LD across early childhood - BioMedical Approaches &
• Kenneth R. Pugh, PhD
• President and Director of Research,
• Haskins Laboratories, and
• Associate Professor, Yale University School of
• 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 re cent years, res earch on assessment
and treatment of R
eadin g Disabilit y
(RD) has b ecome a ma g net for the
application of new t
echniques and
technolo gies from g enet ics, basic
neuroscien ce, co gnitive science, and
co gnitive neuroscie n ce.
 Man y findin g s ha ve b een reported
showin g differe n ces be tween typicall y
and at ypicall y developi ng read ers at
several le v els of anal ysis .
Language 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
• No brain specialization for reading.
• Implication: Literacy acquisition is a major
challenge to brain plasticity.
Reading Disability: Behavioral phenotype
• 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 of
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 Disability
• 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
The Neurobiology of Reading Disability
• 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 temporoparietal 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 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
The Neurobiology of Reading Disability
• 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 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 Locations
Auditory vs Visual Sentence Task
RH on left side
print(red) speech(blue)
Constable, Pugh et al. (2004)
Updated view: The Reading Network (Pugh
et al., 2005)
• Hypothesized Role of
component circuits
• ‘Phonological’
• ‘Semantic’
• AG
• Putative ‘Visual word form
• “Skill Zone” is phonologically
and morphologically tuned
Reading Disability
• 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
Left Hemisphere
TD & RD Reading Children (Temple et
al., 2003)
Normal Readers
Dyslexic Readers
& Temporoparietal
but NO
Summary 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
neurobiological 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 Reading
• 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
• Question: Does
remediation normalize this
Remediation in RD
• Are these under-engaged LH systems
fundamentally disrupted, or does observed deactivation 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 phonological
remediation in RD in emergent 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.,
• 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 (posttreatment), 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)
• 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
• Key behavioral result: Reliable
improvement on a battery of readingrelated tests for the treatment
relative to the control RD group
(Blachman et al., 2005) after nine
months of intensive evidence based
• Effects stable at one year follow up.
Year 3 (followup) minus Year
1 (PreTreatment)
Temple et al. (2003): fMRI Data
L. Inferior frontal and
L. temporo-parietal
Some L.inferior frontal
but no L. temporoparietal activation
Increases in L.inferior
frontal and L. temporoparietal activation and
right hemisphere
• 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.
• 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 genebrain-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
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

Neuroimaging Studies of Adaptive Learning in typically …