The role of white matter

connections in reading

development and dyslexia

DYSlexia Collaboration Leuven

(DYSCO)

Dr. Maaike Vandermosten

Prof. Dr. Pol Ghesquière

Prof. Dr. Jan Wouters

OVERVIEW

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1. Introduction

1. Dyslexia

2. fMRI-studies on reading and dyslexia

2. Structural brain connections in reading and dyslexia

1. Diffusion Tensor Imaging (DTI) technique

2. Structural connections in adults with dyslexia?

3. Structural connections in pre-readers (at risk for) dyslexia?

1.1. Dyslexia

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• Prevalence: 5 -10%

• Severe, persistent and

specific

underachievement

• Causes?

o Phonological deficit

Inferior frontal

Temporoparietal

Occipitotemporal

= phonological aspects of reading

= Orthographic aspects of reading

= neural anomalies in dyslexics

1.2. fMRI-studies in dyslexia

See meta-analysis Jobard et al., 2003

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3. Structural reading network in dyslexia

1. DTI-technique

2. Structural reading network in adults

3. Structural reading network in children

What is DTI?

• MRI-technique that gives an

indication of white matter

organization

•White matter consists of

myelinated axons

•Function: efficient communication

between cortical areas

3.1. DTI-technique: MRI

3.1. DTI-technique: diffusion

‘free’ diffusion ‘hindered’ diffusion

D is equal in all directions D is not equal in all directions

ISOTROPIC ANISOTROPIC

3.1. DTI-technique: diffusion

gray matter white matter

6 unknowns

3.1. DTI-technique: diffusion in the brain

‘summarize’ tensor:

fractional anisotropy

DTI measures

3.1. DTI-technique: parameters

FA decrease

Myelination

Axon density and caliber

Fiber mixture

FA increase

less

less

less more

more

more

Microscopic

Macroscopic

INTERPRETATION OF FA

‘integrity of white matter’

‘efficient communication’

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3.1. DTI-technique: parameters

‘summarize’ tensor:

fractional anisotropy

DTI measures

fibertracking

3.1. DTI-technique: parameters

For details see Vandermosten et al., 2012, Neuroscience & Biobehavioral Reviews

- Quantitatively meta-analysis of 11 studies that used VBA (60 foci, 257

participants)

-272 mm³ and centred at -29, -30, 18

PREVIOUS DTI-STUDIES

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3.2. Structural reading network in adults with dyslexia

PARTICIPANTS

Dyslexic readers

M (SD)

Normal readers

M (SD)

Test statistics

N 20 20 Subject characteristics

Sex (male/female) 7/13 8/12 p = .75 Age (years) 22.1 (3.1) 21.4 (3.0) p = .51 Non-verbal IQ (WAIS) 108 (10) 106 (10) p = .59

Defining literacy measures Word reading 66.1 (1.9) 99.8 (11.4) p < .0001 Pseudoword reading 66.0 (1.8) 107.9 (9.8) p < .0001 Spelling 69.3 (6.5) 105.8 (9.6) p < .0001

Reading underlying processes

Phoneme awareness (effect size) -2.79 (1.25) 0 (1) p <.0001

Speech perception in noise (SRT in dB) -8.2 (0.9) -8.5 (1.1) p = .30

Orthographic processing (raw score) 28.2 (3.6) 34.5 (2.6) p <.0001

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3.2. Structural reading network in adults with dyslexia

Inferior frontal Temporoparietal

Occipitotemporal

fMRI DTI

= phonological aspects of reading

= Orthographic aspects of reading

= neural anomaliesin dyslexics

3.2. Structural reading network in adults with dyslexia

Arcuate Fasciculus (AFFTP)

Posterior Arcuate Fasciculus

(posterior AFTP)

Inferior Fronto-Occipital Fasciculus (IFOF)

+ right hemispheric tracts

RESULTS: GROUP COMPARISON of FA

(controlled for IQ and quality index of DTI-acquisition)

Normal Readers

Mean FA (sd)

Dyslexic Readers

Mean FA (sd)

P-value

ANCOVA

Left AFFTP 0.474 (0.017) 0.460 (0.025) .029*

Left posterior AFTP 0.455 (0.026) 0.444 (0.027) .14

Left IFOF 0.485 (0.027) 0.486 (0.024) .81

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AFFTP

posterior AFTP

IFOF

3.2. Structural reading network in adults with dyslexia

RESULTS: GROUP COMPARISON of FA

(controlled for IQ and quality index of DTI-acquisition)

Normal Readers

Mean FA (sd)

Dyslexic Readers

Mean FA (sd)

P-value

ANCOVA

Left AFFTP 0.474 (0.017) 0.460 (0.025) .029*

Left posterior AFTP 0.455 (0.026) 0.444 (0.027) .14

Left IFOF 0.485 (0.027) 0.486 (0.024) .81

Right AFFTP 0.422 (0.030) 0.426 (0.021) .68

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AFFTP

posterior AFTP

IFOF

3.2. Structural reading network in adults with dyslexia

RESULTS: CORRELATIONS with FA

Phoneme

awareness

Speech-in-noise

perception

Orthography

Left AFFTP

Left posterior AFTP

Left IFOF

(controlled for literacy, IQ and quality index of DTI-acquisition)

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3.2. Structural reading network in adults with dyslexia

AFFTP

posterior AFTP

IFOF

RESULTS: CORRELATIONS with FA

Phoneme

awareness

Speech-in-noise

perception

Orthography

Left AFFTP .33* .31(*) -.04

Left posterior AFTP .21 .42** .00

Left IFOF .04 .18 .39*

(controlled for literacy, IQ and quality index of DTI-acquisition)

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3.2. Structural reading network in adults with dyslexia

No significant correlations

in right hemispheric tracts AFFTP

posterior AFTP

IFOF

Predicting variables FA left IFOF FA left direct

AFFT

Step 1: Control Variables .04 .04 Step 2: Group variable .00 .10* Step 3a: Phoneme awareness .02 .10* Step 3b: Orthographic processing .16** .00 Total R² .21 .24

RESULTS: MULTIPLE REGRESSION

Predicting variables FA left IFOF FA left posterior

AFTP

Step 1: Control Variables .04 .02 Step 2: Group variable .00 .06 Step 3a: Speech in noise perception .01 .18** Step 3b: Orthographic processing .12* .01 Total R² .19 .26

Correlational double dissociation

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3.2. Structural reading network in adults with dyslexia

Left IFOF

- No group difference

- Corresponds to ventral

orthographical route

Left AF

- Lower FA in dyslexic adults (AFFTP)

- Corresponds to dorsal phonological route

(AFFTP & posterior AFTP)

- Right hemispheric tracts

- No FA-difference between dyslexic and typical reading adults

- No FA-relation with phonological and orthographic tasks

3.2. Structural reading network in adults with dyslexia

- No involvement of the Corona Radiata

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Which network sustains reading at the very beginning?

- Brain not genetically pre-wired for reading!

Where is the primary deficit of dyslexia?

- White matter is plastic!

Predictions developmental sequence:

Predictions dyslexia:

• Primary deficit (phonological processing) in left dorsal regions

• Secondary deficit (building up orthographic word representations) in left ventral regions

STANDARD NEUROANATOMICAL MODEL:

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3.3. Structural reading network in pre-readers at risk for dyslexia

1

2

fMRI DTI

!Validation needed, especially on connections!

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• first data collection before children are able to read

• continuous registration of developmental pathway

• direction of causal influence?

• early detection and prediction early prevention

3.3. Structural reading network in pre-readers at risk for dyslexia

• Last year of kindergarten

• 35 family-risk for dyslexia pre-readers

• at least one first-degree relative diagnosed as dyslexic

• 35 no family risk for dyslexia pre-readers

• Individual matching

• Educational environment, i.e. same school!

• Sex

• Age

• Non-verbal IQ (CPM)

• Educational level of father and mother

PARTICIPANTS:

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3.3. Structural reading network in pre-readers at risk for dyslexia

FRD+

(n = 36)

FRD-

(n = 35)

Test statistics

Demographic data

Gender (boy/girl) 23/13 18/17 Fisher’s exact test: p = .34

SES 5.3 (1.6) 5.6 (1.6) Fisher’s exact test: p = .18

ADHD 2.5 (2.2) 1.5 (1.5) Fisher’s exact test: p = .40

Handedness (left/right) 5/30 2/32 Fisher’s exact test: p = .43

Age in months 61.4 (3.1) 61.7 (3.0) F(1,27) = 0.14; p = .71

Non-verbal IQ 109.9 (13.2) 110.4 (10.0) F(1,27) = 0.01; p = .83

Cognitive predictors (composite score )

Phonological Awareness -0.06 (1.28) 0 (1) F(1,27) = 0.20; p = .66

Rapid Automatized Naming -0.46 (1.08) 0 (1) F F(1,27) = 3.41; p = .09

Letter Knowledge -0.51 (1.25) 0 (1) F(1,27) = 9.75; p = .02

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PARTICIPANTS:

3.3. Structural reading network in pre-readers at risk for dyslexia

DTI to examine ventral and dorsal tracts on:

1. pre-reading anomalies related to family-risk factors of dyslexia?

2. their specific cognitive function at that young age?

• Correlation with phonological tasks (phonological awareness)

• partial orthographic tasks (letter knowledge and rapid automatized naming)

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3.3. Structural reading network in pre-readers at risk for dyslexia

RESULTS: GROUP COMPARISON of FA

Group x Hemisphere x Tract interaction [F(2,344) = 3.17, p = .043]

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3.3. Structural reading network in pre-readers at risk for dyslexia

RESULTS: CORRELATIONS with FA

LEFT RIGHT

AFFTP Posterior

AFTP IFOF

AFFTP

Posterior

AFTP IFOF

Phonological Awareness

Rapid Automatized

Naming Letter Knowledge

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3.3. Structural reading network in pre-readers at risk for dyslexia

LEFT RIGHT

AFFTP Posterior

AFTP IFOF

AFFTP

Posterior

AFTP IFOF

Phonological Awareness 0.30* 0.24 * 0.36** 0.27* 0.19 0.37**

Rapid Automatized

Naming 0.13 0.07 0.20 0.16 -0.09 0.31**

Letter Knowledge 0.16 0.15 0.26 * 0.21 0.17 0.26 *

• phonological awareness was the only significant predictor of FA

- no unique contribution of letter knowledge & rapid automatized naming

RESULTS: MULTIPLE REGRESSION

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RESULTS: CORRELATIONS with FA

3.3. Structural reading network in pre-readers at risk for dyslexia

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IFOF

Posterior AFTP

AFFTP

Group difference high vs low risk pre-readers?

Phonological vs Orthographic function?

PHONOLOGY

PHONOLOGY

3.3. Structural reading network in pre-readers at risk for dyslexia

Preliminary conclusions

• White matter anomalies :

•predate reading causal?

•are located in left ventral and posterior dorsal connections

opposes the standard neuroanatomical model

• White matter function:

• Phonological awareness is sustained bilaterally by both dorsal and ventral tract

gradual left lateralization and a gradual phonological versus orthographic specialization

• Longitudinal follow-up needed

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3.2. Structural reading network in pre-readers at risk for dyslexia

Acknowledgments

Maaike.Vandermosten@ppw.kuleuven.be

DYSlexia COllaboration Leuven (DYSCO)

Parenting and Special Education Research Group, KU Leuven

Pol Ghesquière

Maaike Vandermosten

Jolijn Vanderauwera

Bart Boets

ExpORL, Dept. Neurosciences, KU Leuven

Jan Wouters

Heleen Luts

Hanne Poelmans

Sophie Vanvooren

Astrid De Vos

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Thank you!