Neuroimaging Studies of Adaptive Learning in typically and atypically developing children

1
Neuroimaging studies of language development
reading and reading disabilities

• Kenneth R. Pugh, PhD
• President and Director of Research,
• Haskins Laboratories, and
• Associate Professor, Yale University School of
  Medicine

2

• 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

3
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 languages.
• No brain specialization for reading.
• Implication Literacy acquisition is a major
  challenge to brain plasticity.

4
Language Reading and Brain

• The development of fluent reading skill is
  essential for success in the modern world.
• Significant numbers of children in all countries
  fail to acquire adequate literacy skills.
• For many this is due largely to lack of good
  learning opportunities but for some will reflect
  difficulties that are brain-based (Specific
  Reading Disability).

5
Pre-literacy Risk for Reading Disability

• Language milestones early on are critical for
  adequate reading development later on
• 1) Early receptive and expressive language
  development predicts reading acquisition.
• Phonological Awareness is critical in
  preschoolers.
• Key Pre-school exposure to phonological (spoken
  language) and simple orthographic experience is
  very important in potentially preventing later
  reading difficulties.

6
Reading Disability Behavioral phenotype

• Phonological deficits are 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.

7
Behavioral phenotype in reading disability

• Word identification is slow, labored, and error
  prone in RD (bottleneck for comprehension).
• Early deficits in developing fine-grained
  phonemic awareness predict word reading
  difficulties later on.
• These deficits in phonological awareness impede
  the development of efficient phonological
  assembly routines (grapheme to phoneme mapping)
  which, in turn, places severe limits on word (and
  pseudoword) reading fluency.

8
How do skilled readers recognize words

• 1) Skilled readers can read words fast (approx.
  200 msec.)
• 2) Pseudoword reading is nearly as fast!
• QUESTION Do skilled readers continue to rely on
  sub-lexical phonological assembly?

9
The primacy of sublexical phonology

• Lukatela Turvey 1992Pseudo-associative masked
  priming in naming.
• Prime Mask TARGET
• TOAD FROG
• TOLD FROG

10
The primacy of sublexical phonology

• Lukatela Turvey 1992Pseudo-associative masked
  priming
• Prime Mask TARGET
• TOAD FROG
• TOLD FROG
• TOWED FROG
• TOWEL FROG
• TODE FROG
• TOGE FROG

11
The primacy of sublexical phonology

• Identity Priming (Lukatela Frost and Turvey,
  2003)
• While the best prime for a word is the word
  itself (identity priming) under fast masked
  priming this effect is diminished for
  orthographic to phonological inconsistent (BOWL)
  words relative to consistent (BEND) words.
• Implication of these studies lexical access in
  skilled readers is sensitive to the phonological
  code

12
Implications for reading development

• Struggling readers have difficulty establishing
  phonological coherence. Fluent lexical access
  requires adequate binding of orthography,
  phonology, morphology, and semantics. Phonology
  may be the glue that holds this all together (Van
  Orden et al., 1999)

13
The Neurobiology of Reading Disability

• Genetics
• A) heritability (co-twin) studies establish a
  genetic linkage 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.
• Gene/environment interaction shapes cognitive
  development!

14
The Neurobiology of Reading Disability

• Brain organization in RD
• 1) Post-mortum studies implicate cell
  abnormalities (ectopias) in LH language zones.
  Relevant genes have been targeted (Gruen et
  al.,).
• 2) Morphometry studies are complex but some
  suggest differences in laterality ratios in
  auditory cortex (Hynd and others).
• 3) New directions examine connectivity with DTI,
  suggest fiber tract anomalies (Klingberg,
  McCandliss).

15
(No Transcript)
16
(No Transcript)
17
The Language Brain

• Damage/lesion studies
• Brocas area Thought to be specialized for
  speech production, grammar
• Wernickes area Thought to be specialized for
  speech comprehension, semantics

18
Limitations of lesion studies

• Extreme localization view is simplistic.
• Language processes involve many regions operating
  in dynamic fashion.
• WE NEED TO EXAMINE SYSTEMS LEVEL PROCESSING. NEW
  IMAGING TECHNOLOGIES CAN BE HELPFUL.

19
The Neurobiology of Reading Disability

• Functional brain imaging
• two major classes of techniques
• electrophysiological (EEG MEG)
• hemodynamic (fMRI, PET).
• The former give information on timing of brain
  activity while the latter provide information on
  localization.

20
Potential roles for neuroimaging

• Neurobiological measures provide mediating levels
  of analysis between gene and behavioral
  phenotype.
• 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.

21
Reading Language and Brain Brain mapping

• Q) What are the underlying neurobiological
  mechanisms associated with the development of
  reading skill?
• Q) What are the neurobiological underpinnings of
  reading disability (RD), and how does training
  and remediation modify brain organization for
  printed language in children and adolescents with
  RD?

22
Slice Locations
23
Auditory vs Visual Sentence Task
common
print(red) speech(blue)
RH on left side
Constable, Pugh et al. (2004)
24
The Reading Circuit (Pugh et al., 2005)

• 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

25
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

26
TD RD Reading Children (Temple et al., 2003)
Normal Readers
Frontal Temporo-parietal
Frontal but NO Temporo-parietal
Dyslexic Readers
27
Pugh, et al., (2000), Psychological Science

• A fuller account requires focus not only on
  within-region group differences, but also on
  group differences in patterns of inter-regional
  correlations or functional connectivity (e.g.,
  Horwitz, Rumsey Donahue, 1998).
• 32 adult NI readers vs. 29 adult RD readers.
• Task Hierarchy Two alternative forced choice
  same/different Line (//\\, //\\) Letter case
  (BTbT, BTbT) Single Letter Rhyme (B, T)
  Non-word Rhyme (LETE,JEAT) Word Category
  (CORN,RICE).

28
(No Transcript)
29
Key Finding Given that NWR shares with C
multi-letter processing and with SLR Phonological
analysis the breakdown in FC for NWR appears
relational. Implication LH posterior systems are
weak but not fundamentally disrupted In RD. This
encourages optimism with respect to intervention
effects.
30
Plasticity and learning Developmental
trajectories in NI and RD children (Shaywitz,
Shaywitz, Pugh et al., 2002) N144 (ages 7-17
74 NI controls, 70 RD)
31
Correlating activation with age and skill.

• 1) Correlating brain activation with
  chronological age in NI and RD to examine
  development.
• 2) Correlating activation with reading skill
  (after co-varying out age effects) allows us to
  isolate those neural systems that support fluent
  and accurate reading.

32
(No Transcript)
33
Plasticity in Reading Development
Temporoparietal
Anterior
Occipitotemporal
34
Reading Development Skill Zone in Putative
VWFA
35
Initial reading acquisition

• We need to examine development longitudinally
  with integrated brain/behavior designs.
• We have two ongoing NIH funded longitudinal
  studies asking What are the behavioral and
  neurobiological preconditions for successful
  literacy acquisition?
• Study 1) from 7-9 years examines at risk children
  with multiple levels of analysis (genetics,
  neuroanatomy, neurochemistry, neurocircuitry,
  behavior).
• Study 2) From 5-11 years examines brain/behavior
  trajectories in three languages that vary in
  orthographic depth (English, Finnish, Mandarin
  Chinese).

36
(No Transcript)
37
MR Spectroscopy scanning

• Neurochemicals examined in a region of interest
  centered on medial occipital cortex
• GABA, N-acetyl aspartate (NAA), Creatine (Cr),
  and Glutamate
• Initial analyses of Time 1 data indictate
  significant correlations between MRS, FMRI, AND
  BEHAVIORAL MEASURES. WE ARE NOW TRACKING
  DEVELOPMENT

38
Schematic of fMRI Task
Event-related fMRI match/mismatch judgment via
button press of speech and print targets to a
picture
Mismatch/Match ratio (80-20) Only mismatch
trials included in analyses
39
Key Contrasts

• Modality print vs speech
• Lexicality words vs. pseudowords
• Pronounceability printed pseudowords vs
  consonant strings

40
Effects of Early Language Development Preston et
al., in prep.

• Several studies of late talkers have suggested
  residual deficits in reading in young school-age
  children (Rescorla 2002, 2005, 2009 Scarborough
  Dobrich, 1990)
• Parents complete questionnaire on child/family
  background and childs development
• Asked to report on when child began to Speak 2-3
  word sentences.
• Parent rated child as Early, On Time or Late

41
Talker Group Comparisons on Reading
MeasuresWoodcock-Johnson Tests of Achievement
42
Talker Group Comparisons on Reading
MeasuresGray Oral Reading Test (GORT)
43
Late versus early talkers Brain activation in
reading and speech at at 7.5
p lt .025, FDR corrected
44
(No Transcript)
45
(No Transcript)
46
Phonemic awareness and speech/print integration
(Frost et al,. 2009)

• Phonemic awareness scores reflect reading
  readiness.
• How do children with higher reading readiness
  differ in initial brain organization?

47
Modality Effects
gtPrint gtSpeech Overlap
p lt .001
48
PA x Modality

p lt .01
49
PA x Modality

r 0.44
p lt .01
50
Correlation of PA with BOLD Modality Effect
51
PA x Pronounceability
p lt .01
52
PA x Pronounceability
r 0.57
p lt .01
53
Key finding

• This finding suggests that children who are
  developing normally in reading modify brain
  systems for spoken language processing to become
  available for processing visual graphemes.
• It is crucial to promote learning experiences in
  beginning readers that help to connect spoken
  language and printed language to one another.

54
Comprehension is the goal of most acts of reading.

• But comprehension is not easy to pin down.
• Comprehension reflects
• the reader,
• the text,
• the purpose of reading.

55
Comprehension isnt just about reading

• Depends on general language abilities and memory.
• Implicates all structural elements of language
  that reading shares with speech
• phonologic, morphologic/lexical, syntactic,
  semantic.
• Comprehension is the outcome of multiple
  processes that bridge between knowledge of
  language and knowledge of the world.

56
If a reader does poorly on a reading
comprehension test,

• The reader may lack
• a) Background knowledge and
  vocabulary?
• b) Requisite language abilities?
• c) Sufficient word decoding skills?
• d) Some combination of a, b, and c.

57

• Sentence processing study Shankweiler et al.,
  2008.
• Reading is possible because the language brain is
  supramodal
• Questions
• Where do speech and print streams merge during
• sentence processing?
• 2. Does convergence co-vary with reading skill?

58
Speech-Print Intersection and Differences Non-Ano
malous Baseline Sentences. Skilled readers.
R L
59
Illustrating high and low values of the
Convergence Index
60
Correlation of convergence and skill at dorsal IFG
r .7
61
Plasticity and Remediation in Reading Development
Temporoparietal
Anterior
Occipitotemporal
62

• RD readers do not tend to show this
  neurodevelopmental trend.
• Trajectory is rightward and frontward.
• Question Does remediation normalize this
  trajectory?

Temporoparietal
Anterior
Occipitotemporal
63
Remediation 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.

64
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.,
  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)

65
Training

• 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

66

• 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.

67
Treatment Year 2 Vs RD Control Year 2
Treatment Year 2 Vs Treatment Year 1
RD Control Year 2 Vs RD Control Year 1
68
Treatment Group Year 3 (follow-up) minus Year 1
(Pre-Treatment)
69
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
70

• We thus have evidence that appropriate training
  has a normalizing effect on the neurobiological
  trajectory in emergent at risk readers.
• Plasticity is strong even in struggling beginning
  readers. LH posterior system appears to be
  unstable but trainable in young at risk readers.

71

• What about older RD readers?
• Children whose RD persists may be more severely
  congenitally effected.
• Also, years of reading experience may limit
  plasticity in older RD kids.
• First question Can we demonstrate potential
  reading responsiveness in LH systems in
  adolescent RD readers?

72
Adolescent RD vs. NI study Repetition (learning)
Effects (Pugh et al., 2009, JOCN)

• To examine potential LH posterior functionality
  in RD readers we examined repetition effects on
  words (seen 6 times over the course of a scanning
  run).
• We know that RD readers will benefit from
  repetition behaviorally.

73

• Effects of repetition on behavior will be similar
  for both groups, but
• For NI with generally more stable LH system,
  repeated words will be associated with reduced
  activation (increased neural efficiency).
• For RD, with generally unstable LH system,
  repeated words will show increased activation in
  unstable LH posterior regions.

74
characterization

• Repetition Study
• present 56 words in each 5-minute imaging run
  judge animacy
• 6 of these are presented 6 times pseudorandomly
  throughout
• 20 intermixed novel words serve as controls
• repeat up to 10 runs with different words
• subjects
• NI readers RD readers
• N 18 14
• age 14.7 12.8
• WA 71 24
• FSIQ 112 104

75
(No Transcript)
76
Group X Rep Interaction
77
LH Occipitotemporal
78
LH STG
79
LH IFG
80
Theoretical characterization
Learning Curve Hypothesis Activation levels
(BOLD) follow an inverted-U shaped function with
respect to familiarity and/or skill in processing
words.
good readers
poor readers, high-freq words
U
good readers, high-freq words
poor readers
gt activation gt
good readers, repeated words
gt familiarity gt
81
Adaptive learning beyond repetition

• These findings suggest that even in older readers
  the LH language areas are potentially trainable
  and capable of learning and plasticity.
• Repetition demonstrates latent functionality in
  RD but hardly constitutes an ideal remediation
  strategy.
• We are currently investigating how different
  kinds of training contexts modulate brain
  responses in these LH regions. Focus is on what
  works for whom (e.g., Sandak et al., 2004).

82
Looking ahead
How does speech-print integration come about?
How is the brain structured by different
learning experiences and instructional
environments? Which structures within the
inferior frontal region and elsewhere support the
skill-induced convergence of speech and print?
How are plastic connections within the
language network modulated by skill
differences?
83
Conclusions

• Early language development is key to later
  reading success.
• LH circuit develops with learning.
• Early and intense remediation can promote good
  brain development even in severe reading
  disabled children.

84
Collaborators

• 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, Mark Seidenberg
• Yale Reading Center Ken Pugh (Director), Gina
  Della Porta, Eleanor Tejada, Kelley Delaney,
  Ashley Zennis, Anish Kurian, Heatherly Carlson,
  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