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PI: Chow, Ho Ming Title: Neural Markers of Persistence and Recovery from Childhood Stuttering: An 

fMRI Study of Continuous Speech Production 

Received: 02/23/2016 FOA: PAR16-057 Council: 10/2016 

Competition ID: FORMS-C FOA Title: NIDCD EARLY CAREER RESEARCH (ECR) AWARD (R21) 

1 R21 DC015853-01 Dual: Accession Number: 3911289 

IPF: 1506502 Organization: 

Former Number: Department: Psychiatry 

IRG/SRG: CDRC AIDS: N Expedited: N 

Subtotal Direct Costs 

(excludes consortium F&A) 

Animals: N 

Humans: Y 

Clinical Trial: N 

Current HS Code: 30 

HESC: N 

New Investigator: 

Early Stage Investigator: 

Senior/Key Personnel: Organization: Role Category: 

Ho Ming Chow PD/PI 

Allen Braun NIH Consultant 

Soo-Eun Chang Co-Investigator 

Nan Ratner University of Maryland Co-Investigator 
OMB Number 4040-0001

Expiration Date 06/30/2016

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057 . Received Date:

2016-02-23T15:48:23.000-05:00

APPLICATION FOR FEDERAL ASSISTANCE

SF 424 (R&R)

3. DATE RECEIVED BY STATE State Application Identifier

1. TYPE OF SUBMISSION* 4.a. Federal Identifier

❍ Pre-application ● Application ❍ Changed/Corrected

Application

b. Agency Routing Number

2. DATE SUBMITTED Application Identifier

16-PAF04924

c. Previous Grants.gov Tracking Number

5. APPLICANT INFORMATION Organizational DUNS*: 

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Person to be contacted on matters involving this application

Prefix: Ms. First Name*: Colleen Middle Name: L Last Name*: Vogler Suffix: 

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7. TYPE OF APPLICANT* H: Public/State Controlled Institution of Higher Education

Other (Specify):

Small Business Organization Type ❍ Women Owned ❍ Socially and Economically Disadvantaged

8. TYPE OF APPLICATION* If Revision, mark appropriate box(es).

● New ❍ Resubmission ❍ A. Increase Award ❍ B. Decrease Award ❍ C. Increase Duration

❍ Renewal ❍ Continuation ❍ Revision ❍ D. Decrease Duration ❍ E. Other (specify) :

Is this application being submitted to other agencies?* ❍Yes ●No What other Agencies?

9. NAME OF FEDERAL AGENCY*

National Institutes of Health

10. CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER

TITLE:

11. DESCRIPTIVE TITLE OF APPLICANT'S PROJECT*

Neural Markers of Persistence and Recovery from Childhood Stuttering: An fMRI Study of Continuous Speech Production

12. PROPOSED PROJECT

Start Date* Ending Date*

09/01/2016 08/31/2019

13. CONGRESSIONAL DISTRICTS OF APPLICANT

 

 

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Contact PD/PI: Chow, Ho Ming

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057 . Received Date:

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SF 424 (R&R) APPLICATION FOR FEDERAL ASSISTANCE Page 2

14. PROJECT DIRECTOR/PRINCIPAL INVESTIGATOR CONTACT INFORMATION

Prefix: First Name*: Ho Ming Middle Name: Last Name*: Chow Suffix: 

Position/Title: Research Investigator

Organization Name*:

Department: Psychiatry

Division: Medical School

Street1*:

Street2:

City*:

County:

State*:

Province:

Country*: USA: UNITED STATES

ZIP / Postal Code*:

Phone Number*: Fax Number: Email*: 

15. ESTIMATED PROJECT FUNDING

a. Total Federal Funds Requested*

b. Total Non-Federal Funds*

c. Total Federal & Non-Federal Funds*

d. Estimated Program Income*

16. IS APPLICATION SUBJECT TO REVIEW BY STATE

EXECUTIVE ORDER 12372 PROCESS?*

a. YES ❍ THIS PREAPPLICATION/APPLICATION WAS MADE

AVAILABLE TO THE STATE EXECUTIVE ORDER 12372

PROCESS FOR REVIEW ON:

DATE:

b. NO ● PROGRAM IS NOT COVERED BY E.O. 12372; OR

❍ PROGRAM HAS NOT BEEN SELECTED BY STATE FOR

REVIEW

17. By signing this application, I certify (1) to the statements contained in the list of certifications* and (2) that the statements herein

are true, complete and accurate to the best of my knowledge. I also provide the required assurances * and agree to comply with

any resulting terms if I accept an award. I am aware that any false, fictitious, or fraudulent statements or claims may subject me to

criminal, civil, or administrative penalties. (U.S. Code, Title 18, Section 1001)

● I agree*

* The list of certifications and assurances, or an Internet site where you may obtain this list, is contained in the announcement or agency specific instructions.

18. SFLLL or OTHER EXPLANATORY DOCUMENTATION File Name: 

19. AUTHORIZED REPRESENTATIVE

Prefix: Mr. First Name*: Craig Middle Name: Last Name*: Reynolds Suffix: 

Position/Title*: Director

Organization Name*:

Department: Research & Sponsored Projects

Division:

Street1*:

Street2:

City*:

County:

State*:

Province:

Country*: USA: UNITED STATES

ZIP / Postal Code*:

Phone Number*: Fax Number: Email*: 

Signature of Authorized Representative*

Craig.Reynolds

Date Signed*

02/23/2016

20. PRE-APPLICATION File Name: 

21. COVER LETTER ATTACHMENT File Name:CoverLetter.pdf 

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Table Of Contents Page Numbers

SF 424 R&R Cover Page----------------------------------------------------------------------------------------- 1

 Table of Contents------------------------------------------------------------------------- 3

Performance Sites--------------------------------------------------------------------------------------------- 4

Research & Related Other Project Information------------------------------------------------------------------ 5

 Project Summary/Abstract(Description)----------------------------------------------------- 6

 Project Narrative------------------------------------------------------------------------- 7

 Facilities & Other Resources-------------------------------------------------------------- 8

 Other Attachments------------------------------------------------------------------------- 11

 AuthenticationOfKeyBiologicalChemicalResources------------------------ 11

Research & Related Senior/Key Person-------------------------------------------------------------------------- 12

PHS398 Cover Page Supplement---------------------------------------------------------------------------------- 30

PHS 398 Modular Budget---------------------------------------------------------------------------------------- 32

 Personnel Justification------------------------------------------------------------------- 36

 Consortium Justification------------------------------------------------------------------ 37

PHS 398 Research Plan----------------------------------------------------------------------------------------- 38

 Specific Aims----------------------------------------------------------------------------- 39

 Research Strategy------------------------------------------------------------------------- 40

 Human Subjects Section-------------------------------------------------------------------- 46

 Protection of Human Subjects------------------------------------------ 46

 Women & Minorities---------------------------------------------------- 51

 Planned Enrollment Report--------------------------------------------- 52

 Children-------------------------------------------------------------- 53

 Bibliography & References Cited----------------------------------------------------------- 54

 Letters Of Support------------------------------------------------------------------------ 56

 Resource Sharing Plans-------------------------------------------------------------------- 61

Contact PD/PI: Chow, Ho Ming

Table of Contents Page 3
Contact PD/Pl: Chow, Ho Ming 

0MB Number: 4040-0010 

Expiration Date: 06/30/2016 

Project/Performance Site Location(s) 

Project/Performance Site Primary Location O I am submitting an application as an individual, and not on behalf of 

a company, state, local or tribal government, academia, or other type of 

organization. 

Organization Name: 

Duns Number: 

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a company, state, local or tribal government, academia, or other type of 

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Organization Name: University of Maryland 

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T Funding Opportunity Number: PAR-16-057. Received Date: racking Number: GRANT1 2102741 

2016-02-23T15:48:23.000-05:00 
Contact PD/PI: Chow, Ho Ming

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

OMB Number: 4040-0001

Expiration Date: 06/30/2016

RESEARCH & RELATED Other Project Information

1. Are Human Subjects Involved?* ● Yes ❍ No

1.a. If YES to Human Subjects

Is the Project Exempt from Federal regulations? ❍ Yes ● No

If YES, check appropriate exemption number: 1 2 3 4 5 6

If NO, is the IRB review Pending? ● Yes ❍ No

IRB Approval Date:

Human Subject Assurance Number 00004969

2. Are Vertebrate Animals Used?* ❍ Yes ● No

2.a. If YES to Vertebrate Animals

Is the IACUC review Pending? ❍ Yes ❍ No

IACUC Approval Date:

Animal Welfare Assurance Number

3. Is proprietary/privileged information included in the application?* ❍ Yes ● No

4.a. Does this project have an actual or potential impact - positive or negative - on the environment?* ❍ Yes ● No

4.b. If yes, please explain:

4.c. If this project has an actual or potential impact on the environment, has an exemption been authorized or an

environmental assessment (EA) or environmental impact statement (EIS) been performed?

❍ Yes ❍ No

4.d. If yes, please explain:

5. Is the research performance site designated, or eligible to be designated, as a historic place?* ❍ Yes ● No

5.a. If yes, please explain:

6. Does this project involve activities outside the United States or partnership with international

collaborators?*

❍ Yes ● No

6.a. If yes, identify countries:

6.b. Optional Explanation:

Filename

7. Project Summary/Abstract* ProjectSummary.pdf 

8. Project Narrative* Project_Narrative_v3.pdf 

9. Bibliography & References Cited Bibliography_Reference.pdf 

10.Facilities & Other Resources FacilitiesAndOtherResources.pdf 

11.Equipment

12. Other Attachments AuthenticationOfKeyBiologicalChemicalResources pdf

 

 Page 5
Although symptoms of childhood stuttering fully manifest during overt, continuous speech production, little is 

known about the neural processes associated with speech production in children, and how these processes are 

disrupted, resulting in the overt manifestation of stuttering instances. Moreover, the majority of children who 

stutter recover naturally, but we do not know how children’s brains functionally adapt to cope with the disorder 

and achieve fluent speech. Absent such knowledge, the neurological deficits underlying stuttering and how the 

disorder resolves itself cannot be fully understood, a difficulty that limits our ability to develop advances in 

clinical assessment and intervention. Our long-term goal is to develop effective therapeutic interventions to 

treat and prevent persistent stuttering during childhood. The objective of the present application, which is the 

next step in pursuing that goal, is to determine brain activity patterns associated with continuous speech 

production in children with persistent (pCWS) and children who recovered from stuttering (rCWS). The 

central hypothesis of the application is that persistent stuttering is associated with anomalous brain activity in 

the neural circuits for speech-motor control, while recovery from stuttering is associated with greater 

involvement of right frontal areas. The rationale of this proposed research is that an empirically-based 

understanding of brain activity patterns associated with continuous speech production of pCWS and rCWS is 

foundational for the development of future therapeutic interventions attempting to modify anomalous activity. 

Using a novel fMRI technique, we will test our central hypothesis by pursuing the following specific aims: 1) 

Identify brain activity associated with continuous speech production that characterizes persistent stuttering, 

and 2) Identify brain activity associated with continuous speech production that characterizes recovery from 

stuttering. To achieve Aim #1, brain activity associated fluent speech production between pCWS and controls 

will be compared. Furthermore, brain activity associated with fluent and stuttered speech production in pCWS 

will be separated and compared. To achieve Aim #2, brain activity associated with fluent speech production 

between rCWS and controls will be compared. This application is innovative because it will be the first study to 

examine both cortical and subcortical activity associated with continuous speech production in children with 

high spatial resolution using a novel fMRI de-noising technique. Findings of this project will be significant

because they are expected to fundamentally advance our understanding of the neural processes associated with 

fluent and disfluent continuous speech production in children who stutter and provide insights into 

neuroplasticity associated with recovery from childhood stuttering. Ultimately, this new knowledge may guide 

the future development of better treatment strategies for childhood stuttering. 

Contact PD/PI: Chow, Ho Ming

Project Summary/Abstract Page 6
Project Narrative 

The proposed studies address an important and under-investigated area of childhood developmental stuttering 

that is relevant to the mission of NIDCD. Findings of these studies are expected to advance our understanding 

of the neural processes associated with fluent and disfluent continuous speech production in children who 

stutter and provide insights into neuroplasticity associated with recovery from childhood stuttering. This new 

knowledge may guide the development of more effective treatment strategies for childhood stuttering. 

Contact PD/PI: Chow, Ho Ming

Project Narrative Page 7
Contact PD/PI: Chow, Ho Ming

FACILITIES AND RESOURCES 

 

This project has access to the state-of-the-art functional magnetic imaging (fMRI) equipment and research 

resources to successfully accomplish the objectives outlined in our proposal. The fMRI laboratory involved in 

data collection is located in the North Campus of the , near the Department of Psychiatry 

at the . The fMRI laboratory has participant-dedicated parking spaces, and is 

connected by high-speed networks to laboratories on the campuses of the . The fMRI 

laboratory is decorated in a child-friendly way and the staff is experienced in pediatric neuroimaging. 

The fMRI Laboratory 

The fMRI laboratory is equipped with two state-of-the-art 3.0T GE MRI scanners (MR750, DV25.0 software 

version). They both have high performance gradient systems (peak 50 mT/m, slew rate 200 T/m/s). This 

model has a full set of functional imaging capabilities, including single-shot imaging (spiral and EPI), 

automated shimming, real-time image reconstruction and processing. This project will use a standard eightchannel coil for parallel imaging, but two 32-channel receive arrays from Nova Medical are available for greater 

image acquisition speed-up factors and improved SNR, and implementation of cutting-edge multi-band 

acquisitions. The latest version (FOMRI-III) of noise cancellation optical microphone from OptoAcoustic 

(Moshav Mazor, Israel) and 2 MRI compatible cameras from MRC Systems (Heidelberg, Germany) are 

available for recording participants’ audio and video during speech production. Two large scale Linux servers 

with dedicated backup are available for reconstruction, processing and archival storage (Main machine: 24 

core/16G RAM/15T storage; secondary machine: 8 core/16G/5T). Software packages available for data 

collection and analysis include EPrime, Presentation, MATLAB, SPM12, FSL, AFNI, C++ and a variety of 

custom packages. A patient waiting room and examination rooms are available in the fMRI laboratory. Two 

mock scanners at nearby locations are available for pediatric participant to get familiar with the scanning 

environment. 

Speech Neurophysiology Laboratory at the 

Dr. Soo-Eun Chang, the co-I of this project, has offered the PI the use of her laboratory’s equipment for fMRI 

data analysis for the proposed project. The Speech Neurophysiology Laboratory is designed for conducting 

multimodal imaging data and advanced data analysis. The laboratory is equipped with a Linux server with 16 

cores, 32G RAM and 12T storage dedicated for MRI data analyses and backup. Software packages available for 

data and statistical analysis include MATLAB, R, SPM, FSL, AFNI and SPSS. In addition to hardware, the 

laboratory has built up a database of about 70 children with developmental stuttering (comprising persistent 

and recovered children) and 70 typically developing children who are interested in participating neuroimaging 

research. Dr. Chang and her team have created an effective work flow for subject recruitment, screening and 

visit scheduling. The laboratory’s participant pool and staff experience with pediatric research greatly enhance 

the chances for success of this project. 

Department of Psychiatry, the

The Department of Psychiatry will provide necessary facilities and support to personnel involved with this 

project at Rachel Upjohn Building. These facilities include office space, furnishings, telephone, desktop 

computer, internet connection and other commonly used office and research utilities. Shared facilities of the 

Department include two interview and testing rooms, a ‘mock fMRI scanner’ facility, printing and fax machine. 

Moreover, the Department of Psychiatry has funded a core facility to provide hardware and software support 

necessary to analyze neuroimaging data (PET, MRI, fMRI). It is fully equipped with latest releases of statistical 

parametric mapping (SPM12) and BrainVoyager software packages and uses a networked cluster of Linux 

Facilities & Other Resources Page 8
Contact PD/PI: Chow, Ho Ming

workstations. This group provides intellectual support for study design, analysis, statistics and interpretation 

across platforms, and periodically requires license renewals, hardware upgrades and parts replacements. 

Scientific Environment 

The environment in which the proposed research will take place is perfectly suited to ensure success. The PI 

holds a research faculty position at the Department of Psychiatry. His position is fully supported through a 

combination of departmental and private foundation funding and is totally dedicated to stuttering research. 

Collaborating with the co-I Dr. Chang’s Speech Neurophysiology Laboratory, which has been conducting the 

largest longitudinal neuroimaging research of childhood stuttering in the last five years, the PI has been 

involved in various aspects of stuttering research. This collaboration is an important part of this proposal 

because it provides an environment to synergize Dr. Chang’s experience in conducting pediatric neuroimaging 

research in stuttering and the PI’s expertise in advanced neuroimaging technologies. Moreover, Department of 

Psychiatry at the university provides a simulating intellectual environment and perspectives from childhood 

development and developmental disorders to foster new ideas on stuttering research. 

The Research Capacity 

The is a nationally-recognized research and academic institution, which provides a wide 

range of resources to investigators to lead novel research. These resources include comprehensive library 

collections and databases, technological and statistical expertise, inter-disciplinary collaboration and training, 

state-of-the art facilities, and a wireless-enabled campus. Collectively, these resources provide the capacity for 

success of the proposed project. The ranks as one of the leading 

medical centers in the U.S. The are situated on an 84-

acre campus in . A major mission of the is to foster academic research; its success has been 

reflected in major contributions to both basic and clinical sciences, in national recognition accorded to its 

faculty, and in levels of outside funding won for research initiatives. In the NIH fiscal year 2014, The

 received ranking twelfth among U.S. public medical 

schools nationwide in total NIH funding. UMHS is the 4th largest teaching hospital in the country according to 

Modern Healthcare magazine, and is highly ranked across a broad range of fields 

including health, medicine, science, engineering, business, and law. 

UNIVERSITY OF MARYLAND 

Ratner Office and Lab Facilities: 

Dr. Ratner has both an office and a dedicated laboratory area with a total of nine computer stations. All 

computers are networked to both the University of Maryland as well as a separate college system that provides 

and maintains programs for email, word processing, statistical analysis and other commonly used office and 

research utilities. The College of Behavioral & Social Sciences also maintains two distance learning classrooms 

which have already been used to conduct CLAN training sessions with laboratories (PI’s and other faculty at the 

University of Michigan) via two-way video hookup. As a consultant to the TalkBank project, 

 Dr. Ratner maintains close and frequent contact with its PI (Dr. Brian 

MacWhinney) and primary programmer (Leonid Spektor); this has historically allowed her the ability to 

contribute to program development that is specifically useful to individual researchers, such as the PI, and to 

obtain immediate assistance for technological difficulties or desired changes to computational utilities. Dr. 

Ratner has the assistance of two Research Assistants, funded through general University funds, as well as a 

large number of undergraduate research volunteers who participate in her lab activities via the very active 

Maryland Center for Undergraduate Research (MCUR); the MCUR is one of a number of campus activities that 

emphasizes the importance of research training for its undergraduates. Dr. Ratner also works within the larger 

Facilities & Other Resources Page 9
local community of fluency researchers, such as Drs. Allen Braun and Dennis Drayna at NIDCD Intramural, 

and Dr. Shelley Brundage at George Washington University. This engagement provides opportunities to 

discuss and interpret research findings. 

Scientific Environment 

The Department of Hearing and Speech Science (HESP), University of Maryland and surrounding area has a 

strong presence in multiple areas of communication sciences and disorders: hearing/perception (e.g., Drs. 

Rochelle Newman, Samira Anderson, Matthew Goupell, & Sandra Gordon-Salant in HESP), neurogenic speech 

and language disorders (Yasmeen Shah, Jared Novick and Nancy Pearl Solomon in HESP) and developmental 

language research (e.g., Yi Ting Huang in HESP; Drs. Jeffrey Lidz and Naomi Feldman in Linguistics; Drs. 

Nathan Fox, D. J. Bolger, and Geetha Ramani in Human Development; Drs. Tracy Riggins, Jonathan Beier, 

and Elizabeth Redcay in Psychology). HESP also has as faculty an ASHA Fellow (Vivian Sisskin, nationally 

known and awarded for her clinical expertise in stuttering). Finally, the University of Maryland is home to the 

largest and most integrated community of language scientists in North America through the Maryland 

Language Science Center (http://languagescience.umd.edu), including researchers from 17 departments, 

programs and affiliated centers and institutes (including the Center for Advanced Study of Language, the 

National Foreign Language Center, the University of Maryland Institute for Advanced Computer Studies, the 

Maryland Neuroimaging Center, and the Institute for Systems Research). 

The University of Maryland Research Capacity 

The University of Maryland offers a number of cross- disciplinary research groups that provide venues for the 

sharing of research findings and consultation. Its program in Neuroscience and Cognitive Science (NACS), the 

Developmental Science Field Committee, the University of Maryland Autism Research Consortium (UMARC), 

and the Center for the Comparative and Evolutionary Biology of Hearing all meet and share research updates 

frequently. The University of Maryland has also just announced the formation of the Maryland Language 

Science Center, which will add further to the scientific richness of the local research community. Several of 

these groups have their own colloquium series, which bring in outside members of the scientific community to 

meet with Maryland faculty. Maryland is thus an ideal location for work in communication sciences and 

disorders. 

Contact PD/PI: Chow, Ho Ming

Facilities & Other Resources Page 10
Authentication of Key Biological and/or Chemical Resources 

None 

Contact PD/PI: Chow, Ho Ming

AuthenticationOfKeyBiologicalChemicalResources Page 11
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Contact PD/PI: Chow, Ho Ming

OMB Number: 4040-0001

Expiration Date: 06/30/2016

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057 . Received Date:

2016-02-23T15:48:23.000-05:00

RESEARCH & RELATED Senior/Key Person Profile (Expanded)

PROFILE - Project Director/Principal Investigator

Prefix:  First Name*: Ho Ming Middle Name  Last Name*: Chow Suffix: 

Position/Title*: Research Investigator

Organization Name*:

Department: Psychiatry

Division: Medical School

Street1*:

Street2:

City*:

County:

State*:

Province:

Country*: USA: UNITED STATES

Zip / Postal Code*:

Phone

Number*: 

Fax Number:  E-Mail*: 

Credential, e.g., agency login: 

Project Role*:  PD/PI Other Project Role Category: 

Degree Type:  PhD Degree Year:  2008

File Name

Attach Biographical Sketch*: Biosketch_Chow.pdf

Attach Current & Pending Support:

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 Page 13

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057 . Received Date:

2016-02-23T15:48:23.000-05:00

PROFILE - Senior/Key Person

Prefix:  First Name*: Allen Middle Name  Last Name*: Braun Suffix: 

Position/Title*: Cheif, Language Section, NIDCD

Organization Name*: NIH

Department:

Division: NIDCD

Street1*:

Street2:

City*:

County:

State*:

Province:

Country*: USA: UNITED STATES

Zip / Postal Code*:

Phone

Number*: 

Fax Number:  E-Mail*: 

Credential, e.g., agency login: 

Project Role*:  Consultant Other Project Role Category: 

Degree Type:  MD Degree Year:  1980

File Name

Attach Biographical Sketch*: Biosketch_Braun.pdf

Attach Current & Pending Support:

PROFILE - Senior/Key Person

Prefix:  First Name*: Soo-Eun Middle Name  Last Name*: Chang Suffix: 

Position/Title*: Research Professor

Organization Name*:

Department: Psychiatry

Division: Medical School

Street1*:

Street2:

City*:

County:

State*:

Province:

Country*: USA: UNITED STATES

Zip / Postal Code*:

Phone

Number*: 

Fax Number:  E-Mail*: 

Credential, e.g., agency login: 

Project Role*:  Co-Investigator Other Project Role Category: 

Degree Type:  PhD Degree Year:  2005

File Name

Attach Biographical Sketch*: Biosketch_Chang.pdf

Attach Current & Pending Support:
-

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Contact PD/PI: Chow, Ho Ming

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057 . Received Date:

2016-02-23T15:48:23.000-05:00

PROFILE - Senior/Key Person

Prefix:  First Name*: Nan Middle Name  Last Name*: Ratner Suffix: 

Position/Title*: Professor

Organization Name*: University of Maryland

Department: Hearing and Speech Sciences

Division:

Street1*:

Street2:

City*:

County:

State*:

Province:

Country*: USA: UNITED STATES

Zip / Postal Code*:

Phone

Number*: 

Fax Number:  E-Mail*: 

Credential, e.g., agency login: 

Project Role*:  Co-Investigator Other Project Role Category: 

Degree Type:  Ed.D Degree Year:  1982

File Name

Attach Biographical Sketch*: Bioshetch_Ratner.pdf

Attach Current & Pending Support:

 Page 14
Contact PD/PI: Chow, Ho Ming

OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018) 

BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors. 

Follow this format for each person. DO NOT EXCEED FIVE PAGES. 

NAME: Chow, Ho Ming 

eRA COMMONS USER NAME (agency login):

POSITION TITLE: Research Investigator 

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, 

include postdoctoral training and residency training if applicable.) 

INSTITUTION AND LOCATION DEGREE 

(if applicable)

Completion Date 

MM/YYYY

FIELD OF STUDY

University of Hong Kong BENG 12/1997 Industrial Engineering 

University of Hong Kong MPHIL 11/2000 Ergonomics 

University of Osnabrueck PHD 11/2008 Cognitive Science 

NIDCD/NIH Postdoctoral Fellow 03/2014 Neuroscience/Neuroimaging 

A. Personal Statement

With a background in cognitive neuroscience, psycholinguistics, engineering, I have been able to develop and

test cutting edge brain imaging techniques to study the neurobiology of human communication. I am

particularly interested in understanding the neural mechanisms of speech production and how these 

mechanisms are disrupted, leading to speech disorders. During the first 3 years (2009-2012) of my

postdoctoral training at the NIH, my research focused on studying discourse-level language comprehension 

and production in healthy volunteers. Additionally, I was actively involved in the entire process of developing a 

novel technique to remove speech-related artifacts from fMRI signals (Xu et al., 2014). With the capability to

use fMRI to examine brain activity associated with continuous speech, in 2012, I started a comprehensive 

research project to study functional and structural anomalies in the brains of adults who stutter (n = 36 adults 

who stutter and 30 matched controls). I led, designed, and implemented this project that included i) three fMRI 

experiments to study word-, sentence-, discourse-level production, ii) diffusion tensor imaging to study whitematter structural anomalies, and iii) genetic sequencing to study potential relationship between stutteringrelated mutation and brain anomalies. The first paper associated with this stuttering project has just been

published (Drayna et al, 2015) and several other manuscripts are in preparation. I am confident that my

technical expertise in neuroimaging and experience in empirically studying stuttering combined with 

demonstrated collaboration with Dr. Chang (since 2015) and Dr. Ratner (since 2013) will significantly 

contribute to the success of the proposed project. For this current project, I will meet weekly with Dr. Chang, 

Dr. Ratner (via videoconferencing) and the research assistant to review project progress. I will be overseeing 

all aspects of this research, including participant recruitment, fMRI data acquisition, data analysis and

interpretations. I expect that successful completion of the proposed research will contribute critical elements in

understanding the neural characteristics of persistence and recovery from childhood stuttering. 

1. Xu Y, Tong Y, Liu S, Chow HM, AbdulSabur NY, Mattay GS, Braun AR. Denoising the speaking brain: 

toward a robust technique for correcting artifact-contaminated fMRI data under severe motion. 

Neuroimage. 2014 Dec;103:33-47. PubMed PMID: 25225001; PubMed Central PMCID: PMC4312243. 

2. Drayna D, Raza M, Domingues C, Webster R, Sainz E, Paris E, Rahn R, Gutierrez J, Chow HM, 

Mundorff J, Kang C, Riaz N, Khan S, Basra A, Braun A, Riazuddin S. Mucolipidosis Types II and III and

non-syndromic stuttering are associated with different variants in the same genes. Eur J Hum Gent. 

PMID: 26130485

Biosketches Page 15
Contact PD/PI: Chow, Ho Ming

B. Positions and Honors

Positions and Employment

2009 - 2014 Postdoctoral Research Fellow, NIDCD/NIH, Bethesda, MD

2014 - 2015 MRI Psychology Researcher, NIDCD/NIH through Kelly Services, Inc, Bethesda, MD

2015 - Research Investigator, 

Other Experience and Professional Memberships

Honors

1997-1999 Postgraduate Studentship, University of Hong Kong 

2005-2008 Research Grants for Doctoral Candidates and Young Academics and Scientists, DAAD

(German Academic Exchange Service) 

2008 Travel Award, Organization of Human Brain Mapping 

2009-2014 Visiting Fellow Award, National Institutes of Health 

2015 Fellows Award for Research Excellence, National Institutes of Health 

2015 Meritorious Poster Award, American Speech-Language-Hearing Association (ASHA) 

C. Contribution to Science

1. Developing an fMRI procedure to study continuous speech. I was actively involved in developing an

effective and flexible de-noising technique to overcome the severe image distortion caused by overt 

speech artifacts during fMRI scanning. These artifacts are primarily related to the interaction between 

various motion effects and the magnetic fields employed by fMRI. Our denoising technique has been 

validated with positron emission tomography (an imaging technique much less susceptible to the above 

artifacts) and demonstrated to perform better than other state-of-the-art de-noising methods. This novel 

method opens new research horizons in studying neural processes of speech production and speech 

disorders using fMRI. In close collaboration with the project leader (Y. Xu), I was involved in developing 

and testing possible fMRI de-noising strategies, and applying the final de-noising procedures to evaluate its 

effectiveness. 

a. AbdulSabur NY, Xu Y, Liu S, Chow HM, Baxter M, Carson J, Braun AR. Neural correlates and network 

connectivity underlying narrative production and comprehension: a combined fMRI and PET study. 

Cortex. 2014 Aug;57:107-27. PubMed PMID: 24845161. 

b. Xu Y, Tong Y, Liu S, Chow HM, AbdulSabur NY, Mattay GS, Braun AR. Denoising the speaking brain: 

toward a robust technique for correcting artifact-contaminated fMRI data under severe motion. 

Neuroimage. 2014 Dec;103:33-47. PubMed PMID: 25225001; PubMed Central PMCID: PMC4312243. 

2. Studying sensorimotor involvement with language comprehension. Findings from our recent 

empirical studies suggest that in addition to the left perisylvian language regions, sensorimotor areas are 

also involved in language comprehension. Results indicate that the activity of sensorimotor areas and their 

functional connectivity with the left language regions are associated with the processing of semantic 

content. Moreover, functional connectivity within sensorimotor areas is modulated by the comprehenders' 

personal experience. These findings indicate that comprehension should be viewed as a mental simulation 

of personal experience. 

a. Chow HM, Kaup B, Raabe M, Greenlee MW. Evidence of fronto-temporal interactions for strategic 

inference processes during language comprehension. Neuroimage. 2008 Apr 1;40(2):940-54. PubMed 

PMID: 18201911. 

b. Chow HM, Mar RA, Xu Y, Liu S, Wagage S, Braun AR. Embodied comprehension of stories: 

interactions between language regions and modality-specific neural systems. J Cogn Neurosci. 2014 

Feb;26(2):279-95. PubMed PMID: 24047383. 

Biosketches Page 16
c. Chow HM, Mar RA, Xu Y, Liu S, Wagage S, Braun AR. Personal experience with narrated events

modulates functional connectivity within visual and motor systems during story comprehension. Hum

Brain Mapp. 2015 Apr;36(4):1494-505. PubMed PMID: 25545633.

3. Studying creative use of language. We use fMRI to study brain activity associated with lyrical

improvisation during freestyle rap, and generation and revision of poetry. We demonstrate that, in both art

forms, creative processes are associated with the deactivation of lateral prefrontal areas that play an

important role in executive control.

d. Liu S, Chow HM, Xu Y, Erkkinen MG, Swett KE, Eagle MW, Rizik-Baer DA, Braun AR. Neural

correlates of lyrical improvisation: an FMRI study of freestyle rap. Sci Rep. 2012;2:834. PubMed PMID:

23155479; PubMed Central PMCID: PMC3498928.

e. Liu S, Erkkinen MG, Healey ML, Xu Y, Swett KE, Chow HM, Braun AR. Brain activity and connectivity

during poetry composition: Toward a multidimensional model of the creative process. Hum Brain Mapp.

2015 May 26. PubMed PMID: 26015271.

4. Multimodal imaging and functional connectivity. Using simultaneous acquisition of EEG and fMRI, my

former colleagues and I discovered that the connectivity patterns in different sleep stages of humans

change dramatically. Comparing rapid eye movement (REM) sleep with slow-wave sleep as well as

wakeful rest, we demonstrated that REM sleep is characterized by temporally dynamic interactions

between unimodal sensorimotor areas and the higher-order association cortices. We speculated that these

interactions in important for dreaming and memory consolidation.

a. Chow HM, Horovitz SG, Carr WS, Picchioni D, Coddington N, Fukunaga M, Xu Y, Balkin TJ, Duyn JH,

Braun AR. Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from

other states of consciousness. Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10300-5. PubMed

PMID: 23733938; PubMed Central PMCID: PMC3690889.

Complete List of Published Work in MyBibliography:

http://www.ncbi.nlm.nih.gov/sites/myncbi/ho%20ming.chow.1/bibliography/48036263/public/?sort=date&directi

on=ascending 

D. Research Support

Ongoing Research Support

none

Completed Research Support

2009/04/02 - 2015/01/16 

1ZIADC000031, NIDCD/NIH Intramural Research Program 

Braun, Allen (PI) 

Functional Neuroimaging Studies in Humans 

The aim of this project is to use multimodal imaging techniques to characterize brain activation patterns 

associated with language comprehension and production in normal subjects and individuals with neurological 

disorders affecting human communication. My major contribution to this project is to investigate functional roles 

of sensorimotor areas in language comprehension, and functional/anatomical brain anomalies associated with 

developmental stuttering. 

Role: Co-Investigator 

Contact PD/PI: Chow, Ho Ming

Biosketches Page 17
OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018) 

BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors. 

Follow this format for each person. DO NOT EXCEED FIVE PAGES. 

NAME: Allen Richard Braun, M.D. 

eRA COMMONS USER NAME (agency login): 

POSITION TITLE: Chief, Language Section, NIDCD, NIH 

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, 

include postdoctoral training and residency training if applicable.) 

INSTITUTION AND LOCATION DEGREE 

(if applicable)

Completion Date 

MM/YYYY

FIELD OF STUDY

Washington University, St. Louis BA 1964 - 1968 English Lit/Biology 

University of Wisconsin, Madison 1974- 1976 Neuroendocrinology 

Rush Medical College, Chicago MD 1976 - 1980 Medicine 

Rush, Pres St. Luke’s, Chicago 1981 - 1984 Neurology Residency 

NIH Clinical Center, Bethesda 1986 - 1988 Nuc Med Residency 

A. Personal Statement

My primary research interest is in understanding how language is instantiated in the brain, how brain-language 

relationships are interrupted by disorders that affect the ability to communicate, and how these disorders can 

be treated. To pursue these goals, my lab recently developed an fMRI de-noising technique, which has been

demonstrated to be able to remove artifacts related to overt, continuous speech production from functional 

magnetic resonance images (Xu et al., 2014). This technique allows us to examine brain activity during 

continuous speech production using fMRI, which was not considered feasible in the past. The ability to study 

brain activity associated with continuous speech is extremely important because this is the context in which 

symptoms of speech disorders such as development stuttering fully emerge. Because I oversaw the team, in

which Dr. Chow was a key member, that developed this de-noising technique, I am well suited to support the 

research studies Dr. Chow proposes to use this technique to study children who stutter. I am excited that Dr. 

Chow is planning to use this method to investigate this important but unexplored topic and look forward to the 

collaboration. 

1. Xu Y, Tong Y, Liu S, Chow HM, AbdulSabur NY, Mattay GS, Braun AR. Denoising the speaking brain: 

toward a robust technique for correcting artifact-contaminated fMRI data under severe motion. 

Neuroimage. 2014 Dec;103:33-47. PubMed PMID: 25225001; PubMed Central PMCID: PMC4312243. 

B. Positions and Honors

Positions and Employment

1984 - 1986 Medical Staff Fellow, Experimental Therapeutics Branch, NINDS/NIH 

1986 - 1988 Senior Staff Fellow, Department of Nuclear Medicine, Clinical Center, NIH 

1988 - 1991 Head, Nuclear Medicine Unit, Clinical Brain Disorder Branch, NIMH/NIH 

1991 - 1994 Medical Officer, Voice and Speech Section, NIDCD/NIH 

1994 - 2003 Acting Chief, Language Section, NIDCD/NIH 

2003 - Chief, Language Section, NIDCD/NIH 

Other Experience and Professional Memberships 

Additional Professional Activities: 

Associate Editor, Human Brain Mapping 

Editorial Board, Journal of Fluency Disorders 

Adjunct Associate Professor, Neuroscience, Cognitive Science, University of MD 

Contact PD/PI: Chow, Ho Ming

Biosketches Page 18
Medical Staff (Research), Suburban Hospital, Bethesda, MD 

NIH Central Tenure Committee 

NIH MRI Steering Committee 

NIH Positron Emission Tomography Steering Committee 

NIH Imaging Probe Development Steering Committee 

NIH Mouse Imaging Facility Steering Committee 

Howard Hughes Medical Institute Scholars Advisor 

NIH LCOM Study Section, 2003, 2005 

NIH Pharmacy and Therapeutics Committee, 1995-2001

NIDCD-NINDS Institutional Review Board, 1995-2002

Chairman, Radiation Safety Committee, NIMH Neuroscience Center, 1988-1991

Chairman, Radioactive Drug Research Committee, NIMH Neuroscience Center 1988-1991

Board Certification: 

National Board of Medical Examiners, 1981 

American Board of Psychiatry and Neurology (Neurology), 1987 

American Board of Nuclear Medicine, 1993 

Professional Affiliations: 

American Academy of Neurology Society of Nuclear Medicine Society for Neuroscience Cognitive 

Neuroscience Society 

Honors

1998 Merit Award (NIDCD) "For innovative and insightful research contributions on neuroimaging 

relevant to communication disorders"

1999 Special Act of Service Award (NIDCD)

1999 Staff Recognition Award 

1999 Special Act of Service Award (EEO) 

2000 Staff Recognition Award 

2004 Special Act of Service Award (NIDCD)

2013 Plenary Address, DC Speech and Hearing Association Annual Meeting 

C. Contribution to Science

1. SLEEP: Used both Positron Emission Tomography and Magnetic Resonance Imaging Methods to

characterize patterns of cerebral activity during the sleep wake cycle. This research documented a novel 

set of findings centered on robust changes in frontal lobe activity that have proved to be foundational in the 

field. 

a. Braun AR, Balkin TJ, Wesensten NJ, Varga M, Baldwin P, Carson RE, Belenky G, Herscovitch P.

Regional Cerebral Blood Flow Throughout the Sleep-Wake Cycle: An H2O-15 Positron Emission 

Tomography Study. Brain, 120:1173-1197, 1997. PMID: 9236630

b. Braun AR, Balkin TJ, Wesensten NJ, Gwadry F, Varga M, Baldwin P, Carson RE, Belenky G, 

Herscovitch P. Dissociated pattern of activity in visual cortices and their projections during human rapid 

eye movement sleep. Science, 279:91-95, 1998. PMID: 9417032 

c. Balkin T, Braun AR, Wesensten N, Jeffries K, Varga M, Baldwin P, Belenky G, Herscovitch, P. The 

Process of Awakening: A PET Study of Regional Brain Activity Patterns Mediating the Reestablishment 

of Alertness and Consciousness. Brain, 125: 2308-2319, 2002. PMID: 12244087 

d. Chow HM, Horovitz SG, Carr WS, Picchioni D, Coddington N, Fukunaga M, Xu Y, Balkin TJ, Duyn JH, 

Braun AR. Rhythmic alternating patterns of brain activity distinguish rapid eye movement sleep from 

other states of consciousness. Proc Natl Acad Sci., 110(25), 2013. PMID: 23733938

2. DISCOURSE: Conducted a series of neuroimaging studies that characterized brain activity during 

naturalistic discourse level language use. Early studies demonstrated engagement of a host of regions 

extending beyond the perisylvian language cortices during real-world language use. Later studies better 

characterized interactions between language and other cognitive and sensorimotor systems during 

comprehension and production of discourse. 

Contact PD/PI: Chow, Ho Ming

Biosketches Page 19
a. Braun AR, Guillemin A, Hosey L, Varga M. The neural organization of discourse: an H2 15O-PET study 

of narrative production in English and American sign language. Brain 124: 2028-2044, 2001. PMID: 

11571220

b. AbdulSabur NY, Xu Y, Liu S, Chow HM, Braun AR. Neural correlates and network connectivity 

underlying narrative production and comprehension: a combined fMRI and PET study Cortex. 57:107-

27, 2014. PMID: 24845161 

c. Chow HM, Mar RA, Xu Y, Liu S, Wagage S, Braun AR. Embodied comprehension of stories: 

Interactions between language regions and modality-specific neural systems. Journal of Cognitive 

Neuroscience. 26(2):279-95, 2014. PMID: 24047383 

d. Chow HM, Mar RA, Xu Y, Liu S, Wagage S, Braun AR. Personal experience with narrated events 

modulates functional connectivity within visual and motor systems during story comprehension. Hum 

Brain Mapp. 36(4):1494-505, 2015. PMID: 25545633 

3. LANGUAGE EVOLUTION: A series of studies in humans and non-human primates provided data 

suggesting a plausible model for language evolution. Early studies demonstrate structural and functional 

similarities in perisylvian cortices that appear to support species specific communication in human and nonhuman primates. Later studies in humans provided data that are consistent with a gestural origins model. 

a. Gannon PJ, Holloway RL, Broadfield DC, Braun AR. Asymmetry of Chimpanzee Planum Temporale: 

Humanlike Pattern of Wernicke’s Brain Language Area Homolog. Science, 279: 220-222, 1998. PMID: 

9422693

b. Gil-da-Costa R, Braun A, Lopes M, Hauser MD, Carson RE, Herscovitch P, Martin A. Towards an

evolutionary perspective on conceptual representation: Species-specific calls activate visual and

affective processing systems in the macaque. Proc Natl Acad Sci USA, 101:17516-17521, 2004. PMID: 

15583132

c. Gil-da-Costa R., Martin A., Lopes M., Munoz, M., Fritz JB, Braun, A.R. Species-specific calls activate 

homologues of Broca’s and Wernicke’s areas in the macaque. Nat Neurosci 9(8):1064-70, 2006. PMID: 

16862150

d. Xu J, Gannon PJ, Emmorey K, Smith JF, Braun AR. Symbolic Gestures and Spoken Language are 

Processed by a Common Neural System. PNAS 106:20664-20669, 2009. PMID: 19923436

4. CREATIVITY: An ongoing series of studies is designed to provide support for a multidimensional model of

creativity, accounting for multiple stages of the creative process, audience responses to a creative product 

and the impact of expertise. Early studies examined musical improvisation, later studies focus on linguistic 

creativity. 

a. Limb CJ, Braun AR. Neural Substrates of Spontaneous Musical Performance: A Functional 

Neuroimaging Study of Jazz Improvisation PLoS One 3(2): e1679, 2008. PMID: 18301756

b. Liu S, Chow HM, Xu Y, Erkkinen MH, Swett KE, Engle MW, Rizik-Baer DA, Braun AR. Neural 

correlates of lyrical improvisation: An fMRI Study of Freestyle Rap. Sci Rep. 2(834), 2012. PMID: 

23155479

c. Liu S, Erkkinen MG, Healey ML, Xu Y, Swett KE, Chow HM, Braun AR. Brain Activity and Connectivity 

during Poetry Composition: Toward a Multi-dimensional Model of the Creative Process. Hum Brain 

Mapp. 36(9), 2015. PMID: 26015271

5. BASAL GANGLIA AND LANGUAGE: Used functional neuroimaging and behavioral methods to examine 

abnormalities of speech-language processing in neurological disorders characterized by abnormalities of

the extrapyramidal system. Each of these studies strongly implicates the basal ganglia in the language 

phenotype characteristic of these disorders. 

a. Braun AR, Stoetter B, Randolph C, Hsiao J, Vladar K, Gernert J, Carson RE, Herscovitch P, Chase TN. 

The Functional Neuroanatomy of Tourette Syndrome: An FDG PET study. I. Regional Changes in

Contact PD/PI: Chow, Ho Ming

Biosketches Page 20
Glucose Metabolism Differentiating Patients and Controls. Neuropsychopharmacology, 9:277-291, 

1993. PMID: 8597526

b. Braun AR, Varga M, Stager S, Shulz G, Selbie S, Maisog JM, Carson RE, Ludlow CL. Altered Patterns 

of Cerebral Activity During Speech and Language Production in Developmental Stuttering. An H2O-15

Positron Emission Tomography Study. Brain, 120:761-784, 1997. PMID: 9183248 

c. So A, Thomasen M, Schulz GM, Guillemin A, Hosey L, Varga M, Ludlow CL, Braun AR. Alterations in

CNS Activity Induced by Botulinum Toxin Treatment in Spasmodic Dysphonia: An H215O-PET Study. 

Journal of Speech, Language, and Hearing Research 49: 1127–1146, 2006. PMID: 17077220

d. Schulz GM, Hosey LA, Bradberry TJ, Stager SV, Lee LC, Pawha R, Lyons KE, Metman LV, Braun AR. 

Selective left, right and bilateral stimulation of subthalamic nuclei in Parkinson’s Disease: Differential 

effects on motor, speech and language function. Journal of Parkinson’s Disease 2(1), 29-40, 2012.

PMID: 23939406

D. Research Support

Ongoing Research Support

1994- 

1ZIADC000031, NIDCD/NIH Intramural Research Program 

Braun, Allen (PI) 

Functional Neuroimaging Studies in Humans 

The aim of the project is to understand how language is instantiated in the brain, how brain-language 

relationships are interrupted by disorders that affect the ability to communicate, and how these disorders can 

be treated. We employs a combination of imaging modalities—hemodynamic methods (PET and fMRI) 

complemented by electrophysiological (EEG/ERP and magnetoencephalography) and PET radiochemical 

tracer techniques—to this end. We investigate both language production and comprehension, since disorders 

that affect speech and language typically have a significant impact on both, and how the brain processes 

language cannot be completely understood by studying either in isolation. We study language at multiple 

levels, from its elementary perceptual and motor features, to higher-level linguistic processing. Most 

importantly, I am interested in more complex, real-world language use because this ecologically valid condition 

is often the only context in which symptoms of many language disorders present. We are interested in a broad 

array of such disorders including TBI, post-stroke aphasia as well as disorders that reflect pathology at the 

borderland between motor and cognitive-linguistic function such as Parkinson1s disease and developmental 

stuttering. In all of our clinical studies, the overarching goal is to use our methods to contribute to the design 

and monitor the efficacy of therapeutic interventions. 

Completed Research Support 

none

Contact PD/PI: Chow, Ho Ming

Biosketches Page 21
Contact PD/PI: Chow, Ho Ming

OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018) 

BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors. 

Follow this format for each person. DO NOT EXCEED FIVE PAGES. 

NAME: Chang, Soo-Eun 

eRA COMMONS USER NAME (agency login): 

POSITION TITLE: Assistant Professor, Rosa Casco Solano-Lopez Research Professor of Child and 

Adolescent Psychiatry 

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, 

include postdoctoral training and residency training if applicable.) 

INSTITUTION AND LOCATION DEGREE 

(if applicable)

Completion 

Date 

MM/YYYY

FIELD OF STUDY

Seoul National University, Seoul BA 02/1996 Psychology 

Vanderbilt University, Nashville, Tennessee MS 08/1999 Hearing and Speech 

Sciences 

University of Illinois at Urbana-Champaign, Champaign, 

Illinois 

PHD 08/2005 Speech and Hearing 

Science 

National Institute of Neurological Disorders and Stroke 

(NINDS) Intramural research program, NIH, Bethesda, 

Maryland 

Postdoctoral 

Fellow 

07/2009 Clinical 

Neuroscience 

A. PERSONAL STATEMENT

I was trained in the field of speech and hearing sciences and have clinical certification in Speech-Language 

Pathology. As a result, I have had regular contact with both children and adults who stutter and have thus

become very aware of the significant burden that stuttering can inflict on one’s academic, emotional, social, 

and vocational life and because of that the deleterious impact this communication disorder has on the nation’s 

health. In attempts to address these issues, I have devoted my research career to a better understanding of

the characteristics, development and etiology of stuttering. Such knowledge, I believe, should eventually 

contribute to more data-based, precise diagnosis of and efficacious treatment of stuttering. This research 

(presently funded through an NIDCD R01 grant) currently involves a longitudinal study of sexually dimorphic 

brain development in children who stutter (CWS), resulting in a collection of over 280 longitudinal MRI scans 

and behavioral data from more than 90 children who do and do not stutter. To date, this plan of study has led 

to publications reporting novel and important insights into the neural bases of childhood stuttering, insights that 

we will continue to publish in the near future and hopefully extend beyond that with support for the proposed 

application. 

Dr. Chow’s proposed studies represent a novel and important extension of the studies that have been 

conducted to date in children who stutter. Capturing brain responses during overt, connected speech 

production with fMRI is an important new technological advance that will allow us, for the first time, to examine 

brain activity patterns that differ in children who stutter compared to controls during fluent and disfluent speech 

production. Although we have evidence of aberrant activity during these speech conditions in adults who 

stutter, we do not know whether these same aberrant brain activity patterns are present in children who stutter. 

Further, it would be important to examine whether children who have recovered from stuttering exhibit brain 

activity differences from children with persistent stuttering: recovered children’s brain responses during fluent 

speech would elucidate neural mechanisms that underlie recovery, which may, in the future serve as neural 

targets for developmentally appropriate intervention strategies for children who stutter. I am very excited to be

a part of this research and am happy to contribute to Dr. Chow’s research by providing access to a relatively 

large pool of children with persistent stuttering as well as those who have recovered from stuttering. The 

longitudinal study sample that I have acquired in the last four years provide a unique opportunity for us to

retroactively examine previously acquired behavioral and neuroimaging data on children who have been

presently identified as persistent or recovered, allowing us to compare these data to new fMRI data during 

overt speech tasks. 

Biosketches Page 22
Contact PD/PI: Chow, Ho Ming

1. Chang SE, Erickson KI, Ambrose NG, Hasegawa-Johnson MA, Ludlow CL. Brain anatomy differences 

in childhood stuttering. Neuroimage. 2008 Feb 1;39(3):1333-44. PubMed PMID: 18023366; PubMed 

Central PMCID: PMC2731627. 

2. Chang SE, Zhu DC. Neural network connectivity differences in children who stutter. Brain. 2013

Dec;136(Pt 12):3709-26. PubMed PMID: 24131593; PubMed Central PMCID: PMC3859219. 

3. Chang SE. Research updates in neuroimaging studies of children who stutter. Semin Speech Lang. 

2014 May;35(2):67-79. PubMed PMID: 24875668. 

4. Chang SE, Zhu DC, Choo AL, Angstadt M. White matter neuroanatomical differences in young children 

who stutter. Brain. 2015 Mar;138(Pt 3):694-711. PubMed PMID: 25619509. 

B. POSITIONS AND HONORS

Positions and Employment

1998 - 1999 Research Assistant, Vanderbilt University, Nashville, TN

1999 - 2000 Research Assistant, Vanderbilt University, Nashville, TN

1999 - 2000 Clinical Fellow, Gateway Health System, Clarksville, TN

2002 - 2005 Research Assistant , University of Illinois at Urbana-Champaign, Champaign, IL

2005 - 2009 Postdoctoral Research Fellow, NINDS/NIH, Bethesda, MD

2009 - 2013 Assistant Professor, Michigan State University, Department of Communicative Sciences and

Disorders, East Lansing, MI

2013 - Assistant Professor, Rosa Casco Solano-Lopez Research Professor of Child and Adolescent 

Psychiatry, 

Other Experience and Professional Memberships

1999 - Certified member, American Speech-Language-Hearing Association 

2003 - Member, Society for Neuroscience (SfN) 

2006 - Member, ASHA division 4, Fluency and Fluency Disorders

2007 - 2009 Member, Organization for Human Brain Mapping 

2009 - 2010 Editorial committee member, ASHA Convention Program Sub-Committee on Fluency 

2011 - Review Editor, Frontiers in Auditory Cognitive Neuroscience 

2011 - Member, Korean Academy of Speech-Language Pathology and Audiology 

Honors

1992 Academic scholarship, Seoul National University 

1993 SK scholarship for distinguished undergraduates, SK group 

2003 University of Illinois Campus Research Board grant award , University of Illinois 

2005 Ehud and Jane Yairi International Student Award, Ehud Yairi 

2005 ASHA student research travel award, American Speech-Language-Hearing Association 

(ASHA) 

2006 NINDS Fellow Special Act Award, NINDS Intramural Research Program 

2007 Functional Mapping of the Human Brain (OHBM) Travel Award , OHBM 

2009 ASHA Lessons for Success Research Conference: Developing the Emerging Scientist , 

American Speech-Language-Hearing Association 

2014 Endowed Professorship in Child and Adolescent Psychiatry, 

2015 Elizabeth Jane Crosby award,

C. Contribution to Science

1. I conducted the first study examining brain anatomical differences in children who stutter, which included 

persistent and recovered children. This study involved group comparisons whole brain gray matter volume 

with voxel based morphometry (VVBM), and vowel-wise analyses of fractional anisotropy (a measure 

reflecting white matter integrity) with Diffusion Tensor Imaging (DTI). I designed the study, independently 

Biosketches Page 23
obtained funding to support the study (as a graduate student, I obtained a campus internal research grant), 

conducted the data collection and analyses, and wrote the paper. 

a. Chang SE, Erickson KI, Ambrose NG, Hasegawa-Johnson MA, Ludlow CL. Brain anatomy differences 

in childhood stuttering. Neuroimage. 2008 Feb 1;39(3):1333-44. PubMed PMID: 18023366; PubMed 

Central PMCID: PMC2731627. 

2. I conducted a study using multimodal neuroimaging techniques that allowed examination of both structural 

and functional connectivity differences in the brains of individuals who stutter compared to a control nonstuttering group. This study showed converging evidence of a possible auditory-motor integration deficit, 

and an aberrant thalamus-cortical network connectivity in stuttering speakers. The task based fMRI study 

involved eliciting speech perception, planning, and overt production processes in normally speaking and

stuttering individuals using a sparse sampling fMRI paradigm. The results revealed differences in brain 

activity patterns during all phases of speech processing in stuttering speakers, which was a novel 

contribution to the field. I conducted data collection, analysis, and wrote the paper. 

a. Chang SE, Kenney MK, Loucks TM, Ludlow CL. Brain activation abnormalities during speech and nonspeech in stuttering speakers. Neuroimage. 2009 May 15;46(1):201-12. PubMed PMID: 19401143; 

PubMed Central PMCID: PMC2693291. 

b. Chang SE, Horwitz B, Ostuni J, Reynolds R, Ludlow CL. Evidence of left inferior frontal-premotor 

structural and functional connectivity deficits in adults who stutter. Cereb Cortex. 2011

Nov;21(11):2507-18. PubMed PMID: 21471556; PubMed Central PMCID: PMC3183422. 

3. I am currently the PI of a large scale longitudinal investigation of childhood developmental stuttering. The 

study involves collecting multimodal neuroimaging data (DTI, resting state fMRI, and structural MRI), 

speech, cognitive and motor performance measures, and language development indices from each child 

for up to 4 time points. This is the largest, and to the best of my knowledge, the only such dataset that 

exists for stuttering children in the 3-10 year range. My group has published a number of novel research 

findings from this study, and expect to publish many more in the next few years as we continue to acquire 

longitudinal data points from most of our existing participants. These data will help elucidate the 

neurological bases of childhood stuttering, which may lead to helping find objective markers for persistent 

stuttering, and neural targets for intervention. 

a. Chang SE, Zhu DC. Neural network connectivity differences in children who stutter. Brain. 2013

Dec;136(Pt 12):3709-26. PubMed PMID: 24131593; PubMed Central PMCID: PMC3859219. 

b. Chang SE. Research updates in neuroimaging studies of children who stutter. Semin Speech Lang. 

2014 May;35(2):67-79. PubMed PMID: 24875668. 

c. Chang SE, Zhu DC, Choo AL, Angstadt M. White matter neuroanatomical differences in young children 

who stutter. Brain. 2015 Mar;138(Pt 3):694-711. PubMed PMID: 25619509. 

d. Wieland EA, McAuley JD, Dilley LC, Chang SE. Evidence for a rhythm perception deficit in children 

who stutter. Brain Lang. 2015 May;144:26-34. PubMed PMID: 25880903. 

D. RESEARCH SUPPORT

Ongoing Research Support

2014/12/01-2017/11/30 

Matthew K. Smith Foundation grant 

Chang, Soo-Eun (PI) 

Neuroscience guided translational research in stuttering 

The goals of the projects include testing novel methods in real-time neurofeedback and non-invasive brain 

stimulation to apply to therapeutic interventions in stuttering. 

Role: PI

2014/11/21-2016/12/01 

American Speech-Language Hearing Foundation Clinical Research Grant 

Chang, Soo-Eun (PI) 

Enhancing speech motor function in stuttering speakers with neuromodulation: A tDCS Study 

Contact PD/PI: Chow, Ho Ming

Biosketches Page 24
The goal of this project is to test the potential of using a noninvasive brain stimulation technique to drive 

neuroplastic changes conducive to fluent speech motor processing. 

Role: PI

2014/10/01-2016/09/30 

Rauner Family Foundation Pilot Grant 

Fitzgerald, Chang (PI) 

Psychological and neurophysiological risk markers of persistent stuttering in early development 

This project aims to establish psychological and neurophysiological predictors of persistent stuttering in early 

development. 

Role: CPI

2010/09/29-2016/03/31 

R01 DC011277-05, National Institute on Deafness and Other Communication Disorders (NIDCD) 

Chang, Soo-Eun (PI) 

Sexual dimorphism of neural development underlying childhood stuttering 

Role: PI

2010/09/29-2016/03/31 

R01 DC011277-04S1, National Institute on Deafness and Other Communication Disorders (NIDCD) 

Chang, Soo-Eun (PI) 

Sexual dimorphism of neural development underlying childhood stuttering 

Role: PI

2014/03/01-2016/02/29 

Research in Autism, Intellectual and Neurodevelopmental Disabilities Grant 

McAuley, Chang, Wade (PI) 

Neural mechanisms of developmental stuttering: Translation of an animal model of rhythm processing to

assessment and intervention 

The project aims are to foster an innovative interdisciplinary collaborative research program in stuttering to

advance understanding of the neural mechanisms of developmental stuttering, which may lead to finding ways 

to improve diagnosis, assessment and treatment of stuttering. 

Role: CPI

Completed Research Support

2013/03/14-2014/05/14 

Grammy Foundation grant 

McAuley, Chang, Wade (PI) 

Rhythm processing deficits in developmental stuttering 

The project goals are to conduct the first systematic investigation of the potential role of rhythm processing 

deficits in developmental stuttering. 

Role: CPI

Contact PD/PI: Chow, Ho Ming

Biosketches Page 25
Contact PD/PI: Chow, Ho Ming

OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018) 

BIOGRAPHICAL SKETCH

Provide the following information for the Senior/key personnel and other significant contributors. 

Follow this format for each person. DO NOT EXCEED FIVE PAGES. 

NAME: Ratner, Nan Bernstein 

eRA COMMONS USER NAME (agency login): 

POSITION TITLE: Professor 

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, 

include postdoctoral training and residency training if applicable.) 

INSTITUTION AND LOCATION DEGREE 

(if applicable)

Completion Date 

MM/YYYY

FIELD OF STUDY

Tufts University, Medford, MA B. A. 06/1974 Child Study/Linguistics 

Temple University, Philadelphia, PA M. A. 06/1976 Speech Pathology 

Boston University, Boston, MA Ed.D. 05/1982 Applied Psycholinguistics 

A. Personal Statement: 

My research program over the past thirty years has spanned a number of areas in both typical and atypical 

speech/language processing, in both children and adults. More specifically, my most common recurrent 

themes have addressed typical and atypical fluency across the lifespan (e.g., stuttering, use of fluency as a 

marker of language proficiency in other populations), and the role of the language environment in first 

language learning. 

My most recent and ongoing collaborations involve 1) linguistic predictors of persistence and recovery from 

developmental stuttering (with Christine Weber, [previously publishing as Weber-Fox] at Purdue, and with 

Soo-Eun Chang/Ho Ming Chow at Michigan); 2) use of the NIH-supported TalkBank initiative to generate 

both new norms for clinical language assessment measures in children and adults (with Brian 

MacWhinney of CMU), as well as education of researchers and clinicians to make use of this resource; 3) 

potential input predictors of preschool language development (with Rochelle Newman, at UMD, and with 

Erika Hoff at FAU). 

These first two efforts make me an appropriate co-investigator on this ECR R21 application for the 

following reasons: 

1) I have been affiliated with the TalkBank project since its inception, and as current consultant to the

project, I have collaborated on the development of fluency codes (integral to the proposed grant)

and child language appraisal routines currently implemented by the KidEval utility. This grant

application proposes to use KidEval output (e.g., lexical appraisal by TTR, NDW, VocD; syntactic

appraisal by MLU, IPSYN and DSS) to contrast language performance of the children in the

persistent, recovered and peer comparison groups, as well as inform activation profiles obtained

during the story generation task.

2) I have historically led the fruitful investigation of potential linguistic deficits in both children and

adults who stutter, starting with my early work in the 1980’s and continuing to the present day. This

work is now broadly viewed as critical to understanding stuttering, which appears to intersect with

the language production system.

Recent publications most relevant to this proposal:

a) Bernstein Ratner, N. & Newman, R. (2009) Effects of word frequency and phonological

neighborhood characteristics on confrontation naming in children who stutter and normally fluent

peers. Journal of Fluency Disorders, 34, 225-241. PMID: 20113768

b) Berl, M., Mayo, J., Parks, E., Rosenberger, L., Van Meter, J., Bernstein Ratner, N., Vaidya, C.,

& Gaillard, W.D. (2012) Regional differences in the developmental trajectory of lateralization of

the language network, Human Brain Mapping, doi:10.1002/hbm.22179. PMID: 23033058

c) Bauman, J., Hall, N., Wagovich, S., Weber-Fox, C. & Bernstein Ratner, N. (2012). Past tense

marking in the spontaneous speech of preschool children who do and do not stutter. Journal of

Fluency Disorders, 37(4):314-24. PMID: 23218214

Biosketches Page 26
Contact PD/PI: Chow, Ho Ming

B. Positions and honors 

Positions: 

1983-1989 The University of Maryland, College Park 

Assistant Professor, Department of Hearing and Speech Sciences 

1989-1992 The University of Maryland, College Park 

Associate Professor, Department of Hearing and Speech Sciences 

1993-1999 The University of Maryland, College Park 

Associate Professor and Chairman, Department of Hearing and Speech Sciences 

1999-2014 The University of Maryland, College Park 

Professor and Chairman, Department of Hearing and Speech Sciences 

2014- pres Professor, Department of Hearing and Speech Sciences 

Participating faculty, Program in Neuroscience and Cognitive Science 

Research professor, Language Sciences 

Other positions: 

Co-editor-in-Chief, Seminars in Speech and Language 

Editorial Board, Journal of Communication Disorders 

Editorial consultant (past 3 years): Journal of Speech, Language and Hearing Research (language and 

speech sections), Journal of Child Language, American Journal of Speech-Language Pathology, Journal of 

Fluency Disorders, Child Development, JASA. 

Honors: 

1991 Honors of the Maryland Speech-Language-Hearing Association 

1996 Fellow, American Speech-Language-Hearing Association 

2006 Distinguished Researcher Award, International Fluency Association 

2012 Miegunyah Visiting Fellow, University of Melbourne 

2013 Dean’s Medal, University of Maryland 

2015 Fellow, American Association for the Advancement of Science (AAAS) – Psychology 

2015 Honors, American Speech-Language-Hearing Association 

C. Contribution to Science 

1. A longstanding focus of my research is in trying to better understand stuttering. As a unique childhoodonset communication disorder, it now appears clear that stuttering involves language processing difficulties

as well as speech production problems. I was among the first to notice this relationship, which has now

been incorporated into multi-factorial models of stuttering developed by diverse research labs worldwide.

a. Bernstein, Nan (1981). Are there constraints on childhood dysfluency? Journal of Fluency

Disorders, 6, 341-350. doi:10.1016/0094-730X(81)90021-8

b. Bernstein Ratner, Nan & Catherine C. Sih (1987). The effects of gradual increases in sentence

length and complexity on children's dysfluency. Journal of Speech and Hearing Disorders, 52 (3),

278-287. PMID: 3455450

c. Newman, R. & Bernstein Ratner, N. (2007). The role of selected lexical factors on confrontation

naming accuracy, speed and fluency in adults who do and do not stutter. Journal of Speech,

Language and Hearing Research, 50, 196-213. PMID: 17344559

d. Wagovich, S. & Bernstein Ratner , N. (2007). Frequency of verb use in young children who stutter.

Journal of Fluency Disorders, 32, 79-94. PMID: 17499123

e. Bernstein Ratner, N., Newman, R., & Strekas, A. (2009). Effects of word frequency and

phonological neighborhood characteristics on confrontation naming in children who stutter and

normally fluent peers. J. of Fluency Disorders, 34, 225-241. PMID: 20113768

2. A natural outgrowth of this program of research has been the realization that speech fluency serves as a

marker of language formulation difficulty in other populations. This discovery may enable language-free

indicators of language disorder, as well as inform impairment in both first and subsequent language

acquisition by both children and adults with most of my recent work in stuttering, this work has relied

extensively in approach on using TalkBank utilities to augment experimental work with computer-assisted

language sample analysis.

Biosketches Page 27
a. Steinberg ME, Ratner NB, Gaillard W, Berl M. (2013) Fluency patterns in narratives from children

with localization related epilepsy. Journal of Fluency Disorders, 38, 193-205. PMID: 23773671

b. Bernstein Ratner, Nan (2013). Fluency in late talkers. In L. Rescorla & P. Dale (eds.) Late talkers:

from theory to practice. Baltimore: Brookes (pp 129-144).

c. Boscolo B, Ratner NB, Rescorla L. (2002) Fluency characteristics of children with a history of

Specific Expressive Language Impairment (SLI-E). American Journal of Speech-Language

Pathology, 11, 41-49. PMID: 26225412

3. Much of my other research focuses on parental contributions to children’s language development and other

precursors of preschool language skill. Can we identify earlier indicators of children’s success in learning

language? Are children’s caretakers important influences on their language development – if so, how can

we use this knowledge to improve children’s communicative outcomes?

a. Newman, R. S., Bernstein Ratner, N., Jusczyk, A. M., Jusczyk, P. W. & Dow, K. A. (2006). Infants’

early ability to segment the conversational speech signal predicts later language development: A

retrospective analysis. Developmental Psychology, 42(4), 643-655. PMID: 16802897

b. Torrington Eaton C. & Bernstein Ratner N. (2013) Rate and phonological variation in preschool

children: effects of modeling and directed influence. J Speech Lang Hear Research, 56(6):1751-63.

PMID: 23882009

c. Miles S., & Bernstein Ratner N. (2001) Parental language input to children at stuttering onset. J

Speech Lang Hear Research. 44(5):1116-30. PMID: 11708531

d. Newman, R. S., Rowe, M. & Bernstein Ratner, N. (2015) The role of child-directed-speech and

infant processing skills in language development. Journal of Child Language,1-16. PMID:

26300377

4. A more recent focus of my research is the investigation of progressive language impairment in childhood

temporal lobe epilepsy (TLE), which has been carried out in conjunction with Madison Berl and William

Gaillard at CNMC. We have discovered progressive attrition of language skills in children with TLE not

currently monitored by most academic and medical protocols. Relevant to this proposal, I have helped the

team to integrate behavioral (language use) manifestations of the disorder with brain imaging results to

achieve a more nuanced view of how atypical anatomy/physiology relates to functional use of language in

children.

a. Strekas, A., Bernstein Ratner N., Berl, M., & Gaillard WD. (2013) Narrative abilities of children with

epilepsy. Int J Lang Commun Disorders; 48(2):207-19. PMID: 23472960

b. Berl, M., Mayo, J., Parks, EN, Rosenberger, LR, VanMeter, J, Bernstein Ratner, N., Vaidya, CJ, &

Gaillard, WD. (2014) Regional differences in the developmental trajectory of lateralization of the

language network. Hum Brain Mapping, 35(1):270-84. PMID: 23033058

c. Berl MM, Duke ES, Mayo J, Rosenberger LR, Moore EN, VanMeter J, Ratner NB, Vaidya CJ,

Gaillard WD. (2010) Functional anatomy of listening and reading comprehension during

development. Brain & Language,114(2):115-25. PMID: 20656105

5. I have also investigated the strengths and pitfalls of translating research findings to evidence-based

practice in speech-language pathology:

a. Nail-Chiwetalu, B. & Bernstein Ratner N. (2007) An assessment of the information-seeking abilities

and needs of practicing speech-language pathologists. J Med Libr Assoc, 95(2):182-8. PMID:

17443251

b. Bernstein Ratner N. (2006) Evidence-based practice: an examination of its ramifications for the

practice of speech-language pathology. Lang Speech Hear Serv Sch. 37(4):257-67. PMID:

17041074

c. Bernstein Ratner, N. (2005) Evidence-based practice in stuttering: Some questions to consider. J

Fluency Disorders, 30(3):163-88. PMID: 15961152

Complete List of Published Work in MyBibliography: 

http://www.ncbi.nlm.nih.gov/sites/myncbi/1-

UVaaDdREZ/bibliography/40436718/public/?sort=date&direction=ascending

Contact PD/PI: Chow, Ho Ming

Biosketches Page 28
D. Research Support 

Ongoing research support 

9R01HD082736-11 (2014-2019); PI: Brian MacWhinney. Role: Consultant. 

“Computational Analysis of Child Language Transcript Data” 

This grant exploits the richness of the TalkBank/Childes archive to re-norm basic clinical measures of child 

language ability (such as MLU, TTR, etc.) and offers outreach to expand archive/CLAN use by clinicians. 

NIDCD: 1 R01 HD068421-01 (2011-16; Erika Hoff, PI; Role: Consultant). 

“Early Dual Language Development in Children from Spanish-Speaking Families”. 

This grant investigates the pace of bilingual language acquisition in toddlers, with special emphasis on the role 

of parental input in each household language.

University of Maryland BSOS Dean’s Research Initiative, Collaboratory Grant (Role: Co-PI) 2014/2015 

“Language as a means of assessing children’s concussion” 

This internally-funded research grant includes series of studies investigating the effect of sports-related 

concussion on children’s language skills, and supports developing a device to help assess concussion in 

young children. It includes a collaboration between 6 faculty members, 3 of whom (Colin Phillips, Nan 

Bernstein Ratner, and Rochelle Newman) serve as core faculty on the current proposal. 

Completed Research Support (last 3 years) 

NSF BCS 074512 (2008-2013) Role: Co-I 

“Speech and nonspeech predictors of later language development” (PI: Rochelle Newman) 

This project explores the potential contributing roles of speech segmentation, statistical learning, and maternal 

input in children’s later language acquisition by examining skills concurrently in the same child cohort. 

NSF IGERT (2008-2013) Role: Participating Faculty 

“Biological and computational foundations of language diversity” This IGERT project supports interdisciplinary 

doctoral training and research in the foundations of language diversity. 

NSF ADVANCE Program for Inclusive Excellence Dougherty (Role: Co-PI) 5/12-5/13 

 “Maternal depression and child language development” 

This internally-funded project with a junior faculty member in Psychology investigated the potential role of 

depressed, previously depressed and typical mothers’ speech and language behaviors on the expressive 

language outcomes of their children. 

. 

Contact PD/PI: Chow, Ho Ming

Biosketches Page 29
Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

PHS 398 Cover Page Supplement

OMB Number: 0925-0001

1. Project Director / Principal Investigator (PD/PI)

Prefix:

First Name*: Ho Ming

Middle Name:

Last Name*: Chow

Suffix:

2. Human Subjects

Clinical Trial? ❍ No ● Yes

Agency-Defined Phase III Clinical Trial?* ● No ❍ Yes

3. Permission Statement*

If this application does not result in an award, is the Government permitted to disclose the title of your proposed project, and the name,

address, telephone number and e-mail address of the official signing for the applicant organization, to organizations that may be

interested in contacting you for further information (e.g., possible collaborations, investment)?

● Yes ❍ No

4. Program Income*

Is program income anticipated during the periods for which the grant support is requested? ❍ Yes ● No

If you checked "yes" above (indicating that program income is anticipated), then use the format below to reflect the amount and source(s).

Otherwise, leave this section blank.

Budget Period* Anticipated Amount ($)* Source(s)*

Contact PD/PI: Chow, Ho Ming

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Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

PHS 398 Cover Page Supplement

5. Human Embryonic Stem Cells

Does the proposed project involve human embryonic stem cells?* ● No ❍ Yes

If the proposed project involves human embryonic stem cells, list below the registration number of the specific cell line(s) from the following

list: http://grants.nih.gov/stem_cells/registry/current.htm. Or, if a specific stem cell line cannot be referenced at this time, please check the box

indicating that one from the registry will be used:

Cell Line(s): Specific stem cell line cannot be referenced at this time. One from the registry will be used.

6. Inventions and Patents (For renewal applications only)

Inventions and Patents*: ❍ Yes ● No

If the answer is "Yes" then please answer the following:

Previously Reported*: ❍ Yes ❍ No

7. Change of Investigator / Change of Institution Questions

❏ Change of principal investigator / program director

Name of former principal investigator / program director:

Prefix:

First Name*:

Middle Name:

Last Name*:

Suffix:

❏ Change of Grantee Institution

Name of former institution*:

Contact PD/PI: Chow, Ho Ming

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Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

OMB Number: 0925-0001

Expiration Date: 10/31/2018

PHS 398 Modular Budget

Budget Period: 1

Start Date: 09/01/2016 End Date: 08/31/2017

A. Direct Costs Funds Requested ($)

Direct Cost less Consortium Indirect (F&A)*

Consortium Indirect (F&A)

Total Direct Costs*

B. Indirect (F&A) Costs

Indirect (F&A) Type Indirect (F&A) Rate (%) Indirect (F&A) Base ($) Funds Requested ($)

1.

2.

3.

4.

Cognizant Agency

(Agency Name, POC Name and Phone Number)

Department of Health and Human Services, Jackie

Garner, 312-886-6432

Indirect (F&A) Rate Agreement Date 05/10/2013 Total Indirect (F&A) Costs

C. Total Direct and Indirect (F&A) Costs (A + B) Funds Requested ($)

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Contact PD/PI: Chow, Ho Ming

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

PHS 398 Modular Budget

Budget Period: 2

Start Date: 09/01/2017 End Date: 08/31/2018

A. Direct Costs Funds Requested ($)

Direct Cost less Consortium Indirect (F&A)*

Consortium Indirect (F&A)

Total Direct Costs*

B. Indirect (F&A) Costs

Indirect (F&A) Type Indirect (F&A) Rate (%) Indirect (F&A) Base ($) Funds Requested ($)

1. MTDC

2.

3.

4.

Cognizant Agency

(Agency Name, POC Name and Phone Number)

Department of Health and Human Services, Jackie

Garner, 312-886-6432

Indirect (F&A) Rate Agreement Date 05/10/2013 Total Indirect (F&A) Costs

C. Total Direct and Indirect (F&A) Costs (A + B) Funds Requested ($)

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Contact PD/PI: Chow, Ho Ming

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

PHS 398 Modular Budget

Budget Period: 3

Start Date: 09/01/2018 End Date: 08/31/2019

A. Direct Costs Funds Requested ($)

Direct Cost less Consortium Indirect (F&A)*

Consortium Indirect (F&A)

Total Direct Costs*

B. Indirect (F&A) Costs

Indirect (F&A) Type Indirect (F&A) Rate (%) Indirect (F&A) Base ($) Funds Requested ($)

1. MTDC

2.

3.

4.

Cognizant Agency

(Agency Name, POC Name and Phone Number)

Department of Health and Human Services, Jackie

Garner, 312-886-6432

Indirect (F&A) Rate Agreement Date 05/10/2013 Total Indirect (F&A) Costs

C. Total Direct and Indirect (F&A) Costs (A + B) Funds Requested ($)

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Contact PD/PI: Chow, Ho Ming

 Page 35

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

PHS 398 Modular Budget

Cumulative Budget Information

1. Total Costs, Entire Project Period

Section A, Total Direct Cost less Consortium Indirect (F&A) for Entire Project Period ($)

Section A, Total Consortium Indirect (F&A) for Entire Project Period ($)

Section A, Total Direct Costs for Entire Project Period ($)

Section B, Total Indirect (F&A) Costs for Entire Project Period ($)

Section C, Total Direct and Indirect (F&A) Costs (A+B) for Entire Project Period ($)

2. Budget Justifications

Personnel Justification ModularJustification.pdf

Consortium Justification UofMaryland_Justification.pdf

Additional Narrative Justification
Contact PD/PI: Chow, Ho Ming

Budget Justification

Senior/key personnel:

Ho Ming Chow, Ph.D., PD/PI (4.8 calendar months) will be responsible for overseeing the overall 

direction and implementation of this project to achieve the proposed specific aims. Dr. Chow is 

experienced in managing fMRI studies in adults who stutter and is an expert fMRI de-noising techniques 

and analyses.

Soo-Eun Chang, Ph.D., Co-I (0.6 calendar month) will provide her expertise in pediatric neuroimaging

and work in collaboration with the PI on the interpretation of imaging results. Dr. Chang has extensive 

experience in using multimodal neuroimaging techniques to study functional and structural anomalies in 

children who stutter. She is also a certified Speech-Language Pathologist who can supervise all 

behavioral and fluency assessment procedures that take place prior to MRI participation.

Other Personnel:

Emily O’Dell Garnett, Ph.D. (2.4 calendar months) is a certified Speech-Language Pathologist and 

experienced in stuttering research. Dr. Garnett will carry out behavioral and speech assessments and 

assist in subject recruitment and MRI data collection.

Personnel Justification Page 36
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-

Contact PD/PI: Chow, Ho Ming

Budget Justification for University of Maryland

Personnel

Nan Bernstein Ratner, Ph.D., Co-I (.45 academic months) is a widely published expert in

stuttering research and will be responsible for the execution of fluency analyses and generation

of clinical language assessment measures using the NIH-supported TalkBank initiative in this

project. She will also assist the PI in the interpretation of participants’ linguistic profiles in related

to recovery and persistence of stuttering. 

Research Assistant, TBA, (2.9 CM) An undergrad or master’s level research assistant will work 

hourly under supervision of Co-I Ratner in assisting with fluency analyses and generation of 

clinical language assessment measures using the NIH-supported TalkBank initiative in this 

project. 

Fringe Benefits

The University of Maryland does not have a fringe benefit rate. Contract/grant accounts will be

charged for the actual fringe benefit amount used. Fringe benefits have been calculated for Dr.

Ratner at a rate of Included: pension plan contributions; social security; Medicare taxes;

unemployment compensation insurance; subsidies for health, life, and disability insurance;

vacation; and sick leave.

Indirect Costs

Indirect costs are computed at a rate of applied to all costs. 

Indirect Costs 

Indirect costs are computed at a rate of applied to all costs. 

Year 1: Estimated Total Costs 

Year 2: Estimated Total Costs 

Year 3: Estimated Total Costs 

Consortium Justification Page 37
 

PHS 398 Research Plan

Please attach applicable sections of the research plan, below. OMB Number: 0925-0001

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date:

2016-02-23T15:48:23.000-05:00

1. Introduction to Application

(for RESUBMISSION or REVISION only)

2. Specific Aims SpecificAims.pdf

3. Research Strategy* ResearchStrategy.pdf

4. Progress Report Publication List

Human Subjects Sections

5. Protection of Human Subjects ProtectionOfHumanSubjects.pdf

6. Inclusion of Women and Minorities InclusionOfWomanAndMinorities.pdf

7. Inclusion of Children InclusionOfChildren.pdf

Other Research Plan Sections

8. Vertebrate Animals

9. Select Agent Research

10. Multiple PD/PI Leadership Plan

11. Consortium/Contractual Arrangements

12. Letters of Support LetterOfSupport_Combined.pdf

13. Resource Sharing Plan(s) ResourseSharingPlan.pdf

Appendix (if applicable)

14. Appendix

Contact PD/PI: Chow, Ho Ming

 Page 38
SPECIFIC AIMS 

Developmental stuttering is a speech disorder with a prevalence of 1% and a lifetime-incidence of approximately 5% in the U.S.A. Stuttering can have a strong negative impact on the individual’s social, emotional, academic, and vocational development. Interestingly, about 80% of children who stutter (CWS) recover naturally 

within a few years of stuttering onset [1, 2]. The high rate of recovery during childhood signifies that neuroplasticity in children play a critical role in overcoming whatever deficits that underlie stuttering. The current challenge is to understand the deficits that disrupt fluent speech production and the neural processes associated 

with recovery from stuttering in CWS. Without such understanding, we are hindered in our ability to develop 

more effective therapeutic interventions for childhood stuttering. 

Finding from recent neuroimaging studies of CWS, employing non-discourse, relatively simple speaking 

tasks (e.g., single-word production) or non-speaking contexts (e.g., wakeful rest), indicate that stuttering is associated with functional and structural anomalies in (sub)cortical areas classically associated with speechmotor control [3, 4]. However, these procedures are limiting because stuttering typically do not occur during 

simple speaking tasks. Thus, they do not optimally inform the neurophysiology of childhood stuttering. The 

most ecologically-valid context to study stuttering is continuous speech production, because in this context, 

symptoms of stuttering are most apparent. A major obstacle to studying children’s continuous speech is that 

speech-related movements severely contaminate data collected from non-invasive neuroimaging methods such 

as functional magnetic resonance imaging (fMRI). To overcome this obstacle, the current application proposes 

a novel methodology [5] by which fMRI can be used to empirically study children’s neural processes associated 

with fluent and stuttered speech occurring during continuous speech production to help identify the neurological deficits underlying stuttering and how the disorder resolves itself. 

Our long-term goal is to develop effective therapeutic interventions to treat and prevent persistent stuttering during childhood. In pursuit of that goal, the immediate objective of the present application, which is the 

next step in pursuing that goal, is to determine brain activity patterns associated with continuous speech production in children with persistent (pCWS) and recovered from stuttering (rCWS). The central hypothesis is 

that persistent stuttering is associated with anomalous brain activity in the neural circuits for speech-motor 

control in the left hemisphere, while recovery from stuttering is associated with greater involvement of right 

frontal areas. The rationale of this proposed research is that an empirically-based understanding of brain activity patterns associated with continuous speech production of pCWS and rCWS is foundational for the development of therapeutic interventions attempting to modify anomalous activity. The proposed work tests our central hypothesis and accomplishes our objective with the following aims: 

Specific Aim 1: Identify brain activity associated with continuous speech production that 

characterizes persistent stuttering. In this aim, we examine brain activity associated with fluent (subaim 1a) and stuttered speech (sub-aim 1b) in children with persistent stuttering (pCWS). Based on our preliminary data, we hypothesize that H1a: The analysis of fluent speech production of pCWS, compared to that of 

children who do not stutter (CWNS), will reveal anomalous brain activity associated with persistent stuttering 

in the cortical areas supporting speech monitoring, including the posterior temporal gyrus and the inferior 

frontal gyrus in the left hemisphere. H1b: Instances of stuttering in pCWS, in contrast to their fluent speech 

will reveal anomalous brain activity associated with stuttering behaviors in the areas supporting motor planning and control, including the supplementary motor area, the premotor cortex and the basal ganglia. 

Specific Aim 2: Identify brain activity associated with continuous speech production that 

characterizes recovery from stuttering. Based on preliminary data, we hypothesize that H2a: children 

who are recovered from stuttering (rCWS) will exhibit less anomalous activity than pCWS in the left perisylvian 

areas and H2b: rCWS, in comparison to CWNS, will exhibit increased activity in the right frontal areas. 

Findings of the proposed projects are expected to i) identify patterns of brain activity associated with persistent stuttering during continuous speech (the context in which stuttering is most likely to occur), ii) advance 

our understanding of children’s speech production and how these processes are disturbed, resulting in overt 

instances of stuttering (e.g., sound/syllable repetitions, prolongations, and blocks) and iii) provide insights into 

the neural processes of continuous speech after recovery from stuttering. Such outcomes will have a positive 

translational impact on future development of better treatment strategies for childhood stuttering. Moreover, 

applying a validated fMRI methodology that studies neural processes of continuous speech production provides the groundwork for future investigations using advanced data analysis approaches (e.g., functional connectivity), new fMRI technologies (e.g. multiband acquisition) and longitudinal experimental designs to study 

speech disorders. 

Contact PD/PI: Chow, Ho Ming

Specific Aims Page 39
Contact PD/Pl: Chow, Ho Ming 

A. SIGNIFICANCE 

Burden of childhood stuttering: While most speakers take fluent speech for granted, approximately 3 

million children and adults in the U.S.A with developmental stuttering struggle to speak fluently every day. 

Such struggle results in lower quality of life for people who stutter [6]. To develop better treatment strategies 

and minimize the potentially adverse impacts of stuttering on children's academic, social, and future vocational 

accomplishments and development [7], there is a need to better understand the neurophysiology underlying 

childhood developmental stuttering and the neural processes associated with its persistence and recovery. 

A gap in the current understanding ofneurophysiology associated with childhood stuttering: 

Neuroimaging studies of people who stutter have contributed important insights into the neural processes associated with both speech production and stuttering [8-10]. To date, however, these studies have mainly focused on adults, and neuroimaging studies examining speech production in children who stutter (CWS) remain 

scarce. The absence of neuroimaging studies on CWS's speech processes is largely due to technological constraints in imaging children's brains during continuous speech production. 

Advancing our understanding ofneural processes of continuous speech production: A recent 

advancement in fMRI de-noising techniques now permits the use of fMRI to study continuous speech [5]. This 

technique - developed by the present application's PI (Chow) - uses spatial Independent Component Analysis 

(slCA), a signal un-mixing algorithm to separate speech and movement a1tifacts from signals originating from 

neuronal activity. By using fMRI with this sICA de-noising technique, it is possible to empirically study the 

anomalous brain activity associated with pCWS's continuous speech production as well as pCWS's compensato1y adaptations to these brain anomalies. It also allows acquisition of data from the whole brain including 

subcortical areas important for speech-motor conn·ol. 

Impact on future development ofbetter interventions: Identification of activity patterns associated 

with persistence and recove1y of childhood stuttering would potentially guide future development of therapeutic interventions by providing targets for brain simulation techniques such as transcranial direct current simulation and other neuromodulation techniques to augment brain regions related to recove1y and fluent speech. 

Scientific premises: The proposed study assumes that fMRI measurements (i.e., BOLD) is a good estimation 

of brain activity. BOLD, an indirect measure of neuronal activity, arises from local changes in capillary blood 

oxygenation level triggered by nearby neuronal firing. Although this neurovascular coupling is not fully understood, tight correspondence between BOLD and neuronal activity has been demonstrated using simultaneous 

recordings of fMRI and neurophysiological measures in animals [11, 12] and humans [13]. Another premise is 

the validity ofthe proposed de-noising method. It will be addressed comprehensively in the Approach section. 

B. INNOVATION 

Imaging methodologies: To date, using fMRI to capture brain responses associated with longer speech 

utterances has been severely limited because speech-related artifacts considerably contaminate fMRI images 

[14]. The only brain imaging technologies appropriate to study neural correlates of continuous speech production were positron emission tomography (PET) and functional near-infrared specn·oscopy (fNIRS). However, 

PET is not justified with children because of radioactive exposure. FNIRS, on the other hand, cannot detect 

activity in deep brain structures including the basal ganglia, a subcortical structure seemingly essential for fluent speech production [15] which has been linked to stuttering behaviors [16]. 

Thus, neither PET nor fNIRS are optimal for studying CWS's continuous speech 

production. In contrast, our approach removes speech-related noise from fMRI by 

using sICA to decompose fMRI signals into a set of statistically independent components, each consisting of a spatial map and a time course. Because brain activity 

and speech-related noise are associated with distinct spatial patterns (Fig. 1), they 

will be decomposed into separate components by sICA. Our previous research 

shows that noise spatial patterns can be identified effectively by using six noise 

templates and three measures of components' signal intensity: i) out-of-the-brain 

ratio, ii) scattering degree (detection of checkerboard patterns) and iii) slice-wise 

variation ( detection of interleaved patterns) [5]. Noise components can then be 

removed from functional images. Thus, the proposed research is innovative because the sICA fMRI de-noising technique will, for the first time, enable the study Figure 1. Examples of distinctive 

of continuous speech production in children with high spatial resolution. Moreo- noise and signal spatial patterns in 

slCA components (ICs) of an adult ver, the sICA fMRI procedure can examine the activity of cortical and subcortical participant. Top row (A) shows ICs 

areas during children's continuous speech production, data previously unattaina- associated with slow (left) and 

ble using methodologies such as fNIRS. Furthermore, since fMRI provides relative- abrupt head movements (right) 

Bottom Row (8) shows ICs associ- ly high temporal resolution compared to PET, we can potentially distinguish brain ated with neuronal activity. Images 

activity associated with stuttering instances from that associated with fluent adopted from [5] 

Research Strategy Page 40 
Contact PD/Pl: Chow, Ho Ming 

speech, providing insights into how stuttering instances emerge from continuous speech. 

Neural characteristics ofpersistence and recovery: The proposed project exploits an existing pa1ticipant pool from a longitudinal neuroimaging study of CWS headed by Co-I Dr. Chang. Since 2010, Dr. Chang's 

team has monitored neural, cognitive, and speech development ofover 60 CWS and 60 fluent peers. This longitudinal participant tracking allows objective identification of pCWS and rCWS. Thus, the present proposal is 

uniquely positioned to empirically study brain activity associated with stuttering persistence and recovery. 

C.APPROACH 

C1. FEASIBILITY. The validation and technical details of the proposed sICA fMRI de-noising method have 

been published in [5]. Moreover, PI's previous work has demonstrated we can obtain meaningful information 

about the neural processes of continuous speech production using fMRI [17, 18]. Three preliminary feasibility 

studies of the proposed method important to the current application are reported immediately below. 

C1.1. Preliminary Study 1: Feasibility of removing image artifacts associated with abrupt head 

movements. Because severe movement artifacts may occur during children's continuous speech production, 

removing these aitifacts is critical to the proposed project. In fact, even during resting-state scans, young participants often make large, abrupt head movements. Such artifacts are known to drastically increase volume-tovolume va1iation of BOLD signals, i.e., DVARS [14, 19]. Thus, we employed extant resting-state data to evaluate 

the effectiveness of our sICA de-noising technique in removing movement artifacts. The association between 

head movements and DVARS, measured by framewise displacement (FD) before sICA de-noising is illustrated 

in Fig. 2A and Fig. 2B (red line), generated from a 7-year-old pa1ticipant during a resting-state fMRI scan. After sICA de-noising, movement-induced DVARS diminished markedly (Fig. 2B, green line). To show that 

these findings are not isolated to this participant, we 

calculated DVARS before (i.e., uncorrected) and after 

de-noising of all 45,000+ volumes of our 281 restingstate fMRI scans collected from 50 CWS and 45 CWNS 

(aged 3-13 years). The red bars in Fig. 2C show that, as 

expected, DVARS before sICA de-noising (uncorrected) 

increased with head movement magnitude (r=o.55, p<0.001). Similar results has been published in [5] 

using a third-party pediatric fMRI data set. In contrast, 

after sICA de-noising, DVARS remained at a similar 

level (<1%) for head movements less than 9 mm (Fig. 

2C, green bars). These findings strongly indicate that 

our technique can remove fMRI artifacts related to 

abrupt head movements in children. In PI's previous · h d · ( C fMRI d f 2·

2 stU YO contmuous speec pro uctwn see 

for details), abrupt head movements > 9 mm were very 

rare in adults who stutter (AWS), occurring only in less 

· d f 

than 0.15%°of the tota l tMRI volumes Obtame rom 29 

AWS. We expect that abrupt head movements occur 

more frequent in CWS but most of them will still be 

within the workable range of our de-noising technique. 

 

 

 

Figure 2_ Rel;;~~=~ip between framewise displa~~;;~t (FD), i.e., an 

empirical sum of motion between consecutive volumes in all 6 motion 

directions and volume-to-volume variation of fMRI signals (DVARS) 

before and after slCA de-noising Panel A shows FD of a 7-year-eld participant during a 6-minute resting-state scan. Panel B shows that DVARS 

(red line) of that participant is strongly associated with FD. After slCA denoising (Panel B, green line), movement-induced DVARS reduced to the 

normal range. Panel C shows the means and standard errors of DVARS 

before (uncorrected) and afterslCA de-noising at different levels of head 

movements, based on 45,000+ fMRI volumes from 50 cws and 45 

CWNS. DVARS of the uncorrected volumes increased with FD (red bars) 

but this relationship greatly diminished after slCA de-noising (green bars). 

C1.2. Preliminary Study 2: Feasibility of detecting brain activity 

associated with continuous speech production using fMRI. Another 

critical issue is to determine whether our sICA de-noising technique can remove noise, without also unintentionally discarding a substantial propo1tion 

of signals originating from neuronal activity. Thus, we compared fMRI with 

our technique to PET [5]. PET is considered the gold standard for imaging 

speech production because it is less susceptible to movement artifacts. Fig. 3 

shows that the activity pattern associated with a storytelling task vs. overlearned speech in 18 healthy adults obtained from fMRI with sICA de-noising 

was highly similar to that obtained from PET. This confirms that signals originated from neuronal activity ai·e preserved after sICA de-noising. Moreover, 

statistical power is considerably higher for de-noised fMRI than PET. 

C1.3. Preliminary Study 3; Feasibility of using fMRI to image clilldren's brain activity during continuous speech production. In this 

preliminary study, a typically-developing, 8-year-old child successfully comFigure 3. Brain activity pattern associated 

with a continuous speech production task 

measured by fMRI with the proposed slCA 

de-noising technique (A) and PET (8 ) (n = 

18 adults). Both imaging methods generated highly similar results, indicating that 

brain activity associated with continuous 

speech production can be studied using 

fMRI. Images adopted from (17). 

Research Strategy Page 41 
Contact PD/Pl: Chow, Ho Ming 

pleted the fMRI study of speech production proposed in the current application 

(see C3.4 for details), with moderate head movements (FD= 0-2.5 mm). Results 

of this child's storytelling compared with overlearned speech (e.g., "A B C ...") 

were similar to those from previous adult studies (10, 17] (also see Fig. 3), that is, 

there was increased activity in the perisylvian regions (Fig. 4). Thus, results of 

this preliminary study indicate that it is feasible to obtain usable fMRI data from 

h"ld ' . h d . Figure 4. Compared with automatic 

c 1 ren s contmuous speec pro uction. speech, storytelling elicited increased 

C2. JUSTIFICATION. Theoretical (C2.1) and empirical (C2.2 & C2.3) suppo1ts brain activity (indicated in orange) in 

ofthe hypotheses related our Specific Aims are presented immediately below. the perisylvian regions of an 8-yearC2.1. N euroanatomical model of stuttering. Early imaging studies using old participant (p<O 01 , corrected) 

PET to examine neural activity associated vvith continuous speech production in adults who stutter (AWS) reported anomalous brain activity in the ventral premotor co1tex (vPMC), the supplementa1y motor area (SMA), 

the basal ganglia (BG), the cerebellum, the inferior frontal gyrus (IFG), and the superior temporal gyrus (STG) 

(8, 9]. Theoretical accounts suggest that these regions form the neural circuits for speech-motor control and 

that disruptions to these circuits lead to stuttering behaviors [20]. A simplified neuroanatomical model of stuttering based on the models proposed by Guenther and colleagues [21, 22] posits that stuttering is a result of 

deficits in monitoring and converting sound- to motor-based representations of speech via the interactions 

among left STG and IFG/vPMC (Fig. s, Path 1). This deficit is believed to be partially compensated for by the 

involvement of right IFG/vPMC, leading to fluent speech produced by stuttering speakers (20] (Fig. s, Path 2). 

When this compensatory process fails, execution of articulato1y movements subserved by (sub )cortical motor 

areas including SMA, BG, and motor cortex (MC) will be affected, resulting in stuttering instances and incorrect feedback sent to left STG for speech monitor- Figure 5. Based on a simplified version of Guenther 

· (F" p h ) Al h h · h IFG/ PMC · and colleagues' model of stuttering [21, 22], the 

mg ig. 5, at 3 · t OU~ ng t V IS core deficit of stuttering is posited to be related to 

thought to be related to an imperfect compensa- the interactions between speech and motor areas

to1y process in AWS we hypothesize that it may (Path 1). Sometimes, this deficit can be compen-

. l · ' · CWS b c ·   sated for by the right IFG/ vPMC (Path 2). When P 1 ay a k~y Io e Ill recov~ry Ill Y iormmg an this compensatory process fails, the execution o

alternative pathway (Fig. 5, Path 4) to bypass    articulatory movements is affected, leading to stutdeficits in left frontotemporal pathway (Fig. 5 tering behaviors (Path 3) The current proposal's 

. ' suggests that recovery of stuttering may be related Path 1). Recove1y may a lso resu 1 t from norma 11za- to normalization of Path 1 or the use of an alternation of deficits in this pathway. tive path in the right hemisphere (Path 4) 

C2.2. Preliminary Study 4: Empirical support for the hypotheses of Specific Aim 1 - Identify 

brain activity associated with continuous speech production that characterizes persistent stuttering. Specific Aim 1 involves the investigation of brain activity in CWS using two approaches (sub-aim la 

and 1b). The objective of Specific Aim la is to identify differences in brain activity exhibited 

by pCWS vs. CWNS during fluent continuous speech production. According to the theoretical model presented in C2.1, we hypothesize that Hta: pCWS, when compared to CWNS, 

will exhibit anomalous activity in left perisylvian areas, including left IFG and posterior 

STG. The objective of Specific Aim 1b is to identify differences in brain activity exhibited by 

pCWS during instances of stuttered vs. fluent continuous speech production. Based on the 

theoretical model, we hypothesize that Htb: stuttered vs. fluent speech in pCWS will elicit 

anomalous brain activity in cortical and subcortical networks supporting motor planning with controls (n=26), 

adults who stuttering and control, including SMA, vPMC and BG. Preliminary Study 4: This investigation in- (n=29) elicited attenuvolved the empirical study of brain activity associated with continuous speech production in ated activity (indicated 

in blue) in the perisyl- 29 AWS and matched controls using the same fMRI de-noising method and analysis ap- vian areas during proaches proposed in the current application. Although results obtained from adults may storytelling (p<0.01, 

not be fully applicable to children as mentioned previously, Preliminary Study 4 may be the corrected) 

closest approximation presently available given the lack of extant brain imaging 

data on children's continuous speech production. In Preliminary Study 4, participants told stories or recited nursery rhymes in 40-second trials. Each participant's speech was modelled as a sustained effect using a block regressor while 

stuttering instances were modeled as a transient effect using an event regressor 

(i.e., a mixed block/event-related design (23]) in the framework of the general 

linear model (GLM). Fig. 6 shows that AWS, when compared to controls, exhibited decreased activity in left perisylvian areas including left IFG and STG dur- fluent speech production and that with 

stuttering instances in adults who stut- ing fluent segments of sto1ytelling. This attenuation of activity in AWS com- ter, we observed increased activity in 

pared to controls has been found consistently in studies using various speaking vPMC and the putamen (indicated in 

paradigms (24-26]. Regarding H1b, AWS at stuttering instances, when com- orange, p<0.05, corrected) 

Figure 6. Compared 

Figure 7. Comparing activity associated 

Research Strategy Page 42 
Contact PD/Pl: Chow, Ho Ming 

pared to fluent speech production, exhibited increased activity in the putamen, SMA and vPMC. These results 

are consistent with previous reports of significant correlations between stuttering frequency and activity in the 

basal ganglia [8, 27, 28]. In conclusion, results of Preliminary Study 4 provide strong suppo1t of our working 

hypotheses for Specific Aim ta and 1b. Remarks on Specific Aim 1b: Although we do not know the effect of 

scanner noise on CWS's stuttering frequency, both Preliminary Study 4 and a previous study suggest that 

AWS's stuttering frequency may be reduced by 25% in association with scanner noise [29]. Taking this into 

consideration, we estimate that most of our pediatric participants would stutter 10-15 times while performing 

the proposed speaking tasks in the scanner. While the number of in-scanner stuttering instances may seem 

low, in event-related fMRI studies of error processing in children, it has been demonstrated that 10-15 instances can provide sufficient power to detect the effect of interest [30-32]. 

C2.3. Preliminary Study 5: E1npirical support for the hypotheses of Specific Aim 2 - Identify 

brain activity associated with continuous speech production that characterizes recoverv fro111 

stuttering. The objective of Specific Aim 2 is to identify differences in brain activity exhibited by rCWS vs. 

CWNS and pCWS during continuous speech production. Based on the theoretical model presented in C2.1, we 

hypothesize that H2a: recovery from stuttering related to the nor- malization of deficits in the left frontotemporal regions and H2:   increased involvement of the right frontal areas. There is no dir

evidence to support H2a and H2b because functional imaging studies 

on recove1y from childhood stuttering do not exist. Since functional 

and structural changes usually co-occur, our working hypothesis is 

primarily based on our Preliminary Study 5, in which white-matter 

structural anomalies associated with rCWS and pCWS were exam-

ined. Based on 18 rCWS, 14 pCWS and 26 CWNS, results of Prelimi

nary Study 5 (Fig. 8) shows that rCWS did not exhibit white-matter 

structural anomalies in left IFG that were associated with persistent  stuttering. This finding suggests that, for rCWS, anomalies in the left Figure 8. Fractional anisotropy (FA), a measure of

IFG had normalized or did not exist at all in the past. In contrast, white-matter structural coherence based on diffusion 

tensor imaging, of left and right IFG in children be- rCWS exhibited an increase in white-matter structural coherence in 

tween 5-11 years of age, including those who recov- right IFG. This confirmed our earlier observation with a smaller ered from stuttering (rCWS, n=14), with persistent 

sample size [33]. These structural changes in right IFG may reflect stuttering (pCWS, n=18) and controls (CWNS, n=26). 

increased functional involvements underlying recovery of stuttering. Finding indicated that relative to CWNS, rCWS did 

not exh bit a significant reduction of FA in left IFG, as Although increased activity in right IFG may reflect an imperfect it was in pCWS. Instead, rCWS exhibited a significant 

compensatory mechanism in AWS [34, 35], our and others' studies of increase of FA in right IFG. Bars represent standard 

error and asterisks indicate a significant difference CWS suggest that it may be an important element in recovery for between groups (two sample t-test, p<0.05). CWS during the critical period ofbrain plasticity. 

C3. EXPERIMENTAL DESIGN AND METHODS 

C3.1 Participants. Twenty pCWS, 20 rCWS, and 20 CWNS (ages 5 to 11) will be recruited from the participant pool of co-I Dr. Chang's longitudinal neuroimaging study of childhood stutte · ' dy 

has recruited more than 60 CWS and 60 normally fluent peers from areas around 11 

proposed participants will be monolingual English speakers without any diagnosed psychiatric or developmental disorders, other than stuttering. Since persistence or recovery from stuttering is best judged at least 2 years 

after onset (around 2 to 5 years of age), children who are identified as recovered or persistent are generally 5 

years or older. Thus, the present proposal will involve participants from 5 to 11 years old. Diagnosis: According 

to the 4 yearly speech assessments per child obtained from Chang's study, diagnoses of recovered and persistent were determined retrospectively using these criteria: recovered if a child's stuttering severity score on the 

Stuttering Severity Instrument Edition 4 (SSI-4, [36]) decreased from 10 at intake assessment (year 1) to <10 

in later assessments (year 3 or 4) and persistent ifhis or her SSI scores in years 3 and 4 exceeded 10. Diagnoses 

of recovered and persistent were also supported by clinician and parental repo11s. Inclusion criteria for CWNS 

included: never diagnosed as stuttering, no family history ofstuttering, lack ofparental concern for their child's 

fluency and the child's SSI score was <6. Using these criteria, we have identified 17 rCWS and 28 pCWS with 

ce11ainty. By June 2016, we expect to have 25 rCWS, 32 pCWS and 60 CWNS available for the proposed project. Pru1icipants in the proposed study will undergo fmther fluency assessment using the SSI-4 to confirm 

diagnoses and a series of behavioral tests has been used in Chang's study [4]. History of participants' fluency 

treatment will also be noted. According to Chang's study, children produce about 300 syllables during the proposed storytelling task (see C3.4). To allow for the possibility that scanner noise may reduce stuttering frequency by 25% on average [29], only pCWS whose stuttering frequency is >4-4% during a speech assessment in 

a quiet environment will be recruited. This will help to ensure that we can obtain >10 in-scanner stuttering 

Research Strategy Page 43 

Persistent (P) Control (C) Recovered (R)

(P) (C) (R) (P) (C) (R)
Contact PD/PI: Chow, Ho Ming

instances (4.4% x 0.75 x 300 syllables) for achieving Specific Aim 1b. In case a participant generate <10 inscanner stuttering instances, he or she will be excluded from the fMRI analysis related to Specific Aim 1b. 

C3.2 Scientific rigor. Based on Preliminary Study 4 (see C2.2), we assume that the proposed study will obtain an effect size of 0.7 with a standard deviation of 0.65 in the comparison between pCWS and CWNS in the 

brain activity associated with fluent speech production (Specific Aim 1a), and an effect size of 0.58 with a 

standard deviation of 0.74 in comparison between activity associated with stuttered and fluent speech in pCWS 

(Specific Aim 1b). With an alpha of 5% and power of 0.8, a sample size of 15 per group should suffice to observe 

a difference in both comparisons and potentially in the comparison between rCWS and CWNS (Specific Aim 2). 

However, considering a potentially higher exclusion rate of images or participants due to severe motion despite 

our de-noising technique and potentially smaller effect size comparing rCWS and CWNS, we plan to recruit an 

initial sample size of 20 per group. Additionally, several measures will be implemented to ensure robust and 

unbiased results: i) participants’ speech assessments will be carried out by two independent speech-language 

pathologists to ensure reliable stuttering diagnoses and identification of stuttering instances, ii) fMRI data analysts will be blinded to participants’ diagnoses to ensure unbiased group comparisons, iii) permutation procedures [37] will be used to control false positives related to multiple comparisons in fMRI analyses because false 

positives may not be controlled appropriately using other methods [38], and iv) details of diagnosis criteria, 

definitions of stuttering instances, experimental design, scanning parameters as well as analysis procedures 

will be fully explicated in any resulting publications to maximize study reproducibility. 

C3.3 Equipment and hardware. Functional and anatomical images will be acquired with the latest generation GE 3T MRI scanner, MR750, with an 8-channel head coil at the fMRI Laboratory, . 

Functional images will be acquired using a standard echoplanar (EPI) pulse sequence with the following key 

parameters: recovery time (TR) =2 sec; voxel size=3.45x3.45x4 mm; 38 interleaved sagittal slices; acceleration 

factor=2. Anatomical images (MPRAGE) with resolution of 1 mm3

 will be acquired at the end of the experiment. Speech during the fMRI experiment will be recorded with an optical noise cancellation microphone 

(OptoAcoustic) and a MR-compatible camera (MRC Systems) mounted on the scanner’s head-coil. Timing of 

scanning acquisition, video/audio recordings and stimulus presentation will be synchronized using E-Prime 

2.0 Professional (Psychology Software Tools, Inc.). Participants’ hearing will be protected by noise-shielding 

headphones or earplugs. All required equipment is available for the proposed study. The same setup was used 

in Preliminary Study 4 presented in C2.2; for details of scanning parameters, see [5].

C3.4 Speech tasks during fMRI. The child’s main speaking task is to tell a story guided by a textless picture 

book, “Frog, where are you?” to elicit continuous speech during fMRI [39]. This book portrays an ageappropriate story in 30 vivid pictures. This task has been successfully administered by our team to 120+ children (aged 3 to 11). To permit comparison of our results with children to similar studies of adults, we will include a control task, where children will produce overlearned speech (e.g., “A B C ...”) prompted by a picture. 

This task has been used as a baseline condition in brain imaging studies of speech production in adults (e.g., 

[40]) and as an assessment of childhood speech disorders [41]. Prior to scanning, participants will be familiarized with the experimental procedure. During scanning, story pictures will be presented via a projector sequentially with intermittent presentations of control task pictures. Each picture will be presented for 15 seconds, 

followed by a 10-second rest period. The entire fMRI experiment will be less than 15 minutes per participant. 

C4 ANALYSES 

C4.1 Speech data analysis. The Co-I Ratner’s team will transcribe participants’ speech and identify the precise onset times of stuttering instances using a text-based speech analysis software CLAN/CHAT [42]. We consider part-word or single-syllable-word repetitions and dysrhythmic phonations (i.e., blocks and prolongations) as instances of stuttering. The onset and offset of a stuttering instance will be determined by stuttered 

sound for repetitions and prolongations and observable lips movements (e.g., mouth open, lips trembling, etc.) 

for blocks. Onset and offset times of stuttering instances will be used for the fMRI analysis to identify their associated brain activity (Specific Aim 1b). Additionally, using the transcripts, individual linguistic measures including speech rate, utterance length, semantic diversity (e.g., TTR, VocD) and syntactic complexity (e.g., DSS, 

IPSYN) will be computed by CHAT. Along with other variables, they will be used as covariates in the fMRI 

analyses to control potential sources of variation for example [43]. 

C4.2 fMRI data analysis. Preprocessing steps include: i) slice timing correction, ii) head movement correction, iii) sICA de-noising, iv) normalization to a standard brain template, and v) spatial smoothing (see [5] for 

details). As in Preliminary Study 4 (see C2.2), functional images of each participant will be modeled using a 

mixed block/event-related design in GLM framework implemented in software SPM12 [23]. Specifically, our 

participants’ speech and stuttering instances will be modeled by a block and an event regressors, respectively. 

Participants’ first 2-3 principle components of the linguistic measures, stuttering severity, types of treatment 

received, intelligence quotient, socioeconomic status, and biological variables including sex and age will be 

Research Strategy Page 44
entered as covariates in the model. At the group level, individual model estimates (β) will be compared using ttests. False positives due to multiple comparisons will be corrected by a permutation procedure [37]. 

Data analyses for Specific Aim 1. Identify brain activity associated with continuous speech production that characterizes persistent stuttering. The first data analysis will test the hypothesis regarding Specific Aim 1a (H1a) that brain activity of pCWS during fluent speech production differs from that of 

CWNS in cortical areas supporting speech monitoring. This analysis will compare individual estimates of fluent 

speech between pCWS and CWNS using two-sample t-tests. Results will reflect the neural characteristics associated with fluent speech segments in pCWS. The second analysis will test the hypothesis regarding Specific 

Aim 1b (H1b) that brain activity associated with instances of stuttering in pCWS, in contrast to their fluent 

speech, will differ in brain areas supporting motor planning and control. This analysis will compare individual 

model estimates of stuttering instances vs. fluent speech in pCWS using paired t-tests. Findings from this analysis will reflect pCWS’s brain activity associated with instances of stuttering in addition to the activity during 

fluent speech segments. Overall, analyses associated with Specific Aims 1 should provide insights into the neural processes associated with persistent stuttering. 

Data analyses for Specific Aim 2. Identify brain activity associated with continuous speech production that characterizes recovery from stuttering. The analyses will test the hypotheses regarding 

Specific Aim 2 that brain activity of rCWS during fluent speech production will differ from that of pCWS and 

CWNS. Specifically, H2a: rCWS, when compared with pCWS, are hypothesized to exhibit lesser anomalous 

activity in the left perisylvian regions and H2b: rCWS, when compared with CWNS, are hypothesized to exhibit increased activity in the right frontal areas. These analyses will compare individual estimates of fluent speech 

between rCWS and pCWS as well as rCWS and CWNS using two-sample t-tests. Findings are expected to reflect the neurological characteristics associated with rCWS. Overall, analyses associated with Specific Aim 2 

should provide insights into the neural processes associated with recovery from stuttering. 

C4.3 Potential problems and alternative approaches. The present proposal’s hypotheses are mainly 

based on evidence from neuroimaging studies of continuous speech in adults or indirect evidence such as 

structural anomalies associated with children’s stuttering persistence and recovery. First, although results from 

CWS and AWS appear to be converging, it is also possible that there are marked differences in brain activity 

between adults and children associated with stuttering and fluent speech production. If so, our hypotheses may 

need to be revised. Given that the proposed study would be the first attempt to examine brain functional differences during continuous speech production in CWS, we believe that even if the original hypotheses are in need 

of revision, the data obtained from this study will contribute novel and important information regarding neural 

bases of childhood stuttering. Second, extremely abrupt head movements exceeding the workable range of our 

de-noising method (>9 mm) may occur during our participants’ speech production. It should be rare because 

movements of participants’ heads are restrained. In case extremely abrupt head movements occur, in addition 

to our sICA de-noising, we will use a conventional technique called image scrubbing [19] to remove the affected 

fMRI volumes. Third, there is always a chance of data loss due to lack of compliance with the task by some 

children. This possibility is expected to be low because most of our potential participants will have already been 

scanned by our research group and performed the storytelling task several times successfully in the past. If a 

child does not perform the task correctly, or is not able to complete the experiment, we will attempt to reschedule the visit and provide extra training sessions for that child. 

C5. TIMELINE 

Month 1-18: Recruit participants, conduct fMRI experiments and prepare for data analysis to address hypotheses associated with the Specific Aims. Month 12-24: Analyze speech and fMRI data. Present preliminary 

findings at national and international conferences. Begin to prepare manuscripts. Month 24-36: Prepare and 

submit manuscripts to peer reviewed journals, respond to reviews, publish reviewed/revised manuscripts and 

present final results at national and international conferences. 

C6. SUMMARY OF PROJECT/FUTURE DIRECTIONS 

The outcomes of the proposed study are expected to further enhance our understanding of neural processes of 

continuous speech production associated with persistence and recovery of stuttering. Such understanding 

should be foundational to future investigations of how stuttering instances are initiated by tracking brain activity transitioning from fluent speech to the onsets of stuttering instances using time-resolved fMRI [44]. Moreover, to extend the proposed study, we plan to apply functional connectivity techniques to study interregional 

interactions during continuous speech production that characterize stuttering persistence and recovery [17]. 

Findings of the proposed study will also provide guidance for a future longitudinal study of CWS, in which we 

plan to track the neurodevelopment of speech production starting from CWS’s stuttering onset to recovery/persistence to reveal early prognostic neural markers of recovery/persistence. Such a program of studies, 

we believe, will eventually assist in developing more effective treatment strategies for childhood stuttering. 

Contact PD/PI: Chow, Ho Ming

Research Strategy Page 45
PROTECTION OF HUMAN SUBJECTS 

1. Risks to Human Subjects 

1.1 Human Subjects Involvement, Characteristics, and Design 

The proposed study will involve behavioral testing and brain imaging in a single visit of each 

participant. Approximately 72 school-age children from 5 to 11 years will be recruited from our 

ongoing longitudinal neuroimaging studies of childhood stuttering, in which more than 60 

children who stutter and a like number of fluent control peers were drawn around , 

and have been assessed annually in the last 3-4 years. Of 72, 24 will be persistent in 

stuttering, 24 recovered from stuttering, and 24 fluent controls who have never been diagnosed 

with stuttering nor have family history of stuttering. Recovery and persistence as well as no 

history of stuttering will be determined according to the most recent two annual speechlanguage assessments and parental reports of our ongoing longitudinal study. After ~15% 

attrition (maximum rate estimated from our ongoing longitudinal study) and potential data loss 

due to failure to complete experimental task, movement artifacts, and so forth (which may add 

another ~20% of data loss), around 16 samples in each of the three groups will be obtained. 

Because the aim of the proposed project is to compare brain activity associated persistence and 

recovery of childhood stuttering, it is important to objectively identify children who persist in 

and have recovered from stuttering. Since the determination of persistence and recovery from 

stuttering is best accomplished at least 2 years after onset, children who stutter younger than 5 

years of age will not be included in the proposed study. Composition of age, gender, and 

wherever possible, race, ethnicity, and social-economic status (using Hollingshead Four-Factor 

Index of Social Position) will be equated between the three groups. As the male-to-female ratio 

in stuttering prevalence is about 3 to 1, we expect that there will be more boys than girls, 

approximately 2-3 boys to 1 girl in each group. All participants will be monolingual English 

speakers without any diagnosed developmental or psychiatric disorders other than stuttering. 

According to the recommendation of the Speech-Language Pathologist and the wishes of the 

parents or guardians, children with persistent stuttering or have recovered may receive 

treatment or no course of treatment. We expect that at least 25-50% of children who stutter in 

our sample, including those recovered, will have received therapy in the past. 

Parents and/or caregivers will complete forms and/or answer questions about the child’s 

behavioral, medical, social, and developmental states and speech, language and hearing 

background. All participants will undergo a standardized speech fluency assessment to confirm 

their group assignment and perform a storytelling task in the scanner. Parents or guardians will 

be in the adjacent interview or observation room or, if necessary, in the experimental testing 

room with the child if he/she is overly distressed at separation. During speech fluency 

assessments and brain imaging procedures, children will be audio-video recorded. 

De-identified speech data recorded during brain imaging will be analyzed by Prof. Nan Ratner, 

Co-Investigator at the University of Maryland. She and authorized students and staff will access 

the data that are stored at the , i.e., the PI’s host institution via passwordContact PD/PI: Chow, Ho Ming

Protection of Human Subjects Page 46
protected virtual private network (VPN) and encrypted remote control desktop connection. In 

this way, no data will be permanently transferred to the collaborator site. 

1.2 Sources of Materials 

This project involves four sources of research material: 1) Questionnaire data (e.g., intake 

screening form, developmental history, demographic information obtained from parents, 

behavioral questionnaires, etc.), 2) brain imaging data (e.g., structural image and functional 

MRI), 3) audio-video speech data during speech-language assessment and brain imaging, and 4) 

Behaviorally coded data (e.g., during testing, some behavioral observations will be coded by 

either paper-and-pencil means and/or subsequently through the use of computerized software 

e.g., frequency of stuttering-like disfluencies per task). All data will be stored in a locked filing 

cabinet or a password-protected computer housed in a locked room at the Rachel Upjohn 

Building, the , accessible only to the PI, Co-Investigators, and authorized 

students and staff. The participant’s identity associated with all data files, either in paper or 

computerized format will be codified. 

1.3 Potential risks 

a. Breach of privacy. The risks involving breach of sensitive private information will be 

minimized by having all subjects' data de-identified and handled only by the PI and other 

authorized investigators. All investigators will receive human research protection training 

according to IRB guidelines of their host institutions. All subject data will be placed in individual 

coded files that will be locked in a cabinet or a password-protected computer housed in a locked 

room at the . 

b. Inconvenience or discomfort during behavioral testing. All participants will be given breaks 

as needed, and will not be pressured to continue if there is excessive anxiety or fatigue. The 

testing sessions will be divided into 2 or 3 sessions as necessary. 

c. Inconvenience or discomfort during MRI scanning. Well-known risks for MRI scanning 

involve the presence of ferromagnetic foreign objects in and/or on the body (e.g., pacemaker, 

surgical clip, staples, etc.), claustrophobia, as well as possible inconvenience or discomfort 

during the scanning due to the requirement of lying still, and exposure to loud noise. The risks 

involved in MRI participation are usually greatly minimized through a thorough screening 

procedure, followed by ample opportunity for exposure to the sights and sounds of the MRI 

setting. Discomfort due to loud noise during scanning will be minimized through use of earplugs, 

headphones, and padding around the head as well as the inside of the MRI bore. One staff 

member will sit next to the child during the length of the MRI session to monitor any discomfort. 

If the child shows any signs of discomfort or anxiety during the scanning, the procedure will be 

interrupted and stopped if necessary. 

d. Incidental MRI and/or behavioral findings. Any MRI scans that appear to have potential 

clinical abnormality will be forwarded to a radiologist, and if confirmed abnormal, the findings 

will be communicated to the study investigator, who would notify the parents and, with 

permission, forwarded to the child’s primary care physician as designated by the parents. 

Further referrals to appropriate clinicians would be made as appropriate. If, during the 

Contact PD/PI: Chow, Ho Ming

Protection of Human Subjects Page 47
Contact PD/PI: Chow, Ho Ming

behavioral assessments, it is found that the child has a clinically significant developmental delay, 

speech-language deficit, or a cognitive, learning, or behavioral problem, that information would 

be shared with the parents as well. The parents would be encouraged to contact the child’s 

physician for follow-up and possible referrals to the appropriate professional for intervention. 

2. Adequacy of Protection Against Risks 

a. Participant Recruitment. Participants of the proposed project will be recruited from the 

participant pool of the ongoing longitudinal neuroimaging study headed by the co-investigator 

Dr. Soo-Eun Chang. This ongoing longitudinal study has recruited around 60 children who 

stutter and a like number of fluent control peers were drawn from 

 and have been assessed annually in the last 3-4 years, via advertisements in 

magazines and recruitment letters. Dr. Chang and her research team will make initial contacts 

with the potential participants’ parents or guardians to inquire whether they are willing to 

participate in the proposed study. 

b. Consent to participate: Parents. Consent to participate will be obtained from the parent(s) or 

guardian(s) of the child, and assent to participate will be obtained from the children. We will 

first obtain consent from the parent because 1) experience indicates that parents must agree, 

understand and be comfortable with participating before their child will be and 2) discussing 

these matters first, with the parent, allows the child a greater period of time to warm up to the 

study environment and to the investigators. Parents will read and sign an IRB-approved consent 

form in the presence of the PI, co-I, the Speech-Language Pathologist, or a doctoral-level project 

team member at the beginning of the visit. The parents/guardians will also be given a verbal 

overview of the project and any questions will be answered and concerns addressed. The 

parents/guardians will also be informed that they may ask questions at any time during the 

procedures and/or stop the procedures at any time during the assessment with no penalty. At 

the end of each assessment, the PI or Co-I or Speech-Language Pathologist will share testing 

results with the parents and answer any questions about the child’s performance, results of 

testing, etc. If the PI, Co-I or Speech-Language Pathologist at the assessment finds that the child 

needs follow-up attention from another professional, he/she will make that recommendation at 

that time and provide resources for the parents to contact. 

c. Assent to participate: School aged children. Once the parent(s) has/have consented, the PI, 

co-I, the Speech-Language Pathologist, or a doctoral-level project team member will obtain 

assent to participate from elementary school-age participants. If they are pre-readers and prewriters, verbal assent will be obtained. For children who can read and write, we have created a 

child assent form that they may sign. Obtaining assent from children involves slow, clear and 

repetitive explication to the child of what we will do and what he or she will need to do in 

response (usually quite simple, e.g., storytelling assisted by pictures or having a conversation). 

We ask the child if he or she understands what we will do and if it is okay. We make clear that 

we will take breaks and stop whenever the child wants. In our experience, less than 1% of 

children that we initially test do not appear to understand the above instructions after three 

attempts to explain them to him or her, and if this is the case, the child is not a viable candidate 

for our work and is excluded from further consideration. All investigators and project members 

Protection of Human Subjects Page 48
Contact PD/PI: Chow, Ho Ming

are or will be trained in appropriate IRB-approved procedures required by the 

 

d. Protection against risks. Risks in participating in standardized testing, videotaping of speech, 

and MRI imaging are minimal. To minimize the risks, we will, before each assessment begins (as 

explained above), thoroughly explain all procedures to both parent/guardian and child. Also, as 

suggested above, ample time will be allowed, during such explanation, and throughout testing, 

for parents/guardians and children to ask questions about procedures, goals, and methods. 

Written consent forms, that have first been verbally described, will be presented to the 

parents/guardians for their review and signature. Verbal or written assent will be obtained from 

school-age children in the presence of their parents. Before brain imaging experiment starts, a 

thorough screening procedure will be carried out to minimize the risks involved in MRI 

participation. 

At any time during any assessment, the parents/guardians and/or children can end the 

session without penalty. If children become upset, we will stop and allow parents to soothe them. 

Breaks will be used to minimize child fatigue and frustration. Parents will stay in the next room 

to their child throughout testing, or in the same room if the child has difficulty separating. 

Families will be reimbursed for their participation, effort, time, and travel to assist them with 

costs and inconvenience to their schedules. Resulting test scores, performance during 

experimental testing, etc. associated with each participant will be, as discussed above, stored in 

locked cabinets or password-protected computer in a locked room at Rachel Upjohn Building, 

the . A non-identifying code will be assigned to each participant for 

organizing the participant’s coded and statistically analyzed data files. 

3. Potential Benefits of the Proposed Research to the Subject and Others 

Risk to benefit ratio. The risks of fatigue, discomfort, and disruption in family schedules are 

outweighed by the benefits received. Indeed, without any financial charge to the family, the 

parents of children will be informed of results based on state-of-the-art speech and language 

testing of their child, and MRI evaluation of the child’s brain, testing that would cost thousands 

of dollars if done in a typical clinical setting. Such information is particularly salient for some 

parents whose children are known or suspected to stuttering as well as parents who are curious 

about the speech and language development of their children. From the experience obtained 

from our ongoing longitudinal neuroimaging study, participation in the project has intrinsic 

value to most parents in terms of learning more about their child. In sum, it is our experience 

that many parents are not merely participating to “help science,” they are participating to better 

understand their child and his or her performance, which suggests that the information 

obtained in this project has more than a little benefit for many families. 

4. Importance of the Knowledge to be Gained 

Results from this project are expected to increase our understanding of neural activity 

associated with persistence and recovery from childhood stuttering. This knowledge will bring 

us one step closer to a more comprehensive understanding of the neural processes of continuous 

speech production and how these processes are disrupted, leading to instances of stuttering. 

This has potential to provide an objective neural marker for evaluating persistence/recovery of 

Protection of Human Subjects Page 49
childhood stuttering and effectiveness of therapeutic strategies or treatments. Thus, benefits 

from this project - advancement of our understanding and possible improvements in 

assessment/treatment of stuttering - would seem to outweigh the minimal risks involved to 

participants. This is particularly so when one weighs, on the one hand, the significant negative 

impact that stuttering has on the academic, emotional, social, and vocational achievements, 

development and potential of individuals who stutter and, on the other, the very minimal risks 

to the child and parents/guardians by having them participate in this project. Additionally, 

considering stuttering has a significant negative impact on the quality of life of people who 

stutter, knowledge derived from this project would appear to far outweigh the minimal risks 

involved to participants. In sum, minimal risks to participants that may occur are more than 

reasonable given the society’s strong need for understanding and treating stuttering. 

Contact PD/PI: Chow, Ho Ming

Protection of Human Subjects Page 50
Inclusion of Women

Children of both genders are included in this proposal. We will strive to have balanced numbers of girls 

and boys in each group in order to analyze potential gender effects. Although girls are underrepresented in samples of children with stuttering, we will make every effort to include girls in the 

proportion they occur in the population with this disorder (boys to girls ratio: 3:1). In the subject pool of 

our ongoing neuroimaging study of childhood stuttering, in which the participants will be recruited 

from, the ratio of boys to girls who stutter is 1.7:1. We expect to be able to recruit a similar ratio of boys 

and girls in the proposed project period. 

Inclusion of Minorities 

We anticipate including minorities in approximately the proportions found in the regional population 

(about 81% White). To maintain the representativeness of our samples, ethnic composition of the 

proposed project will be monitored periodically. Because there is a tendency for low income and African 

American families to live further from campus, transportation costs will be provided to enhance 

recruitment of those families if necessary. No participant will be excluded because of minority status. 

Because some tasks are language based, it is scientifically necessary that all participants are native 

English speakers.

Contact PD/PI: Chow, Ho Ming

Women & Minorities Inclusion Page 51
OMB Number: 0925-0002

Tracking Number: GRANT12102741 Funding Opportunity Number: PAR-16-057. Received Date: 2016-02-23T15:48:23.000-05:00

Planned Enrollment Report

 

Study Title: Neural markers of persistence and recovery from childhood stuttering: An fMRI study of continuous speech production

Domestic/Foreign: Domestic

Comments:

Racial Categories Ethnic Categories

Not Hispanic or Latino

Female Male

Hispanic or Latino

Female Male

Total

American Indian/Alaska Native 0 0 0 0 0

Asian 0 0 0 0 0

Native Hawaiian or Other Pacific Islander 0 0 0 0 0

Black or African American 7 11 0 0 18

White 18 33 0 0 51

More than One Race 0 0 1 2 3

Total 25 44 1 2 72

Study 1 of 1

Contact PD/PI: Chow, Ho Ming

 Page 52
Inclusion of Children 

The current proposal includes children from ages 5-11. Including children is necessary because the 

research focuses on the neural processes associated with persistence and recovery from childhood 

stuttering. Questions about persistence and recovery from childhood stuttering cannot be studied 

without including children in the research. The project team has extensive experience working with 

children in this age range. The Co-I Dr. Soo-Eun Chang is licensed and experienced clinicians (speechlanguage pathologist, neuropsychologist), who will be available on call. 

Contact PD/PI: Chow, Ho Ming

Inclusion Of Children Page 53
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References Cited Page 55
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Letters Of Support Page 56
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2360 Bonisteel Blvd., 1072 BIRB T: 734.936.0558 F: 734.936.4218 

Ann Arbor, MI 48109 

Please recycle 

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RESOURCE SHARING PLAN 

a) Data sharing plan 

Data will be shared in a timely and collegial manner. Once data analysis is completed 

and the manuscripts addressing the specific aims of the proposed study are accepted for 

publication, data sets created in this research program will be made available for other 

qualified researchers upon request for purposes of scientific investigations or review. 

We anticipate that the data will be made available within one year after the study 

closeout date. While making these data as freely available as possible, privacy of 

participants will also be protected. Before distribution, the data will be de-identified, 

and only those relevant to the request will be provided. Investigators who request for the 

data need to sign a formal data-use agreement. Depending on the data types requested, 

data will be sent to the investigator by mail or secure transfer. 

b) Sharing model organisms. 

No applicable 

c) Genome-Wide Association Studies 

Not applicable

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Resource Sharing Plans Page 61