exploring neural and genetic substrates of reading ability

109 Pages·2014·2.79 MB·English

by  Cheng Wang

EXPLORING NEURAL AND GENETIC SUBSTRATES
OF READING ABILITY

by

Cheng Wang

A dissertation submitted in partial fulfillment
of the requirements for the degree of
Doctor of Philosophy
(Psychology)
in the University of Michigan
2014

Doctoral Committee:
Professor Thad A. Polk, Chair
Professor Margit Burmeister
Emeritus Professor Joanne F. Carlisle
Professor Frederick J. Morrison
To my mother,
Yuhua Chen.

.

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Acknowledgements

I want to extend my warmest thanks to all the people who contributed to
my PhD training and to the completion of my dissertation research.
First and foremost, I want to thank Thad Polk for being such an incredibly
amazing advisor, research mentor, teaching mentor and academic coach over
the past five years. The dissertation project has been challenging for me, but
Thad’s patience, reassurance, and constant support were the fuel that kept me
going even in moments of doubt and uncertainty. He always goes out of his way
to help and support me when I go through rough times. Thad’s unwavering
willingness to offer help, his thoughtful research mentoring, and his warm and
friendly personality make him an ideal mentor in every respect. I would not have
had such a great doctoral training experience without him!
I also want to thank Agnes Jasinska, Joonkoo Park and Joshua Carp for
being such great academic siblings. You are wonderful friends, colleagues, and
mentors. I learned a great deal from all of you.
I’m gratefully indebted to the Cognition and Cognitive Neuroscience
Program in the Psychology Department at the University of Michigan. Thank you
for admitting me to the program and providing a very supportive environment. I
also want to thank my friends in the program: Kamin Kim, Sara Festini, Rebecca
Rhodes, Mike Shvartsman, Ziyong Lin, Ronit Greenberg, Ben Katz, and many
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others. I am very lucky to have known you and attended the CCN program
alongside you!
I thank my dissertation committee – Thad Polk, Margit Burmeister,
Fredrick Morrison, and Joanne Carlisle – for their insight, support, and
constructive feedback, all of which helped me complete this dissertation.
I want to thank my family in Ann Arbor: Rui Huang, Felipe Pérez, Luis
Núñez, and Angelica Benito. The best of my time in Ann Arbor was spent with
you!
Lastly, I want to thank my family, especially my mom, Yuhua Chen, who
has always been there for me.

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TABLE OF CONTENTS

DEDICATION…………………………………………………………………………. ii
ACKNOWLEDGMENTS…………………………………………………………….. iii
LIST OF FIGURES…………………………………………………………………… vii
LIST OF TABLES……………………………………………………………………. viii
ABSTRACT…………………………………………………………………………… ix
CHAPTER 1. AN OVERVIEW OF GENETIC AND NEURAL
MARKERS OF READING ABILITY AND DYSLEXIA
1.1 Dyslexia and reading disabilities………………..………………..….. 1
1.2 Significance of understanding reading mechanisms……………….. 2
1.3 Dissertation overview………………….………………….…………… 3
1.4 Neural markers associated with reading………………….………… 6
1.5 Genetics of reading and dyslexia………………….………………….. 11
1.6 Combining imaging and genetics approaches………………………. 17
1.7 Brief summary…………………………………………………………… 19
CHAPTER 2. EXPLORING STRUCTURAL BRAIN MARKERS
OF READING
2.1 Introduction………………………………………………………………. 29
2.2 Methods………………………………………………………………….. 31
2.3 Results……………………………………………………………………. 35
2.4 Discussion……………………………………………………………….. 41
CHAPTER 3. EXPLORING STRUCTURAL CONNECTIVITY
MARKERS OF READING
3.1 Introduction………………………………………………………………. 51
3.2 Methods………………………………………………………………….. 57
3.3 Results……………………………………………………………………. 59
3.4 Discussion……………………………………………………………….. 63
CHAPTER 4. EXPLORING FUNCTIONAL NEURAL MARKERS
OF READING
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4.1 Introduction………………………………………………………………. 71
4.2 Methods………………………………………………………………….. 76
4.3 Results……………………………………………………………………. 80
4.4 Discussion……………………………………………………………….. 87
CHAPTER 5. GENERAL DISCUSSION
6.1 Summary of results and significance…………………………………. 93
6.2 Limitations and future directions……………………………………… 95
6.3 Translational relevance…………………………………………………. 97

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LIST OF FIGURES

Figure 2.1 Flow diagram of recruitment processes……………………………… 31
Figure 2.2 Partial residual plots of significant relationships between structural
markers and TOWRE reading score.………………………………… 38
Figure 2.3 Partial residual plots of significant relationships between posterior
corpus callosum and WJ-III reading score…………………………… 39
Figure 3.1 Partial residual plots of the relationship between fractional anisotropy
and reading performance……………..……………..……..……..…… 60
Figure 3.2 White matter diffusivity measures in the isthmus and correlation to

the volume of the region.…….……….………………….………………
62
Figure 4.1 Illustrative stimuli of in-scanner tasks..……..……..……..…..……..… 77
Figure 4.2 The left supramarginal gyrus in a whole-brain regression analysis of
NWR > Case contrast against TOWRE score..……..……..……....… 83
Figure 4.3 Partial residual plots of relationships between functional connectivity
markers during phonological processing and reading scores……..… 86

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LIST OF TABLES

Table 2.1 Brief description and example(s) of each reading subtest…………… 33
Table 2.2 Behavioral measures with subtests indented …………………………… 35
Table 2.3 Factor loadings of 17 initial structural measures. ……………………… 37
Table 2.4 Multiple regression model of structural markers predicting TOWRE
score.….…………………………………………………………………… 38
Table 2.5 Multiple regression model of structural markers predicting WJ-III
score.….…………………………………………………………………… 39
Table 2.6 Description of behavioral test scores in two genotype groups ……… 40
Table 4.1 Accuracy and reaction time in each condition inside the scanner.…… 81
Table 4.2 Suprathreshold clusters and local maxima information in contrasts of
interest..….………………………………………………………………… 81
Table 4.3 Suprathreshold clusters and local maxima information in PPI analysis
of NWR > Case contrast using left SMG as seed..….………………… 85

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ABSTRACT
The primary research goal of this dissertation was to combine multimodal
neuroimaging data to investigate the neural and genetic substrates of reading
ability. We evaluated structural and functional neural measures for their
association with genetic markers and with reading ability.
Chapter 2 investigated whether any of reading-related volumetric neural
markers were candidate endophenotypes that were associated both with reading
ability and with alleles of the KIAA0319 dyslexia-susceptibility gene. We used
structural Magnetic Resonance Imaging (MRI) to measure volumetric markers
previously associated with reading in 68 adults. The results showed that volume
of posterior corpus callosum (pCC) and right inferior frontal gyrus significantly
predicted reading performance, and pCC volume was also significantly
associated to a risk allele in the KIAA0319 gene. These findings demonstrate
that pCC volume is a plausible endophenotype linking the KIAA0319 gene to
reading ability.
Chapter 3 used diffusion tensor imaging (DTI) to explore the relationship
between structural connectivity markers and both reading behavior and genetic
risk. The results showed that reduced white matter integrity in the left temporo-
parietal region was associated with poor reading performance. Additionally, we
found that greater radial diffusivity, which suggests less insulation of myelin
sheaths, in the mid-posterior corpus callosum (mpCC) were associated with
dyslexia risk alleles of the KIAA0319 gene. We propose that the effect of genetic
risk on the volume of mpCC may be related to white matter microstructural
changes in the region.
Chapter 4 used functional MRI to look for brain regions where neural
activation during phonological processing was associated with reading ability.
The identified region in the left supramarginal gyrus (SMG) was then used to
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search for functional connectivity markers. We found that the strength of
functional connectivity between bilateral SMG was significantly associated with
reading ability, suggesting that this marker is an important neural underpinning of
reading.
Taken together, our findings extend previous research on the neural and
genetic basis of reading and literacy, suggest potential endophenotypes for
dyslexia, and point to the importance of efficient connection among a reading-
related network. This work helps to advance our understanding of the neural and
genetic substrates of reading.

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