Understanding the Brain Basis of Language and Cognitive Functions Through the Study of Individuals With Brain Injury and Healthy Controls
Conditions: Aphasia, Stroke, Alexia
Sponsor: Georgetown University

PROTOCOL TITLE: 2013-0964 
 
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PROTOCOL TITLE: 
2013-0964 Understanding the brain basis of language and cognitive functions 
through the study of individuals with brain injury and healthy controls 
PRINCIPAL INVESTIGATOR: 
Peter Turkeltaub, MD PhD 
Neurology 
202-784-1764 
turkeltp@georgetown.edu 
VERSION DATE: 
April 15, 2020 
 
 
 
 

PROTOCOL TITLE: 2013-0964 
 
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Table of Contents 
1.0 
Study Summary ........................................................................................................ 3 
2.0 
Objectives* .............................................................................................................. 5 
3.0 
Background* ............................................................................................................ 5 
4.0 
Study Endpoints* ..................................................................................................... 6 
5.0 
Study Intervention/Investigational Agent ................................................................ 6 
6.0 
Procedures Involved*............................................................................................... 6 
7.0 
Data and Specimen Banking* ................................................................................ 10 
8.0 
Sharing of Results with Subjects* ......................................................................... 10 
9.0 
Study Timelines* ................................................................................................... 10 
10.0 Inclusion and Exclusion Criteria* .......................................................................... 10 
11.0 Vulnerable Populations* ........................................................................................ 11 
12.0 Local Number of Subjects ..................................................................................... 12 
13.0 Recruitment Methods ............................................................................................. 12 
14.0 Withdrawal of Subjects* ........................................................................................ 13 
15.0 Risks to Subjects* .................................................................................................. 14 
16.0 Potential Benefits to Subjects* .............................................................................. 14 
17.0 Data Management* and Confidentiality ................................................................ 14 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* ........................ 18 
19.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 18 
20.0 Compensation for Research-Related Injury ........................................................... 18 
21.0 Economic Burden to Subjects ................................................................................ 18 
22.0 Consent Process ..................................................................................................... 19 
23.0 Process to Document Consent in Writing .............................................................. 20 
24.0 Setting .................................................................................................................... 20 
25.0 Resources Available............................................................................................... 20 
26.0 Multi-Site Research* ............................................................................................. 21 
 
 
 
GHUCCTS Questions  
 
GHUCCTS is the Georgetown-Howard Universities Center for Clinical and Translational 
Science. 
 
Is this study a GHUCCTS Study?   ____Yes 
__X__No 
 
Is the project being sponsored or funded by GHUCCTS?  ____Yes 
_X___No 
 
Does the project utilize GHUCCTS services or facilities?  ____Yes 
__X__No 
(e.g., is the study conducted on the Clinical Research Unit (CRU), is the study supported 
by a GHUCCTS biostatistician, etc.) 
 

PROTOCOL TITLE: 2013-0964 
 
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1.0 
Study Summary 
 
Study Title 
Understanding the brain basis of language and cognitive 
functions through the study of individuals with brain injury 
and healthy controls 
Study Design 
Hypotheses regarding the psychological and brain bases of 
language and cognitive functions will be tested by examining 
individuals with brain injury and control participants using 
behavioral tests and structural and functional MRI scans. 
Primary Objective 
To improve our understanding of the psychological and brain 
organization of language and cognitive functions through the 
study of individuals with brain injury. 
Secondary 
Objective(s) 
To improve our understanding of how the brain adapts in 
response to brain injury causing cognitive or language 
deficits. 
Research 
Intervention(s)/ 
Investigational 
Agent(s)  
Behavioral Tests of Language and Cognition 
MRI 
IND/IDE #  
N/A 
Study Population 
Inclusion Criteria: 
Patients: 
• Age >=18 
• Brain injury resulting from stroke, trauma, infection (i.e. 
encephalitis), primary progressive aphasia, posterior cortical 
atrophy, or tumor 
• Learned English at 8 years or younger 
Controls: 
• Age >=18 
• No history of brain injury resulting from stroke, trauma, 
infection (i.e. encephalitis), or tumor 
• Learned English at 8 years or younger 
 
Exclusion criteria: 
• History of other brain conditions that could impact 
interpretation of results (such as MS, premorbid dementia) 
• Severe psychiatric condition that would interfere with 
participation in the study 
Additional Exclusion Criteria for MRIs: 
• Presence metal in the body that is incompatible with MRI 
• Pregnancy 
• Claustrophobia 
Sample Size 
400 
Study Duration for 
individual 
participants 
In this study, participants will complete a battery of 
behavioral tests. Additionally, most subjects will complete 
an MRI. Sessions will be completed across approximately 2-

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6 weeks, but may be extended depending on participants’ 
schedules and availability. Some participants will be invited 
to repeat these procedures again at a later date to monitor for 
behavioral and MRI changes over time. 
Study Specific 
Abbreviations/ 
Definitions  
Aphasia is an acquired language disorder that negatively 
impacts one’s ability to speak, comprehend spoken language, 
read, and write. It also impacts understanding of other 
symbols sets, such as numbers and money.  
 
 

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2.0 
Objectives* 
2.1 Objective: This study aims to improve our understanding of the 
psychological and brain organization of language and cognitive 
functions through examination of individuals with brain injury.  
2.2 Hypotheses: Behavioral outcomes from stroke vary across 
individuals, and relate to features of the stroke and features of the 
spared brain tissue.   
3.0 
Background* 
3.1-3.3 Most of our understanding regarding the psychological and brain basis of 
language and other cognitive capacities has come from the study of individuals with brain 
injury. These studies provide two main kinds of information: (1) dissociations between 
psychologically separable processes, and (2) associations between psychological 
functions and the brain structures responsible for them. 
 
Behavioral dissociations are critical to delineating the functional architecture underlying 
cognitive processes. For instance, one can demonstrate through the study of brain injured 
individuals that certain individuals with reading impairment (alexia) have great difficulty 
reading words that do not follow the ordinary rules of spelling to sound correspondences 
(e.g. yacht), but are easily able to read novel words that do follow these rules (e.g flig). In 
contrast, some other patients are easily able to read exception words, but fail completely 
at novel words. This illustrates one type of behavioral dissociation, which strongly 
suggests that exception word and regular word reading are performed through (at least 
partly) independent psychological operations. 
 
The study of individuals with brain injury has also provided a great deal of information 
regarding the brain structures underlying cognitive operations. This work dates to the 
1800s, when such work relied on post mortem examination. Since the advent of modern 
neuroimaging methods, like MRI, this method of investigation has grown dramatically.  
 
From the 1970s to the 1990s, investigators began reporting detailed case series 
demonstrating behavioral deficits in individuals with brain injury, along with images of 
the damage, first as CTs, and later as MRIs. Then, in the 1990s, the Damasios and others 
began collating lesion locations on standard brain templates, in order to associate lesion 
location with behavioral deficits at the group level. Eventually, this led to a new 
technique first published in 2002, voxel-based lesion symptom mapping (VLSM), which 
borrows statistical methods from functional neuroimaging to quantify the degree to which 
damage at various locations in the brain contribute to observed 
behavioral deficits. 
Beginning in the late 2000s, investigators began combining functional and structural 
imaging data along with detailed behavioral data on people with brain injury in order to 
explain both the deficits caused by brain injury AND the adaptations the brain makes 
after the injury to functionally compensate for the damage. Thus, by combining detailed 
behavioral examination with multimodal imaging data in groups of individuals with brain 
injury, we can learn both about how the normal brain performs cognitive operations (by 
examining how lesion patterns impacts behavior), but also how people recover from these 

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injuries (by examining the alterations in functional brain activity). 
 
The PI of this study (Dr. Turkeltaub) is a Cognitive Neurologist, and has several years of 
clinical experience examining patients with cognitive and language deficits due to 
various kinds of brain injury. He is the Director of the MedStar National Rehabilitation 
Hospital Aphasia Clinic, which focuses on language deficits caused by brain injury. His 
laboratory has been conducting behavioral and imaging research on individuals with 
language deficits due to brain injury since 2012. 
 
4.0 
Study Endpoints* 
4.1 Study Endpoint: The primary dependent variables of interest will 
include scores on behavioral tests and various imaging measures of 
brain structure, function, and connectivity. 
4.2 Safety Endpoints: Not Applicable 
5.0 
Study Intervention/Investigational Agent 
5.1 
Not applicable. This is not a treatment study.  
 
6.0 
Procedures Involved* 
6.1 Study Design: 
Behavioral Tests of Language and Cognition: Participants will be examined using a 
combination of standardized tests and in-house tests of language and cognition. 
Typically, participants with brain injury will undergo a general assessment using 
elements of the Western Aphasia Battery-Revised (WAB-R), the Boston Diagnostic 
Aphasia Examination, and other standard language tests. The assessment will also 
include tests of other functions (e.g. line bisection test for visuospatial neglect), and 
questionnaires to be filled out by the patient and his/her family (e.g. the Communicative 
Effectiveness Index, Beck’s Depression Inventory-II). Additional in-house tests of 
language and cognitive functions (e.g. pseudoword repetition, executive function, 
auditory perception, audiovisual integration) may be used. 
 
MRI: MRI will be collected to obtain information regarding structural and functional 
brain data that may be related to performance on the behavioral tasks. Scanning may 
occur either the CFMI at Georgetown or the 3T research scanner at WHC (which is 
connected to NRH via a pedestrian bridge). Subjects will be taken to the scanner facility 
and placed on the bed of the scanning device after having been carefully screened. CFMI 
operates a Siemens 3T Prisma MRI scanner, whereas WHC operates a Phillips 3T 
Achieva scanner. Subjects with the following will not be allowed into the MRI scanner: 
cardiac pacemakers, neural pacemakers, surgical clips in the brain or blood vessels, 
surgically implanted metal plates, screws or pins, cochlear implants or other metal objects 
in their body determined to be unsafe for MRI, especially in the mouth or eyes. After the 
subjects’ head is properly positioned in the head-holder, the patient is moved into the 
scanner. While the scan is being done, the subject is unable to see the 
experimenter or the technicians, but voice contact is maintained throughout, and the 
technician can see the subject. A T1-weighted sequence with 1mm cubic voxels 

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(MPRAGE) will be used for structural scans. Diffusion tensor imaging (DTI), fluid 
attenuated inversion recovery (FLAIR), High resolution T2-weighted, non-contrast 
perfusion (arterial spin labeling), and susceptibility-weighted imaging will use standard 
sequences. Functional MRI will be acquired using standard resting state, block design or 
event-related EPI BOLD sequences. MRI sessions will not last longer than 90 minutes. 
 
Relationship to Protocol Pro00000315: Some participants in this study will have 
previously participated in a study on the use of transcranial direct current stimulation for 
language deficits caused by stroke or brain injury. Data collected under that protocol will 
be included in analyses conducted in the current study. Participants who were consented 
for Pro0000315 prior to approval of this protocol will be asked to provide consent for this 
protocol as well, if possible. 
 
Study Partner: If a participant is unable to transport themselves safely to appointments 
and/or needs assistance with some aspects of the study, then that participant will need to 
select someone with whom they have regular contact (at least 1 day a week) as a study 
partner. The study partner's duties are to attend lab sessions or assist in transporting the 
participant to sessions, to help the participant with questionnaires and to answer questions 
about the subject's health. 
6.2 Research Procedures 
Experiment 1: Case studies of individuals with cognitive and language deficits due to 
brain injury. This study tests hypotheses on the psychological and brain bases of language 
and cognitive functions through the detailed examination of individual subjects with 
brain injury. Typically, the purpose of case study research is to identify dissociations 
between performance of different tasks that demonstrate the independence of different 
psychological or brain processes. Individuals with language or cognitive deficits resulting 
from brain injury will be identified and tested with a series of behavioral and MRI 
assessments as described above, aimed at dissecting the specific psychological and brain 
operations disrupted and spared by the injury. Because the specific hypotheses to be 
addressed in this experiment depend critically on the characteristics of the individual 
participants (i.e. we cannot know which specific hypothesis will be testable until we 
encounter a specific patient), and the testing is often time-critical (a dissociation may be 
observable at one time after the brain injury, but then resolve shortly thereafter either due 
to spontaneous recovery or therapy), it is not feasible to submit a new amendment 
describing the specific hypothesis to be addressed in each subject. 
 
Experiment 2: Obtaining control MRI data for protocol Pro00000315. We are 
conducting a study investigating the use of transcranial direct current stimulation for 
aphasia or alexia due to stroke or traumatic brain injury. In order to interpret MRI data 
obtained in this study, we will require similar MRI data from a group of age-matched 
control subjects. Subjects will be screened for history or stroke or traumatic brain 
injury, and will be evaluated using a brief behavioral battery to confirm normal language 
and cognition. They will then complete an MRI session to obtain T1 and T2-weighted 
images, diffusion tensor imaging, perfusion images, resting BOLD images, and 
functional MRI data testing naming, reading, or speech comprehension matching that 
performed in Pro00000315. 

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Experiment 3: Group study investigating speech production. This study examines the 
brain basis of deficits in speech production caused by brain injury. Participants with brain 
injury will be tested using a general battery to characterize their language and cognitive 
deficits, as well as specific behavioral tests of speech production (e.g. picture description, 
story-telling, naming, repetition, reading, tests of inner speech), related functions relevant 
to specific models of speech production (e.g. procedural memory) and control tasks (e.g. 
written picture description, written naming, declarative memory). Performance on 
these tasks will be related to MRI measurements of lesion location and distribution, local 
cerebral perfusion, white matter connectivity, cortical thickness in preserved brain areas, 
and functional activity during speech production tasks (e.g. naming). Age-matched 
control subjects without history of brain injury will be used to determine a normal 
distribution of performance on behavioral tasks, and normal patterns of 
brain structure, connectivity and function. 
 
Experiment 4: Group study investigating speech perception/processing. This study 
examines the brain basis of deficits in speech perception and processing caused by brain 
injury. Participants with brain injury will be tested using a general battery to characterize 
their language and cognitive deficits, as well as specific behavioral tests of speech 
perception/processing (e.g. word-to-picture matching, auditory lexical decision, 
Englishness judgement on pseudowords, statistical learning of novel speech, audiovisual 
speech perception) and control tasks (e.g. sound-to-picture matching, statistical learning 
of motor sequences, audiovisual non-speech perception). Performance on these tasks will 
be related to MRI measurements of lesion location and distribution, local cerebral 
perfusion, white matter connectivity, cortical thickness in preserved brain areas, and 
functional activity during speech perception/processing tasks (e.g. listening to speech). 
Age-matched control subjects without history of brain injury will be used to 
determine a normal distribution of performance on behavioral tasks, and normal patterns 
of brain structure, connectivity and function. 
 
Experiment 5: Group study investigating reading and writing. This study examines the 
brain basis of deficits in reading and writing caused by brain injury (i.e. alexia and 
agraphia). Participants with brain injury will be tested using a general battery to 
characterize their language and cognitive deficits, as well as specific behavioral tests of 
reading and writing (e.g. reading of various kinds of words, pseudoword 
reading, letter identification, letter case matching, written word recognition, paragraph 
reading, reading comprehension, writing to dictation, oral spelling, written picture 
description, written naming), and control tasks (e.g. naming, drawing simple shapes, 
pseudoword repetition). Performance on these tasks will be related to MRI measurements 
of lesion location and distribution, local cerebral perfusion, white 
matter connectivity, cortical thickness in preserved brain areas, and functional activity 
during reading/writing tasks (e.g. single word reading). Age-matched control subjects 
without history of brain injury will be used to determine a normal distribution of 
performance on behavioral tasks, and normal patterns of brain structure, connectivity and 
function. 
 

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Experiment 6: Group study investigating cognition and subjective symptom reports. 
This study examines cognitive deficits and subjective reports of symptoms, disability, 
and independence related to brain injury. Participants with brain injury will be tested 
using a general battery to characterize their language and cognitive deficits, as well as 
questionnaires about their subjective experience of having brain injury (e.g, depression 
symptoms, subjective disability, functional independence, and quality of life). Subjective 
reports will be related to objective measures of cognitive and language deficits. 
Subjective reports and performance on cognitive tasks will be related to MRI 
measurements of lesion location and distribution, local cerebral perfusion, white matter 
connectivity, cortical thickness in preserved brain areas, and functional activity during 
cognitive tasks. Age-matched control subjects without history of brain injury will be used 
to determine a normal distribution of performance on behavioral tasks, and normal 
patterns of brain structure, connectivity and function. 
6.3 Risks:  
• Behavioral measures: 
• Risk of discomfort or fatigue with testing- If subjects find the behavioral tasks too 
onerous, they will be told that they can stop the study at any time.  
• If specific questions make them uncomfortable, they will be told that they may omit 
responses to these questions. 
• MRI: 
• To reduce this risk of flying object injury during MRI scans, subjects are screened using 
the standard MRI screening form provided by the CFMI. We require that all people 
involved with the study remove all metal from their clothing and all metal objects from 
their pockets. No metal objects are allowed in the magnet room at any time. In addition, 
once a volunteer is in the magnet, the door to the room will be closed so that no one 
inadvertently walks into the magnet. 
• The risk of discomfort during scans will be managed by informing volunteers that they 
may stop the experiment at any time if these effects are not tolerable. 
• If an incidental abnormal finding is noted in a subject’s MRI scan, they will be notified of 
it by the PI and given a written report describing it. It will then be up to the subject to 
pursue it with their physician. 
• Although study personnel may be able to provide some advice, the decision of whether 
and how to pursue an incidental finding can only be made by the subject’s physician who 
has knowledge of their full medical history. 
6.4 Screening Process 
We will use a screening form to determine inclusion/exclusion eligibility, an 
information sheet to collect information regarding past medical history and 
demographic information, and several questionnaires to gain information about 
psychosocial state, socieoeconomic status, quality of life, communication 
effectiveness, etc. All forms are attached.  
6.5 Data Collected 

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Data will be collected via behavioral tasks, MRI, and questionnaires (see above 
section). De-identified information will be kept indefinitely. Identifiable 
information will be retained for the duration of the study.  
6.6 Long-term follow-up: Not applicable 
6.7 Humanitarian Use Device (HUD): Not applicable.  
7.0 
Data and Specimen Banking  
7.1 Not applicable.  
8.0 
Sharing of Results with Subjects* 
8.1 Information Sharing with Subjects 
If the study elicits an unexpected finding (e.g., stroke in an enrolled control subject), the 
information will first be confirmed with the PI, Peter Turkeltaub, who is a licensed 
physician. The information will then be shared with the subject by study personnel 
verbally and in writing if requested. Follow-up with their primary care physician or 
another appropriate healthcare professional will be recommended as appropriate.  
 
Subjects with a history of stroke may receive a written/electronic document outlining a 
portion of their study results, including both behavioral data and brain images.  
 
9.0 
Study Timelines* 
9.1 Study Timeline: 
Sessions will be completed across a timeframe of approximately 2-6 weeks, but 
may be extended depending on participants’ schedules and availability. Some 
participants will be invited to repeat the study procedures again at a later date to 
monitor for behavioral and MRI changes over time. 
This study will be open for enrollment of subjects for 9 years. The timeline for 
study completion is 12 years.  
10.0 Inclusion and Exclusion Criteria* 
10.1 Screening for Eligibility 
When potential participants express interest in the study, either in the PI's clinic, 
over the phone after a referral, or by contacting the lab, they will complete a 
screening that covers inclusion/exclusion criteria with a study personnel using a 
telephone screening script (see attachments). If unable to complete over the 
phone, interested participants can elect to receive and return the screening via 
mail or a Box upload. In this instance, if any questions arise about inclusion 
eligibility, the researcher will contact the person for further information. At times, 
subjects may be screened in-person as well (e.g., when visiting the lab for 
participation in another study and they express interest in this study). A partial 
HIPAA waiver is in place to allow screening prior to consent.  
10.2 Inclusion and Exclusion 

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Inclusion criteria: 
Patients: 
• Age >=18 
• Brain injury resulting from stroke, trauma, infection (i.e. encephalitis), primary 
progressive aphasia, posterior cortical atrophy, or tumor 
• Learned English at 8 years or younger 
Controls: 
• Age >=18 
• No history of brain injury resulting from stroke, trauma, infection (i.e. encephalitis), 
or tumor 
• Learned English at 8 years or younger 
 
Exclusion criteria: 
• History of other brain conditions that could impact interpretation of results (such as 
MS, premorbid dementia) 
• Severe psychiatric condition that would interfere with participation in the study  
• History of a learning disability that could impact interpretation of results 
• Unable to understand basic instructions with visual supports (i.e., due to profound 
language impairment) 
 
Additional Exclusion Criteria for MRIs: 
• Presence of a pacemaker or other metal that is incompatible with MRI 
• Pregnancy 
• Claustrophobia 
 
10.3 Pregnant women can participate in behavior testing, but will be 
excluded from the MRI. Pregnancy will be determined by self-
report.  
This study may include some adults who are unable to consent for 
themselves. Inability to give consent would result from brain injury 
and loss of comprehension abilities. Safeguards for these 
participant’s protection are outlined below in section 11.0.  
11.0 Vulnerable Populations* 
11.1 If the research involves individuals who are vulnerable to coercion 
or undue influence, describe additional safeguards included to 
protect their rights and welfare. 
In general, individuals who participate in this sort of research have capacity to 
provide consent because comprehension deficits sufficient to limit capacity can 
impact the ability to understand task instructions or comply with study procedures 
(e.g., staying still inside the scanner).  At the first session, the consent form will 

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be reviewed and explained by an experimenter. Consent will be obtained from 
both the participant and a, LAR, family member, or caregiver (termed, the “study 
partner”) when appropriate.  
Some subjects may have alexia (i.e., reading impairment) due to their brain injury. 
For these individuals, we will read the informed consent and HIPAA documents 
to them aloud.  
Study personnel will closely monitor the subject’s well-being during the 
behavioral and MRI session, providing breaks when necessary. If a participant 
becomes unduly stressed, the session will be terminated and options for 
continuation in the study or termination in the study will be discussed. 
12.0 Local Number of Subjects 
12.1 Total Number of Subjects to be accrued locally: 400 
12.2 Not applicable.  
13.0 Recruitment Methods 
13.1 Recruitment Methods: Informal recruitment through social 
networks, Advertisements/media (e.g., email, advertisements, flyers, 
letters, text for verbal presentations, etc.), PI/collaborators will 
recruit participants from his/her/their own patient population, IRB 
approved subject pool, Online social networks, Online classifieds 
 
13.2 Sources of Subjects:  
• The primary source of subjects is the PI's clinic and consultation service at the 
MedStar National Rehabilitation Hospital (NRH). Additional patients will be 
identified from the speech therapy service at NRH, and from MGUH and MNRH, or 
may be referred by other clinicians who are familiar with our research (e.g. the Stroke 
Comeback Center in Vienna, VA; Towson University Speech-Language Pathology 
Graduate Clinic). Other subjects may be identified through our other approved studies 
(Pro00000315), IRB-approved database of patients with cognitive and language 
problems (#2011-463) or the Stroke Recovery Database and Advanced Recovery 
Registry of stroke patients at NRH (MHRI #2009-171) who have agreed to be 
contacted for research projects. Finally, subjects will be recruited through flyers and 
advertisements placed around GUH, NRH, and the DC area. Of note, although the 
studies allow patients at any age over 18, control subjects will need to be recruited to 
match the patients for age and health status. Therefore, different versions of 
advertising flyers for controls have been produced in advance with different age 
ranges. 
• We have included a partial HIPAA waiver request to allow access to limited PHI 
prior to the formal informed consent process in the context of database searches and 
provider referrals. 
• We will also recruit through ResearchMatch- ResearchMatch is a free and secure 
registry that has been developed by major academic institutions across the country 
who want to involve you in the mission of helping today’s studies make a real 

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difference for everyone’s health in the future. ResearchMatch has a simple goal – to 
bring together two groups of people who are looking for one another: (1) people who 
are trying to find research studies, and (2) researchers who are looking for people to 
participate in their studies. ResearchMatch is funded in part by the National Institutes 
of Health (NIH) Clinical and Translational Science Award (CTSA) program, grants 
UL1TR000445 and 1U54RR032646-01 .The CTSA program is led by the NIH’s 
National Center for Advancing Translational Sciences (NCATS). 
https://www.researchmatch.org/volunteers/ 
 
Below are subject pools and their IRB reference # used in our recruitment for this 
study: 
• Georgetown University: Language and cognitive disorders patient database-- IRB# 
2011-463 
• National Rehabilitation Hospital: Advanced Recovery Registry-- MHRI IRB# 2009-
171 
• Stroke National Capital Areal Network for Research (SCANR) Participant 
Database--MHRI IRB# 2014-112, GUH IRB# 2015-0485 
13.3 Subjects will be identified through the aforementioned subject pools, 
provider referrals, and advertisements (as listed below). 
13.4 Recruitment materials: Advertisements include Electronic mail, 
physical placement (e.g., bulletin board, hallway, doorway, kiosk, 
etc.), Hard copy (e.g., US Mail, inter-departmental, etc.), Online 
advertisements.  
All advertisements are attached.  
13.5 Participants will receive $50 for each behavioral session and $50 for 
MRI session. We expect patients will typically participate in 4 
sessions ($200). If they participate in an additional MRI session, the 
expected total will be $250. We expect control subjects will typically 
participate in 2 behavioral sessions ($100). If they participate in an 
additional MRI session, the expected total will be $150. For any 
additional sessions that are conducted virtually and are not full-
length testing sessions, participants will receive $25.    
In some instances, a participant may complete the sessions in fewer 
sessions or may require more sessions based on their abilities. Thus, 
total payment amount will be determined by each participant’s total 
number of sessions completed.  
14.0 Withdrawal of Subjects* 
14.1 Participants will be withdrawn from the study if they undergo any 
new neurological changes, such as a new cerebral vascular accident, 
that alter their eligibility for the study. These participants may be 
eligible to re-enroll at a later time if they continue to meet the 
inclusion criteria. They may also be withdrawn if they are unable to 
comply with study procedures. 

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14.2 De-identified data obtained prior to withdrawal will be maintained. 
Identifiable participant information will be destroyed at their request 
via shredding.  
 
14. 3 Participants may choose to withdraw from the study if they find any 
procedures to be uncomfortable. There are no safety implications from partial 
withdrawal. 
 
Subjects are screened for exclusion criteria. The study personnel will monitor 
participants during sessions, and will be available to discuss concerns with 
participants at any time. Participants will be able to discontinue participation at 
any time. Peter Turkeltaub, the Principal Investigator, will serve as the Study 
Monitor. He will talk to each person who withdraws to ascertain the reason for the 
withdrawal. If there are a significant number of withdrawals, we will re-evaluate 
our protocol to see whether the participants are unduly burdened. 
 
15.0 Risks to Subjects* 
15.1 Foreseeable Risks: 
• Behavioral Tests 
o Some subjects may become bored, uncomfortable, or frustrated during 
performance of the tests. 
o Some questions on questionnaires (e.g. questions about depression symptoms) 
may make the subject uncomfortable. 
• MRI 
o The known risks associated with MRI are minimal. The greatest risk is a 
metallic object flying through the air and hitting the subject. Some volunteers 
experience transient discomfort from lying in the scanner for prolonged 
periods. MRI carries theoretical risks if the subject has implanted metal 
medical devices (e.g., cardiac pacemakers), but such subjects will be excluded 
from participation.  
15.2 Not applicable.  
 
16.0 Potential Benefits to Subjects* 
16. 1 Potential Benefits: In general, subjects will not receive direct clinical 
benefit from their participation in the study. However, individuals with brain 
injury have a tendency to withdraw socially, which can have adverse impact on 
their functioning and well-being. Participating in this study may provide a way to 
engage in the community and provide a sense of contributing to society, which 
could be beneficial for them. They may also learn about their own deficits and 
strengths by completing the behavioral testing battery. 
16.2 
Please see section 16.1 
17.0 Data Management* and Confidentiality 

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17.1 Analyses: 
Case studies: 
Statistical analyses of individual cases will examine differences between scores on 
different behavioral measures using standard parametric and non-parametric statistics as 
appropriate. For example, differences in accuracy of exception word and pseudoword 
reading can be examined using a Fisher's Exact test. In addition, behavioral scores of 
individual cases will be compared to normative control groups using the single case 
statistical methods of Profs. John Crawford, Paul Garthwaite, and David Howell (see 
http://homepages.abdn.ac.uk/j.crawford/pages/dept/SingleCaseMethodology.htm). These 
methods are essentially adaptations of between-group t-tests in which one group has a 
sample size of 1. The sample size for the patient group in these experiments is obviously 
1, and the sample size of the control group is typically 10 or more for the purposes of 
confirming behavioral deficits which are usually fairly dramatic (i.e. the effect size is 
large). 
 
Group Studies: 
Analysis of behavioral data from group studies will be conducted using between-group 
parametric and non-parametric statistics to compare scores with that of a normative 
control group. In addition, comparisons between different behavioral scores will be 
conducted within the group of patients. The sample size for comparisons of behavioral 
scores in group studies of brain injury patients is typically 10 or more, with 
approximately 20 control subjects. 
 
MRI analyses: 
MRI results will be compared with behavioral results using several methods, for 
example: Lesion-symptom mapping-- this method uses the presence or absence of brain 
damage at each location in the brain to sort patients into test and control groups, and 
statistical tests are then performed to identify locations at which the behavior differs 
depending on the presence or absence of damage. fMRI analysis-- analysis of fMRI data 
proceeds using fairly standard pre-processing (slice time correction, realignment, spatial 
and temporal smoothing), and typically uses a generalized linear modeling approach to 
identify areas activated by various task conditions. Connectivity analyses will also be 
conducted examining the temporal relationships between activity at various locations in 
the brain. In addition, behavioral data obtained outside the scanner will be correlated with 
functional data, and between-group comparisons may be conducted to compare patients 
and controls, or subgroups of patients (e.g., patients with discrete lesion distributions, or 
patients with different patterns of behavioral deficits). 
17.2 Data Security:  
Upon initiation of the study, each participant will sign a HIPAA waiver, providing study 
personnel to collect, access, and maintain records. Subject name, date of birth, social 
security number, phone number, email address, and medical history relevant to 
inclusion/exclusion must be collected for participation and compensation. A unique 
subject ID will be assigned to each participant and will be used as the sole identifier on 
all physical or electronic records that do not require identifying information (e.g. 
informed consent form, HIPAA authorization, payment forms). A computer file linking 

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the identity of subjects to their subject ID will be stored on a password protected data 
server in a locked room only accessible to lab staff. In certain tasks video of subjects may 
be recorded in a digital fashion for later analysis. The subjects will only be identified 
using their subject ID in these recordings but their voices and images will be unaltered. 
All computers or servers containing identifiable subject information will be stored in 
locked rooms and will be password protected. Transfer of PHI and communication of 
PHI among study personnel will utilize GU Box. All physical files containing personal 
information and data will be kept in a locked filing cabinet within a locked room 
accessible only to lab staff. 
 
In addition to the subject’s information, we will collect contact information (i.e., phone 
number, email address) of a family member or caregiver. Communication with 
individuals with brain injury typically involves their spouse, a close family member, or 
caregiver. These individuals’ names and contact information will be kept on file for 
communication purposes and will stored with the same safeguards as described above. 
No other information on these individuals in needed.  
 
Study personnel will complete appropriate CITI training courses prior to receiving 
authorization to access subject research records. Only study personnel will be granted 
access to research data containing identifying information. We may require advice from 
other researchers regarding interpretation of data, in which case deidentified data will be 
used.  
17.3 Quality Control: 
Procedures for testing sessions (e.g., general ordering of testing, testing 
instructions) will be established across all study personnel administering 
behavioral tests. Interrater reliability will be performed on a given number of 
tests, and consensus meetings will be held to ensure accuracy in scoring on tests 
not undergoing inter-rater reliability scoring.  
17.4 Data Handling 
After a research session is held, data will be transferred to the secure server and/or the 
data repository (i.e., GU Box). Video images will be deleted from the memory card once 
successful transfer is confirmed.  
 
17.5 Type of Data being Collected 
Protected health information may be collected during this study, including:  
• Hospital/medical records 
• Lab, pathology and/or radiology records 
• Interviews/questionnaires 
• Mental Health records 
• Data previously collected for research purposes under another approved GU or 
MedStar IRB study (i.e., Pro315 under GU IRB) 
• Database or repository, including: The cognitive and language patient database – 
GU IRB# 2011-463; The Advanced Recovery Registry- MHRI IRB# 2009-171; 

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and Stroke National Capitol Area Network for Research (SCANR) Patient 
Database- MHRI IRB# 2014-112, GU IRB# 2015-0485) 
 
Identifying information that may be collected, includes:  
• Names 
• Initials 
• Residential/mailing addresses 
• Dates directly related ot the individual (birth date, admission date, discharge date, 
etc) 
• Phone numbers 
• Email addresses 
• Social security numbers 
• Medical record numbers 
• Videos/images with subjects’ faces and voices 
• Any other unique identifying number, characteristic, or code 
 
Medical records with identifying information will be kept separately and stored securely. 
Names of subjects will not be used in publications. No digital, video, or photographic 
recordings of the subjects will be made public.   
 
After the retention period, electronic files will be deleted and paper files will be shredded.  
 
17.6 Data Sharing 
 
Deidentified data used for publications may be posted publicly in supplemental materials 
of publications or posted on our lab website.  
 
De-identified data (i.e., structural MRI scans, lesion tracing images) will be transferred to 
the University of Pittsburgh via a secure Box folder. This data will be used to develop 
automated lesion analysis methods. Collaborating researchers will receive approval from 
the IRB at the University of Pittsburgh and store data securely per their IRB guidelines.  
 
Video and voice recordings with no further identifiable information will be transferred to 
the University of North Carolina (UNC) via a secure Box folder. This data will be used to 
contribute to research investigating diagnosis and treatment of motor speech disorders. 
Collaborating researchers have received approval from the IRB at the University of North 
Carolina for reception of this data. They will store data securely per their IRB’s 
guidelines (i.e., on a secured server). UNC will send motor speech behavioral scores and 
electronic brain scan files back to Georgetown University.  
 
A section in the Confidentiality section of the Informed Consent Form was added for 
sharing of deidentified data. Consent for sharing identifiable data will be obtained via an 
addendum on the Informed Consent Form for new participants from this point forward 
(protocol dated 4/15/20). Past participants will be contacted for provision of verbal or 
email consent using the attached script. If consent is not granted by the participant, data 
will not be shared. Consent will be waived when it is impracticable to gain consent (e.g., 

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the participant is deceased, participant is unable to be contacted). All attempts at contact 
and provision/declination of consent will be documented.  
 
 
18.0 Provisions to Monitor the Data to Ensure the Safety of Subjects* 
18.1 
N/A. This study has minimal risk. The PI will monitor the safety of the 
study. Any adverse events will be reported to the IRB promptly.  
 
19.0 Provisions to Protect the Privacy Interests of Subjects 
19.1 Privacy of Data Stored 
Electronic research information will be kept on a password protected server and 
RedCap accessed through a secure network only. Subjects will be assigned a code 
that will separate their research results from their identifying information. A 
computer file linking the identity of subjects to their subject ID will be stored on 
on GU Box and on a password protected data server in a locked room only 
accessible to lab staff. The master list linking codes to the subjects’ names will be 
kept on a secure repository (i.e., GU Box). Hard copies of research information 
(questionnaires, test forms), ICF, etc. will be kept in a locked filing cabinet in a 
locked office which can only be accessed by research personnel. Research data 
will be shared without any identifying information (e.g., with assigned random 
code). 
If medical records are needed, subjects will sign a Medical Release form for study 
personnel to collect necessary records from other medical facilities.  
19.2 Steps for Keeping Participants “at ease” 
Subjects will be given rationale as to why information is being collected, 
however, subject can decline to answer any items on questionnaires or tests that 
make them feel uncomfortable. We will contact patients by phone or email during 
the periods between sessions to encourage subject retention. We will also arrange 
transportation to the study site for subjects who have difficulty with transport, or 
travel to the subject’s home if necessary. Subjects will be allowed breaks during 
testing sessions to limit fatigue. They will be encouraged to participate in all 
experimental sessions, but they may voluntarily withdraw at any time.  
19.3 Access to Subject Information 
Study personnel will be authorized to access subject information after completing 
CITI training and receiving training on privacy procedures within the protocol. 
Only study team members who have duties/functions pertaining to documents 
containing identifying information will be given access to these records. Other 
study personnel will only access de-identified research data.  
20.0 Compensation for Research-Related Injury 
20.1 Not applicable. This study has minimal risk.  
21.0 Economic Burden to Subjects 

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21.1 Participant Costs 
Subjects may pay for transportation to and from study sessions (e.g., gas to drive 
to GU, handicap accessible taxi, metro/bus fare). All subjects will be reimbursed 
for any parking expenses during study sessions. If subjects are unable to pay for 
transportation to the study site, reimbursement may be arranged or a study 
personnel may travel to the subject’s home to complete testing.  
 
22.0 Consent Process 
22.1 Obtaining Informed Consent 
The informed consent process will follow HRP-090. When possible, study 
personnel will provide a copy of the informed consent document at least one day 
prior to the first study visit. The first study visit will begin with the formal 
informed consent process at a study site. Study personnel will go through the 
consent documents with the participant and provide sufficient time for them to 
review the documents and ask questions. 
If there is any question regarding whether the participant's comprehension abilities allow 
the participant to consent to participate for him/herself, a second signature will be 
obtained from the participant's spouse, adult son/daughter, parent, or adult sibling. The 
second signature will document that the spouse/relative has observed and participated in 
the consent process with the participant, that the spouse/relative and participant 
understand what was explained to them, and that all of their questions were answered. 
The spouse/relative of a participant whom study staff determines to have no more than 
mild comprehension deficits will not be asked to sign. (This procedure for handling 
questions regarding comprehension ability has previously been approved by the GU IRB 
for similar study populations under 1996-311 and other protocols from Dr. Rhonda 
Friedman's group). 
 
Study Partner Consent: 
If a participant requires help to answer health-related questions or travel to appointments, 
a caregiver/study partner will sign a separate caregiver/study partner consent to confirm 
their willingness to provide contact information and help the participant in the ways 
described. 
 
There is a separate informed consent form for use of audio or visual recordings. 
Non-English Speaking Subjects 
• N/A. English proficiency is an inclusion criterion for this study.  
Cognitively Impaired Adults 
• 
Auditory comprehension is inquired about on the screening 
form for individuals who have history of a stroke. When 
participants indicate they have more than mild deficits, further 

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assessment will be made to determine if they will need a family 
member or caregiver to sign the informed consent.  Order of 
priority for signature is listed below.  
Adults Unable to Consent 
• 
Informed consent will be obtained in the following priority: 
o Legally Authorized Representative (if not local, 
consent may be reviewed over the phone and 
consent documents may be obtained via fax, email, 
or mail).  
o Spouse/Partner 
o Adult Child 
o Sibling 
• 
All subjects, whether signing the consent form themselves or 
having a relative/caregiver sign the consent, will be asked for 
their verbal assent for participation in the study.  
 
23.0 Process to Document Consent in Writing 
23.1 We will follow HRP-091.  
 
24.0 Setting 
24.1 Research Sites 
• 
Potential subjects will be recruited form the databases listed in 
section 13.0. They will also be recruited from MedStar NRH, 
GUH, Towson University, through advertisements online and 
in the regional community, through healthcare provider 
referrals, and through word-of-mouth from former participants.  
• 
Behavioral assessment and MRI sessions will be performed at 
Georgetown University Medical Center, MedStar National 
Rehabilitation Hospital, and Towson University Department of 
Speech-Language Pathology. Behavioral assessment may be 
conducted in a participant’s home or other mutually agreed 
upon private setting for their convenience.  
• 
Of note, Georgetown-MedStar IRB will be the IRB of record 
for MedStar NRH, but will not be the IRB of record for 
Towson University at this time as Towson University will be 
conducting their own IRB review.  
25.0 Resources Available 
25.1 Describe the resources available to conduct the research: For 
example, as appropriate: 

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• 
Our current cohort of stroke survivors includes approximately 
100 people who have completed or express interest in previous 
research within our lab. In our experience conducting this 
research over the past several years we are able to recruit 20-50 
new stroke survivors per year, and 50-100 control participants 
per year from the sources listed above.  
   
• 
Several study personnel will work full time on this project, and 
several others will work part time. The PI and other members 
of the study team will be available for weekly meetings to 
discuss progress, troubleshoot, and make scoring decisions.  
 
• 
We have access to two separate behavioral testing rooms on the 
GUMC campus, and an additional testing room at MedStar 
NRH. These facilities allow for testing of up to 3 participants at 
one time. The CFMI houses a state-of-the-art MRI facility. We 
have adequate office space for all study personnel at GUMC, 
and each has a computer to work on.  
 
• 
The PI and project manager assigned to this study will ensure 
the protocol and research procedures are followed by closely 
monitoring recruitment, research data, and data 
scoring/storage. Checklists outlining the procedures have been 
created and are used by all study personnel administering 
testing. The study team meets on a weekly basis, as well as 
often in smaller groups, to discuss study procedures and 
scoring of behavioral tests. A report is given to the team after 
each MRI session. All these systems will provide continuity 
between team members, allow for team members to ask 
questions about their duties/functions, and monitor for any 
procedures that need adjusted within the protocol.  
26.0 Multi-Site Research* 
N/A. This is not a multicenter study.