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CA Dept of Ed - Neuroscience of Dyslexia

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A talk given at the California Department of Education in the Dyslexia Guidelines Work Group

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CA Dept of Ed - Neuroscience of Dyslexia

  1. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 22. “Rich get richer and poor get poorer (in reading)” Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 22
  23. 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. 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. 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. 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. 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. 28. Before Birth PreSch/K 2nd-4thGr Adult Early identification Preventive intervention Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 28
  29. 29. Reading & Dyslexia | Neural Markers | Definition | Early Identification & Intervention | Conclusion 29

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