------ ---

SUMMARY STATEMENT 

PROGRAM CONTACT: ( Privileged Communication ) Release Date: 07/22/2016 

Revised Date: 

Application Number: 1 R21 DC015853-01 

Principal Investigator 

CHOW, HO MING 

Applicant Organization: 

Review Group: CDRC 

Communication Disorders Review Committee 

Meeting Date: 06/23/2016 RFAIPA: PAR16-057 

Council: OCT 2016 PCC: VS02 

Requested Start: 09/01 /2016 

Project Title: Neural Markers of Persistence and Recovery from Childhood Stuttering: An fMRI 

Study of Continuous Speech Production 

SRG Action: Impact Score:20 

Next Steps: Visit http://grants.nih.gov/grants/next_steps.htm 

Human Subjects: 30-Human subjects involved - Certified, no SRG concerns 

Animal Subjects: 10-No live vertebrate animals involved for competing appl. 

Gender: 1A-Both genders, scientifically acceptable 

Minority: 1A-Minorities and non-minorities, scientifically acceptable 

Children: 2A-Only Children, scientifically acceptable 

Project Direct Costs Estimated 

Year Re uested Total Cost 

1 

2 

3 

TOTAL 

ADMINISTRATIVE BUDGET NOTE: The budget shown is the requested budget and has not been adjusted 

to reflect any recommendations made by reviewers. If an award is planned, the costs will be calculated by 

Institute grants management staff based on the recommendations outlined below in the COMMITTEE 

BUDGET RECOMMENDATIONS section. 

ADMINISTRATIVE NOTE 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

1 R21 DC015853-01 2 CDRC 

CHOW, H 

1R21DC015853-01 Chow, Ho Ming 

RESUME AND SUMMARY OF DISCUSSION: This application for an NIDCD Early Career Research 

(ECR) Award (R21) seeks three years of support for Dr. Chow to determine brain activity patterns 

associated with continuous speech production in children with persistent stuttering and children who 

recovered from stuttering. Strengths of the application include the potential impact of the research, 

which could lead to treatments for persistent stuttering, and the PI, who participated in the development 

of the experimental method of de-noising motion artifacts in fMRI scanning. While preliminary data and 

data on head movements come from experiments with adults, this application proposes to apply the 

method to children who stutter, and is an interesting approach. The study represents the next step in 

investigating brain function during natural speaking in normal and clinical populations. The hypotheses 

are well articulated, the experimental design is well thought through, and the approach is rigorous and 

feasible. 

DESCRIPTION (provided by applicant): 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. 

PUBLIC HEALTH RELEVANCE: 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. 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

-

1 R21 DC015853-01 3 CDRC 

CHOW, H 

CRITIQUE 1: 

Significance: 1 

Investigator(s): 3 

Innovation: 1 

Approach: 3 

Environment: 1 

Overall Impact: The study aims at (1) understanding brain function during fluent and disfluent 

continuous speech in children who stutter and (2) capturing differences between those with persistent 

stuttering and those who recover from stuttering. The study addresses a very important research topic 

and represents the next step in studying brain function during natural speaking in normal and clinical 

populations. The PI was trained in the lab where the method for recording and analyzing fMRI during 

continuous speaking was developed; he took part in the process of its development (a co-author on a 

methodological paper). The PI appears to be the first to implement this method with a stuttering 

population. He appears to have great support through his collaborators and at the institution. Overall 

significance of this research and innovation are very high and there are no concerns regarding the PI’s 

level of technical expertise and team support to deliver the results. There are few minor methodological 

questions, but they do not affect the overall enthusiasm for this project. 

1. Significance: 

Strengths 

 Being able to examine brain function during fluent and disfluent continuous speech is very 

exciting. The development of the method to do so is very timely as it is a natural next step in the 

progression of an investigation into the brain of those who stutter (and hopefully other clinical 

populations in the future). 

 Scientific premise for this line of research has been sufficiently well presented. 

 Examining the differences in the brain function of those who stutter and those who recovered 

from stuttering is very promising as well as it may lead to the development of a predictive 

marker of stuttering recovery and lead to the subgrouping of the children early on with clear 

implications to speech therapy planning etc. The clinical implications are described very 

realistically in the application. 

Weaknesses 

 None 

2. Investigator(s): 

Strengths 

 PI – appropriate, diverse background in engineering and neurosciences (neurolinguistics); 

Postdoc at NIDCD with mentor (Allen Braun) who developed the fMRI de-noising technique. 

 PI – NIH award for research excellence 

 Great and appropriately assembled team, which includes Allen Braun; Soo-Eun Chang – who 

leads a large and productive research group at with research focus on stuttering; 

and Nan Bernstein Ratner – who is an expert in the analysis of speech of stutterers. 

 Although Allen Braun was the post-doc mentor, his involvement is justified by the novelty of the 

fMRI method, which will be central to the study. 

Weaknesses 

 PI’s productivity to date (since 2009) – only moderate – 4 first-author pubs (in imaging journals, 

which is great); 4 other pubs. No history of previous funding. 
 

 

 

1 R21 DC015853-01 4 CDRC 

CHOW, H 

3. Innovation: 

Strengths 

 A novel (published) method of fMRI data de-noising will be used for the first time in children who 

stutter. 

 Continuous speech will be studied in order to elicit stuttering events. 

Weaknesses 

 None. 

4. Approach: 

Strengths 

 Access to a large pool of participants who are already part of ongoing research (R01) and 

familiar with the overall procedures (MRI) and task (story telling); the recovered stutterers are 

also known, which is a significant strength. 

 A validated fMRI de-noising method 

 Connected speech task to elicit disfluencies 

 Clearly described preliminary works 

 Well stated hypotheses 

 Connected speech measures collected, analyzed and used as co-variates. 

 Well defined inclusion criteria with provisions around stuttering severity 

 Nice estimate of stuttering events in the MRI 

Weaknesses 

 It would have been nice to see pilot data (or maybe someone published this) on the head 

movement characteristics during stuttering event in either kids or adults (In a scanner with head 

restrain if possible). This issue, however, is dealt with appropriately in “limitations”. 

 Limited details on the screening of participants – language testing/ IQ testing etc. 

 Would parents agree on an additional fMRI session for kids that are already in the study or will 

this recording be a part of the other data collections? 

 Not sure how the “normal” dysfluencies will be handled 

5. Environment: 

Strengths 

 Sufficient institutional support 

 Appropriate laboratory resources 

 Appropriate resources at the University of Maryland 

Weaknesses 

 None 

Protections for Human Subjects: Acceptable Risks and/or Adequate Protections 

 well described Protection of human subjects; numbers are justified; risks are minor and justified 

Inclusion of Women, Minorities and Children: 

 Sex/Gender: Distribution justified scientifically 

 Race/Ethnicity: Distribution justified scientifically 

 Inclusion/Exclusion of Children under 18: Including ages <18; justified scientifically 

 the study is about childhood stuttering; inclusion of children is justified; risks are small 

Vertebrate Animals: Not Applicable 

Biohazards: Not Applicable 
 

 

 

 

 

 

 

 

 

 

1 R21 DC015853-01 5 CDRC 

CHOW, H 

Select Agents: Not Applicable 

Resource Sharing Plans: Acceptable 

Authentication of Key Biological and/or Chemical Resources: Not Applicable 

Budget and Period of Support: Recommend as Requested 

CRITIQUE 2: 

Significance: 2 

Investigator(s): 2 

Innovation: 2 

Approach: 2 

Environment: 2 

Overall Impact: This is a well-designed application that seeks to understand brain mechanisms 

contributing to either recovery from, or persistence of, stuttering in children. There is significant 

potential knowledge to be gained in understanding recovery from, as opposed to persistence of, 

stuttering in children, which could ultimately lead to improved, data-driven treatments for persistent 

stuttering. The team includes seasoned pioneers in investigating the behaviors and neuroscience of 

normal and disordered speech and language and many of them have already worked together in 

productive collaborations. The main weakness is in the risk that assumptions driving the experimental 

design and analysis are based on pilot work acquired from adults who stutter, wherein mechanisms 

may not be the same; however, at the risk of having to implement alternative methods, the distinction 

between mechanisms underlying adult and childhood stuttering would also be important to understand. 

The likelihood for the project to exert a significant and sustained impact on the study of childhood 

stuttering and potentially other developmental communication disorders is high, especially if the team 

succeeds in demonstrating the reliability of this novel fMRI analysis technique in children who stutter. 

1. Significance: 

Strengths 

 Although advances have been made in understanding speech-motor control brain circuitry and 

its breakdown in adult stuttering, very little is known about speech-motor circuits in children who 

stutter (CWS) and those who don’t (CWNS). 

 This study will improve our understanding of brain mechanisms that underlie both persistence of 

and recovery from stuttering. 

 If its aims are met, the study results could lead to a biomarker that dissociates persistent from 

recovered stuttering, potentially aiding in the development of new, targeted interventions aimed 

at preventing the development of persistent stuttering. 

 If successful, this project will not only demonstrate the feasibility of using fMRI to study 

continuous speech production in persistent (p) and recovered (r)CWS and CWNS, it will also 

lead to new ecologically valid applications of the de-noising methodology in neuroimaging 

studies of other communication disorders across the lifespan. 

Weaknesses 

 None noted by the reviewer 

2. Investigator(s): 

Strengths 
 

 

 

 

 

 

 

 

 

 

 

 

 

1 R21 DC015853-01 6 CDRC 

CHOW, H 

 The PI brings extensive expertise in fMRI acquisition and analysis of continuous speech in 

healthy and disordered populations. 

 This is a strong team that includes pioneers in the fields of brain-language neuroscience 

(Braun), language and fluency across the lifespan (Ratner), and neural bases of pediatric 

stuttering (Chang). Many of them have already worked together in productive collaborations 

Weaknesses 

 None noted by the reviewer 

3. Innovation: 

Strengths 

 If successful, the use of fMRI de-noising techniques, in part developed by the PI, will allow for 

examination of the brain during continuous speech production with vastly reduced motion 

artifact 

 Investigation of stuttering and fluent speech in pCWS, rCWS, and CWNS during continuous 

speech production provides ecological validity since stuttering is more likely to occur during 

continuous speech-language planning and production, i.e., at the sentence and discourse level 

 Study of brain mechanisms supporting fluent speech production in children who have recovered 

from stuttering has not been done before 

 Mixed block/event fMRI design allows investigators to characterize patterns of fluent and 

dysfluent speech within children with persistent stuttering, as well as to characterize differences 

between fluent speech patterns in children who have recovered vs. those with persistent 

stuttering. 

Weaknesses 

 Being the first to investigate brain mechanisms underlying fluent and dysfluent connected 

speech production in children using fMRI, the project risks that their assumptions regarding 

similarities between children and adults are invalid. 

4. Approach: 

Strengths 

 Use of fMRI (vs fNIRS) allows for whole brain interrogation, including subcortical regions 

involved in speech-motor circuitry; fMRI also has superior spatial resolution to fNIRS and is noninvasive (unlike PET). 

 Use of spatial independent component analysis (sICA) in fMRI data analysis to separate motion 

artifacts from neuronally correlated signals allows for the study of continuous speech 

production, the most likely context in which to elicit stuttering 

 The PI and team have demonstrated feasibility of removing motion artifacts related to head 

movements in children without discarding true BOLD signal. They also demonstrated feasibility 

of collecting fMRI during continuous speech in an 8-year-old child, with results similar to their 

prior findings in adults re: perisylvian activity for storytelling vs. automatic speech. 

 Preliminary structural and functional MRI studies of persistent and recovered adults who stutter 

support the model-driven hypotheses in their specific aims 

Weaknesses 

 The application acknowledges a potential issue with assuming that brain activity in children who 

stutter will resemble that of adults who stutter. 

 8-channel head coil is not state-of-the-art but should be adequate for the task 

 Could there be an issue with the fact that these children have been tested on multiple occasions 

with the same stimuli, i.e., that some of what accounts for the right hemisphere activity 

compared to CWNS is an effect of practice or overlearned speech? 

5. Environment: 
 

 

 

 

 

 

1 R21 DC015853-01 7 CDRC 

CHOW, H 

Strengths 

 There is sufficient lab, office, and clinical space to support the research program 

 Co-I Chang contributes a significant database of children who stutter or have recovered from 

stuttering and have already been studied longitudinally 

 The neuroimaging facility includes required peripheral equipment to successfully perform the 

study, including the FOMRI-III optical noise cancelling system, and a mock scanner for 

participant training. 

 Co-I Ratner contributes inclusion of continuous speech data from CWS and (recovered) CWDS 

to the TalkBank registry and provides use of CLAN/CHAT text-based speech analysis software 

which enables computation of diverse linguistic measures above and beyond fluency as well as 

comparison to other groups 

 The Dept. Chair has expressed full support of Dr. Chow’s proposal 

Weaknesses 

 None noted by the reviewer 

Protections for Human Subjects: Acceptable Risks and/or Adequate Protections 

 Research Strategy calls for 3 groups of 20 participants but Planned Enrollment Report states 72 

participants 

Inclusion of Women, Minorities and Children: 

 Sex/Gender: Distribution justified scientifically 

 Race/Ethnicity: Distribution justified scientifically 

 Inclusion/Exclusion of Children under 18: Including ages <18; justified scientifically 

Vertebrate Animals: Not Applicable 

Biohazards: Not Applicable 

Select Agents: Not Applicable 

Resource Sharing Plans: Acceptable 

Authentication of Key Biological and/or Chemical Resources: Not Applicable 

Budget and Period of Support: Recommend as Requested 

CRITIQUE 3: 

Significance: 2 

Investigator(s): 1 

Innovation: 1 

Approach: 2 

Environment: 1 

Overall Impact: This is an interesting R21 proposal to identify differences in neural activity and circuitry 

between children who recover from stuttering versus those who have persistent stuttering, using 

continuous speech in a novel fMRI paradigm. They hypothesize that children with persistent stuttering, 

like adults who stutter, will show reduced activation of normal perisylvian cortex activation (left IFG, 

STG) and increased activation of subcortical structures. Those who recover from stuttering may show 

increased activation of right IFG (based on some structural connectivity data they have obtained). What 
 

 

 

 

 

 

 

 

 

 

 

 

 -

1 R21 DC015853-01 8 CDRC 

CHOW, H 

they do not really discuss is the implications of the findings, if confirmed. The results could suggest 

differences in the brain that permit (lead to) recovery from stuttering, or simply reflect the effect of 

recovery. 

1. Significance: 

Strengths 

 Stuttering is common and disabling, and can be persistent. It is not well understood why it 

persists in some children and not others. 

Weaknesses 

 There is brief mention that the research once accomplished would lead to treatment, but it is not 

clear how the findings would constrain treatment 

2. Investigator(s): 

Strengths 

 Dr. Chow is an accomplished investigator in neuroimaging of language. 

 He has recruited Dr. Chang and Dr. Bernstein-Ratner, who are leading experts on stuttering, to 

make up for his own limited experience in the area of stuttering research. 

 Dr. Braun also complements the team with expertise in the neural basis of broad range of 

disordered and normal language and speech processes, especially during continuous speech 

production (as proposed here) 

Weaknesses 

 Dr. Chow has very little research experience in the domain of stuttering. He is the middle author 

of one published paper. 

3. Innovation: 

Strengths 

 The idea, to identify neural circuits where activation and connectivity differ between children 

who have persistent versus recovered stuttering, seems sound and unique. 

 The fMRI paradigm has been used before by this group, but is relatively unique to their group. 

 Although others have studied the neural basis of stuttering, this is a new approach with fresh 

hypotheses 

Weaknesses 

 Applying to children the method developed with adults does not seem that innovative. However, 

given the preliminary data, it might have been an appropriate R01 application. 

4. Approach: 

Strengths 

 Rigor: Sufficient detail is provided in the scientific method to replicate the studies. Biological 

variables are accounted for 

 Transparency: The premises are clear and justified 

Weaknesses 

 Rigor: the power analysis assumes an effect size obtained from preliminary studies with adults. 

While this is understandable (they have no preliminary data from fMRI with children) the effect 

sizes might be smaller in children, who tend to have more variable fMRI results than adults. This 

is a minor weakness. 

5. Environment: 

Strengths 

 clearly has all the resources available to conduct the research 
 

 

 

 

 

1 R21 DC015853-01 9 CDRC 

CHOW, H 

 There is an existing population of children with history of stuttering (some of whom who have 

recovered) that has already been followed annually for a few years. 

Weaknesses 

 None 

Protections for Human Subjects: Acceptable Risks and/or Adequate Protections 

 The main risk is privacy and discomfort of scanning. There is no mention of possible risk of 

drawing attention to their stuttering. Children will provide assent. 

Inclusion of Women, Minorities and Children: 

 Sex/Gender: Distribution justified scientifically 

 Race/Ethnicity: Distribution justified scientifically 

 Inclusion/Exclusion of Children under 18: Including ages <18; justified scientifically 

 Only children; an effort will be made to recruit more minorities by providing transportation 

Vertebrate Animals: Not Applicable 

Biohazards: Not Applicable 

Select Agents: Not Applicable 

Resource Sharing Plans: No Reviewer response 

Authentication of Key Biological and/or Chemical Resources: Not Applicable 

Budget and Period of Support: Recommend as Requested 

THE FOLLOWING RESUME SECTIONS WERE PREPARED BY THE SCIENTIFIC REVIEW 

OFFICER TO SUMMARIZE THE OUTCOME OF DISCUSSIONS OF THE REVIEW COMMITTEE ON 

THE FOLLOWING ISSUES: 

PROTECTION OF HUMAN SUBJECTS: ACCEPTABLE 

The protocol features minimal risk to subjects and employs adequate protection against risks. 

INCLUSION OF WOMEN PLAN: ACCEPTABLE 

Due to the prevalence of rate of stuttering, this study will recruit more boys than girls. An effort will be 

made to test an equal number of boys and girls. 

INCLUSION OF MINORITIES PLAN: ACCEPTABLE 

There is no information on whether the prevalence of stuttering varies according to race and ethnicity. 

Minorities will be included in the proportion found in the regional population. 

INCLUSION OF CHILDREN PLAN: ACCEPTABLE 

The study is aimed at children ages 5-11, which is scientifically justified. 

VERTEBRATE ANIMAL: Not Applicable (No Vertebrate Animals) 

BIOHAZARD COMMENT: Not Applicable (No Biohazards) 

SELECT AGENTS: Not Applicable (No Select Agents) 
 

 

1 R21 DC015853-01 10 CDRC 

CHOW, H 

SHARING RESEARCH DATA: Acceptable plans 

ADMINISTRATIVE NOTE: Non-compliant Biosketches 

During the review of this application, reviewers and/or NIH staff noted that one or more biosketches did 

not comply with some elements of the required format (NOT-OD-15-032). The requirements are as 

follows: 

Briefly describe up to five of your most significant contributions to science. For each contribution, 

indicate the historical background that frames the scientific problem; the central finding(s); the influence 

of the finding(s) on the progress of science or the application of those finding(s) to health or technology; 

and your specific role in the described work. For each of these contributions, reference up to four peerreviewed publications or other non-publication research products (can include audio or video products; 

patents; data and research materials; databases; educational aids or curricula; instruments or 

equipment; models; protocols; and software or netware) that are relevant to the described contribution. 

The description of each contribution should be no longer than one half page including figures and 

citations. Also provide a URL to a full list of your published work as found in a publicly available digital 

database such as SciENcv or My Bibliography, which are maintained by the US National Library of 

Medicine. 

Some of the biosketches do not include an URL to a full list of publications, or have more than 4 

references per contribution. 

COMMITTEE BUDGET RECOMMENDATIONS: The budget was recommended as requested. 

Footnotes for 1 R21 DC015853-01; PI Name: Chow, Ho Ming 

NIH has modified its policy regarding the receipt of resubmissions (amended applications). 

See Guide Notice NOT-OD-14-074 at http://grants.nih.gov/grants/guide/notice-files/NOT-OD14-074.html. The impact/priority score is calculated after discussion of an application by 

averaging the overall scores (1-9) given by all voting reviewers on the committee and 

multiplying by 10. The criterion scores are submitted prior to the meeting by the individual 

reviewers assigned to an application, and are not discussed specifically at the review meeting 

or calculated into the overall impact score. Some applications also receive a percentile 

ranking. For details on the review process, see 

http://grants.nih.gov/grants/peer_review_process.htm#scoring. 
MEETING ROSTER 

Communication Disorders Review Committee 

NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS 

CDRC 

06/23/2016 - 06/24/2016 
SCIENTIFIC REVIEW OFFICER 
• Temporary Member. For grant app cat ons, temporary members 

may part c pate n the entre meet ng or may rev ew on y se ected 

app cat ons as needed. 

Consu tants are requ red to absent themse ves from the room 

dur ng the rev ew of any app cat on f the r presence wou d 

cons! tute or appear to cons! lute a conf ct of nterest.