Ele lena L a L. Grig rigore renk nko Yale ale Unive Universi - - PowerPoint PPT Presentation

Dysle yslexia To a Today: ay: Lesso ssons ns fro from m the Past Past and and Hopes Hopes for

• r the

the Futu ture Ele lena L a L. Grig rigore renk nko Yale ale Unive Universi rsity

I I am fa m faci cing a an n impo impossible ta task… k…

elena.grigorenko@yale.edu

Goal

• al &

& Struct Structure

• Goal

– Summary of the field

• Neurobiological and genetic correlates of …

– Developmental dyslexia – Specific reading disability (disabilities) – Reading difficulties – Reading

• Structure

– Eight statements

• Numbered

Cont Contex ext

Reading (as is the case with any acquired academic skill) is a complex skill that evolves from a solid foundation of componential cognitive skills.

Poi Points ts of

• f the

the ei eight statem ght statemen ents

• Bad teaching &

reading

• Biological bases of

reading

• Correlation & causation
• Reading & the brain

– In SRD/DD – In reading acquisition – In remediation

• Reading & the genome

– Where – What – How

• Heritable ≠

unmodifiable

• Environmental

influences on the genome

• SRD/DD assessment

and the relevance of RTI to studies of the brain and the genes

SR SRD/DD D/DD does es no not aris arise fro e from m bad bad t teac eachi hing g (1) (1)

SR SRD/DD D/DD does es no not aris arise fro e from m bad bad t teac eachi hing

• SRD/DD has a specific etiology & genesis
• 15-20% school-aged children have

difficulties reading, but only 85% of them have SRD/DD

– http://www.interdys.org, Fact Sheet #62-05/00

• Bad teaching makes SRD/DD worse

– But bad teaching does not cause SRD/DD

• Reading problems generated by bad

teaching/bad schooling are preventable and remediable

“True “True” SR ” SRD/DD D/DD is is bio biolo logic gicall lly y gro groun unded (2) (2)

“True “True” SR ” SRD/DD D/DD is is bio biolo logic gicall lly y gro groun unded

• SRD/DD has its own biological

signature

– Where?

• In the eyes
• In the blood
• In the belly
• In the brain
• In the genes
• SRD/DD is a disorder of genetic origin

with a basis in the brain

We We kno know w a a lo lot abo about ut the e correl elates tes of SR f SRD/DD in D/DD in the e brain brain and and in in the genes e genes (3 (3)

SR SRD/DD D/DD in in the brain & e brain & in in the e genes genes

• We know a lot about the correlates
• We know little about the causes
• What we know is

– Who the “players” are – Where things are happening

• What we do not know

– How things are happening – Why they are happening

Th The brain e brain does es no not h have “t ave “the e part part(s (s)” fo )” for r rea readin ing g (4) (4)

Th The brain e brain does es no not h have “t ave “the e part part(s (s)” fo )” for r rea readin ing

• Reading in the brain unfolds via a

complex chain of activation of various structures, which is distributed in space and in time

– There is no brain “locus” for reading, but there is a “reading brain” – The “reading brain” is a developmental stage of the brain – We are born with an “illiterate brain” that has the capacity to become a “reading/literate brain”

• This chain is malleable

– Developmentally – As a result of interventions

Readi Reading brai ng brain n (1) (1)

• A number of areas appear

to be engaged in reading

• Robust multivariate

differences between people w and w/o difficulties

• Developmental differences

(before and after the

• nset of reading)
• Differences between

remediated and nonremediated readers

Readi Reading brai ng brain n (2) (2)

Elliott & Grigorenko, 2014

Readi Reading brai ng brain n (3) (3)

Elliott & Grigorenko, 2014

Readi Reading brai ng brain n (4) (4)

Elliott & Grigorenko, 2014

Il Illustr lustrati tion One:

• n One:

Pa Pathwa thway(s y(s) f ) for rea

• r readin

ing

Elliott & Grigorenko, 2014

Abnormal activity: Phonological processing (rhymes, segmentation) Word reading Attenuated activity: Single words Pseudowords Rapid naming Enhanced activity: Articulatory recodibng Word reading Pseudoword reading

Illustr llustration tion O One: ne: Pathw Pathway(s (s) fo ) for r read reading

Schulte-Körne et al., 2007

Illust strati ration

• n Two:

Two: Readi Reading ng ac acqu quis isiti tion

Schlagger & McCandliss, 2007

Simos et al., 2002

Illust strati ration

• n Th

Three: ree: Readi Reading ng i interv nterventi ention

• n (1

(1)

Illust strati ration

• n Th

Three: ree: Readi Reading ng i interv nterventi ention

• n (2)

(2)

Elliott & Grigorenko, 2014

The The readi reading brai g brain

• Is a dynamic system that

– Is characterized by temporal and spatial distribution of activity – Is sensitive to the nature of stimuli – Changes developmentally – Is malleable in response to intervention

Both t th typic pical and l and at atypi pical (DD) (DD) read reading g are are familial familial and and herita eritabl ble (5) e (5)

Read eadin ing g is is familial and familial and herita eritabl ble

• Family studies

– High risk for relatives of probands with DD – High relative risk

• Twin studies

– Reading itself and all its components (e.g., phonemic awareness, decoding, single-word reading) are heritable

Illustr llustration tion O One: ne: Famil Family St y Stud udie ies

• First observations on the familiality of DD

– Thomas, 1905; Orton, 1937; Norrie, 1939; Kagen, 1943

• Multiple prospective, retrospective, and

concurrent family studies

– Familiality is very high – Estimates (Ziegler et al., 2005):

• Spelling (cutoff at 10%): GRR S = 3.813 (CI:

3.217–4.437)

• Reading (cutoff at 10%): GRR S = 3.516 (CI:

2.825–4.257)

Illustr llustration tion Two Two: : Twin st Twin stud udies es

0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1

The C e Colorado L

• Lear

arni ning ng D Disabi abilities lities Re Resea earch C Cent nter er

Davis et al., 2001 Gayán & Olson, 2001, 2003

The L e London ndon Twin S Studies ies

Stevenson et al., 1987 Hohnen & Stevenson, 1999

Twins E s Early Devel elop

• pment

ental S al Study (TE (TEDS DS)

Harlaar, Spinath, Dale, & Plomin, 2004

Grigorenko, 2004

h2 c2 e2

There i re is no “

• “gene f

ne for r r read eading ing”

Read eadin ing g the geno e genome me fo for r “rea “readin ing” genes g” genes

• There is no single “gene” for reading
• There are many genes that

contribute to the formation of the biological bases of both typical and atypical (SRD/DD) reading acquisition

• These genes exert small effects
• These genes are multi-task genes

Illustr llustration tion O One: ne: Wh Where in e in the geno e genome me (1) (1)

Schulte-Körne et al., 2007

Il Illustr lustrati tion One:

• n One:

Wher Where i in n the the gen genome

• me (2)

(2)

Elliott & Grigorenko, 2014

Illustr llustration tion Two Two: Cand : Candidate genes te genes

• DYX1C1 (also known as EKN1)

– Dyslexia Candidate Region 1, Candidate 1

• KIAA0319

– Human Unidentified Gene-Encoded (HUGE) protein, cDNAs identified in the Kazusa cDNA sequencing project

• DCDC2

– Doublecortin domain containing 2

• SEMA6D

– Sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6D

• ROBO1

– Roundabout 1

Candidate gene expression patterns in the brain

Paracchini et al., 2007

Disrupted migration in the developing rat neocortex

Joe LoTurco et al., 2006-2007

Prot Protei ein-pr prot

• tein

in interac acti tion (

• n (1)

Prot Protei ein-pr prot

• tein

in interac acti tion (

• n (2)

Illustr llustration tion Th Three ee: : Ty Types pes o

• f

f genes genes

• The “migration” genes can, indeed, contribute to

the initial anatomical differences characteristic

• f the brains of individuals with SRD/DD; they

cannot explain the whole story

• There are many types of genes and genetic

mechanisms that could potentially be involved in the manifestation of SRD/DD

– Brain development – Brain connectivity – Signal transduction

Key Key indi ndicat cators (1) (1)

Familial Congenital Genetic Molecular CDCV 1900s 1950s 1960s-… 1983-… CDRV Heritable Differentiated by… (age, ethnicity/language, severity, IQ, environment –SES, instruction,…) Oligogenic Substantial relative risk regions genes & markers SV

Key Key indi ndicat cators (2) (2)

AC & NGS Transcriptome Methylome Modeling Genome Exome In vivo In vitro iPSC

Di Discovery scovery cycl cycle

Acquis isit itio ion Develo elopmen ent Cha Change Pri rime S Stru tructure (Genom nome) Epi ( Epi (der erived) Struc uctur ure (Epigen igenome) Expresse ssed Struc uctur ure (Transcript iptome) e) In v n vitr tro models els In vi vivo vo models ls Behavi avior

Heritable ≠ Unmodifiable (6)

Heritable ≠ Unmodifiable

• Mean effects
• Structured environment

(controlling the variance)

Environ Environme menta tal influen l influences o

• n

n genes genes (7) (7)

Environ

• nmen

enta tal in influences ces on gen genes es

• Nonlinear G-by-E effects

– Gene–environment correlations refer to genetic effects on individual differences in liabili ability to to exposure sure to particular environmental circumstances.

• Evidence suggests that environmental risk exposure is NOT randomly

distributed

– Gene–environment interactions concern genetically influenced individual differences in se sensit nsitivity to specific environmental factors.

• Remarkable individual differences in vulnerability to a variety of types of

environmental hazards

• Regulatory effects
• Epigenetic effects

SR SRD/D /DD a asse ssessment a ent and nd th the e releva elevance of nce of RTI to s to stud tudie ies s of

• f th

the b e brain in and th nd the genes e genes ( (8) 8)

Further Further Task Tasks

• Inclusion of/transfer to other learning

disabilities (e.g., dyscalculia, SMD) within the same framework of “pedagogical neuroscience”*;

• Development of ‘tools’ of pedagogical

neuroscience [general and specific assessments (i.e., educational, neuropsychological, genetic, and neuronal)];

• Development of a meta-theory of pedagogical

neuroscience for multiple domains of achievement.

*Fawcett & Nicolson, 2007

Conclusions usions

• There is an overwhelming amount of evidence suggesting that

reading difficulties are heterogeneous and that many are due to bad schooling/teaching.

• Yet, there is a group of children in whom those difficulties cannot be

explained only by bad/unfortunate schooling experiences.

• Such kids are typically characterized by a family history of

learning/reading problems (as compared to the “generic” category of bad readers).

• The skills of such children are typically harder to remediate.
• Accurate and theory-informed assessment/phenotyping of children

with SRD/DD is crucial for establishing biological (including genetic) correlates and causes of SRD/DD.

• The concept/approach of RTI might be informative in differentiating

“true” from teaching-based reading problems. Independent schools, where the ideology/pedagogy of RTI unfolds in reality as everyday practices are especially important for making ground-breaking contributions to the search for the biological foundations of SRD/DD.