without degrading the quality of the MR image. Although the feasibility of using the ultrasonic motor, in 
terms of the MR signal-to-noise ratio (SNR), has been demonstrated previously (Izawa et al. 2005, Suzuki et al. 
2007), we verified the electromagnetic interference with our planned setup in a 3T MR scanner at the 
Montreal Neurological Institute. Functional MR images were recorded with the motor activated, but in the 
absence of a connection between the motor and the facial skin. The motor ON and OFF were alternated every 
Figure 5 Scanner skin stretch protocol. 
20
40
60
80
100
120
160
140
Volume recording number
...
...
Resting
Resting
20.0 s
Multi
Aud
Soma
Stimulus onset
TR = 1.0 s
Volume acquisition
...
...
A
S
M
A-1
S
M-2
S
M-1
Single block sequence
Figure 6. Ultrasound motor (left) and skin stretch system for MRI recording 
with ultrasound motor (right).  

Page 10 of 24 
 
10 volume recordings. In total, 100 volumes were recorded in each 
condition. The SNR was calculated as the ratio of the average intensity in 
the center region to the average of the standard deviation of the 
intensity at the four corners of the image as done in Suzuki (2007). The 
accompanying figure shows the obtained SNR in the motor ON and 
motor OFF conditions. Error bars show standard errors across 100 trials. 
We found the SNR was comparable to that reported previously by Suzuki 
et al. (2007). Importantly, there was no significant difference in the SNR 
between the ON and OFF conditions (p > 0.1). In visual inspection, there 
was no indication of noise on the MR image. We thus concluded that the 
proposed experimental configuration with the ultrasonic motor will 
permit functional MR imaging even when the motor is active during MR volume recording. 
 
Expectations and Interpretations: It is expected that auditory speech stimuli will produce activity in both 
auditory and somatosensory regions of the brain and somatosensory stimuli will also activate auditory and 
somatosensory cortical regions. We expect that this pattern of reciprocal activation will only be seen for 
speech. This would be consistent with the idea that somatosensory cortex participates in speech perception. 
In a second study for this aim, we expect a strengthening of functional connectivity between auditory and 
somatosensory cortex offline in the resting brain. This would be consistent with the idea that, independent of 
motor outflow, the auditory somatosensory pairing that normally accompanies speech motor learning 
engages both auditory and somatosensory circuits in speech perception.  
 
Additional Procedures: EEG and fMRI 
 
Electroencephalography: In studies involving EEG recording, participants will be asked to repeat aloud words 
presented auditorily or on a computer monitor, or to listen to pre-recorded speech material or sounds. The 
procedure involves one session lasting approximately 150 minutes. 
 
EEG data will be obtained using the non-invasive BioSemi recording system. Subjects will wear a 64-channel 
electrode cap. Water-soluble electrode gel will be placed in each electrode gap in the cap, in order to create a 
conductive path from the scalp to the electrode. If necessary, a wooden Q-tip will be inserted into the gel and 
twisted lightly against the scalp to ensure that the gel reaches through the hair all the way to the scalp. Data 
will be sampled at 1024 Hz and analyzed off-line with open-source software. After the experiment subjects 
will have the choice of either cleaning the gel out of their hair themselves, or having an experimenter assist in 
removing the gel from their hair. 3D representations of the scalp locations of the electrodes will be recorded 
in a separate procedure in which a plastic stylus that contains a small magnetic coil is placed at each of the 64 
electrode locations.  
 
Speech Motor Learning and fMRI: Subjects will be asked to complete one session lasting approximately 120 
minutes in which they will complete an fMRI while participating in behavior tasks.   
 
We will obtain fMRI measures to assess changes in functional connectivity that occur in conjunction with 
speech motor learning. The fMRI data will be acquired with multi-band neuroimaging sequences (x6 
acceleration) using the scanners at the Yale University MRRC. The resting-state data will be acquired using a 
T2* weighted EPI sequence using a 32-channel head-coil channel. The functional images will be superimposed 
on a T1 weighted anatomical image. Each session typically involves resting-state scans, task-based scanning, 
field-map acquisition and a T1-weighted high-resolution anatomical scan. 
 

Page 11 of 24 
 
Additional On-Line Procedures: Subjects will be recruited by Prolific, an on-line testing website, to participate 
in variants of currently approved studies of speech motor learning and perception. The motor learning studies 
involve adaptation to altered auditory feedback (described above in Aim 2.1). The speech perception task is a 
variant of the task in Aim 3.1. 
 
The experiment will involve both a listening task and a word-reading task. Participants will need a computer 
or mobile device that has a microphone and they will also need headphones to participate. In the listening 
task, speech sounds will be played through their headphones (at comfortable listening levels) and participants 
will be required to indicate which of a number of alternatives they heard by pressing a key. In the reading 
task, words will be presented on their device screen and they will have to read them aloud. They will be 
required to wear their headphones for both parts of the experiment. 
 
5. Genetic Testing    
N/A ☒ 
A. Describe 
 
6. Subject Population: Provide a detailed description of the types of human subjects who will be recruited into 
this study. 
 
We will test healthy right-handed adults (21-40 years) that will be recruited in equal number from both sexes. 
All participants will be native English speakers. We will screen for handedness using the Waterloo Handedness 
Questionnaire.  
 
7. Subject classification: Check off all classifications of subjects that will be specifically recruited for enrollment in 
the research project. Will subjects who may require additional safeguards or other considerations be enrolled 
in the study? If so, identify the population of subjects requiring special safeguards and provide a justification 
for their involvement. 
 
☐Children 
 
 
☒ Healthy  
 
 
☐Fetal material, placenta, or dead fetus 
☐Non-English Speaking  
☐ Prisoners 
 
 
☐Economically disadvantaged persons 
☐Decisionally Impaired  
☐ Employees 
 
 
☐Pregnant women and/or fetuses 
☐Yale Students  
 
☐ Females of childbearing potential 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as potential subjects? 
Yes ☐  No ☒  
 
8. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or exclusion? 
 
The subjects will be normal right-handed adults of both sexes between the ages of 21 and 40. The subjects will 
have no known physical or neurological abnormalities. Subjects will be naive as to the objectives of the 
experiments. The experimental procedures will be performed one subject at a time.  
 
Subjects will be excluded from these studies which involve MRI and TMS (including cTBS) if they report any of 
the following pre-existing conditions: cardiac pacemaker, surgical clips or values on the heart, implants, metal 
or metallic fragments in any part of the body, cochlear implants, claustrophobia. They are additionally 
excluded if they have a personal or family history of epilepsy, or are taking antipsychotic drugs, antidepressant 
drugs or antianxiety drugs. 
 

Page 12 of 24 
 
9. How will eligibility be determined, and by whom? Write here 
 
Potential participants will complete a questionnaire in which exclusion criteria are identified. The screening 
will be conducted by a trained team member. For on-line experiments, subjects will be recruited and 
screened by Prolific for age, handedness and psychoactive medication. Pre-screening for these categories is 
provided during Prolific recruitment. 
 
10. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, discomforts, or 
inconveniences associated with subjects participating in the research.  
 
The principal potential risk is injury caused by the robotic manipulator. However, injury is very unlikely, and 
we have implemented a range of safety precautions (see below) that are widely used for the prevention of 
injury in studies of human motor control involving robots. There are no known risks associated with any of the 
other behavioral tasks. 
 
Continuous theta-burst transcranial magnetic stimulation (cTBS) may cause mild adverse effects such as mild 
headache, non-specific discomfort, mild discomfort due to cutaneous sensation and neck muscle contraction. 
There have been three cases of seizure. One ten years ago in a healthy adult was reported in Oberman and 
Pascual-Leone (2009). More recently, two seizures occurred in conjunction with cTBS to insular cortex (2019) 
in which a double-cone coil designed for deep brain stimulation was used.  
 
There have been no reports of seizure with single pulse TMS. The main risk with single pulse TMS is syncope. 
There may be presently unknown risks of TMS to a fetus however none have been reported to date. In my 
laboratory at McGill University we have tested about three hundred subjects using this same cTBS protocol. 
We have had four cases of syncope with single pulse TMS and no serious adverse events with cTBS.  
 
One further rare risk is damage to hearing. A single incident of permanent threshold shift was reported in 
2005 in which a highly non-focal H-shaped coil was used for stimulation.  
 
The use of magnetic resonance imaging may cause discomfort due to the need to remain still during the 
experiment and the noise that is generated by the MRI when images are being acquired.  Subjects may also 
feel a certain sense of stress or anxiety or a sense of claustrophobia. On rare occasions, some people might 
feel dizzy, get an upset stomach, have a metallic taste or feel tingling sensations or muscle twitches.  
 
There is a risk of an allergic reaction to the electrode gel used on the EEG cap, and/or to the adhesive tape 
used to secure the EMG electrodes. Turning the Q-tip against the scalp to spread the electrode gel is a 
painless procedure but may result in slight tugging of the hair that gets wrapped around the Q-tip. 
 
The on-line study has no known risks. 
 
11. Minimizing Risks: Describe the manner in which the above-mentioned risks will be minimized. 
 
A number of safety precautions have been implemented. In addition to minimizing the applied force in 
studies involving robotic devices, we test for forces at the endpoint. If forces exceed 10 N all forces are 
immediately set to zero. Additional vendor supplied algorithms limit the workspace over which forces may be 
applied. Moreover, all experimental protocols are tested in full prior to introducing the subject into the setup. 
In studies over the past fifteen years using this set up we have not had a single incident of injury. In the event 
of an injury, the subjects will receive treatment as necessary. 
Commented [GG1]: Describe how Prolific screen participants? 
Do they have a pool of participants form where they choose form?  

Page 13 of 24 
 
 
The precautions for neuroimaging and brain stimulation studies are as follows: Before participating either in 
an MRI or TMS session participants must complete detailed screening forms so as to detect any 
contraindications, for example, a cardiac pacemaker, an aneurysm clip, a metal prostheses or cardiac valve 
replacement, the presence of metal in an eye or any part of the body, tattoos, body piercing, certain dental 
work, cochlear implants and claustrophobia.  Additional screening for cTBS includes personal or family history 
of epilepsy, psychopharmacological agents (antipsychotic drugs, antidepressant drugs, antianxiety drugs). 
Verification of the presence of contraindications will be strictly enforced. 
 
Another risk in MR imaging studies is the possibility of metal objects being pulled into the magnet and hitting 
the subject. To lower this risk, all people involved with the study must remove all metal from their clothing 
and all metal objects from their pockets. All people involved with the study will be asked to walk through a 
detector designed to detect metal objects. No metal will be brought into the magnet room at any time. Once 
the participant is in the magnet, the door to the room will be closed so that no one from outside accidentally 
goes near the magnet. 
 
There are no reported cases of single-pulse TMS triggering seizures. For cTBS, there have been only three 
reports of seizure, ten years ago in a healthy adult, reported in Oberman and Pascual-Leone (2009), and more 
recently, two in the same study in which cTBS was delivered to insular cortex with a double-coned coil 
specifically designed for deep brain stimulation (Lenoir et al., 2019). Seizure risk will be migitated in the 
present studies by strictly adhering to the exclusion criteria below. In the event of seizure, standard first 
responder procedures for dealing with aware, unaware and generalized seizures will be followed.  
 
In light of unknown risks to a fetus, the consent form indicates that if a participant thinks there is a possibility 
she might be pregnant, she will be excluded.  To guard against possible damage to hearing participants will be 
tested wearing earplugs. 
 
12. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan (DSMP) based on 
the investigator’s risk assessment stated below. (Note: the HIC will make the final determination of the risk to 
subjects.) 
 
a.  
What is the investigator’s assessment of the overall risk level for subjects participating in this 
study? Greater than minimal risk 
b. 
If children are involved, what is the investigator’s assessment of the overall risk level for the 
children participating in this study? n/a 
c. 
Include an appropriate Data and Safety Monitoring Plan. Examples of DSMPs are   
available here http://your.yale.edu/policies-procedures/forms/420-fr-01-data-and-safety-
monitoring-plans-templates for 
i. Minimal risk 
ii. Greater than minimal 
 
1. Personnel responsible for the safety review and its frequency: 
 
The principal investigator will be responsible for monitoring the data, assuring protocol compliance, and 
conducting the safety reviews at a minimum of every 6 months (including when reapproval of the protocol is 
sought).  During the review process, the principal investigator (monitor) will evaluate whether the study should 
continue unchanged, require modification/amendment, or close to enrollment. Either the principal investigator or 
the IRB have the authority to stop or suspend the study or require modifications. 
 

Page 14 of 24 
 
2. The risks associated with the current study are deemed greater than minimal for the following reasons:  
 
1. We do not view the risks associated with the TMS as minimal risks since syncope is a side-effect and in 
one case reported in 2009 a seizure was reported in a healthy adult. 
2. Given the now established safe use of this procedure in our prior work, we do not view the proposed 
studies as high risk. 
 
Although we have assessed the proposed study as one of greater than minimal risk, the potential exists for 
anticipated and/or unanticipated adverse events, serious or otherwise, to occur since it is not possible to predict 
with certainty the absolute risk in any given individual or in advance of first-hand experience with the proposed 
study methods. Therefore, we provide a plan for monitoring the data and safety of the proposed study as follows: 
 
3. Attribution of Adverse Events: 
 
Adverse events will be monitored for each subject participating in the study and attributed to the study 
procedures / design by the principal investigator David Ostry according to the following categories: 
 
a.) Definite: Adverse event is clearly related to investigational procedures(s)/agent(s). 
b.) Probable: Adverse event is likely related to investigational procedures(s)/agent(s). 
c.) Possible: Adverse event may be related to investigational procedures(s)/agent(s). 
d.) Unlikely: Adverse event is likely not to be related to the investigational procedures(s)/agent(s). 
e.) Unrelated: Adverse event is clearly not related to investigational procedures(s)/agent(s). 
 
4. Plan for Grading Adverse Events: 
 
The following scale will be used in grading the severity of adverse events noted during the study: 
 
1. Mild adverse event 
2. Moderate adverse event 
3. Severe  
 
5. Plan for Determining Seriousness of Adverse Events: 
 
Serious Adverse Events: 
In addition to grading the adverse event, the PI will determine whether the adverse event meets the criteria for a 
Serious Adverse Event (SAE).  An adverse event is considered serious if it results in any of the following outcomes: 
 
1. Death; 
2. A life-threatening experience in-patient hospitalization or prolongation of existing hospitalization;  
3. A persistent or significant disability or incapacity;  
4. A congenital anomaly or birth defect; OR 
5. Any other adverse event that, based upon appropriate medical judgment, may jeopardize the subject’s 
health and may require medical or surgical intervention to prevent one of the other outcomes listed in 
this definition.  
 
An adverse event may be graded as severe but still not meet the criteria for a Serious Adverse Event.  Similarly, an 
adverse event may be graded as moderate but still meet the criteria for an SAE.  It is important for the PI to 

Page 15 of 24 
 
consider the grade of the event as well as its “seriousness” when determining whether reporting to the IRB is 
necessary. 
 
6. Plan for reporting UPIRSOs (including Adverse Events) to the IRB 
  
The principal investigator will report the following types of events to the IRB: Any incident, experience or 
outcome that meets ALL 3 of the following criteria: Is unexpected (in terms of nature, specificity, severity, or 
frequency) given (a) the research procedures described in the protocol-related documents, such as the IRB-
approved protocol and informed consent document and (b) the characteristics of the subject population being 
studied; AND Is related or possibly related to participation in the research (possibly related means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the procedures 
involved in the research); AND Suggests that the research places subjects or others at greater risk of harm 
(including physical, psychological, economic, legal, or social harm) than was previously known or recognized. 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) may be medical or non-medical in nature, 
and include – but are not limited to – serious, unexpected, and related adverse events and unanticipated adverse 
device effects.  
 
These UPIRSOs/SAEs will be reported to the IRB in accordance with IRB Policy 710, using the appropriate forms 
found on the website. All related events involving risk but not meeting the prompt reporting requirements 
described in IRB Policy 710 should be reported to the IRB in summary form at the time of continuing review. If 
appropriate, such summary may be a simple brief statement that events have occurred at the expected frequency 
and level of severity as previously documented.  In lieu of a summary of external events, a current DSMB report 
can be submitted for research studies that are subject to oversight by a DSMB (or other monitoring entity that is 
monitoring the study on behalf of an industry sponsor). 
 
7. Plan for reporting adverse events 
 
For the current study, the following individuals, funding, and/or regulatory agencies will be notified: 
 
All Co-Investigators listed on the protocol, National Institutes of Health, Yale HIC 
 
The principal investigator David Ostry will conduct a review of all adverse events upon completion of every study 
subject. The principal investigator will evaluate the frequency and severity of the adverse events and determine if 
modifications to the protocol or consent form are required. 
 
d. For multi-site studies for which the Yale PI serves as the lead investigator: 
i. How will adverse events and unanticipated problems involving risks to subjects or others be 
reported, reviewed and managed? Write here 
ii. What provisions are in place for management of interim results? Write here 
iii. What will the multi-site process be for protocol modifications? Write here 
 
13. Statistical Considerations: Describe the statistical analyses that support the study design.  
 
Performance will be quantified for each subject on a trial-by-trial basis. Statistical analyses will be conducted using 
analyses of variance followed by Bonferroni-corrected post-hoc tests. The analysis of neuroimaging data is also 
described above. We have chosen sample size based on power analyses using our preliminary data. We estimated 
the required sample size necessary to detect the hypothesized effects using Bonferroni corrected tests with α = 
0.01 and β = 0.2 (power = 0.8). For our behavioral studies involving sensorimotor adaptation, including cTBS, we 

Page 16 of 24 
 
will need 20 subjects per group to obtain an estimated power of 0.8. Based on our preliminary fMRI results, 25 
subjects per condition would provide 80% power (α=0.01) to detect changes in connectivity following learning. 
 
The following tables give a breakdown on subjects in each experimental condition. 
 
 
Experimental Condition 
Number of Subjects 
Aim 1 
Adaptation to altered auditory feedback + cTBS to 
somatosensory cortex 
20 
Adaptation to altered auditory feedback + cTBS to 
auditory cortex 
20 
Adaptation to altered auditory feedback + cTBS to 
motor cortex 
20 
Adaptation to altered somatosensory feedback + 
cTBS to somatosensory cortex 
20 
Adaptation to altered somatosensory feedback + 
cTBS to auditory cortex 
20 
 
Adaptation to altered somatosensory feedback + 
cTBS to motor cortex 
20 
 
Adaptation to altered auditory feedback + sham 
TBS 
20 
 
Adaptation to altered somatosensory feedback + 
sham TBS  
20 
 
 
Experimental Condition 
Number of Subjects 
Aim 2.1 
Auditory and somatosensory working memory + 
adaptation to altered auditory feedback  
20 
Auditory and somatosensory working memory + 
adaptation to altered somatosensory feedback 
20 
 
 
 
Experimental Condition 
Number of Subjects 
Aim 2.2 
Auditory and somatosensory working memory + 
adaptation to altered auditory feedback + cTBS to 
46v 
20 
Auditory and somatosensory working memory + 
adaptation to altered somatosensory feedback + 
cTBS to 46v 
20 
Auditory and somatosensory working memory + 
adaptation to altered auditory feedback + sham 
TBS 
20 
Auditory and somatosensory working memory + 
adaptation to altered somatosensory feedback + 
sham TBS 
20 
 
 
 
Experimental Condition 
Number of Subjects 

Page 17 of 24 
 
Aim 3.1 
Auditory training paired with upward skin stretch 
20 
Auditory training paired with downward skin 
stretch 
20 
Auditory training paired with backward skin stretch 
20 
Auditory training paired without skin stretch 
20 
 
Aim 3.2 
Auditory + somatosensory + paired exposure + 
task-based fMRI  
25 
Resting state scans + paired auditory-
somatosensory stimulation task-based scans 
25 
Resting state scans + no task control condition 
25 
 
 
SECTION II: RESEARCH INVOLVING DRUGS, BIOLOGICS, RADIOTRACERS, PLACEBOS AND DEVICES 
 
 
If this section (or one of its parts, A or B) is not applicable, check off N/A and delete the rest of the section. 
 
A.  RADIOTRACERS 
☒N/A 
 
B.  DRUGS/BIOLOGICS    ☒N/A 
 
4. Use of Placebo:  
☒Not applicable to this research project 
 
B.  DEVICES 
 ☐N/A 
 
The study includes the following devices, but these devices are not the subject of the investigation and are widely 
used in laboratories around the world in research studies/studies involving magnetic brain stimulation. The 
research is not testing the safety and/or effectiveness of these devices. 
 
cTBS will be delivered using the BrainSight neuronavigation system. 
 
Somatosensory stimulation in the scanner will involve the use an MR-compatible ultrasonic motor manufactured 
by Shinsei Co USR60-E3N (see Figure 6). A product description can be found at http://www.shinsei-
motor.com/English/product/nonmagnetic.html. 
 
The safety of the brain stimulation devices in research with humans is described in detail in the following 
publication: 
 
Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group (2009) Safety, ethical 
considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and 
research. Clin Neurophysiol 120: 2008-2039. 
 
 
SECTION III: RECRUITMENT/CONSENT AND ASSENT PROCEDURES  
1. Targeted Enrollment: Give the number of subjects:  
a. Targeted for enrollment at Yale for this protocol: 275 (additional on-line enrollment: 150) 

Page 18 of 24 
 
b. If this is a multi-site study, give the total number of subjects targeted across all sites: 435 
 
2. Indicate recruitment methods below.  Attach copies of any recruitment materials that will be used. 
☒ Flyers 
☐ Internet/web postings 
☐ Radio 
☐ Posters 
☐ Mass email solicitation 
☐ Telephone 
☐ Letter 
☐ Departmental/Center website 
☐ Television 
☐ Medical record review*  
☒ Departmental/Center research boards 
☐ Newspaper 
☐ Departmental/Center newsletters 
☐ Web-based clinical trial registries 
☐ Clinicaltrails.gov  
☐ YCCI Recruitment database 
☐ Social Media (Twitter/Facebook):  
 
☒ Other: Prolific 
 
 
 
* Requests for medical records should be made through JDAT as described at 
http://medicine.yale.edu/ycci/oncore/availableservices/datarequests/datarequests.aspx 
 
3.  Recruitment Procedures:  
a. Describe how potential subjects will be identified. Response to flyers, Departmental and Internet postings, 
Prolific participants. Prolific recruits participants primarily via social media (Facebook, Twitter, Reddit, blog 
posts) and via poster/flyer campaigns at universities, and through referrals from researchers and participants 
already using the site. Participants create an account on Prolific and are then notified of future studies they 
are eligible for based on the demographic information they provide. 
b. Describe how potential subjects are contacted. Email or phone or Prolific contact participants eligible for our 
study 
c. Who is recruiting potential subjects? Trained team member or recruited through Prolific participation. 
 
 
4. Assessment of Current Health Provider Relationship for HIPAA Consideration: 
Does the Investigator or any member of the research team have a direct existing clinical relationship with any 
potential subject?  
☐Yes, all subjects 
☐Yes, some of the subjects 
☒No 
 
If yes, describe the nature of this relationship. Write here 
5. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization for either the 
entire study, or for recruitment purposes only.  Note: if you are collecting PHI as part of a phone or email 
screen, you must request a HIPAA waiver for recruitment purposes.) 
Choose one:  
☐ For entire study  
☒ For recruitment/screening purposes only  
☐ For inclusion of non-English speaking subject if short form is being used and there is no translated HIPAA 
research authorization form available on the University’s HIPAA website at hipaa.yale.edu. 
 
i. Describe why it would be impracticable to obtain the subject’s authorization for use/disclosure of this 
data: Write here 
 
ii. If requesting a waiver of signed authorization, describe why it would be impracticable to obtain the 
subject’s signed authorization for use/disclosure of this data: Because pre-screening information may 
be collected over the phone and signed consent by phone is not possible.   

Page 19 of 24 
 
 
The investigator assures that the protected health information for which a Waiver of Authorization has been 
requested will not be reused or disclosed to any person or entity other than those listed in this application, except 
as required by law, for authorized oversight of this research study, or as specifically approved for use in another 
study by an IRB. 
 
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale HIPAA-Covered 
entity must be accounted for in the “accounting for disclosures log”, by subject name, purpose, date, recipients, 
and a description of information provided.  Logs are to be forwarded to the Deputy HIPAA Privacy Officer. 
 
6. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will be obtained, 
including parental permission or surrogate permission and the steps taken to ensure subjects’ independent 
decision-making.  
 
A trained team member will verify eligibility and obtain consent at the laboratory prior to the start of the 
experiment. An oral description of the experiment will be offered with an opportunity for the subjects to ask 
questions as needed. Moreover, care will be taken to ensure that the subjects are fully informed about the 
risks and discomforts that may be involved. 
 
In online studies, Prolific notifies participants, who based on initial screening are eligible to participate in our 
study. The text of the consent is presented to the subject electronically prior to them commencing study 
procedures.  
 
7. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the personnel obtaining 
consent will assess the potential subject’s ability and capacity to consent to the research being proposed.  
 
Only healthy adults will be tested. If the trained member assigned to obtain consent has any doubt about a 
potential participant’s capacity to provide informed consent, testing will be postponed and the PI will make 
this determination by talking with the team member and if necessary the potential participant.   
 
In on-line studies, in the consent process, participants must indicate that they have read the consent form (or 
have had it read to them) and that the nature of their involvement in the study has been explained to their 
satisfaction.  
  
8. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for research involving 
non-English speaking subjects. If enrollment of these subjects is anticipated, translated copies of all consent 
materials must be submitted for approval prior to use.  
n/a 
As a limited alternative to the above requirement, will you use the short form* for consenting process if you 
unexpectedly encounter a non-English speaking individual interested in study participation and the translation of 
the long form is not possible prior to intended enrollment?  YES ☐  NO ☐ 
 
Note* If more than 2 study participants are enrolled using a short form translated into the same language, then 
the full consent form should be translated into that language for use the next time a subject speaking that 
language is to be enrolled. 
 

Page 20 of 24 
 
Several translated short form templates are available on the HRPP website (yale.edu/hrpp) and translated HIPAA 
Research Authorization Forms are available on the HIPAA website (hipaa.yale.edu). If the translation of the short 
form is not available on our website, then the translated short form needs to be submitted to the IRB office for 
approval via modification prior to enrolling the subject.   Please review the guidance and presentation on use of 
the short form available on the HRPP website. 
 
If using a short form without a translated HIPAA Research Authorization Form, please request a HIPAA waiver in 
the section above.  
 
9. 
Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or a full waiver 
of consent, depending on the study. If you will request either a waiver of consent, or a waiver of signed consent 
for this study, complete the appropriate section below.   
 
☐Not Requesting any consent waivers  
 
☒Requesting a waiver of signed consent: 
☒ Recruitment/Screening only (if for recruitment, the questions in the box below will apply to 
recruitment activities only) 
☒ Entire Study (Note that an information sheet may be required.) Applies to on-line studies only. 
Prolific does not allow subject identifiers (participants are only identified by their Prolific ID). 
Participants provide consent by clicking on “I consent” button after reading and agreeing to 
information in consent form. Participants will be told that they have the option of taking a screen-
shot or printing the consent if they wish. The waiver of consent does not apply to any of the 
procedures to be conducted at Haskins Laboratories or Yale MRRC. 
 
 
  
  ☐ Requesting a waiver of consent: 
 
 
SECTION IV: PROTECTION OF RESEARCH SUBJECTS 
 
    Confidentiality & Security of Data: 
1. What protected health information (medical information along with the HIPAA identifiers) about subjects will 
be collected and used for the research?  
 
The following protected health information will be collected only as part of recruitment and screening: Any of the 
following pre-existing conditions: cardiac pacemaker, surgical clips or values on the heart, implants, metal or 
metallic fragments in any part of the body, pregnancy, claustrophobia. Additional protected health information 
 For a waiver of signed consent, address the following: 
• Would the signed consent form be the only record linking the subject and the research?  YES ☐  NO ☐  
• Does a breach of confidentiality constitute the principal risk to subjects? YES ☐  NO ☐ 
  
 OR 
• Does the research pose greater than minimal risk? YES ☐    NO☒  
• Does the research include any activities that would require signed consent in a non-research context? YES ☐   
NO ☒ 

Page 21 of 24 
 
that will be used to screen potential subjects includes: a personal or family history of epilepsy, or are taking 
antipsychotic drugs, antidepressant drugs or antianxiety drugs. 
 
In on-line experiments, participants are fully anonymized by Prolific. We will screen for antipsychotic drugs, 
antidepressant drugs or antianxiety drugs.  
 
2. How will the research data be collected, recorded and stored? Write here 
 
Data will be collected and stored on laboratory computers. fMRI data (brain activation and structural images) will 
be collected to permit proper placement of the brain stimulation coil. 
 
In online experiments, Prolific provides participants a link to a Yale virtual machine that is hosted by Amazon WebS 
Services. The participants download an application to their device that runs the experiment. When finished, they 
click on a button to upload the data to Storage@Yale, after which the data are deleted from their device. 
 
3. How will the digital data be stored? ☐CD  ☒DVD  ☐Flash Drive  ☒Portable Hard  Drive   ☒Secured Server  ☒
Laptop Computer  ☒Desktop Computer  ☐Other 
 
4. What methods and procedures will be used to safeguard the confidentiality and security of the identifiable 
study data and the storage media indicated above during and after the subject’s participation in the study?  
 
Data will be de-identified at the earliest reasonable time after data collection, meaning we will replace identifying 
information with a code. A link to personal information will be kept for 6 years, after which time the link will be 
destroyed and the data will become anonymous. The data will be kept in this anonymous form indefinitely. No 
names will appear in any publication or be mentioned in any public place in connection with this project. 
 
Data from on-line studies are identified only by the Prolific ID of the participant. 
 
All portable devices must contain encryption software, per University Policy 5100.  If there is a technical reason a 
device cannot be encrypted please submit an exception request to the Information Security, Policy and Compliance 
Office by clicking on url http://its.yale.edu/egrc or email it.compliance@yale.edu 
 
5. What will be done with the data when the research is completed? Are there plans to destroy the identifiable 
data? If yes, describe how, by whom and when identifiers will be destroyed. If no, describe how the data and/or 
identifiers will be secured.  
 
De-identified data will be retained indefinitely. Identifying links to individuals will be maintained by the PI for 6 years 
following data collection, after which the link will be destroyed by the PI. 
 
6. If appropriate, has a Certificate of Confidentiality been obtained?  
 
This study has been granted a Certificate of Confidentiality by the NIH, although no sensitive information is 
collected.   
  
SECTION V: POTENTIAL BENEFITS 
 

Page 22 of 24 
 
 
Potential Benefits: Identify any benefits that may be reasonably expected to result from the research, either to 
the subject(s) or to society at large. (Payment of subjects is not considered a benefit in this context of the risk 
benefit assessment.)  
 
The individual subjects receive no direct benefits to health or well-being and are fully aware of this before 
participating. The principal benefits that may develop from the research are related to the development of an 
understanding of the sensory changes that accompany motor learning. 
 
         SECTION VI: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS 
 
1. Alternatives: What other alternatives are available to the study subjects outside of the research?  
 
Not applicable 
 
2. Payments for Participation (Economic Considerations): Describe any payments that will be made to subjects, 
the amount and schedule of payments, and the conditions for receiving this compensation. 
 
Participants will receive $15/hour monetary compensation for behavioral studies, $20/hour for studies 
involving EEG and $25/hour for participation in the experiments involving fMRI or magnetic brain stimulation. 
 
Participants in on-line studies receive $4 from Prolific for completion of a 30-minute experiment. 
 
3. Costs for Participation (Economic Considerations): Clearly describe the subject’s costs associated with 
participation in the research, and the interventions or procedures of the study that will be provided at no cost 
to subjects.  
 
The participants need to provide their own transportation to Haskins Laboratories. 
 
4. In Case of Injury: This section is required for any research involving more than minimal risk, and for minimal 
risk research that presents the potential for physical harm (e.g., research involving blood draws). 
 
a. Will medical treatment be available if research-related injury occurs? Yes 
b. Where and from whom may treatment be obtained? Emergency help will be provided including 
transport to the emergency room if needed. 
c. Are there any limits to the treatment being provided? The treatment is limited to the injury 
sustained as a result of the experimental procedure.  
d. Who will pay for this treatment? Haskins liability insurance will cover the cost of emergency 
medical treatment. 
e. How will the medical treatment be accessed by subjects? The laboratories will contact emergency 
medical personnel.  
 
 
 
 
 
 
 
Deleted: 20
Deleted: 50
Deleted:  

Page 23 of 24 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Page 24 of 24 
 
IMPORTANT REMINDERS 
 
Will this study have a billable service?  Yes ☐  
 No☒ 
 
A billable service is defined as any service rendered to a study subject that, if he/she was not on a study, would 
normally generate a bill from either Yale-New Haven Hospital or Yale Medical Group to the patient or the patient’s 
insurer. The service may or may not be performed by the research staff on your study, but may be provided by 
professionals within either Yale-New Haven Hospital or Yale Medical Group (examples include x-rays, MRIs, CT 
scans, specimens sent to central labs, or specimens sent to pathology). Notes: 1. There is no distinction made 
whether the service is paid for by the subject or their insurance (Standard of Care) or by the study’s funding 
mechanism (Research Sponsored). 2. This generally includes new services or orders placed in EPIC for research 
subjects.  
 
If answered, “yes”, this study will need to be set up in OnCore, Yale’s clinical research management system, for 
Epic to appropriately route research related charges. Please contact oncore.support@yale.edu 
 
Are there any procedures involved in this protocol that will be performed at YNHH or one of its affiliated entities?  
Yes ☐  No ☒  
 
If Yes, please answer questions a through c and note instructions below.   
a. Does your YNHH privilege delineation currently include the specific procedure that you will perform? Yes ☐  No 
☐ 
b. Will you be using any new equipment or equipment that you have not used in the past for this procedure? Yes 
☐  No ☐ 
c. Will a novel approach using existing equipment be applied? Yes ☐  No ☐ 
  
If you answered “no” to question 4a, or "yes" to question 4b or c, please contact the YNHH Department of 
Physician Services (688-2615) for prior approval before commencing with your research protocol. 
 
IMPORTANT REMINDER ABOUT RESEARCH AT YNHH  
Please note that if this protocol includes Yale-New Haven Hospital patients, including patients at the HRU, the 
Principal Investigator and any co-investigators who are physicians or mid-level practitioners (includes PAs, APRNs, 
psychologists and speech pathologists) who may have direct patient contact with patients on YNHH premises 
must have medical staff appointment and appropriate clinical privileges at YNHH. If you are uncertain whether 
the study personnel meet the criteria, please telephone the Physician Services Department at 203-688-2615. By 
submitting this protocol as a PI, you attest that you and any co-investigator who may have patient contact has a 
medical staff appointment and appropriate clinical privileges at YNHH.