OMB Number: 4040-0001 SF 424 (R&R) Expiration Date: 10/31/2019researchdevelopment.byu.edu/wp-content/uploads/... · Tracking Number: GRANT12511027 Funding Opportunity Number: PA-16-200

OMB Number: 4040-0001

Expiration Date: 10/31/2019

Tracking Number: GRANT12511027 Funding Opportunity Number: PA-16-200 . Received Date:2017-10-25T17:55:58.000-04:00

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/CorrectedApplication

b. Agency Routing Number

2. DATE SUBMITTED2017-10-25

Application Identifier c. Previous Grants.gov Tracking Number

5. APPLICANT INFORMATION Organizational DUNS*: 0090940120000Legal Name*: BRIGHAM YOUNG UNIVERSITYDepartment: ORCADivision:Street1*: A-285 ASB Campus DriveStreet2:

City*: PROVOCounty:State*: UT: UtahProvince:Country*: USA: UNITED STATESZIP / Postal Code*: 84602-1231

Person to be contacted on matters involving this applicationPrefix: First Name*: Gene Middle Name: Last Name*: Larson Suffix:

Position/Title: ORCA DirectorStreet1*: A-285 ASB Campus DriveStreet2:

City*: ProvoCounty:State*: UT: UtahProvince:Country*: USA: UNITED STATESZIP / Postal Code*: 84602-1231Phone Number*: 801-422-3360 Fax Number: 801-422-0620 Email: [email protected]

6. EMPLOYER IDENTIFICATION NUMBER (EIN) or (TIN)* 87-02172807. TYPE OF APPLICANT* O: Private Institution of Higher EducationOther (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 NUMBERTITLE:

11. DESCRIPTIVE TITLE OF APPLICANT'S PROJECT*Are visual attention deficits in dyslexia reading-specific? A combined eye-tracking/fMRI investigation.12. PROPOSED PROJECTStart Date* Ending Date*09/01/2018 08/31/2020

13. CONGRESSIONAL DISTRICTS OF APPLICANT

UT-003

Page 1


SF 424 (R&R) APPLICATION FOR FEDERAL ASSISTANCE Page 214. PROJECT DIRECTOR/PRINCIPAL INVESTIGATOR CONTACT INFORMATIONPrefix: Dr. First Name*: Steven Middle Name: G. Last Name*: Luke Suffix: Position/Title: Assistant ProfessorOrganization Name*: Brigham Young UniversityDepartment: Psychology and NeuroscienceDivision:Street1*: 1062 SWKTStreet2:

City*: ProvoCounty:State*: UT: UtahProvince:Country*: USA: UNITED STATESZIP / Postal Code*: 84602-1231Phone Number*: 8014225978 Fax Number: Email*: [email protected]. ESTIMATED PROJECT FUNDING

a. Total Federal Funds Requested* $328,580.00b. Total Non-Federal Funds* $0.00c. Total Federal & Non-Federal Funds* $328,580.00d. Estimated Program Income* $0.00

16. IS APPLICATION SUBJECT TO REVIEW BY STATEEXECUTIVE ORDER 12372 PROCESS?*

a. YES ❍ THIS PREAPPLICATION/APPLICATION WAS MADEAVAILABLE TO THE STATE EXECUTIVE ORDER 12372PROCESS FOR REVIEW ON:

DATE:

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

❍ PROGRAM HAS NOT BEEN SELECTED BY STATE FORREVIEW

17. By signing this application, I certify (1) to the statements contained in the list of certifications* and (2) that the statements hereinare true, complete and accurate to the best of my knowledge. I also provide the required assurances * and agree to comply withany resulting terms if I accept an award. I am aware that any false, fictitious, or fraudulent statements or claims may subject me tocriminal, 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 REPRESENTATIVEPrefix: Dr. First Name*: Alan Middle Name: Last Name*: Harker Suffix: Position/Title*: Associate Academic Vice PresidentOrganization Name*: Brigham Young UniversityDepartment: ORCADivision:Street1*: A-285 ASB Campus DriveStreet2:

City*: ProvoCounty:State*: UT: UtahProvince:Country*: USA: UNITED STATESZIP / Postal Code*: 84602-1231Phone Number*: 801-422-3582 Fax Number: 801-422-0620 Email*: [email protected]

Signature of Authorized Representative*Gene Larson

Date Signed*10/25/2017

20. PRE-APPLICATION File Name: Mime Type:

21. COVER LETTER ATTACHMENT File Name: Mime Type:

Contact PD/PI: Luke, Steven G.

Page 2


Table of Contents

424 R&R and PHS-398 SpecificTable Of Contents

SF 424 R&R Cover Page............................................................................................................1Table of Contents...................................................................................................................3

Performance Sites.....................................................................................................................4Research & Related Other Project Information......................................................................5

Project Summary/Abstract(Description)..............................................................................6Project Narrative....................................................................................................................7Facilities & Other Resources................................................................................................8

Research & Related Senior/Key Person................................................................................10PHS398 Cover Page Supplement...........................................................................................15PHS 398 Modular Budget........................................................................................................17

Personnel Justification........................................................................................................19PHS 398 Research Plan...........................................................................................................20

Specific Aims........................................................................................................................21Research Strategy................................................................................................................22Human Subjects Section.....................................................................................................34

Protection of Human Subjects........................................................................................34Inclusion of Women and Minorities................................................................................37PHS Inclusion Enrollment Report...................................................................................38Inclusion of Children........................................................................................................39

Bibliography & References Cited.......................................................................................40

Page 3



Tracking Number: GRANT12511027 Funding Opportunity Number: PA-16-200. Received Date:2017-10-25T17:55:58.000-04:00

Project/Performance Site Location(s)

Project/Performance Site Primary Location ❍ 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: Brigham Young UniversityDuns Number: 0090940120000Street1*: A-285 ASB Campus DriveStreet2:

City*: ProvoCounty:

State*: UT: UtahProvince:

Country*: USA: UNITED STATES Zip / Postal Code*: 84602-1231Project/Performance Site Congressional District*: UT-003

Additional Location(s) File Name:


Page 4


OMB Number: 4040-0001Expiration Date: 10/31/2019

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: 08-28-2017 Human Subject Assurance Number X14325

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* Project_Summary.pdf

8. Project Narrative* Project_Narrative.pdf

9. Bibliography & References Cited References.pdf

10.Facilities & Other Resources Facilities_and_Other_Resources.pdf

11.Equipment


Page 5

Project Summary

Dyslexia is a learning disorder that impairs reading in childhood and throughout life. This is, at least in part, because of language-related problems in dyslexia. However, it is currently unclear if dyslexia is solely a language-based disorder or if there are other deficits as well. When dyslexic individuals read, their eye movements differ from readers without dyslexia, indicating decreased visual attention efficiency. More specifically, research suggests that dyslexic readers have a narrower ‘attentional spotlight’ when they read, meaning that they extract useful information from a smaller section of the text than do typical readers. This deficit in visual attention may be caused by an underlying language deficit or may be partly independent of the language deficit – the current literature is unclear. The purpose of this research is to reveal whether visual attention deficits are independent of language deficits in dyslexia or not. This will be accomplished by comparing eye movements (which reflect visual attention) in reading and in visual tasks, such as memorizing a picture or searching for an object in a photograph, that do not involve language. A group of adult participants with dyslexia and a group of control participants will perform these tasks while their eye movements are monitored. In the first experiment, visual information will be restricted using a ‘moving window’ of different sizes. This technique helps define the size of the attentional spotlight, which is the smallest window that causes no change in eye movements compared to a no-window control condition. If the visual attention deficit in dyslexia is not entirely caused by the language deficit, then visual attention problems should be apparent, in the form of a narrower attentional spotlight, in the language-free tasks as well as in reading. On the other hand, if the visual attention deficit is solely caused by the language deficit, then the eye movements of dyslexics should only differ from controls in the reading task. These same participants will also perform reading and scene memorization tasks while their eyes are tracked and their brains are being scanned (fMRI) in order to identify the cortical network involved in visual attention and the specific brain regions within this network that are impaired in dyslexia. If dyslexia is primarily a language disorder, then only reading-specific cortical areas should be differentially active in dyslexic participants, and no activation differences should be observed during the scene memorization task. Finally, these eye-tracking and neuroimaging data will be used in combination with scores on a battery of standardized language tasks to identify which aspects of language (phonology, vocabulary, fluency) are predictive of visual attention and to quantify the extent to which attentional problems in dyslexia are dependent on language deficits. This knowledge will help focus interventions and treatments for dyslexia.


Project Summary/Abstract Page 6

Project Narrative

Dyslexia, the most common learning disability, involves difficulty reading. Reading is an essential skill and difficulty reading can impair educational achievements and employment prospects. While research has shown that dyslexia is in part a language problem, it is unclear whether individuals with dyslexia have other deficits besides language that contribute to their difficulty reading. Exploring how individuals with dyslexia read and also perform visual attention tasks that do not require language, such as memorizing a picture or searching for an object in a photograph, should reveal whether dyslexia is solely a language problem or whether it is more complicated than that. This knowledge will help focus interventions and treatments for dyslexia.


Project Narrative Page 7

Facilities and Resources

Institution Brigham Young University (BYU) is a comprehensive undergraduate university that houses more than 33,000 students from over 120 nations, making it one of the largest private universities in the nation. The undergraduate students are highly talented, having an average GPA of 3.8 and a 28 ACT. According to a 2005-2009 survey of doctoral recipients, BYU was ranked #5 in the country in the number of baccalaureate graduates going on to earn a PhD. Strengthening the Research Environment As a primarily undergraduate institution, BYU has not been a major recipient of NIH support. However, BYU recruits and trains a high number of talented students, preparing them for successful graduate careers. Undergraduate students have the opportunity each year to apply for mentored research scholarships ($1500) from the BYU Office of Research and Creative Activities (ORCA). In the past four years, Dr. Luke has mentored more than two dozen undergraduates in his lab. Eight of these have completed research capstone projects in Dr. Luke’s lab. Four undergraduate research assistants have also received ORCA grants to pursue eye tracking research on topics ranging from second language reading to shared storybook reading in young children to the brain network involved in reading behavior. BYU also provides grants up to $20,000 to faculty to facilitate mentoring of students; Dr. Luke was a co-investigator on one of these grants, which focused on using eye-tracking to study autism. BYU has large and successful programs in Psychology and in Neuroscience; the PI is affiliated with both programs, and teaches and has mentored undergraduate students from both programs. The Psychology program is large and particularly emphasizes cognitive neuroscience and clinical psychology, as well as developmental and social/health psychology. BYU’s Neuroscience program is the largest undergraduate Neuroscience program in the nation (with more than 400 students), 80% of whom seek advanced degrees. Many of these students seek research experiences as undergraduates to prepare them for advanced degree programs. Undergraduates from both programs will be recruited for the proposed project. This grant would significantly increase the number of undergraduate research assistants that the PI is able to support in the lab at one time, the total time dedicated to mentoring each individual undergraduate researcher, and the quality of opportunity that the research experience provides. My graduate student’s educational experience will also be enriched. He (Benjamin Carter) is a neuroscience PhD student who is interested in using eye-tracking to study neurological disorders, and specifically plans to focus his dissertation on dyslexia. The current proposal will provide him with valuable research experience and financial support, as well as allow him to serve as a research mentor for undergraduate students in the lab. In keeping with the student mentoring goals of the AERA program, the largest budget item in this proposal (41% of total budget) is dedicated to direct support of students. Additionally, the travel budget provides for opportunities for participating students to attend conferences to present research and network with other scientists and potential mentors. Laboratory and Clinical Facilities BYU MRI Research Facility: The structural and functional neuroimaging core is located at the BYU Magnetic Resonance Imaging Research Facility (BYU MRI RF), which consists of more than 3,500 sq. ft. of office, classroom, and laboratory space. Data acquisition will occur primarily at this facility (sessions 2 and 3). The facility is located in the McDonald Building on the BYU campus, and is in close proximity (a short walk) to faculty and student offices and laboratories. The imaging facility contains an MRI coil laboratory fully equipped with oscilloscopes, a network analyzer, signal generators, a full size test bore/RF shield to simulate the MRI electrical environment, and other essential test and measurement equipment. In addition, the facility contains wet-lab space with a fume hood, two neurological evaluation rooms, ample preparation space immediately


Facilities & Other Resources Page 8

adjacent to the MRI scanner, and an MR physics laboratory. The imaging facility has 5 high-power multi-core workstations (2.4GHz 12-core Xeon Mac Pro workstation with 64GB memory, 3.2GHz 6-core Xeon Linux workstation with 64GB memory), as well as a high-performance computing cluster consisting of 9 networked 64bit multi-core Linux computers with minimum processor speeds of 2.4GHz and 8GB of memory. A 12 TB RAID storage device is also available at the facility for use on this proposal. Multiple administrative and workstation PCs and several Mac workstations are also available for use in the various lab areas inside the imaging facility. All computers are connected via a gigabit local-area network and to the internet for international electronic communication, and are carefully managed for security and data networking. In addition to the MRI equipment, the MRI RF also has available two dedicated testing rooms for behavioral testing. Eye Tracker: The MRI scanner room is also equipped with an in-bore MRI-compatible long-distance eye-tracking system (EyeLink 1000 Plus; SR Research Ltd.) to allow monitoring and recording real-time eye movements from participants undergoing MRI scanning. This system has high temporal and spatial precision: the sampling rate is 1000Hz and the spatial resolution is 0.01º. Laboratory Space: The PI, Dr. Steven Luke, has been allocated two rooms for lab space: one room on the 11th floor of the Kimball Tower on the BYU campus, and another room on the 1st floor of the Joseph F. Smith Building. The space for these two rooms totals around 350 sq. ft. These labs contain an Eyelink 100 plus eye-tracker, a Tobii X300 eye-tracker, a behavioral testing computer station, and two computer workstations for research assistant and student use. The computers in these rooms are installed with Matlab and E-Prime. Additionally, these stations have software for statistical analysis (R, AFNI and Freesurfer), and are connected to the computers at the BYU MRI Research Facility (see above) and to the Fulton Supercomputer (see below). Other PI’s Other Resources: The PI has 120 sq. ft. of office space on the 10th floor of the Kimball Tower. BYU has provided the following computer equipment to the PI for data acquisition and analysis: One iMac desktop computers with Matlab, R, E-prime, and AFNI software installed, three laptop computers with R, Matlab and Eprime software installed, two Windows desktop computers with Matlab, R and E-prime software installed, and one Windows laptop with Matlab, R and E-prime software installed. Although most of the data processing and analysis will be performed on the Fulton supercomputer (see below), the iMac also has sufficient computing power and storage space to serve as the main analysis machine for fMRI data analyses. Fulton Supercomputer: In addition to the resources that are part of the BYU MRI Research Facility and the PI’s laboratory, BYU has the Fulton Supercomputing Lab, which offers a total of 21,552 CPU cores and over 78 TB of memory across 972 compute nodes. These compute resources are supported by approximately 2 petabytes of storage. The Fulton Supercomputing Lab resources are available at no charge to BYU faculty with computationally intensive data, such as MRI data. Institutional Support: The PI has access to departmental and institutional administrative, accounting, grants management, and computer support services. Brigham Young University provides, as part of its cost sharing, complete photographic, library, machine and electronic support shop, and information technology services. The PI receives travel funds through the BYU Department of Psychology for travel to one scientific conference a year. BYU provides support to new faculty members in a number of forms, including a Faculty Development Series for New Faculty. This series comprises training seminars throughout the first 2 years of employment at the University. BYU has historically been a primarily undergraduate university, but in recent years has begun to invest in research, particularly on student mentored research. In the PI’s laboratory, four undergraduate students obtained mentored research grants in the past few years from the University to support their research efforts. The PI has also received over $30,000 in internal funding in the last two years as either PI or Co-Investigator for student mentoring projects.


Facilities & Other Resources Page 9




RESEARCH & RELATED Senior/Key Person Profile (Expanded)

PROFILE - Project Director/Principal Investigator

Prefix: Dr. First Name*: Steven Middle Name G. Last Name*: Luke Suffix:

Position/Title*: Assistant ProfessorOrganization Name*: Brigham Young UniversityDepartment: Psychology and NeuroscienceDivision:Street1*: 1062 SWKTStreet2:City*: ProvoCounty:State*: UT: UtahProvince:

Country*: USA: UNITED STATESZip / Postal Code*: 84602-1231

Phone Number*: 8014225978 Fax Number:

E-Mail*: [email protected]

Credential, e.g., agency login: STEVENLUKEProject Role*: PD/PI Other Project Role Category:

Degree Type: PhD Degree Year: 2011Attach Biographical Sketch*: File Name: BIOSKETCH_-_Steven_Luke.pdfAttach Current & Pending Support: File Name:


Page 10

OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)

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: Luke, Steven Garet eRA COMMONS USER NAME (credential, e.g., agency login): STEVENLUKE POSITION TITLE: Assistant Professor of Psychology EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATION

DEGREE (if

applicable)

Completion Date

MM/YYYY

FIELD OF STUDY

Brigham Young University BA 08/2003 Psychology & Russian

University of Illinois at Urbana-Champaign MS 04/2008 Educational Psychology

University of Illinois at Urbana-Champaign PhD 04/2011 Educational Psychology

University of South Carolina Postdoctoral 06/2013 Psychology

A. Personal Statement

In my research, I use eye-tracking to investigate visual attention in reading and other visual tasks. In my PhD training I focused specifically on linguistic factors that influence reading behavior. My postdoctoral training focused more on visual/oculomotor factors and I published several studies comparing reading with other eye movement tasks, such as scene memorization and visual search, in the manner proposed in the Research Strategy [1]. Several studies have specifically explored individual differences between readers [2]. During this time, I received extensive training in quantitative data analysis, specifically using mixed-effects (hierarchical) regression models to analyze nested data sets of the sort that come from eye-tracking studies. Most of my publications employ these advances statistical techniques, and I recently published a paper on the best techniques for avoiding Type 1 error when using mixed models in R [3]. Thus, I have the technical expertise to collect and interpret the eye-tracking data from both reading and non-reading tasks. During my postdoctoral training I integrated eye-tracking with MRI, recording data using both technologies simultaneously and using the eye-tracking data to guide interpretation of functional and structural neuroimaging data. I have collaborated on several projects using this combination of technologies [4]. I have continued to employ this combination of technologies in my current position at Brigham Young University, and have included some pilot data illustrating the success of this project in the Research Strategy. This combination of MRI, eye-tracking and the expertise to combine them effectively is available at few universities, making me uniquely suited to address the questions outlined in this project proposal. 1. Luke, S.G., Nuthmann, A. & Henderson, J.M. (2013). Eye movement control in scene viewing and in

reading: Evidence from a stimulus onset delay paradigm. Journal of Experimental Psychology: Human Perception and Performance, 39(1), 10-15.

2. Luke, S.G., Henderson, J.M. & Ferreira, F. (2015). Children's eye-movements during reading reflect the quality of lexical representations: An individual differences approach. Journal of Experimental Psychology: Learning, Memory & Cognition, 41, 1675-1683.

3. Luke, S.G. (2017). Evaluating significance in linear mixed-effects models in R. Behavior Research Methods, 49, 1494-1502.

4. Henderson, J.M., Choi, W., Luke, S.G., & Desai, R. (2015). Neural correlates of fixation duration in natural reading: Evidence from fixation-related fMRI. NeuroImage, 119, 390-397.


Biosketches Page 11

B. Positions and Honors Positions and Employment 2011-2013 Postdoctoral Research Fellow, Dept. of Psychology and Institute for Mind and Brain, University of South Carolina, Columbia, SC 2013- Assistant Professor, Department of Psychology and Neuroscience Center, Brigham Young

University, Provo, UT Other Experience and Professional Memberships Reviewer for Child Development, Cognitive Psychology , International Journal of Psychophysiology, Journal of Educational Psychology, Journal of Experimental Psychology: Learning, Memory & Cognition, Journal of Experimental Psychology: Human Perception & Performance, Journal of Memory and Language, Neuropsychology, Perception, Psychonomic Bulletin & Review, Quarterly Journal of Experimental Psychology, Visual Cognition. Fellow, Psychonomic Society Member, Vision Sciences Society Member, Association for Psychological Science Honors 2017 Young Alumni Achievement Award, University of Illinois College of Education 2011 Raymond W. Kulhavy Prize for Student Research in the Cognitive Science of Learning 2010 Beckman Institute Cognitive Science/Artificial Intelligence Award 2008 Sandra Goss Lucas Award for Excellence in Teaching Introductory Psychology B. Contributions to Science

1. My primary research interest is attentional control, as manifested by eye movements, during reading and

other visual tasks. I have explored a variety of factors that influence where we look and for how long, from low-level oculomotor factors such as inhibition of return to visual factors such as luminance to cognitive factors such as linguistic processing, meaningfulness and task. The focus of this work is to identify cross-task commonalities and differences in attentional control, in order to better understand how efficient reading occurs.

a. Luke, S.G. & Christianson, K. (2016). Limits on Lexical Prediction during Reading. Cognitive Psychology, 88, 22-60.

b. Luke, S. G., & Henderson, J. M. (2016). The Influence of Content Meaningfulness on Eye Movements across Tasks: Evidence from Scene Viewing and Reading. Frontiers in psychology, 7.

c. Luke, S.G. & Christianson, K. (2015). Predicting inflectional morphology from context. Language, Cognition & Neuroscience, 30, 735-748.

d. Luke, S.G., Henderson, J.M. & Ferreira, F. (2015). Children's eye-movements during reading reflect the quality of lexical representations: An individual differences approach. Journal of Experimental Psychology: Learning, Memory & Cognition, 41, 1675-1683.

e. Luke, S. G., Smith, T. J., Schmidt, J., & Henderson, J. M. (2014). Dissociating temporal inhibition of return and saccadic momentum across multiple eye-movement tasks. Journal of Vision, 14(14), 9.

f. Luke, S.G. & Christianson, K. (2013). The influence of frequency across the time-course of morphological processing. Journal of Cognitive Psychology, 25, 781-799.

g. Luke, S.G. & Henderson, J.M. (2013). Oculomotor and cognitive control of eye movements during reading: Evidence from mindless reading. Attention, Perception and Psychophysics, 75, 1230-1245.

h. Luke, S.G., Nuthmann, A. & Henderson, J.M. (2013). Eye movement control in scene viewing and in reading: Evidence from a stimulus onset delay paradigm. Journal of Experimental Psychology: Human Perception and Performance, 39(1), 10-15.

i. Luke, S. G., Schmidt, J., & Henderson, J. M. (2013). Temporal oculomotor inhibition of return and spatial facilitation of return in a visual encoding task. Frontiers in Psychology, 4.

j. Luke, S.G., & Christianson, K. (2012). Semantic predictability eliminates the transposed-letter effect. Memory & Cognition, 40(4), 628–641.


Biosketches Page 12

k. Luke, S. G. & Christianson, K. (2011). Stem and whole-word frequency effects in the processing of inflected verbs in and out of a sentence context. Language and Cognitive Processes, 26, 1173-1192.

2. I have been involved in groundbreaking studies which have combined eye-tracking and fMRI to explore the

cortical network underlying expert reading. This work, while still in its infancy, has already confirmed many established findings using the more naturalistic task of connected-text reading, revealed new brain regions associated with visual attention in reading, and clarified the function of these brain regions in the reading process.

a. Henderson, J.M., Choi, W., Luke, S.G. & Schmidt, J. (in press). Neural correlates of individual differences in fixation duration during natural reading. Quarterly Journal of Experimental Psychology.

b. Henderson, J.M., Choi, W., Luke, S.G., & Desai, R. (2015). Neural correlates of fixation duration in natural reading: Evidence from fixation-related fMRI. NeuroImage, 119, 390-397.

c. Henderson, J.M., Choi, W., & Luke, S.G. (2014). Morphology of Primary Visual Cortex Predicts Individual Differences in Fixation Duration during Text Reading. Journal of Cognitive Neuroscience, 26, 2880-2888.

3. A major thrust of my research has been improving the openness and rigor within my field. Many of my

publications are dedicated to quantifying the reliability of measures or statistical techniques, while others share new methods or data sets.

a. Carter, B.T. & Luke, S.G. (in press). Individuals’ eye movements in reading are highly consistent

across time and trial. Journal of Experimental Psychology: Human Perception and Performance. b. Luke, S.G. & Christianson, K. (in press). The Provo Corpus: A Large Eye-Tracking Corpus with

Predictability Ratings. Behavior Research Methods. c. Luke, S.G. (2017). Evaluating significance in linear mixed-effects models in R. Behavior Research

Methods, 49, 1494-1502. d. Henderson, J.M., Luke, S.G., Schmidt, J., & Richards, J.E. (2013). Co-registration of Eye

Movements and Event-Related Potentials in Connected-Text Paragraph Reading. Frontiers in Systems Neuroscience 7:28. doi: 10.3389/fnsys.2013.00028

e. Luke, S.G. & Christianson, K. (2013). SPaM: A combined self-paced reading and masked-priming paradigm. Behavior Research Methods, 45, 143-150.

Complete list of published works: https://eyetrackinglab.byu.edu/Pages/Published-Research.aspx D. Additional Information: Research Support and/or Scholastic Performance Ongoing Research Support

NONE Completed Research Support

2016 MRI Research Initiation Grant Brigham Young University MRI Research Facility Project: Skilled Reading in the Brain

Role: Primary Investigator Award: $10,000

2015 Mentoring Environment Grant Brigham Young University Office of Research and Creative Activities Project: A Multimodal Imaging Study of Sensory Sensitivity & Anxiety in Autism. Role: Co-Investigator (PI, Mikle South, BYU) Award: $20,000


Biosketches Page 13

2012 Biomedical Imaging Pilot Grant South Carolina Clinical and Translational Research Institute Project: Examining transcranial direct current stimulation dosage and task effects

using eye movements in reading Role: Co-Investigator (PI: Richardson, J., University of South Carolina)

Award: $47,113 2011 M-Funds Grant

McCausland Center for Brain Imaging, University of South Carolina Project: Cortical networks for language-vision interactions Role: Principal Investigator Award: $6,000


Biosketches Page 14

PHS 398 Cover Page SupplementOMB Number: 0925-0001



1. Human Subjects Section

Clinical Trial? ❍ Yes ● No

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

2. Vertebrate Animals Section

Are vertebrate animals euthanized? ❍ Yes ● No

If "Yes" to euthanasia

Is the method consistent with American Veterinary Medical Association (AVMA) guidelines?

❍ Yes ❍ No

If "No" to AVMA guidelines, describe method and proved scientific justification

3. *Program Income Section

*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 andsource(s). Otherwise, leave this section blank.

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


Page 15

PHS 398 Cover Page Supplement


4. Human Embryonic Stem Cells Section

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

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

❏ Specific stem cell line cannot be referenced at this time. One from the registry will be used.Cell Line(s) (Example: 0004):

5. Inventions and Patents Section (RENEWAL)*Inventions and Patents: ❍ Yes ● No

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

*Previously Reported: ❍ Yes ❍ No

6. Change of Investigator / Change of Institution Section❏ Change of Project Director / Principal InvestigatorName of former Project Director / Principal InvestigatorPrefix: *First Name: Middle Name: *Last Name: Suffix:

❏ Change of Grantee Institution

*Name of former institution:


Page 16

Tracking Number: GRANT12511027 Funding Opportunity Number: PA-16-200. Received Date: 2017-10-25T17:55:58.000-04:00

OMB Number: 0925-0001Expiration Date: 03/31/2020

PHS 398 Modular Budget

Budget Period: 1

Start Date: 09/01/2018 End Date: 08/31/2020

A. Direct Costs Funds Requested ($)Direct Cost less Consortium Indirect (F&A)* 225,000.00

Consortium Indirect (F&A) Total Direct Costs* 225,000.00

B. Indirect (F&A) Costs

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

1. MTDC 50.00 207,160.00 103,580.00

2.

3.

4.

Cognizant Agency(Agency Name, POC Name and Phone Number)

DHHS, Robert Lee, 415-437-7820

Indirect (F&A) Rate Agreement Date 11/08/2016 Total Indirect (F&A) Costs 103,580.00

C. Total Direct and Indirect (F&A) Costs (A + B) Funds Requested ($) 328,580.00


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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 ($) 225,000.00Section A, Total Consortium Indirect (F&A) for Entire Project Period ($) 0.00Section A, Total Direct Costs for Entire Project Period ($) 225,000.00Section B, Total Indirect (F&A) Costs for Entire Project Period ($) 103,580.00Section C, Total Direct and Indirect (F&A) Costs (A+B) for Entire Project Period ($) 328,580.00

2. Budget Justifications

Personnel Justification Personnel_Justification.pdfConsortium Justification Additional Narrative Justification


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Personnel Justification A. Senior Personnel Dr. Steven Luke, Principle Investigator (10% effort) Dr. Luke will provide laboratory infrastructure, supervise data collection and analysis and provide intellectual input and support in the design and implementation of all proposed experiments. Dr. Luke has specific expertise in analyzing eye tracking data from a variety of tasks, co-registration of eye-tracking and fMRI data, and exploring individual differences in eye movements and brain function and structure. B. Other Personnel Graduate Student: Benjamin Carter – stipend and tuition benefit Undergraduate Research Assistants: 6 undergraduate students to be recruited. They will each receive financial support (10 hours/week). Each of these students will be integrally involved in participant recruitment, data collection, data analysis, and the presentation and write-up of results.


Personnel Justification Page 19

PHS 398 Research PlanOMB Number: 0925-0001



Introduction1. Introduction to Application(Resubmission and Revision)

Research Plan Section2. Specific Aims Specific_Aims.pdf

3. Research Strategy* Research_Strategy.pdf

4. Progress Report Publication List

Human Subjects Section5. Protection of Human Subjects Protection_of_Human_Subjects.pdf

6. Data Safety Monitoring Plan

7. Inclusion of Women and Minorities Inclusion_of_Women_and_Minorities.pdf

8. Inclusion of Children Inclusion_of_Children.pdf

Other Research Plan Section9. Vertebrate Animals

10. Select Agent Research

11. Multiple PD/PI Leadership Plan

12. Consortium/Contractual Arrangements

13. Letters of Support

14. Resource Sharing Plan(s)

15. Authentication of Key Biological and/orChemical Resources

Appendix16. Appendix


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Specific Aims

Dyslexia is a learning disability that involves a difficulty reading words. This difficulty cannot be explained by low intelligence, instructional inadequacy, or sensory impairment (Lyon, Shaywitz, & Shaywitz, 2003). Dyslexia is thought to be primarily a language disorder (see e.g. Peterson & Pennington, 2012), but some evidence suggests that it is not solely a language disorder; a separate deficit of visual attention may also be present that is independent of the language deficit (see e.g. Bosse, Tainturier, & Valdois, 2007; Vidyasagar & Pammer, 2010). When dyslexic individuals read, their eye movements differ from readers without dyslexia (see e.g. Bellocchi, Muneaux, Bastien-Toniazzo, & Ducrot, 2013; Rayner, 1998). This indicates that dyslexia does involve a deficit of visual attention, but this attention deficit may be caused by the language deficit or may have some other cause. The research on this topic is currently inconclusive. The proposed project will therefore explore the following question: Why are eye movements in dyslexic readers different from normal readers? More specifically, the proposed project will ask whether visual attention problems in dyslexic reading are caused by an underlying phonological deficit or reflect a separate, more general deficit of visual attention arising from some non-linguistic source. If the former, then visual attention deficits should be restricted to reading and other visuo-linguistic tasks. But if visual attention deficits are more general, then they should be apparent even in non-linguistic visual tasks such as visual search or scene memorization. The primary goal of the current project is to address this question by comparing eye movements in dyslexic and control subjects during reading and during non-linguistic visual tasks. This knowledge will help focus interventions and treatments for dyslexia. Specific Aim 1: Measuring the Perceptual Span in Dyslexia during Reading and Visual Search. The ‘perceptual span’ is the size of the attentional spotlight during visual tasks such as reading. Visual information outside of this span is not used during visual tasks. Research suggests that this perceptual span is smaller in dyslexia, reflecting a deficit of visual attention. Using a standard method called the moving window paradigm (McConkie & Rayner, 1975) that is commonly used in reading research, the size of the perceptual span in dyslexia will be examined. This method will be applied to both a reading task and a (non-linguistic) visual search task. If visual attention deficits in dyslexia are independent of language, then the perceptual span should be smaller in reading and in visual search. Specific Aim 2: Identifying Differences in the Reading Network in the Dyslexic Brain. A few left hemisphere language-related cortical areas are consistently identified as associated with dyslexia. However, almost all neuroimaging studies of dyslexia have utilized single word recognition tasks which do not involve visual attention in the way that normal reading of connected text does (Norton, Beach, & Gabrieli, 2015). By combining eye-tracking and fMRI (Henderson, Choi, Luke, & Desai, 2015) while participants read entire paragraphs, the present study will reveal differences in the attentional control network of the dyslexic brain. Further, the same group of adult dyslexic and control participants will also complete a scene memorization task in the scanner. If visual attention deficits in dyslexia are independent of language, then dyslexics should show impairment in language-independent cortical regions that are also recruited for scene memorization. Specific Aim 3: Quantifying the Contribution of Linguistic Deficits to Attentional Problems in Dyslexia. Dyslexia is known to involve linguistic deficits, but the contribution of those deficits to observed visual attention problems in reading has yet to be quantified. A mediation analysis will be conducted to examine the relationship between the observed perceptual span differences (Aim 1) and differences in the reading network (Aim 2) and scores on standardized tests of language skill. This analysis will quantify the contribution of deficits in different aspects of language (phonology, vocabulary, fluency) to attentional problems in dyslexia. If visual attention deficits in dyslexia are independent of language, then differences in language skill will not fully explain perceptual span differences (Aim 1) or neural differences (Aim 2) between dyslexics and controls.


Specific Aims Page 21

Research Strategy

When dyslexic individuals read, their eye movements differ from readers without dyslexia. The proposed project will explore the following question: Why are eye movements in dyslexic readers different? More specifically, the proposed project will ask: are visual attention problems in dyslexic reading caused by an underlying phonological deficit, or do they reflect a separate, more general deficit of visual attention arising from some non-linguistic source? If the former, then visual attention deficits should be restricted to reading and other visuo-linguistic tasks. But if visual attention deficits are more general, then they should be apparent even in non-linguistic visual tasks such as visual search or scene memorization. The primary goal of the current project is to address this question by contrasting eye movements in dyslexic and control subjects during reading and during non-linguistic visual tasks. First, I propose to explore the size of the attentional spotlight (perceptual span) in reading and in visual search in adult dyslexic and control participants (Specific Aim 1). Second, by combining eye-tracking and MRI I will explore differences in the attentional control network of the brain in the same group of adult dyslexic and control participants during a reading task and during a scene memorization task (Specific Aim 2). Finally, I will correlate observed behavioral and neural differences with scores on standardized tests of language in order to quantify the contribution of linguistic deficits to attentional problems in dyslexia (Specific Aim 3). By studying dyslexic eye movements and the neural network controlling them in reading and in non-reading visual tasks, the proposed project will help to reveal whether dyslexia is solely a language problem or whether broader attentional deficits are present that cannot be attributed to language.

Significance

Dyslexia is common and costly. Dyslexia is a learning disability that involves a difficulty reading words. This difficulty cannot be explained by low intelligence, instructional inadequacy, or sensory impairment (Lyon et al., 2003). It has been estimated that 10% of the population meet the criteria for diagnosis, making dyslexia and associated reading disabilities the most common learning disabilities (Peterson & Pennington, 2012). The impact of reading disability is not restricted to childhood; dyslexia continues to impair performance and achievement in adulthood (Bruck, 1990; Swanson & Hsieh, 2009; Welcome & Joanisse, 2012).

Most researchers think dyslexia is a phonological disorder. Dyslexia is a neurological disorder, but the core neuro-biological cause is still unknown (Nittrouer & Pennington, 2010; Peterson & Pennington, 2012). The predominant theory is that dyslexia is the result of difficulty with phonological awareness; individuals with dyslexia have difficulty with the phonology, or sounds, of spoken language, and this difficulty leads in turn to problems mapping sounds to letters in reading (Démonet, Taylor, & Chaix, 2004; Peterson & Pennington, 2012; Ramus, 2003; Shaywitz & Shaywitz, 2005). In line with the phonological account of dyslexia, brain regions that are consistently identified as being structurally and/or functionally different in dyslexia include left-hemisphere regions related to language/reading: the inferior frontal gyrus, the inferior parietal lobe and the inferior temporal gyrus, which includes the visual word form area (Norton et al., 2015).

But dyslexia might involve a visual attention deficit that cannot be attributed to language. However, differences in the dyslexic brain are not restricted to phonological or even reading-related regions (Eckert, 2004; Galaburda, LoTurco, Ramus, Fitch, & Rosen, 2006; Hynd & Semrud-Clikeman, 1989; Linkersdörfer, Lonnemann, Lindberg, Hasselhorn, & Fiebach, 2012; Maisog, Einbinder, Flowers, Turkeltaub, & Eden, 2008; Richlan, Kronbichler, & Wimmer, 2009, 2011, 2013). For example, in prereaders at risk for dyslexia, right parietal and cerebellar regions are different as well (Linkersdörfer et al., 2012; Vandermosten, Hoeft, & Norton, 2016). In fact, many researchers have argued that the impairments associated with dyslexia cannot be fully attributed to a phonological deficit (Bosse et al., 2007; Castles & Friedmann, 2014; Gilger & Kaplan, 2001; Nicholson & Hill, 1985; Schneps, Rose, & Fischer, 2007). Of particular importance to the current study is the suggestion that dyslexia is (or is partly) a visual impairment (Bellocchi et al., 2013; Clark et al., 2014). More specifically, dyslexics appear to have a language-independent visual attention deficit (Bellocchi et al., 2013; Bosse et al., 2007; Lobier, Zoubrinetzky, & Valdois, 2012; Prado, Dubois, & Valdois, 2007; Vidyasagar & Pammer, 2010). Consistent with this idea, studies show behavioral and neurological differences in dyslexic participants in non-linguistic visual tasks (Aleci, Piana, Piccoli, & Bertolini, 2012; Diehl et al., 2014; Olulade,


Research Strategy Page 22

Gilger, Talavage, Hynd, & McAteer, 2012; Paulesu, Danelli, & Berlingeri, 2014; Tafti, Boyle, & Crawford, 2014; Vidyasagar & Pammer, 2010).

Single-word recognition studies are ill-suited to identifying visual attention deficits, so the extent of visual attention impairments in dyslexia is likely underestimated. Traditionally, behavioral and neuroimaging studies have investigated dyslexia almost exclusively using words presented in isolation, with very few studies investigating the reading of sentences and paragraphs (Norton et al., 2015). This is unfortunate because single-word decoding does not reflect the normal reading experience. During normal reading of texts, the eyes move from word to word, taking in visual information. These eye movements reflect visual attention, and studying eye movements can reveal a great deal about reading and reading difficulties (Bellocchi et al., 2013; Rayner, 1998, 2009). Thus, existing studies of dyslexia may have underestimated the scope of visual attention impairments by focusing on single-word reading.

Eye movement studies show that visual attention is impaired in dyslexia, but it is unclear whether this is the result of language deficits or not. A few studies have investigated reading eye movements in dyslexia (see Bellocchi et al., 2013 for a review). For example, Hyönä and Olson (1995) investigated the effect of word length and frequency on eye movements in dyslexia, and observed that English-speaking dyslexics, like normal readers, show these effects. However, dyslexics spent more time re-reading. Hutzler and Wimmer (2004) investigated reading behaviors of German-speaking dyslexics, and observed slower reading overall and a greater sensitivity to word length. In sum, dyslexics make more and longer fixations (pauses between eye movements during which the eyes take in information), shorter eye movements (called saccades), and more eye movements back to previous parts of the text than do normal readers (Bellocchi et al., 2013; Hutzler & Wimmer, 2004; Rayner, 1998). See Figure 1 for an illustration of these eye movement behaviors. It has been proposed that visual attention differences in dyslexia arise from the aforementioned phonological/linguistic deficits (Hawelka, Gagl, & Wimmer, 2010; Hyönä & Olson, 1995). It is possible that this is the case; disordered eye movements in reading could be a symptom of disordered language. More specifically, it may be that eye movements are less efficient in dyslexia because word recognition is impaired. However, there is also some evidence that eye movements (and the associated brain regions) are disordered in dyslexia even for simple, non-linguistic tasks, consistent with the idea that dyslexics have a more general deficit of visual attention that is at least partly independent of language, but findings in this area are inconclusive or contradictory (Bellocchi et al., 2013; Hutzler, Kronbichler, Jacobs, & Wimmer, 2006; Paulesu et al., 2014).

Figure 1. A typical reading pattern. The red circles represent fixations (the numbers show how long the fixation was, in milliseconds), during which the eyes paused to take in visual information about the text. Dyslexic readers have longer fixations than normal readers.

The blue lines represent saccades, movements of the eyes from one point to the next. Dyslexic readers make shorter saccades, suggesting that they take in less visual information from each fixation. In the regions circled in yellow, the reader made several

regressions, which are saccades back to an earlier point in the text. Regressions indicate reading difficulty. Dyslexic readers have been found to make many more regressions than do normal readers.

The proposed study will determine if visual attention problems in dyslexia can be attributed to language

deficits by tracking eye movements during reading and during non-linguistic visual tasks. The question addressed by this project is not are there language-related deficits in dyslexia (the evidence is clear that language deficits are present) but rather is dyslexia solely a language-related disorder? The present project is designed to reveal if dyslexia is solely a language-related disorder or if visual attention deficits are independent of language deficits. If visual attention deficits are observed to be present only in reading, this will show that these visual attention deficits in dyslexia are purely the result of a more fundamental linguistic deficit and associated word recognition difficulties. Observed visual attention problems associated with dyslexia in non-linguistic visual tasks (such as visual search or scene memorization) will indicate that dyslexia is not solely a linguistic disorder.



Innovation

The proposed project is innovative in the following ways. Exploring dyslexic reading of connected text rather than single words. Most research on dyslexia has involved the identification of single words presented in isolation (Norton et al., 2015). While focusing on isolated word recognition eliminates certain confounds and provides experimental control, it also likely mischaracterizes and underestimates reading dysfunction in dyslexia. Most especially, single word tasks do not involve visual attention in the way that reading of connected texts does, so these tasks do not contribute to our understanding of how and why visual attention is impaired in dyslexia. The limiting nature of single word tasks may explain why only a handful of language-related brain regions are consistently implicated in neuroimaging studies of dyslexia. Since normal reading involves visual scanning of connected text, the studies proposed here are more natural and will provide a more accurate representation of the deficits, behavioral and neural, associated with dyslexia. Exploring visual attention in dyslexia using well-established methods from reading research. As noted above, there are many reasons to expect that the attentional spotlight in reading is narrow for dyslexic readers. The moving window paradigm (see Specific Aim 1, below) is used to study the scope of visual attention during reading, and has been used to study reading processes for more than 40 years (McConkie & Rayner, 1975), but it has only been applied once (by Rayner, Murphy, Henderson, & Pollatsek, 1989) to the study of dyslexia. Further, this one study was a case study of a single individual, so the present proposal will apply this well-established technique to dyslexia using a more standard sample size to ensure that findings related to the perceptual span are replicable and generalizable.

Observing a smaller perceptual span in reading would tell us that there are attentional deficits in dyslexia, but in isolation this finding would be theoretically uninformative. As noted in the introduction, such an attentional deficit could be attributed solely to a more fundamental phonological deficit or to a separate attentional problem (partly) arising from a non-linguistic source. The present study is also innovative in applying the moving window technique not just to reading but to visual search. This has not been done in dyslexia research, and will provide not just descriptive data about the nature of dyslexia but theoretically valuable comparative data about the scope and source of these deficits.

Exploring visual attention in dyslexia separately from reading. The few existing studies that have explored visual attention in dyslexia have focused almost exclusively on reading; no eye-movement studies of non-reading visual attention tasks have been reported in the literature. While this is understandable given the theorized linguistic roots of dyslexia, it leaves unaddressed the question of whether the visual attention deficits observed in these studies are reading-specific or not. Combining eye-tracking and fMRI to explore the cortical network underlying dyslexic reading. The present project will combine eye tracking with fMRI to identify brain regions sensitive to specific eye movement behaviors associated with specific words. This technique is innovative and has a great deal of potential for outlining the brain regions involved in reading. It has been applied successfully to normal readers in several studies (Choi, Desai, & Henderson, 2014; Choi & Henderson, 2015; Henderson & Choi, 2015; Henderson, Choi, Lowder, & Ferreira, 2016; Henderson et al., 2015) but has yet to be applied to a disordered population. Research using this technique has shown that the cortical regions involved in reading and scene memorization overlap but also include distinct components (Choi & Henderson, 2015). Contrasting brain activity (BOLD response) across the two tasks will reveal whether regions differentially involved in dyslexic reading are reading-specific or are more task-general, and whether these deficits appear in non-linguistic visual attention tasks. Applying a mediation analysis to quantify the relationship between language and visual attention deficits. Collecting standardized measures of language ability, including especially phonological awareness, is common in dyslexia research. However, the present study is innovative in that these measures will be collected



in conjunction with neuroimaging and visual attention measures. This combined data set will make it possible to perform a mediation analysis on the eye-tracking and fMRI data. This analysis will help identify which language skill (if any) explains visual attention deficits in dyslexia, and will quantify the contribution of that language skill to the deficit. The logic of this approach is that if an effect of dyslexia group (on the perceptual span or on brain activity during reading) is still present once language (e.g. phonology) is accounted for, then the observed differences are not the result of language deficits. If the effect disappears or weakens when phonology is accounted for, then phonology is not a mediator or is only a partial mediator and visual attention deficits in dyslexia are independent of phonology. This type of analysis has not been applied to the question of visual attention in dyslexia, and provides some notable advantages. First, this approach will provide information on which aspect of language (phonology, vocabulary, fluency) are most responsible for visual attention deficits in reading. Further, the mediation analysis will provide a quantitative estimate of how much of the visual attention deficit can be attributed to a given linguistic deficit.

Approach

Specific Aim 1: Measuring the Perceptual Span in Dyslexia during Reading and Visual Search.

Introduction and Preliminary Results. Research exploring visual attention deficits in dyslexic reading has suggested specifically that dyslexics have a smaller ‘attentional spotlight’ than do normal readers (Rayner et al., 1989). This attentional spotlight is referred to as the perceptual span, the area of the visual field from which useful information can be obtained. For typical readers of alphabetic languages, this region extends 3-4 letters to the left of the currently fixated letter and 14-15 letters to the right, although the actual size of this ‘window’ differs depending on reading skill (McConkie & Rayner, 1975; Rayner, Slattery, & Belanger, 2010). Choi, Lowder, Ferreira, and Henderson (2015) discovered significant individual differences in the size of the perceptual span in normal readers. They observed further that differences in perceptual span size were correlated with language ability (see also Veldre & Andrews, 2014). This is consistent with the idea that perceptual span deficits in dyslexia might be attributable to language issues (i.e. word recognition is harder, so attention is focused more narrowly on the currently fixated word), but only one study had directly explored the perceptual span in dyslexia during reading. Rayner et al. (1989) studied a single adult with developmental dyslexia. Their results suggest that the perceptual span is indeed smaller in dyslexia and that the availability of information beyond the current word might hinder rather than help fluent reading.

While the Rayner et al. (1989) study is the only study that investigated the perceptual span in dyslexic reading directly, there is other research that is consistent with the idea that dyslexic individuals have a narrower perceptual span. Silva et al. (2016) explored preview benefit during rapid letter naming, and found that dyslexic individuals appeared to extract less information from upcoming letters. Importantly, Silva et al. also instructed participants to perform a letter search task on the same stimuli. This task did not involve phonological processing, and no difference in preview benefit was observed for dyslexic participants relative to controls. This suggests that the perceptual span deficit in reading may be phonological in nature. However, neither group received any preview benefit during the search task, so these results may simply reflect the fact that no extraction of information from outside the fovea was attempted. Moores, Tsouknida, and Romani (2015) also found evidence using a non-linguistic perceptual task that attention is focused more narrowly in dyslexia. Thus, while there is good reason to believe that attentional focus is narrower in dyslexia, the evidence that this narrowing is due to phonological deficits is limited; it may be that the perceptual span is narrow even when phonological/linguistic processing is not relevant to the current task.

The perceptual span in reading is explored using the moving window technique (McConkie & Rayner, 1975; Rayner et al., 1989). This technique is illustrated in Figure 2, below. In this paradigm, within a window around the currently-fixated word the text is presented normally, but outside that window the letters are replaced with random letters so that no useful information can be extracted from those words. The size of the window varies, and the perceptual span is defined as the smallest window that causes no reading disruption compared to a no-window control condition. In a pilot study of normal readers from the proposed population using the moving window technique, the perceptual span was found to be about 12 letters (i.e. when less than 12 letters were visible to the right of fixation, reading was slowed). Based on these results, it is expected that



dyslexic readers will have a perceptual span smaller than 12 letters. The purpose of experiment 1 is to identify differences between dyslexic and normal readers in the perceptual span during a reading task and a visual search task.

To achieve Specific Aim 1, two experiments will be conducted. These experiments will be conducted together as a separate session (see Table 1). This session will be conducted first and will serve as a screening tool. Participants whose eyes are tracked successfully will be invited back to participate in Sessions 2 and 3, which include the MRI scans and the standardized language assessments (see Specific Aims 2 and 3, below).

Table 1. Proposed Session 1 Schedule Sign Informed Consent Form: 5 minutes Receive Instructions: 5 minutes Experiment 1a: Reading Perceptual Span. Total Time: ~ 15 minutes

o Participants will read 40 texts, taking 10-20 seconds per text. Experiment 1b: Scene Search Perceptual Span. Total Time: ~ 15 minutes

o 80 scenes will be presented for a maximum of 12 seconds each. LexTale. Total Time ~ 5 minutes (see Specific Aim 3) Lexical Decision. Total Time ~ 15 minutes (see Specific Aim 3)

o A total of 444 letter strings (222 words and nonwords, respectively) Note: The order of Experiment 1a and 1b will be randomized across participants.

Experiment 1a: Perceptual Span in Reading. As noted above, this study will use a variant of the moving window technique to address Specific Aim 1. This paradigm is illustrated in Figure 2. In this paradigm, within a window around the currently-fixated word the text is presented normally, but outside that window words will be replaced with non-words so that no useful information can be extracted from those words. The size of the window varies, and the perceptual span is the smallest window that causes no reading disruption compared to a no-window control condition. This span should be smaller in dyslexia.

Participants. One hundred twenty adult participants (18-40) will be recruited for this study. All will be right-handed native English speakers with normal or corrected-to-normal vision. Sixty will be normal readers with no history of learning disorders. The other 60 will be dyslexic readers who have received an official diagnosis of dyslexia and are referred from the Brigham Young University Accessibility Center, which will provide records of any assessments administered. The administration of standardized language assessments in Session 3 (see below) will confirm the diagnosis. All participants will be paid $50 upon completion of the study. Prior to recruitment, all participants will be screened for MRI safety to ensure that they can participate in Experiment 2 as well (see Specific Aim 2).

Materials. Forty paragraphs taken from various sources, including the Nelson-Denny reading test, the

Provo Corpus (Luke & Christianson, in press), and the USA Today online archive, will serve as stimuli. Following Choi et al. (2015), the different window sizes used will be either 4, 8, 12, or 16 letters to the right of fixation or no window (the full text is visible). See Figure 2 for an example of this manipulation.

Procedure. Participants will be instructed to read paragraphs for comprehension, and they will answer a

yes/no comprehension question after every paragraph. At the start of the experiment and after 20 trials, the eye-tracker will be calibrated using a 9-point calibration procedure. The experiment will start with a practice trial. Prior to the start of each trial, the participant will fixate a circle in the top left corner of the screen, at approximately the location of the first word in the text. One this fixation is stable, the paragraph will appear. Participants will read at their own pace, pressing a button when done, after which they will answer the comprehension question using the same button box.



Figure 2. Example of the moving window technique used in Experiment 1a. The blue circle represents where the participant is

looking. The top panel shows the paragraph with no moving window (the whole text is visible). The bottom panel shows the same paragraph with a 12-letter window (including spaces) visible on each side of the fixation point.

Apparatus. Eye-movement data will be collected using an Eyelink 1000 Plus Tower-mounted eye

tracker recording at 1000Hz. Although viewing will be binocular, only the right eye will be monitored. Paragraphs will be presented in black on a white background using 16pt Courier New font, so that three letters subtend approximately 1 degree of visual angle.

Experiment 1b: Perceptual Span in Visual Search. If visual attention deficits in dyslexia are indeed domain-general and not solely the result of phonological or other linguistic impairment, then dyslexic participants should show a reduced perceptual span in a non-linguistic task such as visual search. Experiment 1b will apply the moving window technique to a visual search task, following Nuthmann (2013). If dyslexics have a smaller perceptual span, they should be less disrupted by the moving window than normal readers.

Materials. Eighty images of real-world scenes containing target objects will be used for Experiment 1b.

These scenes will represent a variety of locations, both indoor and outdoor. Each contains some unique object. Nuthmann (2013) observed that the visual span during scene search is 8+ degrees; windows smaller than this slowed visual search. Based on this, Experiment 1b will use windows of 4, 6, 8 and 10 degrees as well as a no-window condition (see Figure 3).

Procedure. At the start of the experiment and after 40 trials, the eye-tracker will be calibrated using a 9-

point calibration procedure. The experiment will start with a practice trial. Each trial will begin with a gaze trigger, a black circle presented in the center of the screen. Once a stable fixation had been detected, an image of an object will appear on the screen for 1 second. Using an object image instead of a printed word name for the search target makes this task more purely non-linguistic. This target object image will be followed by the real-world scene. The next trial will commence once the participant has pressed the button to indicate that they have found the target or after 12 seconds, whichever is sooner. Participants will be instructed to press the button while looking at the target item. Then the next trial will begin.

Apparatus. The apparatus is the same as Experiment 1a.



Figure 3. Example of the moving window technique used in Experiment 1b. The top panel shows the scene with no window. The center plan shows a 4 degree window, while the bottom panel shows an 8 degree window around the point of fixation. In this scene the target object is the clock on the fireplace mantle (right side).



Analysis and Expected Outcomes. Following Choi et al. (2015), the reading rate (words per minute) for each participant in each window condition of Experiment 1a will be computed. For the visual search task, search accuracy and search time for each participant in each window condition of Experiment 1b will also be computed, as described in Nuthmann (2013). In addition, in order to more directly compare the reading and search tasks, saccade amplitude and fixation duration will serve as dependent variables. If dyslexics do indeed have a smaller perceptual span, as Rayner et al. (1989) suggests, they should be less disrupted by the smaller window sizes (i.e. their eye movements should not differ from the no-window baseline), compared to the normal readers. If visual attention in dyslexia is impaired as a result of phonological deficits, than a difference in the perceptual span should be restricted to reading (i.e. the statistical interaction of task and participant group should be significant). If visual attention deficits in dyslexia are more general, and not just in reading, then the same pattern of results should be observed in the visual search task (i.e. the interaction will not be significant). Specific Aim 2: Identifying Differences in the Reading Network in the Dyslexic Brain.

Introduction and Preliminary Results. Recently, researchers have begun to explore the neural system

that controls how the eyes move during reading (visual attention) by combining eye tracking and fMRI (Choi et al., 2014; Choi & Henderson, 2015; Henderson & Choi, 2015; Henderson et al., 2016; Henderson et al., 2015; Schuster, Hawelka, Richlan, Ludersdorfer, & Hutzler, 2015). These studies confirm results of behavioral/eye-tracking studies showing that reading shares a common attentional control system with other tasks, such as scene viewing or search (Henderson & Luke, 2014; Luke & Henderson, 2016; Luke, Nuthmann, & Henderson, 2013). At the same time, reading is separable from these other tasks in that it includes language processes and the associated cortical regions (Choi & Henderson, 2015; Luke & Henderson, 2013). Thus, attentional deficits in dyslexia could be attributed to language-specific (and thus reading-specific) brain regions, which is consistent with a phonological basis for dyslexia. Alternatively, if attentional impairments in dyslexia can be localized to task-general attentional regions, this would contradict a purely phonological account.

Figure 4. Areas of activation significantly correlated (FWE corrected to alpha < 0.05) with fixation duration (left panel) and saccade amplitude (right panel) during text reading. Hot regions show positive correlation and cool regions show negative correlation.



A pilot study has been conducted to explore the feasibility of combining eye-tracking and fMRI and to identify regions associated with reading connected text. Forty-three participants read passages from the Provo Corpus (Luke & Christianson, 2016, in press) in the MRI while their eye movements were recorded. Fixation duration was associated positively with activation in left inferior posterior temporal gyrus (ITG), left frontal eye field (lFEF), right inferior frontal gyrus (rIFG) and right posterior temporal lobe, and negatively with activation in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC; See Figure 4, left panel). Increased saccadic amplitude was associated with activations in occipital lobe, postcentral gyrus, and anterior temporal lobe (ATL), with decreased saccadic amplitude associated with a widespread activation network of in parietal, frontal and right temporal lobes (see Figure 4, right panel). In sum, we found that fixation durations and saccade amplitudes during reading are associated with a different network of regions within the larger eye movement control network. These data reveal that the brain network involved in connected text reading involves many brain regions outside the language network that are not typically explored in studies of dyslexia. These results underscore the importance of studying dyslexic reading using connected texts and not just isolated words.

To explore the neural network underlying attentional control in dyslexia and identify specific regions where differences arise, eye-tracking will be combined with fMRI. To achieve Specific Aim 2, several MRI scans will be conducted. The schedule for these scans is laid out in Table 2. This session will follow session 1 on a different day (see Specific Aim 1).

Table 2. Proposed Schedule for Session 2 – MRI Scan Prior to scan: Total time ~ 20 minutes

o Participant arrives at MRI facility 20 minutes prior to scan time to be screened for MRI safety receive task instructions

Scan Time: Total time ~ 50 minutes o ~10 minutes to get participant in the scanner and set up eye-tracker. o Experiment 2: 4 functional runs: 5.4 minutes each = 21.6 minutes, ~25 with eye tracker

calibrations 18 stimuli per run (9 texts, 9 scenes). Each stimulus displayed for 12 seconds,

with 6 second ITI (no eye movements). o 8 minute structural scan (T1) o 8 minute DTI scan

Experiment 2. Combined Eye-Tracking and fMRI during Reading/Scene Memorization. In

Experiment 2, participants will read paragraphs and memorize visual scenes while their eye movements are monitored. They will be in the MRI while performing these tasks, so that their BOLD activity can be recorded simultaneously.

Materials. For the reading trials, thirty-six paragraphs taken from the Provo Corpus (Luke & Christianson, in press) will be used in this study. For the scene memorization task, thirty-six images of visual scenes will be used. These will be taken from the SCEGRAM scene database (Öhlschläger & Võ, 2016).

Procedure. Eye-tracking and fMRI data will be obtained in four 5.4 minute functional runs. Each

functional run will include 9 paragraphs and 9 scenes. Within each run, the order of stimulus presentation will be randomized for each participant. Each stimulus will be presented for 12 seconds, with a 6 second ITI between trials.

For the paragraphs, participants will be instructed to read the paragraphs silently as if they were reading a novel. They will further be told that they are not required to finish reading the paragraph within the 12 seconds and should read at their normal pace. If they do finish reading early they are to fixate an X in the lower right of the screen until time expired. For the scenes, they will be instructed to view the scenes in order to remember specific objects and details about them for a later test of memory. This test will not be administered.

At the start of each functional run, the eye-tracker will be calibrated using a 9-point calibration procedure. The experiment will start with two practice trials, one for each type of stimulus.



Apparatus. The apparatus is an MRI-compatible version of the same eye-tracker used in Experiment 1a.

Analysis and Expected Outcomes. By contrasting BOLD activation during the reading trials in dyslexic versus normal readers, it will be possible to identify brain regions that are differentially active during dyslexic reading of connected text. Performing the same contrast on the scene memorization trials will reveal if dyslexic participants also process visual scenes differently than normal controls; this would indicate a more general attentional impairment. Comparing BOLD activity during the reading and the scene memorization trials will isolate task-specific versus task-general regions, which will further aid in the interpretation of any dyslexic differences observed. In addition to these basic analysis, the eye-tracking data that is collected simultaneously will be used to perform more fine-grained MRI data analyses (see Henderson, Choi, & Luke, 2014; Henderson et al., 2015; Henderson, Choi, Luke, & Schmidt, in press for examples of analyses combining eye-tracking and MRI data). Specific Aim 3: Quantifying the Contribution of Linguistic Deficits to Attentional Problems in Dyslexia.

Introduction. Another way to phrase the main research question addressed by this project is how much

of the visual attention deficit in dyslexia can be attributed to language deficits? Specific Aim 3 will address this question. By using standardized language measures to assess participants’ language skill, it will be possible to apply a mediation analysis to the data from Experiments 1 and 2. This analysis will indicate whether visual attention differences (Experiment 1) and neural differences (Experiment 2) in dyslexic participants can be attributed entirely to differences in language ability and, if not, what proportion of these differences can be accounted for by language deficits associated with dyslexia.

In Session 3 of the proposed study, two standardized assessments of linguistic ability will be administered. The Comprehensive Test of Phonological Processing (CTOPP-2) assesses reading-related phonological processing skills. To quantify participants’ phonological awareness, the phonological awareness composite score will be computed from the elision, blending words and phoneme isolation subtests. In addition, rapid automatized naming scores will be computed from the rapid digit naming and rapid letter naming subtests. The Gray Oral Reading Test (GORT-5) will also be administered. This test assesses oral reading fluency and comprehension. Fluency and Comprehension scores will be computed. Two additional tests of linguistic ability will be administered. The first is a lexical decision task, during which participants will be presented with strings of letters and will decide whether the string is a real word or a nonword. Reaction times and accuracy rates will be computed to measure visual word recognition efficiency. Finally, LexTale (Lemhöfer & Broersma, 2012), a short measure of English vocabulary, will be administered. The CTOPP-2 and the GORT will be administered in a final session that will immediately follow the MRI scanning (see Table 3 for proposed schedule). The lexical decision task and LexTale are brief and will be administered during session 1 (see Table 1).

Table 3. Session 3 Proposed Schedule CTOPP-2 – 20 minutes total

o The elision, blending words and phoneme isolation subtests will be administered to compute the Phonological Awareness composite Score.

o The rapid digit naming and rapid letter naming subtests will be administered to compute the Rapid Symbolic Naming composite score

GORT – 20-30 minutes o Fluency and Comprehension scores will be computed

Analysis and Expected Outcomes. Scores on the different language tests will be combined using a

latent variable approach, extracting more pure measures of language knowledge from the variance common to the relevant tests. Latent variables will be extracted from the data using exploratory factor analysis on the individual scores. Scores will be entered into a principal components analysis with varimax rotation, using the princomp function in R (R Core Team, 2015). Factors with eigenvalues greater than 1 will be retained as latent variables. Factor loadings of 0.45 and above will be used to guide factor interpretation (i.e. to decide which



latent variable a given factor represents). These latent linguistic variables will then be used in regression analyses to predict perceptual span (Specific Aim 1) in both reading and scene search. More specifically, the question addressed by this analysis is Can differences in perceptual span in dyslexia be attributed to phonological/linguistic difficulties? To address this question, a mediation analysis will be conducted using the mediation package in R (Tingley, Yamamoto, Hirose, Keele, & Imai, 2014). In this analysis, the group variable (dyslexic vs. control) is first used in a regression analysis to predict perceptual span. This stage will have been completed previously (see Specific Aim 1). Then, a separate regression analysis will be conducted with perceptual span as the dependent measure and the linguistic factors as predictors. This stage will identify relationships between linguistic ability and the perceptual span. These two regressions are then submitted to a mediation analysis, to evaluate the direct effects of Group (dyslexic vs. control) on the perceptual span as well as the average causal mediation effects (the effect of language ability). In other words, the mediation analysis will reveal if a diagnosis of dyslexia predicts the perceptual span, and whether this relationship arises via a phonological/linguistic deficit. These relationships are represented in Figure 5. The mediation analysis quantifies how much of the relationship between dyslexia and perceptual span a particular linguistic factor accounts for. This same technique will be applied to the eye-tracking and fMRI data from Experiment 2, to quantify how much observed neural differences in dyslexia can be attributed to phonological/linguistic factors.

Figure 5. Illustration of mediation analysis. This analysis will clarify if the group variable (dyslexia vs. control) influences visual attention (as assessed in Experiments 1 and 2) directly (via c’) or indirectly (via ab). If indirectly, this would indicate that dyslexia influences visual attention via language ability; if directly, this would indicate that language ability is not predictive of visual attention. If the relationship is only partially mediated (i.e. language accounts for some, but not all, of the relationship between dyslexia and visual attention), the analysis will quantify how much of the relationship between dyslexia and visual attention can be attributed to language ability

Anticipated Outcomes

Dyslexia, a neurological disorder and the most common learning disorder, is thought by many researchers to be the result of a deficit in phonological processing that translates into difficulty reading. However, other symptoms, such as deficits in visual attention, have been observed. This has lead some researchers to propose that the roots of dyslexia are not purely linguistic. Thus, it is currently unclear whether dyslexia is only a language disorder or if visual attention deficits arise from some other non-linguistic source. The present study will address this issue by using eye tracking and MRI to investigate visual attention in dyslexia, both during reading and during other non-linguistic visual tasks. It is expected that dyslexics will show impaired visual attention in reading and specifically will have a smaller perceptual span. Further, dyslexic participants should show different cortical involvement during reading, most especially in areas associated with written language processing. If visual attention deficits and the associated neural differences in dyslexia are restricted to reading, this will provide support for the phonological account of dyslexia. On the other hand, if



these deficits appear in non-linguistic tasks and in task-general neural regions of the brain, this will indicate that dyslexia involves separate impairment of visual attention independent of phonology. Finally, phonological ability and other language skills will be assessed to quantify the contribution of these skills to observed attentional deficits in dyslexia.

Research Project Timeline

In addition to the PI, a PhD student and six undergraduates (UG) will participate in this project. Undergraduate students will be recruited early in their education so that they can be involved in the project for the duration. These undergraduate students will take a leading role in data collection, both eye-tracking and MRI, and will work with the PI and PhD student on data analysis and write-up. The schedule for the project is outlined in the table below. Next to each item the relevant Specific Aim and the parties primarily responsible are noted.

Prior to August 2018 Recruit undergraduate student researchers (PI) August 2018 Undergraduate student researchers receive training on (UG)

Operation of the eye tracker MRI Safety Ethics & IRB Compliance Experimental Protocol

September 2018 Begin data collection (PI, PhD, UG) September 2019 Complete data collection (PhD, UG) October-December 2019 Finalize data collection (PhD)

Perform Moving Window Data Analysis (Aim 1; PI, UG) Write Moving Window intro, methods (Aim 1; UG, PI) Preprocess fMRI data in preparation for analysis (Aim 2; PhD, UG) Score Standardized Tests (Aim 3; UG)

January-April 2020 Perform fMRI+eye-tracking Data Analysis (Aim 2; PhD, UG) Write fMRI+eye-tracking intro, methods (Aim 2; UG, PhD, PI) Finalize Moving Window paper for publication & submit (Aim 1, PI)

May-August 2020 Finalize fMRI+eye-tracking paper and submit (Aim 2, PhD) Perform Mediation Analysis (Aim 3, PI, PhD, UG)

September 2020 Finalize, submit Mediation Analysis paper (Aim 3, PI, PhD)



Protection of Human Subjects

Risks to Human Subjects

1. Human subjects involvement and characteristics a. Human subjects will be recruited to participate in the proposed experiments. In

experiment 1, participants will complete two visual attention tasks (reading and visual search) while their eye movements are monitored. In experiment 2, participants will complete a reading and scene memorization task in the MRI while their eye movements are monitored. Finally, participants will complete a set of standardized language assessments.

b. Control participants will be selected from the student population at Brigham Young University.

c. Dyslexic participants will also come from the student population at Brigham Young University. The characterization of dyslexic participants will occur in collaboration with the BYU Accessibility Center.

d. All subjects will be 18 years old or older. e. No vulnerable populations will be included in the proposed work.

2. Sources of materials

a. The types of data to be produced in the course of the project include background demographic information; a record of eye position during the visual attention tasks; structural and functional neuroimaging data from MRI scans, with the functional data collected during reading and scene memorization tasks; and scores on assessments of language ability.

b. The demographic data is needed for published reports to convey the characteristics of the subject population. The eye position data is needed to identify overall efficiency of visual attention during the eye movement tasks. The neuroimaging data will be used to identify differences in brain function and structure associated with dyslexia. The language assessments will be used to measure differences between participants in their language abilities.

c. Only research assistants who have a “need to know” will have access to individually identifiable private information about human subjects.

d. Subjects will be assigned a unique study ID and the data as well as the information described above will be associated with that study ID. The key between the subject’s name and the data will be kept in a locked filing cabinet. The data, which does not contain any personal identifiers, will be stored on labassociated computers for analysis. The data will be stored for a minimum of three years.

3. Potential Risks The risks associated with this research are minimal:

a. Tasks: i. This research involves reading words and looking at pictures on a

computer screen, something the participants do every day, so the risks


Protection of Human Subjects Page 34

from the task are minimal and no greater than those encountered in everyday life.

b. Equipment i. The eye-tracking equipment emits a low intensity infrared light, which

reflects off the retina to determine where participants are looking on the computer screen. The infrared light which is directed at the eye is well below the standards set by the United States Occupational Safety and Health Administration and is not visible.

ii. MRI detects the magnetic properties of fluids and tissues and allows researchers to obtain high-resolution images of the brain. There are no known adverse effects from exposure to magnetic fields, although there are potential risks and discomforts associated with the MRI environment. The MRI scanner makes a loud banging noise while it collects images. Some participants may become claustrophobic or anxious in the scanner. Participants may experience some muscular aches and fatigue from lying still for a prolonged period of time. The brain scans may also incidentally reveal abnormalities present in the brain.

c. Fatigue and Frustration i. Since each of the two experimental session will last for 1 to 2 hours, it is

possible that the subjects will become fatigued. For the participants with dyslexia, it is possible that the reading-intensive nature of the tasks may lead them to become frustrated or to experience other negative emotions.

Adequacy of Protection Against Risks

1. Recruitment and Informed Consent a. Control participants will be recruited via fliers posted on campus. Dyslexic

students will be recruited via fliers or contact via email, in co-operation with the University Accessibility Center, which will confirm that these participants have been officially diagnosed with a reading disorder. All fliers and email scripts will be approved by the institutional review board prior to posting.

b. Before the first experiment, the researcher conducting the experiment will ask subjects to read the Informed Consent form and ask any questions. Subjects will then be invited to give informed consent (by signing the Informed Consent form) if they wish to participate.

2. Procedures to Minimize Risk a. Tasks

i. Participants will be fully informed of the nature of the tasks prior to each session. They will further be informed that they can withdraw from the study at any time.

b. Equipment



i. Participants will be provided with hearing protection in the MRI. ii. In case of claustrophobia or anxiety, participants will be provided with a

squeeze ball that allows them to alert the experimenters and request immediate exit from the magnet.

iii. The sequence of scans is under an hour, and the sans that require wakefulness and attention have been scheduled first, allowing participants to rest for the remainder of the scan session and thereby reducing fatigue and aches.

iv. Participants will be informed of the possibility of incidental findings in the informed consent. If the research team observes any abnormalities on a scan, the scans will be forwarded to be read by a qualified medical professional, who will contact participants with any possible concerns.

c. Fatigue and Frustration i. To help prevent participant fatigue, the subjects will be informed about

what stage of the experimental procedure is the best point to take a break, and encouraged to take a break or breaks when and if they desire. To help alleviate negative emotions or frustration, the dyslexic participants will be informed that they may elect to complete the study in 3-4 sessions instead of 2 session.

Potential Benefits of Research to Human Subjects and Others

There are no direct benefits to the research subjects (and the risk is correspondingly minimal). However, this research will ultimately benefit society by helping to clarify the causes of reading disorders. Importance of Knowledge to be Gained

Dyslexia, a neurological disorder characterized by reading difficulty, is the most common learning disorder. It is thought by many researchers to be the result of a deficit in phonological processing that translates into difficulty reading. However, other symptoms, such as deficits in visual attention during reading, have been observed. This has lead other researchers to propose that the roots of dyslexia are not purely linguistic. Thus, it is currently unclear whether dyslexia is only a language disorder or is a language disorder plus a visual attention disorder. The present project addresses this question. Clearly characterizing the causes of dyslexia is essential for facilitating diagnosis and directing intervention and treatment efforts.



Inclusion of Women and Minorities

Reading difficulties affect both males and females, but with somewhat greater prevalence in males (Hawke, Olson, Willcutt, Wadsworth & DeFries, 2009; Quinn & Wagner, 2013). Given this, we plan to recruit from gender, racial, and ethnic groups in proportion to their approximate representation in the local population surrounding Brigham Young University. More specifically, our enrollment plan reflects the 2011 Census data for Utah (see Targeted/Planned Enrollment Table), but given the gender distribution of dyslexia it is likely that males will be over-represented in the sample.


Inclusion of Women and Minorities Page 37

PHS Inclusion Enrollment ReportThis report format should NOT be used for collecting data from study participants.

OMB Number:0925-0001 and 0925-0002



*Study Title: Are visual attention deficits in dyslexia reading-specific? A combined eye-tracking/fMRI investigation.

*Delayed Onset Study? ❏ Yes ❏✔ No

If study is not delayed onset, the following selections are required:

Enrollment Type ❏✔ Planned ❏ Cumulative (Actual)

Using an Existing Datasetor Resource

❏ Yes ❏✔ No

Enrollment Location ❏✔ Domestic ❏ Foreign

Clinical Trial ❏ Yes ❏✔ No

NIH-Defined Phase IIIClinical Trial

❏ Yes ❏✔ No

Comments: See "Inclusion of Women and Minorities" for explanation.

Racial Categories

Ethnic Categories

Not Hispanic or Latino

Female Male Unknown/Not Reported

Hispanic or Latino


Unknown/NotReported Ethnicity


Total

American Indian/Alaska Native 0 0 0 0 0

Asian 3 3 0 0 6

Native Hawaiian orOther Pacific Islander 0 0 0 0 0

Black or African American 1 1 0 0 2

White 55 65 9 13 142

More than One Race 0 0 0 0 0

Unknown or Not Reported

Total 59 69 9 13 150

Report 1 of 1


Page 38

Inclusion of Children

Dyslexia is a developmental disorder that affects individuals starting in childhood and continuing into adulthood. However, the complexity of the experimental tasks, the length of the sessions and the technical challenges of combining eye-tracking and MRI technologies means that recruitment of children for the present study would greatly increase attrition rates and expense. Given the limited resources of R15 (AREA) grants, we will only recruit subjects who are 18 years old or older.


Inclusion of Children Page 39

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