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Fumiko Hoeft MD PhD
fumiko.hoeft@ucsf.edu | dyslexia.ucsf.edu | brainlens.org | @fumikohoeft
CA Dept of Ed Dyslexia Work Group 4/21/2016
1
R01HD044073 (Cutting, Vanderbilt)
R01HD065794 (Pugh, Haskins/Yale)
P01HD001994 (Rueckl, Haskins/U Conn)
R01MH104438 (Nordahl, UCDavis/MIND)
R01MH103371 (Amaral, UCDavis/MIND)
R01HD078351 (Hoeft)
R01HD086168 (Hoeft/Pugh)
Academic Senate Award
Dyslexia Center (Charles Schwab, Kelly Gorman
& Steve Carnevale, Flora Family Fndtn, Battery
Powered, Thomas & Eva Fong Family Fndtn, Lori &
Ray dePole, Dan & Stacey Case Family Fndtn)
FUNDING
Liebe Patterson
Dennis & Shannon Wong – DSEA ‘88 Foundation
NSF1540854 SL-CN (Gazzaley, Uncapher, UCSF)
Reading & dyslexia
Reading and dyslexia are complicated.
“Biomarkers” for dyslexia
Dyslexia is a neurobiological condition.
Definition of “dyslexia”
Seemingly typical readers with discrepantly high IQ show dyslexia-
like brain patterns.
Early identification & intervention
We can identify dyslexia early.
Crucial in changing the trajectory.
Sound evidence for cost-effectiveness.
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 2
Reading & dyslexia
Reading and dyslexia are complicated.
“Biomarkers” for dyslexia
Dyslexia is a neurobiological condition.
Definition of “dyslexia”
Seemingly typical readers with discrepantly high IQ show dyslexia-
like brain patterns.
Early identification & intervention
We can identify dyslexia early.
Crucial in changing the trajectory.
Sound evidence for cost-effectiveness.
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 3
 Skill unique to humans
 Evolutionarily new skill (~6,000 yrs) with no
time for a dedicated brain circuit to have
evolved (Dehaene. Reading in the Brain ‘09)
 Needs to be explicitly taught
 Heavily influenced by culture and writing
system. But yet,
 Dyslexia: 5-10% & up to 20% in every culture
& language
 Heritable (~1 in 2) (Grigorenko. ‘04)
 Universal neurobiological substrate of reading
& dyslexia
Sumerian pictographs ~4,000 BC
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 4
Dyslexia
TIMING OF
LEARNING
INFLUENCE
OF
ENVIRONMEN
T & CULTURE
NEEDS TO BE
EXPLICITLY
LEARNED
HOW THE
BRAIN IS
ORGANIZED
DLPFC
EXECUTIVE CONTROL
Resiliency Readers
ORTHOGRAPHIC
PHONOLOGICAL
IF
G
o
p
P
r
e
C
G
SMG
pSTG
FusiG
ITG
Insula
ARTICULATION
Compensation
dStr
PPC ATTENTION
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 5
Reading & dyslexia
Reading and dyslexia are complicated.
“Biomarkers” for dyslexia
Dyslexia is a neurobiological condition.
Definition of “dyslexia”
Seemingly typical readers with discrepantly high IQ show dyslexia-
like brain patterns.
Early identification & intervention
We can identify dyslexia early.
Crucial in changing the trajectory.
Sound evidence for cost-effectiveness.
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 6
Xia, Hancock & Hoeft. LLC. under review
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 7
Typical
Readers
Reading Disability
Dyslexic Reader
RD
Low-
Non-Risk
Risk Allele
High-Risk
Convergent evidence suggests LEFT TEMPORO-PARIETAL REGION important for
phonological processing, as the neural signature for dyslexia.
Lt TP & vOT
Left Occipito-Temporal
(Lt OT)
Left Temporo-
Parietal (Lt TP)
Function&Structure
Younger
reading-
matched
Dyslexic children
Age-
matched
But see Krafnick … Eden. J Neurosci 2014
Shaywitz et al. PNAS 1998, Shaywitz et al. Biol Psychiatry 2002, Hoeft et al. J Neurosci 2006, Hoeft et al. PNAS 2007
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 8
Lt TP & vOT
Left Occipito-Temporal
(Lt OT)
Left Temporo-
Parietal (Lt TP)
Function&Structure
Younger
reading-
matched
Dyslexic children
Age-
matched
But see Krafnick … Eden. J Neurosci 2014
LEFT TEMPORO-PARIETAL
REGION dysfunctional
even compared to
reading-matched controls
Shaywitz et al. PNAS 1998, Shaywitz et al. Biol Psychiatry 2002, Hoeft et al. J Neurosci 2006, Hoeft et al. PNAS 2007
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 9
Functional MRI of Print-Speech Binding
in typical readers
Preston et al. Psychol Sci 2016, Rueckl et al. PNAS 2015
Comparison between different writing systems show universal mechanisms
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 10
Xia, Hoeft, Zhang & Shu. Neuropsychologia 2016
See also Linkersdoerfer et al. PLoS ONE 2015 - MetaAnalysis, Paulesu et al. Science 2001, Silani et al. Brain 2005, Debska et al. NeuroImage 2016
But see Siok et al. 2004, 2008 2009, Jednoreg et al. 2015
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 11
0.50
0.60
0.70
0.80
0.90
1.00
1.10
Volume
DYS-younger
TD-younger
older
older
Left temporo-parietal
Constant abnormality across age
Left occipito-temporal
Maturational delay?
0.40
0.50
0.60
0.70
0.80
0.90
Volume
TD-younger DYS-older
DYS-younger TD-older
See also Linkersdoerfer et al. PLoS ONE 2015 - MetaAnalysis, Paulesu et al. Science 2001, Silani et al. Brain 2005, Debska et al. NeuroImage 2016
But see Siok et al. 2004, 2008 2009, Jednoreg et al. 2015
Atypical pattern in LEFT TEMPORO-PARIETAL REGION is consistent across
languages (e.g. Chinese dyslexia)
Hosseini et al. NeuroImage 2013, Black et al. NeuroImage 2012
PREREADERS without
family history
PREREADERS with
family history
See also Raschle Chang & Gaab. NeuroImage 2011. Raschle et al. PNAS 2013. Black et al. NeuroImage 2012. Im et al.
Cerebr Cort 2015. Langer et al. Cerebr Cort 2015. Vandermosten et al. Dev Sci 2015.
And many other EEG studies from neonates
But also see Clark et al. Brain 2015
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 12
Vandermosten Hoeft Norton. Curr Opin Beh Sci. under review
Prereaders at-risk for developing dyslexia show similar patterns of abnormality
Left TP function, structure, white matter &
gene expression
fMRI: FOXP2: Wilcke et al. Eur J Hum Gen ’12; KIAA0319: Pinel et al. J Neurosci ’12; DCDC2: Cope et
al. NeuroImage ’12; GM: DCDC2: Meda et al. NeuroImage ’08; arcuate fasciculus WM DCDC2:
Marino et al. Cortex ’14; WM volume & DYX1C1, DCDC2, KIAA0319: Darki… Klingberg Biol Psychiatry
’12; gene expression: KIAA0319 & postmortem brain: Meng … Olson et al. PNAS ’05; ROBO1a &
human fetus: Johnson et al. Neuron ’09
Left vOT function, structure, white matter &
gene expression
fMRI: DCDC2: Cope et al. NeuroImage ’12; GM: DCDC2: Meda et al. NeuroImage ’08; inferior
fasciculi WM: DCDC2: Marino et al. Cortex ’14; gene expression: DCDC2 & human postmortem brain:
Meng … Olson et al. PNAS ’05
See also Jamadar et al. (KIAA, DCDC2, DYX1C1) GM ‘11, rsfMRI ’13, Scerri et al. PLoS ONE ‘12
DCDC2: DYX2 region on chromosome 6p21.3. Double-cortin gene. Neuronal migration. Glutamate.
KIAA0319: DYX2 region on chromosome 6p21.3. Neuronal migration. Auditory learning.
ROBO1a not b: Axonal guidance. Midline crossing. Rost/Caud gradient. Theta oscillation. Mediates thalamocortical axonal growth.
Glu & GABA: Modulate neuronal migration & oscillation. Glu: vocal learning & verbal short term memory.
Link with risk genes also converge onto LEFT TEMPORO-PARIETAL REGION
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 13
No change/activation in dyslexics in the Left TEMPORO-PARIETAL region after
intervention.
Changes seen generally in “non-dyslexia regions” and typically considered
more “compensatory” networks.
Barquero, Davis & Cutting. PLoS ONE 2014 -- MetaAnalysis
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 14
Reading & dyslexia
Reading and dyslexia are complicated.
“Biomarkers” for dyslexia
Dyslexia is a neurobiological condition.
Definition of “dyslexia”
Seemingly typical readers with discrepantly high IQ show dyslexia-
like brain patterns.
Early identification & intervention
We can identify dyslexia early.
Crucial in changing the trajectory.
Sound evidence for cost-effectiveness.
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 15
 “Specific” learning disability
= achievement below expectation (relative to
who? Peer or self?)
 Underlying phonological deficits and response
to intervention similar between poor readers
with and without low IQ (Fletcher et al. ‘94, Stanovich &
Siegel ‘94, Stuebing et al. ‘02, Vellutino et al. ’06)
 IQ tests no longer required (‘04 reauthorization of
Individuals with Disabilities Education Act, IDEA)
 Many of US schools rely on the discrepancy
between IQ and reading (vs. just looking at
poor reading) (Machek & Nelson ’07)
Brain patterns are similar regardless of IQ
discrepancy in poor readers
Tanaka et al. Psychol Sci. ‘11
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 16
See also Simos et al. Front Hum Neurosci 2014. FYI, Wadsworth et al. J Learn Dis 2000
Dataset A
Dataset B
Good Dyslexia Poor
(discrepant)
Readingbrainactivation
Typical readers with discrepantly high IQ, despite the “IQ advantage”, also
show “dyslexia-like” brain patterns
Sup IQ Norm IQ Sup IQ
sup read norm read norm read
(discrepant)
Hancock et al. TiNE under review
Lt Temporal-Parietal
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 17
FYI, Wadsworth et al. J Learn Dis 2000
Readingbrainactivation
Typical Dyslexics
Gifted Dyslexics
Overlap
p15-16
DYX3
DYX6
p11.2
DYX5
p13-q13
q13-16.2
DYX4
DYX8
p34-36
DYX7
p15.5
DYX1
DYX2
p21.3-22
q21
DYX9
q27.3
DRD4
(ADHD)
KIAA0319, DCDC2 (ADHD)
Plomin Intelligence ’06, “Missing heritability” Eichler et al. Nat Rev Gen ’10
Adapted from: Williams & O’Donovan. Eur J Hum Genet ’06, Poelmans et al. Mol Psychiatr ‘11
DYXC1
ROBO1
KIAA0319L
FMR1 (FXS)
GTF2I (WBS)
q11.23
DIP2A, S100B
q22.3
q31
DOCK2 (FOXP2-language)
q35
CNTNP2 (Autism, ADHD, etc)
q24
ATP2C2
C2ORF3
MRPL19
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 18
G1 E
Network2
Orthographic
Network3
Learning
G1 EG1 E
Network1
Phonological
Network4
Attention
G1 EG2 G2 G2 G2
Network5
Others
G1 EG2
Liability
for
dyslexia
Pennington. Cognition 2006. Pennington et al. J Abnorm Psychol 2012. – Multiple deficit model
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 19
Reading & dyslexia
Reading and dyslexia are complicated.
“Biomarkers” for dyslexia
Dyslexia is a neurobiological condition.
Definition of “dyslexia”
Seemingly typical readers with discrepantly high IQ show dyslexia-
like brain patterns.
Early identification & intervention
We can identify dyslexia early.
Crucial in changing the trajectory.
Sound evidence for cost-effectiveness.
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 20
SLD children served in Special Ed 4.7%
Family History ~50% with family history, poor
foundational skills (vs. est. 7% in low risk)
Cost to individual >£100k less earning ($150k)
Cost to (UK) society £2.5bn/yr in England ($22.5bn/yr in the US)
adj. for population est. & $1.50 exchange rate
High School drop out 2.5x
Prison population 32-46% (note low IQ and not SLD!)
Anxiety disorder 2.0x (5.0x severe test anxiety)
Depression 2.0x
Substance abuse 2.7x
ADHD 4.5x
LD in childhood mental health disorders 79% of bipolar disorders, 71% of ADHD combined type, 67% of
autism, 66% of ADHD inattentive type. (Mayes & Calhoun. Learn Ind Diff ’06)
NICHD website, Pennington & Lefly. Child Develop 2001, Cosden JLD 2001, Wilson et al. JLD 2009, House of
Commons Sci & Tech Committee Report / Early Child a Chance Trust. 2009, DuPaul et al. JLD 2012,
Hendren et al. under prep
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 21
“Rich get richer and poor get poorer (in
reading)”
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 22
Quality intervention at K can lead to 4x
reduction in # of later poor readers (57
vs. 16%)
1 year delay: 50% reduction in
effectiveness (57 vs. 27%)
If early, as little as 5-20min intervention
3x/wk, 16-20wks given by trained
teachers if early.
$16-31 return per $1 (£11-17 return per £1 spent
in England, &b assuming exchange rate of $1.50 to £1)
“The (UK) Government’s position that
early literacy interventions are an
investment that saves money in the long
run is evidence-based.” (UK House of Commons
2009)
0
10
20
30
40
50
60
K K+1st 1st only
Responsiveness to Intervention (%)
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 23
Al Otaiba & Fuchs. J Learn Dis 2006, Wanzek & Vaughn. School Psych Rev 2007 – MetaAnalysis
Beddington et al. Nature 2008. House of Common Report 2009
Family history: 1 in 2 develops dyslexia
Adult reading history questionnaire (ARHQ – Lefly &
Pennington ‘00)
Early cognitive signs: Also 1 in 2
• Poor phonological awareness (develops from word,
syllabic, onset-rime, to phonemic awareness from 2-
5 years of age)
• Poor rapid naming (color, object, letter, number)
• Poor letter (sound) knowledge
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 24
Family history: 1 in 2 develops dyslexia
Adult reading history questionnaire (ARHQ – Lefly &
Pennington ‘00)
Early cognitive signs: Also 1 in 2
• Poor phonological awareness (develops from word,
syllabic, onset-rime, to phonemic awareness from 2-
5 years of age)
• Poor rapid naming (color, object, letter, number)
• Poor letter (sound) knowledge
i-Screener development
CTSI digital health grant
CTSI Catalyst award
UCSF Dyslexia Center
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 25
CENTER of INNOVATION IN NEUROSCIENCE-BASED
TECHNOLOGY FOR EEUCATION AND LEARNING
UCSF | UC Berkeley | Other UC schools | Stanford
adam bruce fumiko
joaquin jyoti melina
miriam roeland silvia
 Dyslexia is a neurobiological condition.
 Seemingly typical readers with discrepantly high IQ show
dyslexia-like brain patterns.
 There are key behavioral & neural markers of dyslexia.
 Early identification & intervention are crucial in changing the
trajectory. $16-31 return per $1 spent on early intervention
(assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that
early literacy interventions are an investment that saves
money in the long run is evidence-based.” (House of Commons 2009)
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 27
Before Birth PreSch/K 2nd-4thGr Adult
Early identification
Preventive intervention
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 28
Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 29

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CA Dept of Ed - Neuroscience of Dyslexia

  • 1. Fumiko Hoeft MD PhD fumiko.hoeft@ucsf.edu | dyslexia.ucsf.edu | brainlens.org | @fumikohoeft CA Dept of Ed Dyslexia Work Group 4/21/2016 1 R01HD044073 (Cutting, Vanderbilt) R01HD065794 (Pugh, Haskins/Yale) P01HD001994 (Rueckl, Haskins/U Conn) R01MH104438 (Nordahl, UCDavis/MIND) R01MH103371 (Amaral, UCDavis/MIND) R01HD078351 (Hoeft) R01HD086168 (Hoeft/Pugh) Academic Senate Award Dyslexia Center (Charles Schwab, Kelly Gorman & Steve Carnevale, Flora Family Fndtn, Battery Powered, Thomas & Eva Fong Family Fndtn, Lori & Ray dePole, Dan & Stacey Case Family Fndtn) FUNDING Liebe Patterson Dennis & Shannon Wong – DSEA ‘88 Foundation NSF1540854 SL-CN (Gazzaley, Uncapher, UCSF)
  • 2. Reading & dyslexia Reading and dyslexia are complicated. “Biomarkers” for dyslexia Dyslexia is a neurobiological condition. Definition of “dyslexia” Seemingly typical readers with discrepantly high IQ show dyslexia- like brain patterns. Early identification & intervention We can identify dyslexia early. Crucial in changing the trajectory. Sound evidence for cost-effectiveness. Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 2
  • 3. Reading & dyslexia Reading and dyslexia are complicated. “Biomarkers” for dyslexia Dyslexia is a neurobiological condition. Definition of “dyslexia” Seemingly typical readers with discrepantly high IQ show dyslexia- like brain patterns. Early identification & intervention We can identify dyslexia early. Crucial in changing the trajectory. Sound evidence for cost-effectiveness. Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 3
  • 4.  Skill unique to humans  Evolutionarily new skill (~6,000 yrs) with no time for a dedicated brain circuit to have evolved (Dehaene. Reading in the Brain ‘09)  Needs to be explicitly taught  Heavily influenced by culture and writing system. But yet,  Dyslexia: 5-10% & up to 20% in every culture & language  Heritable (~1 in 2) (Grigorenko. ‘04)  Universal neurobiological substrate of reading & dyslexia Sumerian pictographs ~4,000 BC Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 4
  • 5. Dyslexia TIMING OF LEARNING INFLUENCE OF ENVIRONMEN T & CULTURE NEEDS TO BE EXPLICITLY LEARNED HOW THE BRAIN IS ORGANIZED DLPFC EXECUTIVE CONTROL Resiliency Readers ORTHOGRAPHIC PHONOLOGICAL IF G o p P r e C G SMG pSTG FusiG ITG Insula ARTICULATION Compensation dStr PPC ATTENTION Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 5
  • 6. Reading & dyslexia Reading and dyslexia are complicated. “Biomarkers” for dyslexia Dyslexia is a neurobiological condition. Definition of “dyslexia” Seemingly typical readers with discrepantly high IQ show dyslexia- like brain patterns. Early identification & intervention We can identify dyslexia early. Crucial in changing the trajectory. Sound evidence for cost-effectiveness. Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 6
  • 7. Xia, Hancock & Hoeft. LLC. under review Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 7 Typical Readers Reading Disability Dyslexic Reader RD Low- Non-Risk Risk Allele High-Risk Convergent evidence suggests LEFT TEMPORO-PARIETAL REGION important for phonological processing, as the neural signature for dyslexia.
  • 8. Lt TP & vOT Left Occipito-Temporal (Lt OT) Left Temporo- Parietal (Lt TP) Function&Structure Younger reading- matched Dyslexic children Age- matched But see Krafnick … Eden. J Neurosci 2014 Shaywitz et al. PNAS 1998, Shaywitz et al. Biol Psychiatry 2002, Hoeft et al. J Neurosci 2006, Hoeft et al. PNAS 2007 Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 8
  • 9. Lt TP & vOT Left Occipito-Temporal (Lt OT) Left Temporo- Parietal (Lt TP) Function&Structure Younger reading- matched Dyslexic children Age- matched But see Krafnick … Eden. J Neurosci 2014 LEFT TEMPORO-PARIETAL REGION dysfunctional even compared to reading-matched controls Shaywitz et al. PNAS 1998, Shaywitz et al. Biol Psychiatry 2002, Hoeft et al. J Neurosci 2006, Hoeft et al. PNAS 2007 Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 9
  • 10. Functional MRI of Print-Speech Binding in typical readers Preston et al. Psychol Sci 2016, Rueckl et al. PNAS 2015 Comparison between different writing systems show universal mechanisms Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 10
  • 11. Xia, Hoeft, Zhang & Shu. Neuropsychologia 2016 See also Linkersdoerfer et al. PLoS ONE 2015 - MetaAnalysis, Paulesu et al. Science 2001, Silani et al. Brain 2005, Debska et al. NeuroImage 2016 But see Siok et al. 2004, 2008 2009, Jednoreg et al. 2015 Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 11 0.50 0.60 0.70 0.80 0.90 1.00 1.10 Volume DYS-younger TD-younger older older Left temporo-parietal Constant abnormality across age Left occipito-temporal Maturational delay? 0.40 0.50 0.60 0.70 0.80 0.90 Volume TD-younger DYS-older DYS-younger TD-older See also Linkersdoerfer et al. PLoS ONE 2015 - MetaAnalysis, Paulesu et al. Science 2001, Silani et al. Brain 2005, Debska et al. NeuroImage 2016 But see Siok et al. 2004, 2008 2009, Jednoreg et al. 2015 Atypical pattern in LEFT TEMPORO-PARIETAL REGION is consistent across languages (e.g. Chinese dyslexia)
  • 12. Hosseini et al. NeuroImage 2013, Black et al. NeuroImage 2012 PREREADERS without family history PREREADERS with family history See also Raschle Chang & Gaab. NeuroImage 2011. Raschle et al. PNAS 2013. Black et al. NeuroImage 2012. Im et al. Cerebr Cort 2015. Langer et al. Cerebr Cort 2015. Vandermosten et al. Dev Sci 2015. And many other EEG studies from neonates But also see Clark et al. Brain 2015 Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 12 Vandermosten Hoeft Norton. Curr Opin Beh Sci. under review Prereaders at-risk for developing dyslexia show similar patterns of abnormality
  • 13. Left TP function, structure, white matter & gene expression fMRI: FOXP2: Wilcke et al. Eur J Hum Gen ’12; KIAA0319: Pinel et al. J Neurosci ’12; DCDC2: Cope et al. NeuroImage ’12; GM: DCDC2: Meda et al. NeuroImage ’08; arcuate fasciculus WM DCDC2: Marino et al. Cortex ’14; WM volume & DYX1C1, DCDC2, KIAA0319: Darki… Klingberg Biol Psychiatry ’12; gene expression: KIAA0319 & postmortem brain: Meng … Olson et al. PNAS ’05; ROBO1a & human fetus: Johnson et al. Neuron ’09 Left vOT function, structure, white matter & gene expression fMRI: DCDC2: Cope et al. NeuroImage ’12; GM: DCDC2: Meda et al. NeuroImage ’08; inferior fasciculi WM: DCDC2: Marino et al. Cortex ’14; gene expression: DCDC2 & human postmortem brain: Meng … Olson et al. PNAS ’05 See also Jamadar et al. (KIAA, DCDC2, DYX1C1) GM ‘11, rsfMRI ’13, Scerri et al. PLoS ONE ‘12 DCDC2: DYX2 region on chromosome 6p21.3. Double-cortin gene. Neuronal migration. Glutamate. KIAA0319: DYX2 region on chromosome 6p21.3. Neuronal migration. Auditory learning. ROBO1a not b: Axonal guidance. Midline crossing. Rost/Caud gradient. Theta oscillation. Mediates thalamocortical axonal growth. Glu & GABA: Modulate neuronal migration & oscillation. Glu: vocal learning & verbal short term memory. Link with risk genes also converge onto LEFT TEMPORO-PARIETAL REGION Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 13
  • 14. No change/activation in dyslexics in the Left TEMPORO-PARIETAL region after intervention. Changes seen generally in “non-dyslexia regions” and typically considered more “compensatory” networks. Barquero, Davis & Cutting. PLoS ONE 2014 -- MetaAnalysis Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 14
  • 15. Reading & dyslexia Reading and dyslexia are complicated. “Biomarkers” for dyslexia Dyslexia is a neurobiological condition. Definition of “dyslexia” Seemingly typical readers with discrepantly high IQ show dyslexia- like brain patterns. Early identification & intervention We can identify dyslexia early. Crucial in changing the trajectory. Sound evidence for cost-effectiveness. Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 15
  • 16.  “Specific” learning disability = achievement below expectation (relative to who? Peer or self?)  Underlying phonological deficits and response to intervention similar between poor readers with and without low IQ (Fletcher et al. ‘94, Stanovich & Siegel ‘94, Stuebing et al. ‘02, Vellutino et al. ’06)  IQ tests no longer required (‘04 reauthorization of Individuals with Disabilities Education Act, IDEA)  Many of US schools rely on the discrepancy between IQ and reading (vs. just looking at poor reading) (Machek & Nelson ’07) Brain patterns are similar regardless of IQ discrepancy in poor readers Tanaka et al. Psychol Sci. ‘11 Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 16 See also Simos et al. Front Hum Neurosci 2014. FYI, Wadsworth et al. J Learn Dis 2000 Dataset A Dataset B Good Dyslexia Poor (discrepant) Readingbrainactivation
  • 17. Typical readers with discrepantly high IQ, despite the “IQ advantage”, also show “dyslexia-like” brain patterns Sup IQ Norm IQ Sup IQ sup read norm read norm read (discrepant) Hancock et al. TiNE under review Lt Temporal-Parietal Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 17 FYI, Wadsworth et al. J Learn Dis 2000 Readingbrainactivation Typical Dyslexics Gifted Dyslexics Overlap
  • 18. p15-16 DYX3 DYX6 p11.2 DYX5 p13-q13 q13-16.2 DYX4 DYX8 p34-36 DYX7 p15.5 DYX1 DYX2 p21.3-22 q21 DYX9 q27.3 DRD4 (ADHD) KIAA0319, DCDC2 (ADHD) Plomin Intelligence ’06, “Missing heritability” Eichler et al. Nat Rev Gen ’10 Adapted from: Williams & O’Donovan. Eur J Hum Genet ’06, Poelmans et al. Mol Psychiatr ‘11 DYXC1 ROBO1 KIAA0319L FMR1 (FXS) GTF2I (WBS) q11.23 DIP2A, S100B q22.3 q31 DOCK2 (FOXP2-language) q35 CNTNP2 (Autism, ADHD, etc) q24 ATP2C2 C2ORF3 MRPL19 Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 18
  • 19. G1 E Network2 Orthographic Network3 Learning G1 EG1 E Network1 Phonological Network4 Attention G1 EG2 G2 G2 G2 Network5 Others G1 EG2 Liability for dyslexia Pennington. Cognition 2006. Pennington et al. J Abnorm Psychol 2012. – Multiple deficit model Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 19
  • 20. Reading & dyslexia Reading and dyslexia are complicated. “Biomarkers” for dyslexia Dyslexia is a neurobiological condition. Definition of “dyslexia” Seemingly typical readers with discrepantly high IQ show dyslexia- like brain patterns. Early identification & intervention We can identify dyslexia early. Crucial in changing the trajectory. Sound evidence for cost-effectiveness. Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 20
  • 21. SLD children served in Special Ed 4.7% Family History ~50% with family history, poor foundational skills (vs. est. 7% in low risk) Cost to individual >£100k less earning ($150k) Cost to (UK) society £2.5bn/yr in England ($22.5bn/yr in the US) adj. for population est. & $1.50 exchange rate High School drop out 2.5x Prison population 32-46% (note low IQ and not SLD!) Anxiety disorder 2.0x (5.0x severe test anxiety) Depression 2.0x Substance abuse 2.7x ADHD 4.5x LD in childhood mental health disorders 79% of bipolar disorders, 71% of ADHD combined type, 67% of autism, 66% of ADHD inattentive type. (Mayes & Calhoun. Learn Ind Diff ’06) NICHD website, Pennington & Lefly. Child Develop 2001, Cosden JLD 2001, Wilson et al. JLD 2009, House of Commons Sci & Tech Committee Report / Early Child a Chance Trust. 2009, DuPaul et al. JLD 2012, Hendren et al. under prep Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 21
  • 22. “Rich get richer and poor get poorer (in reading)” Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 22
  • 23. Quality intervention at K can lead to 4x reduction in # of later poor readers (57 vs. 16%) 1 year delay: 50% reduction in effectiveness (57 vs. 27%) If early, as little as 5-20min intervention 3x/wk, 16-20wks given by trained teachers if early. $16-31 return per $1 (£11-17 return per £1 spent in England, &b assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that early literacy interventions are an investment that saves money in the long run is evidence-based.” (UK House of Commons 2009) 0 10 20 30 40 50 60 K K+1st 1st only Responsiveness to Intervention (%) Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 23 Al Otaiba & Fuchs. J Learn Dis 2006, Wanzek & Vaughn. School Psych Rev 2007 – MetaAnalysis Beddington et al. Nature 2008. House of Common Report 2009
  • 24. Family history: 1 in 2 develops dyslexia Adult reading history questionnaire (ARHQ – Lefly & Pennington ‘00) Early cognitive signs: Also 1 in 2 • Poor phonological awareness (develops from word, syllabic, onset-rime, to phonemic awareness from 2- 5 years of age) • Poor rapid naming (color, object, letter, number) • Poor letter (sound) knowledge Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 24
  • 25. Family history: 1 in 2 develops dyslexia Adult reading history questionnaire (ARHQ – Lefly & Pennington ‘00) Early cognitive signs: Also 1 in 2 • Poor phonological awareness (develops from word, syllabic, onset-rime, to phonemic awareness from 2- 5 years of age) • Poor rapid naming (color, object, letter, number) • Poor letter (sound) knowledge i-Screener development CTSI digital health grant CTSI Catalyst award UCSF Dyslexia Center Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 25
  • 26. CENTER of INNOVATION IN NEUROSCIENCE-BASED TECHNOLOGY FOR EEUCATION AND LEARNING UCSF | UC Berkeley | Other UC schools | Stanford adam bruce fumiko joaquin jyoti melina miriam roeland silvia
  • 27.  Dyslexia is a neurobiological condition.  Seemingly typical readers with discrepantly high IQ show dyslexia-like brain patterns.  There are key behavioral & neural markers of dyslexia.  Early identification & intervention are crucial in changing the trajectory. $16-31 return per $1 spent on early intervention (assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that early literacy interventions are an investment that saves money in the long run is evidence-based.” (House of Commons 2009) Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 27
  • 28. Before Birth PreSch/K 2nd-4thGr Adult Early identification Preventive intervention Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 28
  • 29. Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 29

Editor's Notes

  1. Dyslexia is a neurobiological condition. Seemingly typical readers with discrepantly high IQ show dyslexia-like brain patterns. There are key behavioral & neural markers of dyslexia. Early identification & intervention are crucial in changing the trajectory. $16-31 return per $1 spent on early intervention (assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that early literacy interventions are an investment that saves money in the long run is evidence-based.”
  2. Dyslexia is a neurobiological condition. Seemingly typical readers with discrepantly high IQ show dyslexia-like brain patterns. There are key behavioral & neural markers of dyslexia. Early identification & intervention are crucial in changing the trajectory. $16-31 return per $1 spent on early intervention (assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that early literacy interventions are an investment that saves money in the long run is evidence-based.”
  3. Dyslexia is a neurobiological condition. Seemingly typical readers with discrepantly high IQ show dyslexia-like brain patterns. There are key behavioral & neural markers of dyslexia. Early identification & intervention are crucial in changing the trajectory. $16-31 return per $1 spent on early intervention (assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that early literacy interventions are an investment that saves money in the long run is evidence-based.”
  4. Dyslexia is a neurobiological condition. Seemingly typical readers with discrepantly high IQ show dyslexia-like brain patterns. There are key behavioral & neural markers of dyslexia. Early identification & intervention are crucial in changing the trajectory. $16-31 return per $1 spent on early intervention (assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that early literacy interventions are an investment that saves money in the long run is evidence-based.”
  5. Dyslexia is a neurobiological condition. Seemingly typical readers with discrepantly high IQ show dyslexia-like brain patterns. There are key behavioral & neural markers of dyslexia. Early identification & intervention are crucial in changing the trajectory. $16-31 return per $1 spent on early intervention (assuming exchange rate of $1.50 to £1) “The (UK) Government’s position that early literacy interventions are an investment that saves money in the long run is evidence-based.”
  6. http://www.sciencedirect.com/science/article/pii/S1041608005000415 Family history Pennington Lefly 2001 Cost 100k less: Earnings Foresight Mental Capital and Wellbeing Project. Mental Capital and Wellbeing: Final Project Report (The Government Office for Science, 2008) – Usha Goswami NRN 2015 Grigorenko ADHD various papers 40% (vs. 9% in all children – NIH website) review of comorbidity of LD and ADHD with comorbidity rate estimates (DuPaul et al., 2012) Germano et al. Dev Neuropsychol ’10) Anxiety test anxiety 5x stats (Nelson ’13, Carroll ‘06), 8% from NIH, 2x stats on anxiety disorder (Wilson et al JLD 2009) Depression 14% in children according to NIH, according to Wilson et al. JLD 2009, it’s 14.6% (in LD) vs 7.4% (people without disabilities) Mental health stats in typical children generally come from the NIH website Abuse (Nat’l Assn on Alcohol, Drug, Disability, ’10) on disabilities generally or ID so not good. Abuse (Moody ’00) Karacostas & Fisher 1993 chemical dependence 24% in LD, 9% in non disabled students. Found in article Meredith Cosden et al. JLD 2001 Prison (Quinn, ’05) HS drop out rate - https://nces.ed.gov/fastfacts/display.asp?id=16 for typical population (7%), NCLD report for LD (18%), http://www.ncld.org/reports-and-studies/diplomas-at-risk-a-critical-look-at-the-high-school-graduation-rate/ hispanisc typical 12% HS graduation rate: http://nces.ed.gov/ccd/tables/ACGR_2010-11_to_2012-13.asp 81% (all children) vs. 68% (LD – NCLD 2014 report)
  7. 50% response rate is low. We should be able to do better. But also dramatic decrease in response between K and 1st. Often it takes a long time to notice the symptoms, get people on board and find the right programs for them. So we need to act as early as possible! Otaiba 2006 Ladders to literacy-phonological instruction DIBELS assessment 4th Gr : Change from Learning to read to Reading to learn 3rd Gr then is very important Dys often identified in 2/3rd gr then intervention starts long after http://ideas.time.com/2012/09/26/why-third-grade-is-so-important-the-matthew-effect/ Introduction & Overview: Importance of reading, Problem & Market: Literacy as a global health problem, Our novel solution: A bench to classroom & society model (ABCs model) to personalized education 1. Neuroscience (not the usual kind), 2. Beyond reading (into cognition, and socio-emotional & motivational resilience), 3. Rapid translation Some examples: Neuroscience-based early detection & outcome prediction, Neuroscience evidence for educational policy, Neuroscientifically sound scalable technology for teacher training, teaching and assessment Team Institute’s organizational structure Partnership: BENCH: From Oxford to Yale to within UCSF. From genetics to brain to behavior. CLASSROOM: Specialized school for dyslexia (Armstrong School), School districts (e.g. SFUSD), Ed-related NPOs (WestEd, CCC) SOCIETY: “An eye on Global Literacy Health” Uniskript, Haskins/GraphoWorld global literacy initiatives Revenue Model, Go to market: Current funders Competitors: Other related institutions and how we differ Financials, Milestones, Summary
  8. 50% response rate is low. We should be able to do better. But also dramatic decrease in response between K and 1st. Often it takes a long time to notice the symptoms, get people on board and find the right programs for them. So we need to act as early as possible! Otaiba 2006 Ladders to literacy-phonological instruction DIBELS assessment 4th Gr : Change from Learning to read to Reading to learn 3rd Gr then is very important Dys often identified in 2/3rd gr then intervention starts long after http://ideas.time.com/2012/09/26/why-third-grade-is-so-important-the-matthew-effect/ Introduction & Overview: Importance of reading, Problem & Market: Literacy as a global health problem, Our novel solution: A bench to classroom & society model (ABCs model) to personalized education 1. Neuroscience (not the usual kind), 2. Beyond reading (into cognition, and socio-emotional & motivational resilience), 3. Rapid translation Some examples: Neuroscience-based early detection & outcome prediction, Neuroscience evidence for educational policy, Neuroscientifically sound scalable technology for teacher training, teaching and assessment Team Institute’s organizational structure Partnership: BENCH: From Oxford to Yale to within UCSF. From genetics to brain to behavior. CLASSROOM: Specialized school for dyslexia (Armstrong School), School districts (e.g. SFUSD), Ed-related NPOs (WestEd, CCC) SOCIETY: “An eye on Global Literacy Health” Uniskript, Haskins/GraphoWorld global literacy initiatives Revenue Model, Go to market: Current funders Competitors: Other related institutions and how we differ Financials, Milestones, Summary
  9. Developmental milestone: 1 Word level: recognizing a word 2 Syllabic awareness : e.g. syllable deletion: Say finish. Now say it again without the fin” -> “ish” 3 Onset-rime awareness: “Which word does not rhyme: fish, dish, hook?” 4 Phonemic awareness: "Say coat. Now say it again but don't say /k/” Motor function almost accepted, Roeland now has 2 grants 1 Word level: recognizing a word 2 Syllabic awareness : e.g. syllable deletion: Say finish. Now say it again without the fin” -> “ish” Syllable segmentation: e.g., "How many syllables (or parts) are in the word coffee?"[12] Syllable completion: e.g., "Here is a picture of a rabbit. I'll say the first part of the word. Can you finish the word ra_____?"[13] Syllable identity: e.g., "Which part of complete and compare sound the same?"[12] Syllable deletion: e.g., "Say finish. Now say it again without the fin"[14] 3 Onset-rime awareness: “Which word does not rhyme: fish, dish, hook?” Spoken word recognition: e.g., "Do these words rhyme: shell bell?"[12] Spoken rhyme detection or rhyme oddity task: e.g., "Which word does not rhyme: fish, dish, hook?" [15] Spoken rhyme generation: e.g., "Tell me words that rhyme with bell?"[13] Onset-rime blending [9] 4 Phonemic awareness: "Say coat. Now say it again but don't say /k/” Alliteration awareness (aka phoneme detection and sound or phoneme categorization): e.g., "Which word has a different first sound: bed, bus, chair, ball?"[16] Phoneme matching: e.g., "Which word begins with the same sound as bat: horn, bed, cup?" [16] Phoneme isolation: e.g., "Tell me the sound you hear at the beginning of the word food" [3] Phoneme completion: e.g., "Here is a picture of a watch. Finish the word for me: wa_____ "[13] Phoneme blending with words or non-words: e.g., "What word do these sounds make: m...oo...n?" [9] Phoneme deletion, also referred to as phoneme elision: e.g., "Say coat. Now say it again but don't say /k/"[14] Phoneme segmentation with words or non-words: e.g., "How many sounds can you hear in the word it?[12] Phoneme reversal: e.g., "Say na (as in nap). Now say na backwards"[9] Phoneme manipulation: e.g., "Say dash. Now say it again, but instead of /æ/ say /I/"[14] Spoonerism: e.g., felt made becomes melt fade[12]
  10. Developmental milestone: 1 Word level: recognizing a word 2 Syllabic awareness : e.g. syllable deletion: Say finish. Now say it again without the fin” -> “ish” 3 Onset-rime awareness: “Which word does not rhyme: fish, dish, hook?” 4 Phonemic awareness: "Say coat. Now say it again but don't say /k/” Motor function almost accepted, Roeland now has 2 grants 1 Word level: recognizing a word 2 Syllabic awareness : e.g. syllable deletion: Say finish. Now say it again without the fin” -> “ish” Syllable segmentation: e.g., "How many syllables (or parts) are in the word coffee?"[12] Syllable completion: e.g., "Here is a picture of a rabbit. I'll say the first part of the word. Can you finish the word ra_____?"[13] Syllable identity: e.g., "Which part of complete and compare sound the same?"[12] Syllable deletion: e.g., "Say finish. Now say it again without the fin"[14] 3 Onset-rime awareness: “Which word does not rhyme: fish, dish, hook?” Spoken word recognition: e.g., "Do these words rhyme: shell bell?"[12] Spoken rhyme detection or rhyme oddity task: e.g., "Which word does not rhyme: fish, dish, hook?" [15] Spoken rhyme generation: e.g., "Tell me words that rhyme with bell?"[13] Onset-rime blending [9] 4 Phonemic awareness: "Say coat. Now say it again but don't say /k/” Alliteration awareness (aka phoneme detection and sound or phoneme categorization): e.g., "Which word has a different first sound: bed, bus, chair, ball?"[16] Phoneme matching: e.g., "Which word begins with the same sound as bat: horn, bed, cup?" [16] Phoneme isolation: e.g., "Tell me the sound you hear at the beginning of the word food" [3] Phoneme completion: e.g., "Here is a picture of a watch. Finish the word for me: wa_____ "[13] Phoneme blending with words or non-words: e.g., "What word do these sounds make: m...oo...n?" [9] Phoneme deletion, also referred to as phoneme elision: e.g., "Say coat. Now say it again but don't say /k/"[14] Phoneme segmentation with words or non-words: e.g., "How many sounds can you hear in the word it?[12] Phoneme reversal: e.g., "Say na (as in nap). Now say na backwards"[9] Phoneme manipulation: e.g., "Say dash. Now say it again, but instead of /æ/ say /I/"[14] Spoonerism: e.g., felt made becomes melt fade[12]
  11. Affiliation Associate Professor of UCSF Child & Adolescent Psychiatry Director of the UCSF Hoeft Laboratory for Educational Neuroscience (brainLENS) Director, CINTEL: UCSF - UC Berkeley – Stanford etc. Scientific Board, UCSF Dyslexia Center Scientific Advisor of the BADM’s CCC, etc.. Research Scientist, Haskins Labs, Yale Univ Adjunct faculty, Keio University School of Medicine (Tokyo) Research Training Harvard, Caltech, Stanford Honors Delivered over 120 remarks, lectures & keynotes including UNESCO, White House, International Mind Brain & Education Society (IMBES, International Dyslexia Association (IDA) 2014 IDA’s Normal Geschwind Memorial Lecturership – one of highest honors in dyslexia research 2015 Transforming Education through Neuroscience Award from Learning & the Brain Foundation and IMBES – one of highest honors in educational neuroscience International coverage in media such as The New York Times, NPR, CNN and the New Yorker. Published over 100 articles. UCSF is a public institution within California, and the only medical school that ranks within the top 5 in world and US rankings for both research and clinical care, making it an ideal institution for rapid translation of research to practice. brainLENS combines cutting-edge, cross-disciplinary research with a deep passion for maximizing children’s potential, particularly as it relates to learning, motivation and resilience. Co-leading efforts to establish CINTEL We love to share the love of neuroscience with children of all ages, and collaborate with teachers, clinicians, families & policy makers.