Metaplasticity in the Human Motor Cortex: Validation of an Experimental Design and Comparison of Motor Outcome Measure Sensitivity to Change
Phase: NA
Conditions: Healthy
Sponsor: University of New Mexico

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
Page 1 of 33
Version Date: December 16, 2016
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
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
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prime awardee, include a copy of the grant application and sample 
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
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PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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Version Date: December 16, 2016
PROTOCOL TITLE:
Metaplasticity in the human motor cortex: validation of an experimental design 
and comparison of motor outcome measure sensitivity to change
PRINCIPAL INVESTIGATOR:
Sarah Pirio Richardson, MD
Neurology
Davin Quinn, MD
Psychiatry
VERSION NUMBER:
V2
DATE:
12/16/2016
REGULATORY FRAMEWORK:
Please indicate all that apply:
DOD (Department of Defense)
DOE (Department of Energy)
DOJ (Department of Justice)
ED (Department of Education)
EPA (Environmental Protection Agency)
FDA (Food and Drug Administration)
HHS (Department of Health and Human Services)
VA
Other:      
Is this a clinical trial under ICH-GCP E6?   
 Yes   
 No
If yes, please confirm that the research team is familiar with and agrees to comply 
with the investigator requirements cited in ICH-GCP E6.  
 Yes   
 No 
ICH-GCP E6 can be accessed by copying and pasting this URL into your 
browser: http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
Page 3 of 33
Version Date: December 16, 2016
Table of Contents
1.
Objectives.....................................................................................................................4
2.
Background ..................................................................................................................4
3.
Study Design ................................................................................................................5
4.
Inclusion and Exclusion Criteria ..................................................................................5
5.
Number of Subjects......................................................................................................6
6.
Study Timelines............................................................................................................6
7.
Study Endpoints ...........................................................................................................6
8.
Research Setting...........................................................................................................7
9.
Resources Available.....................................................................................................7
10.
Prior Approvals.........................................................................................................7
11.
Multi-Site Research ..................................................................................................8
12.
Study Procedures ......................................................................................................8
13.
Data Analysis............................................................................................................8
14.
Provisions to Monitor the Data to Ensure the Safety of Subjects.............................9
15.
Withdrawal of Subjects.............................................................................................9
16.
Data Management/Confidentiality............................................................................9
17.
Data and Specimen Banking...................................................................................11
18.
Risks to Subjects.....................................................................................................11
19.
Potential Benefits to Subjects .................................................................................11
20.
Recruitment Methods..............................................................................................12
21.
Provisions to Protect the Privacy Interests of Subjects ..........................................12
22.
Economic Burden to Subjects.................................................................................12
23.
Compensation .........................................................................................................13
24.
Compensation for Research-Related Injury............................................................13
25.
Consent Process......................................................................................................14
26.
Documentation of Consent .....................................................................................16
27.
Study Test Results/Incidental Findings ..................................................................17
28.
Sharing Study Progress or Results with Subjects...................................................18
29.
Inclusion of Vulnerable Populations ......................................................................18
30.
Community-Based Participatory Research.............................................................19
31.
Research Involving American Indian/Native Populations .....................................19
32.
Transnational Research...........................................................................................19
33.
Drugs or Devices ....................................................................................................19
Checklist Section ...............................................................................................................20

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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Version Date: December 16, 2016
1. Objectives
1.1. The overall objective is to validate the methodology of a metaplasticity 
experimental design by assessing change in motor excitability after 
administration of priming transcranial direct current stimulation (tDCS) 
followed by repetitive transcranial magnetic stimulation (rTMS) in healthy 
human participants. Our primary objective is to compare pre- and post-measures 
of cortical excitability before priming tDCS (anodal, cathodal or sham) [M1], 
directly after priming tDCS [M2], directly after inhibitory rTMS [M3], and 10 
minutes after inhibitory rTMS [M4]. Our secondary objective is to evaluate the 
sensitivity of motor excitability outcome measures response to the noninvasive 
neurostimulation (e.g. rTMS and tDCS). Our future direction is to apply this 
validated protocol in patient populations to better understand how disease states 
affect metaplasticity.
1.2. Aim 1: To compare pre- and post- measures of cortical excitability after 
inhibitory and excitatory priming of the motor cortex. Hypothesis 1: We expect 
priming tDCS to affect the response to rTMS, namely we expect “inhibitory” 
cathodal tDCS to cause a reversal of the normal inhibitory effect of 1Hz rTMS. 
Hypothesis 2: We expect “excitatory” anodal tDCS to have no effect on the 
normal inhibitory effect of 1Hz rTMS. Hypothesis 3: We expect sham tDCS to 
have no effect on the normal inhibitory effect of 1Hz rTMS.
Exploratory Aim 2: To evaluate the sensitivity of motor outcome measures to 
changes in cortical plasticity. Hypothesis 1: We expect different measures of 
motor cortex excitability to be more sensitive than others at detecting changes in 
cortical excitability. We will be comparing in an exploratory but systematic 
fashion various measures of motor cortex excitability (e.g. peak-to-peak 
amplitude change in motor evoked potential (MEP), the integrated area of the 
MEP (root mean square), the cortical silent period (CSP)), and behavioral 
measures (reaction time).
2. Background
2.1. rTMS and tDCS are relatively new modalities that have shown promise in the 
evaluation and treatment in a variety of neurologic and psychiatric disorders as 
well as understanding normal brain processes in the healthy human brain.  One 
specific area of interest has been the concept of metaplasticity in the motor 
cortex in healthy brains and how this is modified in the disease state. 
Metaplasticity refers to changes in synaptic efficacy such as long-term 
potentiation (LTP) and long-term depression (LTD), which can be influenced by 
prior neuronal activity. In humans, we can study these LTP-like and LTD-like 
changes using non-invasive neurostimulation (e.g. tDCS and rTMS). 
2.2. Previous studies (Siebner et al. 2004) have shown that preconditioning with 
anodal (“excitatory”) tDCS followed by inhibitory rTMS led to a period in which 
corticospinal 
excitability 
was 
reduced 
below 
baseline. 
Conversely, 
preconditioning with cathodal tDCS followed by 1Hz rTMS caused a resulting 

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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period of corticospinal excitability that was increased above baseline. This will 
be a proof of principle trial to validate the methodology of this protocol. 
2.3. rTMS is a relatively new therapeutic modality that shows great promise in the 
treatment and evaluation of a variety of conditions and is already FDA-approved 
for the treatment of depression. However, various target stimulation parameters 
and protocols make comparison across research groups difficult, leading to a 
knowledge gap. Validating a systematic methodological approach in healthy 
people will allow comparison to previous work as well as establishing a baseline 
for moving forward to compare metaplasticity in brain disease states.
3. Study Design
3.1. This will be a randomized, sham-controlled, double blinded crossover trial in a 
healthy population.
Figure 1: Subjects will enter the randomization at green diamond. Example shown for a subject 
following the red line through 3 interventions and another example shown in the blue line 
receiving a different order of interventions. They will be randomized to a three-visit crossover 
with a week separation between each visit. There will be four measures taken each visit (M1-M4), 
which will be approximately 10 minutes apart. Measures taken at each time point include: 
physiological measures (e.g. MEP), behavioral outcomes (e.g. reaction time) and exploratory 
outcomes. Study is completed at the end of visit 3 (red octagon). C tDCS=cathodal tDCS; A 
tDCS=anodal tDCS.
3.2. Participants will be blinded to treatment group. A team investigator, off-line, will 
conduct the raw data analysis (e.g. MEP amplitude and CSP) and will be 
different than the investigator applying the noninvasive neurostimulation to the 

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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treatment group. This additional blinding of the data analysis will help to 
provide another protection against bias.
4. Inclusion and Exclusion Criteria
4.1. Individuals will be screened for eligibility by a study team member. The study 
team member will ask the potential participant a series of questions to determine 
whether or not they meet the inclusion/exclusion criteria.
4.2. Inclusion Criteria:
a) Participant must be at least 18 years of age (all genders, races, and 
ethnicities)
b) Participant must have no current psychiatric or neurologic issues
c) Participant must not have any conditions listed in the exclusion 
criteria
d) Participant must be fluent in English
Exclusion Criteria:
a) History of major psychiatric illness
b) Actively using a neuropsychoactive medication
c) Legal or mental incompetency
d) Substance use disorder, abuse or dependence, with active use within 
the last 3 months
e) Significant medical or neurological illness
f)
Prior neurosurgical procedure
g) History of seizure
h) History of ECT or TMS treatment within the past three months
i)
Presence of a pacemaker, implanted medical pump or device, metal 
plate, or metal object in skull or eye (including shunts, dental 
implants, facial tattoos with metallic ink)
j)
Pregnant women
4.3. This study will not include any participants from any special populations (adults 
unable to consent, children, pregnant women, or prisoners).
4.4. This study will exclude pregnant women and children (due to safety and potential 
risk), prisoners and those who cannot competently provide their own consent 
(due to these groups being special populations) and will also exclude those who 
do not fluently speak or understand English (as our consent will be in English 
and study team members are fluent in English).

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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Version Date: December 16, 2016
5. Number of Subjects
5.1. This is not a multisite study and will only recruit subjects at this site.
5.2. We will aim to recruit 16 subjects for this study.
5.3. Sixteen subjects will be enrolled for this study according to the MANOVA model 
(anodal, cathodal, and sham) and a specified number of variables (time points—
M1-M4) at the significance level of α=0.05 and 80% power to correspond to the 
very large effect size. We have based the calculation on the very large effect size 
as seen in Quartarone et al., 2005. The desired sample size was found to be 16 
patients per treatment arm. We will fulfill this sample size requirement with a 
crossover design as all 16 subjects will participate in each treatment arm. We 
would request a recruitment ceiling of 20 subjects to account for subject dropout 
and if a subject were to meet exclusion criteria after signing the consent.
6. Study Timelines
6.1. Study subjects will participate in three visits total. Each visit will consist of a 
visit length of 1 to 1 ½ hours in duration. The visits will be approximately one 
week apart. There will be no scheduled follow-up after the third subject visit. We 
anticipate that it will take 8 months to enroll all subjects. We expect to complete 
enrollment of all subjects and completion of experiments in 1 year. We expect 
data analysis and publication to occur within 2 years of study commencement.
7. Study Endpoints
7.1. The primary endpoint will be change in motor evoked potential (MEP) amplitude 
over the first dorsal interosseous (FDI) muscle of the dominant (right) hand pre- 
and post-intervention (tDCS and rTMS—time points M1-M3) as well as 10 
minutes post intervention (time point M4). The secondary endpoint will be the 
comparison in an exploratory but systematic fashion various measures of motor 
cortex excitability (e.g. peak-to-peak amplitude change in motor evoked potential 
(MEP), the integrated area of the MEP (root mean square), the cortical silent 
period (CSP)), and behavioral measures (reaction time).
7.2. We will collect data on the safety of rTMS in this patient population including 
expected side effects: headache (expected 17% with transient headache that 
responds to simple analgesic) and nonspecific feelings of discomfort. We will 
collect data on rare but serious adverse events such as seizures (reported at 
1.4%). No seizures have been reported in the literature on rTMS in the dystonia 
population thus far (Lefaucheur et al., 2014).
8. Research Setting
8.1. The study visits will all take place in the Noninvasive Neurostimulation Lab 
located on the 2nd floor of the Clinical and Translational Science Center (CTSC).
8.2. Potential subjects will be recruited and identified through the healthy participant 
registry through the CTSC as well as fliers placed throughout the Health 
Sciences Center and Main Campus.

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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Version Date: December 16, 2016
8.3. Research procedures will be performed in the Noninvasive Neurostimulation Lab 
located on the 2nd floor of the CTSC. Analysis will be performed between the 
offices of Dr. Pirio Richardson, Dr. Quinn, and the CTSC Biostatistics core.
8.4. N/A
8.5. N/A
9. Resources Available
9.1. PI: Dr. Sarah Pirio Richardson will be responsible for supervising and 
coordinating all aspects of the research. She is well prepared and qualified for 
this role. Her training includes a fellowship at the National Institute of 
Neurological Disorders and Stroke in the Human Motor Control Section with Dr. 
Mark Hallett, which provided her with experience and expertise to undertake 
clinical research with noninvasive neurostimulation. She has completed the NIH 
Clinic 
Center 
Research 
Curriculum 
Certificate 
with 
Commendation. 
Additionally, she has published multiple studies using rTMS in healthy subjects 
and various movement disorders. She is well prepared to conduct research in the 
population. Dr. Pirio Richardson recently completed a KL2 scholar position 
through the CTSC providing formal mentorship and training in clinical and 
translational research.
Co-PI: Dr. Davin Quinn is an Associate Professor in Psychiatry. As a junior PI 
in the UNM Center for Brain Recovery and Repair, Dr. Quinn’s goal is to 
establish an independent NIH-funded research program in neurorehabilitative 
and neurostimulatory therapies for affective, behavioral, and cognitive sequelae 
of traumatic brain injury (TBI).  The current proposal will study the 
administration of high-definition transcranial direct current stimulation and 
transcranial magnetic stimulation to temporarily modulate the homeostatic 
plasticity of the brain in healthy subjects, bringing together several of his 
academic interests in one scientific endeavor. Dr. Quinn has made the treatment 
of TBI the focus of his clinical work for the past several years, achieving board-
certification in neuropsychiatry and behavioral neurology in 2012, and 
establishing a neuropsychiatry clinic in the UNM Clinical Neurosciences Center 
in 2013 to better serve the undertreated population of TBI patients in New 
Mexico. Dr. Quinn joined the UNM Electroconvulsive Therapy (ECT) Service in 
2012 after becoming certified in ECT. He has published several articles on the 
efficacy and safety of various neurostimulation modalities.
Co-I: Dr. Andrew Archer is a third-year Psychiatry resident interested in 
pursuing an academic career and is interested in noninvasive neurostimulation. 
He has participated in several research studies within the Psychiatry department. 
He has completed the required trainings to be able to conduct clinical research 
responsibly.
Research Coordinator: Ms. Ashley Wegele is a research coordinator in the 
Department of Neurology (supervised by Dr. Pirio Richardson). She has 
completed all required training for clinical research and regulation. She will 
manage all regulatory correspondence with the IRB and the funding agency such 

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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Version Date: December 16, 2016
as progress reports and adverse event reporting. She will obtain subject consent 
and HIPAA authorization. She will schedule and facilitate all subject 
interactions, as well as collect and manage research data.
9.2. Drs. Pirio Richardson and Quinn will be responsible for any medical decision-
making and ordering and evaluation of necessary diagnostics and therapeutics.
9.3. Other resources available

This study requires a small number of healthy participants. Given the registry 
maintained by the CTSC along with the number of healthy people who 
frequent the UNM campus and may see our flier, we believe it will be feasible 
to recruit our sample.

Our study team will devote ample time to the all phases of this research 
project. Time necessary may fluctuate depending on how many participants 
are interested at a particular time. Our team comprises of several individuals 
with the training and expertise necessary to devote the time needed until the 
project is completed.

Laboratory space and equipment: Dr. Pirio Richardson’s, Noninvasive 
Neurostimulation Laboratory at UNM (476 nsf), is housed at the University of 
New Mexico Clinical and Translational Science Center (CTSC) on the second 
floor of the building. On this floor, a main reception area and front desk 
check-in for study appointments. The lab contains all equipment necessary to 
conduct noninvasive transcranial magnetic stimulation (TMS) studies. Both a 
Magstim 2002 (plus the Bistim2 unit) (Magstim Co., Whitland, Dyfed, UK) and 
a Magstim Rapid2 (Magstim Co., Whitland, Dyfed, UK) are used in the 
laboratory. The coil inventory includes a Magstim double 70mm coil, 
Magstim custom double 35mm coils, and Magstim double 70mm cooled coil 
system and a Magstim double 70mm sham coil system (1st generation),  
(Magstim Co., Whitland, Dyfed, UK). For this project, a set of real vs. sham 
Magstim (2nd generation) air-cooled coils are requested to match the same set 
of coils in use at all other sites. The TMS units are connected to a commercial 
electromyography machine (Nicolet Viking) through a data acquisition device 
(Micro 1401, Cambridge Electronic Devices, Cambridge, UK). The data are 
collected and analyzed through Signal software (Cambridge Electronic 
Devices, Cambridge, UK). The lab is also equipped with custom hardware, 
including a flexible overhead coil holders and optional chin-rest and neck 
brace for stabilizing the subject's head during experiments and chair with arm 
and leg rests.

A NeuroConn MR transcranial electrical stimulator belonging to the Clinical 
Core will be used.  This is a CE-certified medical device for conducting non-
invasive transcranial direct current stimulation (tDCS), alternating (tACS) or 
random noise (tRNS) current stimulation on subjects. Transcranial 
stimulation using weak electric currents over a period of several minutes is 
demonstrated to modify neuronal excitability and circuit function and can 
serve to promote brain recovery and repair. 

PROTOCOL TITLE: Metaplasticity in the human motor cortex: validation of an 
experimental design and comparison of motor outcome measure sensitivity to change
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Version Date: December 16, 2016

Although risk for seizure is minimal, in the event this occurs the PI (Dr. Pirio 
Richardson) will be on hand to administer immediate first aid and the hospital 
code team would be activated. 

All members of our small study team are involved in the development of this 
protocol. Upon approval, we will meet regularly to ensure that our research 
protocol is being appropriately implemented. Furthermore, there will be at 
least two members of the research team available for participant visits, 
ensuring accountability and safety procedures are being met.

The signed CTSC resources attachment will be uploaded on the CTSC 
Submission page in Click.
10.Prior Approvals
10.1. N/A
10.2. Attached to submission
10.3. N/A
10.4. N/A
11.Multi-Site Research
11.1. N/A
11.2. N/A
11.3. N/A
12.Study Procedures 
12.1. Visit 1:After informed consent, subjects will be seated in a comfortable chair. 
Surface EMG leads will be applied to clean and prepped skin over the right 
hand over the first dorsal interosseous muscle (FDI). The motor hotspot for FDI 
will be identified with TMS on the contralateral hemisphere. Resting motor 
threshold and active motor threshold will be determined.

M1 
(pre-tDCS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

Priming Intervention 10 min tDCS (cathodal, anodal or sham)

M2 
(pre-tDCS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

Inhibitory Intervention 15 min rTMS over the dominant primary 
motor cortex at 1Hz

M3 
(post-rTMS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

M4 (10 minutes post-rTMS measurement): neurophysiological 
outcome assessment (MEP, CSP) and behavioral outcome (reaction 
time task)

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experimental design and comparison of motor outcome measure sensitivity to change
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Version Date: December 16, 2016
Visit 2:

M1 
(pre-tDCS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

Priming Intervention 10 min  tDCS (cathodal, anodal or sham)

M2 
(pre-tDCS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

Inhibitory Intervention 15 min rTMS over the dominant primary 
motor cortex at 1Hz

M3 
(post-rTMS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

M4 (10 minutes post-rTMS measurement): neurophysiological 
outcome assessment (MEP, CSP) and behavioral outcome (reaction 
time task)
Visit 3:

M1 
(pre-tDCS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

Priming Intervention 10 min priming tDCS (cathodal, anodal or 
sham)

M2 
(pre-tDCS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

Inhibitory Intervention 15 min rTMS over the dominant primary 
motor cortex at 1Hz

M3 
(post-rTMS 
measurement): 
neurophysiological 
outcome 
assessment (MEP, CSP) and behavioral outcome (reaction time task)

M4 (10 minutes post-rTMS measurement): neurophysiological 
outcome assessment (MEP, CSP) and behavioral outcome (reaction 
time task)
13.Data Analysis
13.1. Aim 1: To compare pre- and post- measures of cortical excitability after 
inhibitory and excitatory priming of the motor cortex. Hypothesis 1: We expect 
priming tDCS to affect the response to rTMS, namely we expect “inhibitory” 
cathodal tDCS to cause a reversal of the normal inhibitory effect of 1Hz rTMS. 
Hypothesis 2: We expect “excitatory” anodal tDCS to have no effect on the 
normal inhibitory effect of 1Hz rTMS. Hypothesis 3: We expect sham tDCS to 
have no effect on the normal inhibitory effect of 1Hz rTMS. We will use a 
MANOVA model (anodal, cathodal, and sham) and a specified number of 

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experimental design and comparison of motor outcome measure sensitivity to change
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variables (time points—M1-M4). MANOVA assumes normality of the residuals 
and equality of variance across groups. In the case of violation of these 
assumptions, we will explore data transformations, including logarithmic, 
power, and inverse-normal transformations, to identify an analytic scale under 
which modeling assumptions are met. Should transformations not be adequate, 
we will employ non-parametric methods instead.
Exploratory Aim 2: To evaluate the sensitivity of motor outcome measures to 
changes in cortical plasticity. Hypothesis 1: We expect different measures of 
motor cortex excitability to be more sensitive than others at detecting changes in 
cortical excitability. We will be comparing in an exploratory but systematic 
fashion various measures of motor cortex excitability (e.g. peak-to-peak 
amplitude change in motor evoked potential (MEP) and the integrated area of 
the MEP (root mean square)) with the cortical silent period (CSP) and 
behavioral measures (reaction time). We will perform both a linear regression as 
well as a Principal Components Analysis (PCA) to identify which cortical 
excitability factors are most sensitive to change due to noninvasive 
neurostimulation.
13.2. Power analysis: Sixteen subjects will be enrolled for this study according to the 
MANOVA model (anodal, cathodal, and sham) and a specified number of 
variables (time points—M1-M4) at the significance level of α=0.05 and 80% 
power to correspond to the very large effect size. We have based the calculation 
on the very large effect size as seen in Quartarone et al., 2005. The desired 
sample size was found to be 16 patients per treatment arm. We will fulfill this 
sample size requirement through a crossover trial as all 16 subjects will 
participate in each treatment arm. We would request a recruitment ceiling of 20 
subjects to account for subject dropout and if a subject were to meet exclusion 
criteria after signing the consent.
14.Provisions to Monitor the Data to Ensure the Safety of Subjects
14.1. The PIs will consist of the medical monitoring team for this study due to its 
minimal risk status.
14.2. We will collect data on the safety of rTMS including expected side effects: 
headache (expected 17% with transient headache that responds to simple 
analgesic) and nonspecific feelings of discomfort. We will collect data on rare 
but serious adverse events such as seizures (reported at 1.4%). 
14.3. The safety data will be reviewed on an ongoing basis during enrollment and 
conduct of the study.
14.4. We plan to follow the most recent safety recommendations from expert 
consensus panels on rTMS.
14.5. We have no planned formal analysis of the safety data.
14.6. N/A
14.7. We will follow all local and national regulations regarding the reporting of 
adverse events and serious adverse events.

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experimental design and comparison of motor outcome measure sensitivity to change
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15.Withdrawal of Subjects
15.1. The PI may remove a subject from the study at any time if he/she believes that 
continuing in not in his/her best medical interests, or if he/she is unable to 
comply with the requirements of the study.
15.2. N/A
15.3. N/A
15.4. If a subject withdraws from the study, they will be asked if they would like to 
allow us to keep data that has already been collected. If they do not wish for 
this to happen, we will get rid of any CRFs by secured document-shredding 
methods and remove all data on that participant from our secured database.
15.5. The participant will need to speak with either the PI or research coordinator to 
verify they do not want to continue participating. There will be nothing in the 
consent to limit a participant from voluntary withdrawal.
16.Data Management/Confidentiality
16.1. Information and clinical data collected as part of this study will be labeled with 
the subject’s initials and study number, which will be in a locked file cabinet in 
the PI’s office that can be locked as well.
16.2. This research does not require direct identifiers such as name or address to be 
used.
16.3. This research does not require the access, use, or disclosure of Protected 
Health Information.
16.4. This research will ask about substance abuse as it is an exclusion criterion for 
this project, but we will not maintain any data or information with details about 
potential abuse.
16.5. We will not use a Certificate of Confidentiality to protect data. 
16.6. Data (without identifiers) will be entered into a computer database and/or 
locked file cabinet in the PI’s office. All computers with data will be password 
protected and databases will have no linking identifiers to the participant. All 
study team members have completed HIPAA training.
16.7. PI will be on-site at each study visit to ensure quality control standards are 
being met.
16.8. N/A
16.9. N/A
16.10. N/A 
16.11. N/A
17.Data and Specimen Banking
17.1. N/A

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experimental design and comparison of motor outcome measure sensitivity to change
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17.2. N/A
18.Risks to Subjects
18.1. TMS: TMS is a safe procedure that has been used on many people to study the 
brain. Most people do not find the stimulation painful, but occasionally strong 
contractions of scalp muscles can cause some discomfort of headache.  
Headaches usually go away promptly with nonprescription medication. The 
noise of the TMS magnet may affect hearing, so participant will be fitted with 
earplugs. Magnetic stimulation will not be performed in people who have 
pacemakers, implanted pumps or stimulators, or who have metal objects inside 
the eye or skull. The risk of inducing a seizure with single, or paired-pulse, TMS 
is considered very low. Seizures from single/paired-pulse TMS have only been 
reported in subjects with medically-intractable epilepsy very rarely (0.0-3%). 
Safety studies using TMS in patients with neurological disorders have 
demonstrated no permanence.
tDCS: At the beginning of tDCS most people feel a tingling sensation that is 
present for a short period of time. Also, most people feel a warming sensation 
on the scalp that disappears after awhile. tDCS is known to be a safe procedure 
for several hundred patients at UNM, but in a few cases (1%) subjects have 
reported minor skin burns at the electrode spot. For example, a few subjects 
who had recently shaved their heads have reported transient redness and 
irritation at the stimulating electrode site. Prior to stimulation, your scalp will 
be checked for any redness or recent shaving of the head. If any of these are 
seen, we will pause or stop your participation in the study. You will be 
encouraged at the beginning of and throughout the tDCS procedure to report 
any pain or problems at the electrode sites that you may encounter throughout 
the procedure. Any problems, orevidence of redness or pain of the scalp, will 
result in the immediate stopping of stimulation. As with any contact between 
persons and electrical apparatuses, there is a slight possibility of electrical 
shock. To our knowledge, no studies have reported any electrical shock 
resulting from tDCS, and we do not expect this event to occur in our 
experiment. tDCS uses rubber electrode holders. If you think you may be 
sensitive or allergic to rubber or latex, please tell us before the start of the 
experiment. A few people in other studies have experienced drowsiness, 
excitement, or dizziness after tDCS.
Risks of Research: A potential loss of confidentiality, which could result in 
stress, emotional distress, inconvenience, and possibly loss of privacy.
18.2. N/A
18.3. As risk to fetus by TMS is not known, we will not include pregnant women in 
this study. We will administer a pregnancy test to any women of childbearing 
potential at each visit and with confirmation that the test is negative before 
study procedures ensue.
18.4. N/A

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18.5. As noted, women of childbearing potential will be tested for pregnancy prior to 
treatment. Participants with a pre-existing seizure disorder, or who meet 
criteria that may increase likelihood of seizure will be excluded from the study. 
Our study team will take all necessary measures to minimize the risk of loss of 
confidentiality by following all procedures noted in this protocol. 
19.Potential Benefits to Subjects
19.1. There is potential societal benefit in understanding the brain mechanisms 
underlying metaplasticity and has implications in both health and disease.
19.2. There is no direct benefit to subjects for participating in this study.
20.Recruitment Methods
20.1. Participants will be recruited beginning upon IRB approval for this project. We 
will utilize both fliers posted around the North and Main campus of UNM as 
well as the healthy participant registry at the CTSC. 
20.2. We will not reviewing any participant medical charts.
20.3. We will utilize a flier that describes the purpose and scope of this study, it will 
list an email and phone contact for interested subjects to get in touch with us.
21.Provisions to Protect the Privacy Interests of Subjects
21.1. Subjects will be completing the study visit, including consent and giving any 
necessary information in our secured noninvasive neurostimulation lab. The 
nature of the information they may need to provide includes basic 
demographics and health history. We will inform the subject that only members 
of the study team may access any of their information and data.
21.2. Any recruitment phone calls will be taken on a landline in the research 
coordinator’s lab space. The consent and data collection process will be done 
in a lab that has a closed door and will not be access by anyone outside of the 
study team. Once data is collected we will follow all procedures described in 
the protocol, which will be explained to the participant as well, and will include 
password-protected databases and locked file cabinets in private offices. 
22.Economic Burden to Subjects
22.1. N/A
Responsible Party
Research Procedures
Number of 
Samples/Procedures
Study
3rd Party Payer 
or Participant
rTMS
3
tDCS
3
Pregnancy test
1
     
     
     
     
     
     
     
     
     
     
Standard of Care Procedures
Number of 
Responsible Party

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Samples/Procedures
Study
3rd Party Payer 
or Participant
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
22.2. N/A
22.3. N/A
22.4. We will explain to the participant, and also note in the consent form, that if an 
adverse event occurs the participant will be able to receive treatment here at 
UNMH but that it will be at the expense of the participant and that we are not 
liable for any costs incurred.
22.5. N/A
23.Compensation
23.1. In return for a subject’s time and inconvenience due to participating in clinical 
research, he/she will be compensated a total of $70 for the whole study in the 
form of a merchandise cards. 
They will receive $20 for each of the first 2 study visits (subtotal $40). They will 
receive $30 for the last study visit (subtotal $30 plus first 2 visit subtotal = 
$70).
This amount is appropriate for the time and inconvenience of the proposed 
research and would not be construed as coercive nor would the small increase 
for the last visit unduly induce subjects to remain in the study when they 
otherwise would have withdrawn.
24.Compensation for Research-Related Injury
24.1. N/A
24.2. We will explain to the participant, and also note in the consent form, that if an 
adverse event occurs the participant will be able to receive treatment here at 
UNMH but that it will be at the expense of the participant and that we are not 
liable for any costs incurred.
25.Consent Process
25.1. We will be obtaining informed consent from each subject prior to study 
participation. The consent form will discuss the purpose and scope of the study, 
the procedures that will be performed, and the risks/benefits associated with the 
study. We will give the subject a copy of the signed consent form. We will allow 

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plenty of time for the subject to make a decision and ask any questions they may 
have before consent, as well as throughout the study.
25.1.1. The PIs, Co-I and research coordinator will be responsible for obtaining 
consent and they have completed the requisite training.
25.1.2. The consent process will take place in our noninvasive neurostimulation 
lab in the CTSC, which is a private and secure location.
25.1.3. This study does not offer any significant benefit to the subject, and they 
will not be compensated at an amount that may be perceived as coercive. 
We will be sure to inform the subject that the study is entirely voluntary, 
and will not way inhibit any current or future care they receive from us 
here at UNM. 
25.1.4. If the subject is interested, we will e-mail them a copy of the consent prior 
to their participation so that they have time to fully review. Regardless, we 
will take our time walking them through the consent and allow as much 
time as is needed for questions. We will also let them know that they are 
welcome to take the consent home to discuss with friends or family.
25.1.5. We will encourage the subject to ask questions throughout the study, and 
will check in to ensure they are comfortable and feel safe. If subject seems 
uncertain or hesitant, we will remind them that they are welcome to stop 
participation at any time with no consequences.
25.1.6. We will allow for a question and answer period to enhance understanding.
25.1.7. We will not ask the participant to teach back specifically, unless they have 
questions that lead us to believe they do not fully understand, or seem 
hesitant or uncertain.
Subjects not fluent in English
25.1.8. N/A
25.1.9. N/A
25.1.10. N/A
Cognitively Impaired Adults/Adults Unable to Consent/Use of a Legally 
Authorized Representative
25.1.11. N/A
25.1.12. N/A
25.1.13. N/A
25.1.14. N/A
25.1.15. N/A
25.1.16. N/A
25.1.17. N/A

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25.1.18. N/A
25.1.19. N/A
25.1.20. N/A
Subjects who are not yet adults (infants, children, teenagers)
25.1.21. N/A
25.1.22. N/A 
25.1.23. N/A
25.1.24. N/A
25.1.25. N/A
25.1.26. N/A
25.1.27. N/A
Waiver or Alteration of Consent Process (consent will not be obtained, required 
element of consent will not be included, or one or more required elements of 
consent will be altered) 

N/A
26.Documentation of Consent
26.1. We do plan to use a consent form to document informed consent. It is attached 
to the new study application.
26.2. N/A
26.3. N/A 
27.Study Test Results/Incidental Findings
27.1. Individual Results: We do not intend to share study test or procedure results 
with study participants with the exception of the results of the pregnancy test. 
This result will be communicated in person as well as through mail notification.
27.2. Incidental Findings: We do not anticipate that the research may result in 
incidental findings.
28.Sharing Study Progress or Results with Subjects
28.1. We do not intend to provide subjects with a summary of the trial progress while 
the study remains underway.
28.2. We do not intend to provide subjects with a summary of the study results after 
the study is complete. We do intend to disseminate the results through peer-
reviewed publication and presentation at national meetings.
29.Inclusion of Vulnerable Populations
29.1. N/A

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30.Community-Based Participatory Research
30.1 N/A
31.Research Involving American Indian/Native Populations
31.1 N/A
32.Transnational Research
32.1. N/A 
32.2. N/A
32.3. N/A
32.4. N/A
32.5. N/A
32.6.  N/A 
33.Drugs or Devices
33.1. This study utilizes a Magstim Rapid2 rTMS device (The Magstim Company 
Limited, Spring Gardens, Whitland, Carmarthenshire, SA34 0HR, UK). This 
device is FDA approved for the treatment of treatment-resistant depression and 
has been approved for treatment of Migraine. The UNM HRRC has previously 
determined that TMS devices are not significant risk and has also been 
determined by the sponsor-investigator (Sarah Pirio Richardson, MD) to be a 
Non-Significant Risk device. The device is already housed at UNM in the 
Noninvasive Neurostimulation Lab, and access will be limited to the PI who is 
fellowship trained in operating these devices and to study personnel who she 
trains to use these devices safely. 
The TDCS device utilized in this study is determined to be a Non-Significant 
Risk device by the sponsor-investigator (Davin Quinn, MD) for the following 
reasons:
1)    It is not intended as an implant
2)    It does not present a potential for serious risk to the health, safety, or 
welfare of the subjects
3)    It is not proposed to be for a use in supporting or sustaining human life
4)    It is not for a use of substantial importance in diagnosing, curing, 
mitigating, or treating disease, or preventing impairment of human health
According to the FDA, serious adverse events are those in which the outcome is 
death, 
life-threatening, 
hospitalization, 
disability/permanent 
damage, 
congenital anomaly, requiring intervention to prevent permanent impairment, 
or other serious events such as refractory seizures, cardiorespiratory arrest, or 
anaphylactic reaction.  No serious adverse events attributable to TDCS have 
been reported in the more than 10,000 subjects investigated in the 
contemporary TDCS literature since 1998.  This literature includes studies in 
patients with severe brain injury, stroke, epilepsy, and neurodegenerative 

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disorders, none of whom have been reported to experience serious adverse 
events.  Specifically, there have been no reports or evidence presented of 
damage to the brain, seizures, or cardiorespiratory arrest.  Animal studies of 
charge densities necessary to induce brain damage in rats were found to be 100 
times higher than the charge density used in TDCS trials with standard 
parameters (< 2.5 mA, no more than 2 sessions daily, < 60 min per session, use 
of electrodes that minimize skin burns) as determined by world-wide expert 
consensus.  The commonly reported side effects of TDCS are itching, burning, 
tingling, headache, and discomfort (10-40%), all of which are mild and 
transient.  As this trial will be operating within standard parameters as defined 
above, we believe our use of TDCS in subjects represent a Non-Significant Risk.
33.2. N/A
33.3. N/A
33.4. The “Device Checklist” in the Checklist Section of this template has been 
completed.

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Checklist Section
This section contains checklists to provide information on a variety of topics that require special 
determinations by the IRB.  Please complete all checklists relevant to your research.
I.
Waivers or Alterations of Consent, Assent, and HIPAA Authorization
A. Partial Waiver of Consent for Screening/Recruitment
Complete this checklist if you are requesting a partial waiver of consent so that you 
can review private information to identify potential subjects and/or determine 
eligibility prior to approaching potential subjects for consent or parental permission.
1. Describe the data source that you need to review (e.g., medical records):
     
2. Describe the purpose for the review (e.g., screening):
     
3. Describe who will conducting the reviews (e.g., investigators, research staff):
     
4. Do all persons who will be conducting the reviews already have permitted 
access to the data source?
 Yes
 No. Explain:      
5. Verify that each of the following are true or provide an alternate justification 
for the underlined regulatory criteria:
a) The activity involves no more than minimal risk to the subjects 
because the records review itself is non-invasive and the results of the 
records review will not be used for any purposes other than those 
described above.
 True
 Other justification:      
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects because eligible subjects will be approached for 
consent to participate in the research and are free to decline.  Further, 
the information accessed during the records review will not be 
disclosed to anyone without a legitimate purpose (e.g., verification of 
eligibility).
 True

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 Other justification:      
c) The research could not practicably be carried out without the waiver or 
alteration because there is no other reasonably efficient and effective 
way to identify who to approach for possible participation in the 
research.  
 True
 Other justification:      
d) Whenever appropriate, potentially eligible subjects will be presented 
with information about the research and asked to consider 
participation.  (Regulatory criteria: Whenever appropriate, the 
subjects will be provided with additional pertinent information after 
participation.)
 True
 Other justification:      
Partial Waiver of HIPAA Authorization for Screening/Recruitment
Complete the following additional questions/attestations if the records you will 
review to identify potential subjects and/or determine eligibility include Protected 
Health Information (PHI).
6. Will you be recording any PHI when conducting the records review to identify 
potential subjects and/or determine eligibility?
 Yes. Describe:      
 No
7. If you answered “Yes” to question 6 above, please describe when you will 
destroy identifiers (must be the earliest opportunity consistent with the 
conduct of the research) or provide justification for why they must be 
retained:
     
8. The PHI accessed or recorded for identification/screening purposes will not be 
reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under 
the Privacy Rule.
 True
 False

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B. Waiver of Documentation of Consent
Complete this checklist if you intend to obtain consent verbally but will not be 
obtaining signatures from subjects on a consent form to document consent.  Waivers 
of documentation of consent are commonly requested when using scripts, information 
sheets, or email or survey introductions to present the elements of consent instead of 
using a traditional consent form.
1. Are you requesting a waiver of documentation of consent for some or all 
subjects?
 All
 Some. Explain:      
2. Provide justification for one of the following:
a) That the only record linking the subject and the research would be the 
consent document and the principal risk would be potential harm 
resulting from a breach of confidentiality. Each subject will be asked 
whether the subject wants documentation linking the subject with the 
research, and the subject's wishes will govern.
     
b) That the research presents no more than minimal risk of harm to 
subjects and involves no procedures for which written consent is 
normally required outside of the research context.
     
3. Do you intend to provide subjects with a written statement regarding the 
research in lieu of a traditional consent form?
 Yes. Please attach a copy to your submission in Click.
 No
C. Alteration of Consent
Complete this checklist if you intend to obtain consent but will be eliminating or 
altering one or more of the required elements of consent. Alterations of consent are 
commonly requested for research involving deception or for minimal risk research 
when an abbreviated consent is desired and one or more of the required element are 
not relevant to the research.
Note: FDA-regulated research is not eligible for an alteration of consent.
1. Which element(s) of consent do you wish to eliminate and why?
     

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2. Which element(s) of consent do you wish to alter and why?
     
3. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     
c) The research could not practicably be carried out without the waiver or 
alteration:
     
d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
D. Full Waiver of Consent/Parental Permission
Complete this checklist if you are requesting a full waiver of consent for all subjects 
or certain subject groups (e.g., retrospective cohort).  Full waivers of consent are 
commonly requested when the research does not include any opportunity for 
interaction with subjects (e.g., chart review).
Note: FDA-regulated research is not eligible for a full waiver of consent using these 
criteria.  If you believe that your FDA-regulated research may be eligible for a waiver 
under another mechanism, such as planned emergency research, contact the HRPO 
for assistance in determining what information to provide to the HRRC.
1. Are you requesting a waiver for some or all subjects?
 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     

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c) The research could not practicably be carried out without the waiver or 
alteration:
     
d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
E. Full Waiver of Consent/Parental Permission (Public Benefit or Service 
Programs)
Complete this checklist if you are requesting a full waiver of consent for all subjects 
or certain subject groups (e.g., retrospective cohort) and the research involves the 
evaluation of a public benefit or service program.  
1. Are you requesting a waiver for some or all subjects?
 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research or demonstration project is to be conducted by or subject 
to the approval of state or local government officials and is designed to 
study, evaluate, or otherwise examine: (i) public benefit or service 
programs; (ii) procedures for obtaining benefits or services under those 
programs; (iii) possible changes in or alternatives to those programs or 
procedures; or (iv) possible changes in methods or levels of payment 
for benefits or services under those programs:
     
b) The research could not practicably be carried out without the waiver or 
alteration.
     
F. Full Waiver of HIPAA Authorization
Complete this checklist if you are requesting a full waiver of the requirement to 
obtain HIPAA authorization for all subjects or certain subject groups (e.g., 
retrospective cohort).  Full waivers of HIPAA authorization are commonly requested 
when the research does not include any opportunity for interaction with subjects 
(e.g., chart review).
1. Are you requesting a waiver of authorization for some or all subjects?
 All
 Some. Explain:      

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2. Describe your plan to protect health information identifiers from improper use 
and disclosure:
     
3. Describe your plan to destroy identifiers at the earliest opportunity consistent 
with conduct of the research (absent a health or research justification for 
retaining them or a legal requirement to do so):
     
4. Describe why the research could not practicably be conducted without the 
waiver or alteration:
     
5. The PHI accessed or recorded for identification/screening purposes will not be 
reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under 
the Privacy Rule.
 True
 False
G. Other Waiver Types
If you are seeking another waiver type (e.g., Planned Emergency Research, Waiver of 
Parental Permission to Protect Child Participants, Enforcement Discretion for In 
Vitro Diagnostics, etc. contact the HRPO office for assistance in determining what 
information to submit for the HRRC’s consideration.
II. Vulnerable Populations
A. Adults with Cognitive Impairments
Complete this checklist if the subject population will include adults with cognitive 
impairments.  
This checklist does not need to be completed if the research doesn’t involve 
interactions or interventions with subjects and will be conducted under a waiver of 
consent.
1. Describe why the objectives of the study cannot be met without inclusion of 
adults with cognitive impairments.
     
2. Describe how capacity to consent will be evaluated.

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3. If subjects may regain capacity to consent, or if subjects may have fluctuating 
capacity to consent, describe your plans to evaluate capacity to consent 
throughout the research and to obtain consent to continue participation if 
capacity is regained.
     
4. Describe your plans, if any, to provide information about the research to 
subjects and the steps you will take to assess understanding.
     
5. Describe your plans to obtain assent, including whether assent will be 
obtained from none, some, or all subjects.
     
6. Describe why risks to subjects are reasonable in relation to anticipated 
benefits to the subjects.
     
7. If this study involves a health or behavioral intervention, describe why the 
relation of the anticipated benefit to the risk of the research is at least as 
favorable to the subjects as that presented by alternative procedures.
     
8. Describe your plans for monitoring the well-being of subjects including any 
plans to withdraw subjects from the research if they appear to be unduly 
distressed.
     
B. Children
Complete this checklist if the subject population will include children.
1. Select the category of research that you believe this research falls within and 
provide justification for any associated criteria.  If there are different 
assessments for different groups of children or arms (e.g., placebo vs. drug), 
include a memo to provide an assessment for each group.  
 Research not involving greater than minimal risk. (Minimal risk means 
that the probability and magnitude of harm or discomfort anticipated 
in the research are not greater in and of themselves than those 
ordinarily encountered in daily life or during the performance of 
routine physical or psychological examinations or tests.)

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 Research involving greater than minimal risk but presenting the 
prospect of direct benefit to the individual subjects.
Provide justification for each of the following criteria:
(1) The risk is justified by the anticipated benefit to the subjects:
     
(2) The relation of the anticipated benefit to the risk is at least as 
favorable to the subjects as that presented by available 
alternative approaches:
     
 Research involving greater than minimal risk and no prospect of direct 
benefit to individual subjects, but likely to yield generalizable 
knowledge about the subject's disorder or condition.
Provide justification for each of the following criteria:
(1) The risk represents a minor increase over minimal risk:
     
(2) The intervention or procedure presents experiences to subjects 
that are reasonably commensurate with those inherent in their 
actual or expected medical, dental, psychological, social, or 
educational situations:
     
(3) The intervention or procedure is likely to yield generalizable 
knowledge about the subjects' disorder or condition which is of 
vital importance for the understanding or amelioration of the 
subjects' disorder or condition
     
C. Pregnant Women and Fetuses
Complete this checklist if the subject population will include pregnant women and 
fetuses.
This checklist does not need to be completed if the research is both minimal risk and 
is not conducted, funded, or otherwise subject to regulation by DHHS, DOD, EPA, or 
VA.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical studies, including studies on 
pregnant animals, and clinical studies, including studies on non-pregnant 
women, have been conducted and provide data for assessing potential risks to 
pregnant women and fetuses.

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2. The risk to the fetus is caused solely by interventions or procedures that hold 
out the prospect of direct benefit for the woman or the fetus; or, if there is no 
such prospect of benefit, the risk to the fetus is not greater than minimal and 
the purpose of the research is the development of important biomedical 
knowledge which cannot be obtained by any other means.
     
3. Any risk is the least possible for achieving the objectives of the research.
     
D. Neonates of Uncertain Viability or Nonviable Neonates
Complete this checklist if the subject population will include neonates of uncertain 
viability.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.
     
2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     
4. The research holds out the prospect of enhancing the probability of survival of 
the neonate to the point of viability, and any risk is the least possible for 
achieving that objective, or, the purpose of the research is the development of 
important biomedical knowledge which cannot be obtained by other means 
and there will be no added risk to the neonate resulting from the research
     
E. Nonviable Neonates
Complete this checklist if the subject population will include nonviable neonates.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.

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2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     
4. The purpose of the research is the development of important biomedical 
knowledge that cannot be obtained by other means.
     
Verify each of the following:
5. Vital functions of the neonate will not be artificially maintained
 True
 False
6. The research will not terminate the heartbeat or respiration of the neonate
 True
 False
7. There will be no added risk to the neonate resulting from the research
 True
 False
F. Biomedical and Behavioral Research Involving Prisoners
Complete this checklist if the subject population will include prisoners.
Note: Minimal risk for research involving prisoners is the probability and magnitude 
of physical or psychological harm that is normally encountered in the daily lives, or 
in the routine medical, dental, or psychological examination of healthy persons.
1. Select and justify which allowable category of research involving prisoners 
this research falls within:
 Study of the possible causes, effects, and processes of incarceration, and of 
criminal behavior, provided that the study presents no more than minimal 
risk and no more than inconvenience to the subjects
     

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 Study of prisons as institutional structures or of prisoners as incarcerated 
persons, provided that the study presents no more than minimal risk and 
no more than inconvenience to the subjects
     
 Research on conditions particularly affecting prisoners as a class (for 
example, vaccine trials and other research on hepatitis which is much 
more prevalent in prisons than elsewhere; and research on social and 
psychological problems such as alcoholism, drug addiction, and sexual 
assaults)
     
 Research on practices, both innovative and accepted, which have the intent 
and reasonable probability of improving the health or well-being of the 
subject
     
 Epidemiologic studies in which the sole purpose is to describe the 
prevalence or incidence of a disease by identifying all cases or to study 
potential risk factor associations for a disease, the research presents no 
more than Minimal Risk and no more than inconvenience to the subjects, 
and Prisoners are not a particular focus of the research.
     
2. Provide justification for each of the following regulatory criteria:
a) Any possible advantages accruing to the prisoner through his or her 
participation in the research, when compared to the general living 
conditions, medical care, quality of food, amenities and opportunity 
for earnings in the prison, are not of such a magnitude that his or her 
ability to weigh the risks of the research against the value of such 
advantages in the limited choice environment of the prison is impaired
     
b) The risks involved in the research are commensurate with risks that 
would be accepted by nonprisoner volunteers
     
c) Procedures for the selection of subjects within the prison are fair to all 
prisoners and immune from arbitrary intervention by prison authorities 
or prisoners. Unless justification is provided, control subjects must be 
selected randomly from the group of available prisoners who meet the 
characteristics needed for that particular research project
     

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d) The information is presented in language which is understandable to 
the subject population
     
e) Adequate assurance exists that parole boards will not take into account 
a prisoner's participation in the research in making decisions regarding 
parole, and each prisoner is clearly informed in advance that 
participation in the research will have no effect on his or her parole
     
f)
When appropriate, adequate provision has been made for follow up 
examination or care after research participation, taking into account 
the varying lengths of individual prisoners' sentences, and for 
informing participants of this fact
     
III.Medical Devices
Complete this checklist if the research evaluates the safety or effectiveness of a medical device.  
If more than one medical device is being evaluated, provide the requested information for each.
A. Device Name:  Magstim Rapid2 rTMS device
B. Manufacturer:  The Magstim Company Limited, Spring Gardens, Whitland, 
Carmarthenshire, SA34 0HR, UK
C. Does the research involve a Significant Risk Device under an IDE?
 Yes. Include documentation of the FDA approval of the IDE with your submission.  
Acceptable methods of documentation include: (1) FDA letter noting IDE number 
and approval status; (2) Industry sponsor letter noting IDE number and FDA 
approval status; or (3) FDA-approved industry sponsor protocol with IDE number 
noted 
 No
D. Is the research IDE-exempt?
 Yes. Include a FDA letter with your submission noting the determination that the 
research is IDE-exempt or a letter from the sponsor (or sponsor-investigator) 
justifying why they believe the research is IDE-exempt*.  
 No
E. Does the research involve a Non-Significant Risk (NSR) Device?

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 Yes. Include a FDA letter with your submission noting the determination that the 
research is NSR or a letter from the sponsor (or sponsor-investigator) justifying why 
they believe the research is NSR**.  
 No
F. Device Name:  MR transcranial electrical stimulator 
G. Manufacturer:  NeuroConn
H. Does the research involve a Significant Risk Device under an IDE?
 Yes. Include documentation of the FDA approval of the IDE with your submission.  
Acceptable methods of documentation include: (1) FDA letter noting IDE number 
and approval status; (2) Industry sponsor letter noting IDE number and FDA 
approval status; or (3) FDA-approved industry sponsor protocol with IDE number 
noted 
 No
I.
Is the research IDE-exempt?
 Yes. Include a FDA letter with your submission noting the determination that the 
research is IDE-exempt or a letter from the sponsor (or sponsor-investigator) 
justifying why they believe the research is IDE-exempt*.  
 No
J.
Does the research involve a Non-Significant Risk (NSR) Device?
 Yes. Include a FDA letter with your submission noting the determination that the 
research is NSR or a letter from the sponsor (or sponsor-investigator) justifying why 
they believe the research is NSR**.  
 No
* This FDA guidance includes a description for when a device study is exempt from the 
IDE requirements: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf 
**This FDA guidance includes information on how to differentiate between Significant 
Risk and Non-Significant Risk device studies: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf