LD across early childhood - BioMedical Approaches & Treatment

• Kenneth R. Pugh, PhD

• President and Director of Research,

• Haskins Laboratories, and

• Associate Professor, Yale University School of Medicine

• Perhaps the most practical, near-term synergy between education and cognitive neuroscience …is in the service of predicting reading difficulty and then offering intervention to avoid reading failure.

John Gabrielli, Science 17 July, 2009

• In recent years, research on assessment and treatment of Reading Disability (RD) has become a magnet for the application of new techniques and technologies from genetics, basic neuroscience, cognitive science, and cognitive neuroscience.

• Many findings have been reported showing differences between typically and atypically developing readers at several levels of analysis.

•

Language Reading and BrainLanguage Reading and Brain

• Spoken language is a biological specialization but written language is largely a cultural invention. Moreover, spoken language is mastered naturally in almost all people, without direct instruction:

• but reading is difficult and reading failure occurs in large numbers of children across all written languages.

• No brain specialization for reading.• Implication: Literacy acquisition is a major challenge to brain plasticity.

Reading Disability: Behavioral Reading Disability: Behavioral phenotypephenotype

• Phonological deficits are nearly universal, but what is the underlying cause?

• Proposals include sensory deficits, compromised neural systems for language, metalinguistic deficits, attentional deficits.

• ** It is possible that there are multiple sub-types, with different pathways but a common end-state (phonological processing deficit).

• Neurobiological (brain) research may help address this heterogeneity.

Potential roles for neuroscience Potential roles for neuroscience of reading disabilityof reading disability

1) Neurobiological measures provide mediating levels of analysis between gene and behavioral phenotype. Also constraint on computational models.

2) Sensitivity: A potentially deeper account of individual differences in either typical or atypical development and individual differences in optimal intervention strategies for at-risk children. What works for whom.

3) Early detection of “biomarkers” predictive of risk for atypical development.

The Neurobiology of Reading The Neurobiology of Reading DisabilityDisability

• Genetics:

• A) heritability (co-twin) studies establish a genetic involvement in RD

• B) A number of molecular-genetic investigations (e.g., Fisher & DeFries, 2002) have reported linkages between reading-related processes and regions on chromosomes 2, 3, 6, 15, and 18. These studies are at an early stage thus far.

• Multiple genes likely.

• **Gene/environment interaction shapes cognitive development.

The Neurobiology of Reading The Neurobiology of Reading DisabilityDisability

• Brain anatomy in RD:

• 1) Early post-mortum studies implicate subtle neuronal abnormalities (ectopias) in LH language zones (Galaburda).

• 2) Recent structural MR studies reveal reduced grey matter density in reading-related temporo-parietal regions (Brambati).

• 3) New research examining cortico-cortico pathways with MRI/DTI, suggest white matter tract anomalies (Klingberg, McCandliss), between reading related subsystems.

The Language BrainThe Language Brain

•Damage/lesion studies

•Broca’s area: Thought to be specialized for speech production, grammar

•Wernicke’s area: Thought to be specialized for speech comprehension, semantics

•Implication for reading: skilled reading circuits must support efficient communication between visual areas and these Left Hemisphere language zones

The Neurobiology of Reading The Neurobiology of Reading DisabilityDisability

• Functional brain imaging:

• 1) two major classes of techniques: electrophysiological (EEG; MEG) and hemodynamic (fMRI, PET).

• The former give information on timing of brain activity while the latter provide information on localization. Need both!

Reading Language and BrainReading Language and Brain

• Q) What are the underlying neurobiological mechanisms associated with the development of reading skill?

• Q) What are the neurobiological underpinnings of reading disability (RD)?

• Q) How does training and remediation modify brain organization for printed language in children and adolescents with RD?

Slice LocationsSlice Locations

Auditory vs Visual Sentence Task

Constable, Pugh et al. (2004)

common print(red) speech(blue)

RH on left side

Updated view: The Reading Network Updated view: The Reading Network (Pugh et al., 2005)(Pugh et al., 2005)

IFG MTG/ITG

OT/VWFA

SMG/STG AG

• Hypothesized Role of component circuits•‘Phonological’

•IFG•SMG/STG

•‘Semantic’•MTG/ITG•AG

•Putative ‘Visual word form Area’•“Skill Zone” is phonologically and morphologically tuned

• Frequent finding: A large number of studies indicate that RD readers tend to under-activate both LH temporoparietal and LH ventral (occipitotemporal) regions during reading- and language tasks; this has been seen in several languages to date (Paulesu et al., 2001).

• RH and frontal compensatory shift in RD often reported

Reading DisabilityReading Disability

Occipitotemporal

Anterior

Temporoparietal

Left Hemisphere

Normal Readers

Dyslexic Readers

TD & RD Reading Children (Temple TD & RD Reading Children (Temple et al., 2003)et al., 2003)

Frontal& Temporo-

parietal

Frontalbut NO

Temporo-parietal

Summary of findings in RDSummary of findings in RD

• RD children and adolescents fail to coherently engage left hemisphere (LH) temporoparietal and occipitotemporal regions robustly during reading.

• Additionally, recent structural neuroimaging studies reveal differences in both grey matter density and white matter connectivity in these LH regions.

Next steps in establishing a Next steps in establishing a neurobiological accountneurobiological account

• It is critical that we move beyond identification of structural and functional neuro-phenotypes in RD toward learning models focused on how and why brain differences impede literacy skill acquisition. Focus on how to facilitate learning and plasticity.

• A gene-brain-behavior account will be key to understanding individual differences and eventually tailoring treatment to the brain.

• Treatment studies are key to understanding potential to change brain in RD children.

Plasticity and Remediation in Plasticity and Remediation in Reading DevelopmentReading Development

Anterior Occipitotempor

al

Temporoparietal

•Increases in reading skill are associated with increased specialization of ventral LH areas for print

• RD readers do not tend to show this neurodevelopmental trend.

• Trajectory is rightward and frontward.

• Question: Does remediation normalize this trajectory?

Anterior Occipitotempor

al

Temporoparietal

Remediation in RDRemediation in RD

• Are these under-engaged LH systems fundamentally disrupted, or does observed de-activation reflect an unstable but potentially “trainable” state?

• Can remediation focused on training up phonemic awareness (PA) skills modulate the neurocognitive risk profile in beginning reading.

Testing effects of intensive Testing effects of intensive phonological remediation in RD in phonological remediation in RD in

emergent readersemergent readers

• Overview: In collaboration with Dr. Benita Blachman (Syracuse University) we examined neurobiological changes associated with a nine month intervention emphasizing phonemic awareness, alphabet principle, and vocabulary development in young children (Shaywitz et al., 2004)(Shaywitz et al., 2004).

• 3 Groups: NI (N = 28); RD control (N =12), RD Treatment (N = 32). Each group scanned at baseline (average age = 6.5), one year later (post-treatment), and for the RD Treatment Group at one year follow up.

• (see Simos et al.,2002 Temple et al.,2003 for similar findings with different phonological training protocols)

TrainingTraining

• 50 min tutoring, 5 days per week, 9 months (105 hours total)

• 5 step plan (unscripted) & individualized

• Letter-sound associations• Phoneme manipulation• Reading words• Reading text • Assessment

• Key behavioral result: Reliable improvement on a battery of reading-related tests for the treatment relative to the control RD group (Blachman et al., 2005) after nine months of intensive evidence based training.

• Effects stable at one year follow up.

Treatment Group:

Year 3 (follow-up) minus Year 1

(Pre-Treatment)

Temple et al. (2003): fMRI Data

L. Inferior frontal and L. temporo-parietal activation

Some L.inferior frontal but no L. temporo-parietal activation

Increases in L.inferior frontal and L. temporo-parietal activation and right hemisphere comologues

• We thus have evidence that appropriate training has a normalizing effect on the neurobiological trajectory in emergent in a large percentage of “at risk” readers.

• Plasticity can be strong even in struggling beginning readers. LH posterior system appears to be unstable but trainable in young at risk readers.

ConclusionsConclusions

• Early language development is key to later reading success.

• RD has been associated with a variety of functional and structural brain differences to date. Left hemisphere problems are frequently implicated.

• We need integrative neural models that predict reading acquisition; longitudinal research to establish key gene-brain-behavior links.

• Early and intense remediation can promote good brain development in a large number of reading disabled childre, but we need to learn more about the brains of treatment resistors.

CollaboratorsCollaborators

• Haskins Laboratories: Einar Mencl, Rebecca Sandak, Stephen Frost, Dina Moore, Nicole Landi, Leonard Katz, Jay Rueckl, Jim Magnuson, Donald Shankweiler, Jun Ren Lee, Carol Fowler, Alvin Liberman

• Yale Reading Center: Ken Pugh (Director), Gina Della Porta, Eleanor Tejada, Kelley Delaney, Ashley Zennis, Priya Pugh,

• Yale Center for the Study of Learning and Attention: Bennett Shaywitz, Sally Shaywitz, Karen Marchione, John, Holahan, Jack Fletcher

• Yale University/Diagnostic Radiology: John Gore, Todd Constable, Robert Fulbright, Doug Rothman, Graeme Mason, Pawel Skudlarski, Cheryl Lacadie

• Yale University/Psychiatry: Leslie Jacobsen

• Yale Child Study Center: Elena Grigorenko