1 Neuroimaging Studies of Cognitive Development: Insights from Reading Research Kenneth R. Pugh, PhD Yale University School of Medicine and Haskins Laboratories, New Haven CT.

2 Collaborators Haskins Laboratories: Einar Mencl, Rebecca Sandak, Stephen Frost, Dina Moore, Stephanie Mason, Leonard Katz, Jay Rueckl, Donald Shankweiler, Annette Jenner, Jun Ren Lee, Carol Fowler, Alvin Liberman Yale Reading Center: Ken Pugh (Director), Gina Della Porta, Kelley Delaney, Vanessa Dinicola, Priya Pugh, Michael Kochis 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, Pawel Skudlarski, Cheryl Lacadie

3 Why study brain? Reasons vary with discipline (e.g.,neuroscience, cognitive science, development or educational psychology) 1) Heritability studies suggest complex gene/environment contributions to atypical development. Neurobiological measures (e.g., measures of neuroanatomy, neurochemistry, or functional organization) yield mediating levels of analysis between gene and behavioral phenotype. 2) Better computational models: neural constraints from cooperative and competitive dynamics. 3) A potentially better 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. 4) Early detection of biomarkers associated with atypical cognitive development.

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 experience but for some will reflect difficulties that are brain-based (Reading Disability).

5 Outline of talk 1) Neurobiological research must be grounded by solid cognitive/behavioral knowledge of strengths and weaknesses in typically and atypically developing readers. 2) Mapping the reading circuit in typically or atypically developing readers: Basic taxonomy and developmental trajectories. 3) Mapping the reading circuit in typically developing readers:Sub- specialization across the reading circuitry. 4) Mapping the reading circuit in typically developing readers: Tradeoffs and dynamic changes associated with learning. 5) Remediation and plasticity in struggling (RD) readers. 6) New directions: multiple levels of analysis, cross linguistic accounts, early identification of risk factors.

6 How do skilled readers recognize words 1) Skilled readers can read words fast (approx msec. to initial lexical acess) 2) Pseudoword reading is nearly as fast! Fluency depends on adequate integration of orthography, phonology, and semantics.

7 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. Impaired Word recognition in reading disability

8 Outline of talk 1) Neurobiological research must be grounded by solid cognitive/behavioral knowledge of typical and atypical strengths and weaknesses. 2) Mapping the reading circuit in typically and atypically developing readers: Basic taxonomy and developmental trajectories. 3) Mapping the reading circuit in typically developing readers:Sub- specialization across the reading circuitry. 4) Mapping the reading circuit in typically developing readers: Tradeoffs and dynamic changes with learning. 5) Remediation and plasticity in struggling (RD) readers. 6) New directions: multiple levels of analysis, cross linguistic accounts, early identification of risk factors.

9 Language 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. Implication: Literacy acquisition is a major challenge to brain plasticity.

10 Slice Locations

11 Auditory versus Visual Sentence Task Constable, Pugh et al., (2004)

12 Initial ModelIndividual Regions Pugh et al., 2000

13 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 Reading Disability Occipitotemporal Anterior Temporoparietal Left Hemisphere

14 Normal Readers Dyslexic Readers TD & RD Reading Children (Temple et al., 2004) Frontal & Temporo- parietal Frontal but NO Temporo- parietal

15 Reading development: Establishing skill-related trajectories in NI and RD children (Shaywitz, Shaywitz, Pugh et al., 2002) (n= 144; ages 7-17)

16 Correlating activation with age and skill. 1) Correlating brain activation with chronological age in NI and RD. This is aimed at addressing the question of whether neuro-developmental trajectories are similar or dissimilar in the two cohorts. 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.

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18 Reading Development: “Skill Zone” in Putative VWFA Woodcock-Johnson Word Attack Activation

19 Beginning TD readers activate a widely distributed set of regions including temporoparietal and anterior sites. Plasticity in Reading Development Anterior Occipitotemporal Temporoparietal Increases in reading skill are associated with increased specialization of ventral LH areas

20 Overview of talk 1) Neurobiological research must be grounded by solid cognitive/behavioral knowledge of typical and atypical strengths and weaknesses. 2) Mapping the reading circuit in typically and atypically developing readers: Basic taxonomy and developmental trajectories. 3) Mapping the reading circuit in typically developing readers:Sub-specialization across the reading circuitry. 4) Mapping the reading circuit in typically developing readers: Tradeoffs and dynamic changes with adaptive learning. 5) Remediation and plasticity in struggling (RD) readers. 6) New directions: multiple levels of analysis, cross linguistic accounts, early identification of risk factors.

21 Initial ModelIndividual Regions

22 Developing a more fine-grained taxonomy (Pugh et al., 2005) Using multiple tasks (and by manipulating orthographic, phonological, morphological, and semantic variables) we hope to develop a more detailed account of sub-specializations in the major LH reading systems (e.g.,determine which sub-regions are phonologically, morphologically, or semantically “tuned”). Provides a more precise foundation from which to interpret RD differences.Provides a more precise foundation from which to interpret RD differences. Major focus is on the “tuning” characteristics of the skill correlated VWFA and yoked regions. Garner’s principle of converging operations*General Design feature: Multiple experiments, each manipulating demands on a given factor in different ways, allows us to implement Garner’s principle of converging operations

23 Expt. 1: Comparison of semantic vs. phonological priming We used a double lexical decision task with 20 NI adolescent readers: Prime types: BRIBE-TRIBE (O and P similar); COUCH-TOUCH (O similar, P dissimilar), OCEAN- WATER (semantically related) vs. HORSE-BRIBE (unrelated control).

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25 Phonologically-tuned subsystems (Pugh et al.,2005) Across seven studies identical voxels in the supramarginal gyrus (within the temporoparietal system), IFG (within the anterior system) and the Putative VWFA (“Skill Zone” within the occipitotemporal system) showed phonological tuning characteristics. * A crucial functional linkage between the skilled-related “VWFA” and more phonologically-analytic SMG and IFG regions is implied.

26 Semantically-tuned subsystems By contrast, the angular gyrus (within the temporoparietal system) the middle/inferior temporal gyrus (within the ventral system), and ventral sites in frontal lobe, appear to have more abstract lexico-semantic functions across our studies (see Price et al., for similar claims). Key: individual differences in activation patterns across subsets of these regions may be linked to individual differences in core deficits in behavioral performance, suggesting different approaches to remediation.

27 Updated view: The Reading Network 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

28 Outline of talk 1) Neurobiological research must be grounded by solid cognitive/behavioral knowledge of typical and atypical strengths and weaknesses. 2) Mapping the reading circuit in typically developing readers: Basic taxonomy and developmental trajectories. 3) Mapping the reading circuit in typically developing readers:Sub- specialization across the reading circuitry. 4) Mapping the reading circuit in typically developing readers: Tradeoffs and dynamic changes with adaptive learning. 5) Remediation and plasticity in struggling (RD) readers. 6) New directions: multiple levels of analysis, cross linguistic accounts, early identification of risk factors.

29 Implications of tradeoff and adaptive learning studies An adequate theory, whether behavioral or neurobiological must be able to account not just for “main effects”, but instead such models stand or fall on their handling of complex interactions. The data on tradeoff and adaptive learning, properly integrated into computational models, can yield key insights into individual differences in performance and development.

30 Frost, Mencl, Sandak, Moore, Mason, Rueckl, Katz, & Pugh (2005). Can we identify the neural signature of the trade-off between semantics and phonology? Phonology: The consistency effect. Consistent words (e.g., BEND) have a one to one orthographic to phonology mapping are named more rapidly than inconsistent words (e.g. BOWL)which have a one to many O > P mapping. Semantics: Imageability. Concrete words (e.g., HORSE) have “richer” semantics and are named more quickly than abstract words (E.G., TRUTH). Frequency: Word familiarity; high frequency words are named more quickly than low frequency words

31 Modulation of consistency effect by frequency and imageability consistency effect1) Inconsistent words (e.g.,BOWL) are named more slowly than consistent words (e.g.,BEND) in general; this is referred to as the consistency effect. 2) But this consistency effect on latencies is reduced for both high frequency and/or for high imageable words. Top down modulation on phonological assembly (tradeoff) is seen behaviorally. Q) WHAT ARE THE BRAIN CORRELATES OF THIS THREE WAY INTERACTION?

32 Design Go/no-go naming in a block fMRI session Stimuli: Words (Consistency x Imageability x Frequency) Pseudowords

33 IFG = Consistency MTG =Imageability Region of interest analysis (Main effect)

34 Implication: A tradeoff in activation patterns between semantically and phonologically tuned subsystems, suggests complex interactions among subsystems in response to stimulus characteristics. Activation patterns directly mirror latency and accuracy data in this three way interaction between consistency, imageability, and frequency.

35 Sandak, Mencl, Frost, Rueckl, Katz, Moore, Mason, Fulbright, Constable, & Pugh (2004). Isolating the neurobiological signature of adaptive learning What roles do distributed brain systems play in learning to read new words? Three training conditions with multiple exposures: focused on orthographic, phonological, or semantic features.

36 Design Pre-MRI behavioral training: NOIST CCVCV PLOTE BROAT LANG BUG Orthographic PhonologicalSemantic

37 Behavioral Results: transfer to simple naming Pilot cohortfMRI cohort

38 fMRI Session: Participants simply named: trained pseudowords untrained (novel) pseudowords real words (high- & low-imageable)

39 Effect of Phonological Training z= Higher activation Lower activation Conjoint p <.01, uncorrected R L

40 Effect of Semantic Training z= Higher activation Lower activation Conjoint p <.01, uncorrected R L

41 Implications Reinforcing different dimensions (e.g. phonological or semantic) facilitate word learning via different neural pathways. Deficits in one or another pathway in subtypes of poor readers might suggest different training foci. *Note: follow-up study recently examined combined training and showed greater learning with combined phonological and semantic conditions.

42 Neural Dynamics: Tradeoffs and Adaptive Learning We need neurobiologically grounded computational models of reading development to help us make sense of learning dependent decreases and increases in brain responses, and to more adequately account for individual differences. Neuroimaging Computational Modeling

43 Outline of talk 1) Neurobiological research must be grounded by solid cognitive/behavioral knowledge of typical and atypical strengths and weaknesses. 2) Mapping the reading circuit in typically developing readers: Basic taxonomy and developmental trajectories. 3) Mapping the reading circuit in typically developing readers:Sub- specialization across the reading circuitry. 4) Mapping the reading circuit in typically developing readers: Tradeoffs and dynamic changes with adaptive learning. 5) Remediation and plasticity in struggling (RD) readers. 6) New directions: multiple levels of analysis, cross linguistic accounts, early identification of risk factors.

44 Beginning readers activate a widely distributed set of regions including temporoparietal and anterior sites. Plasticity in Reading Development Anterior Occipitotemporal Temporoparietal Increases in reading skill are associated with increased reading specialization at ventral LH zones.

45 RD readers do not tend to show this neurodevelopmental trend. Trajectory is rightward and frontward. Question: Does intervention normalize this trajectory? Anterior Occipitotemporal Temporoparietal

46 Testing effects of intensive phonological remediation in RD in emergent readers (Shaywitz et al., 2004)Overview: In collaboration with Dr. Benita Blachman (Syracuse University) we examined neurobiological changes associated with a nine month intervention emphasizing phonological 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., Temple et al., and Eden et al for similar intervention data with different phonological training protocols)

47 Testing effects of intensive phonological remediation in RD in emergent readers 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.

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49 Treatment Group: Year 3 (follow- up) minus Year 1 (Pre- Treatment)

50 What have we gained from these neurobiological studies of remediation in at risk readers? The identification of a neurobiological signature of successful intervention (LH posterior increases) yields a potentially very sensitive outcome measure to help discriminate between different approaches that might all produce some transient gains in reading performance.

51 What is missing to date? Limitation of extant remediation studies: Contrast of single intervention with no-treatment control gives no information on treatment resistors (individual difference focus is needed). We must use designs that contrast multiple interventions and examine learner/intervention- type interactions. What works for whom.

52 Supported by the National Institute of Child Health and Human Development (NICHD) and by the Office of Vocational and Adult Education (OVAE) and the Office of Special Education and Rehabilitative Services (OSERS) of the U. S. Department of Education. Adolescent Reading Project Educational Testing Service Haskins Laboratories Kennedy Krieger Institute

53 Primary Question What instructional approach is most effective for struggling adolescent readers with particular types of skills and backgrounds? (What works for whom?) 1.To learn more about what struggling adolescent readers are like with regard to their reading skills, reading-related cognitive skills, and brain activation patterns. 2.To provide 3 kinds of reading intervention and compare their effectiveness for improving reading skills of adolescents with different initial behavioral and neurobiological profiles. 3.To see what kinds of behavioral and neurobiological changes accompany improvements in reading, and under what conditions these changes occur. Major Aims:

54 30% fluencydecoding 70% Corrective Reading (CR) Highly scripted, systematic phonics curriculum. Word recognition efficiency and text-reading fluency are practiced using decodable passages. 90% fluency 10% Guided Repeated Reading (GRR) Lessons include tutor modeling, shared reading, and multiple student readings of passages. Texts are selected for appeal to adolescents. Embedded phonics instruction occurs occasionally as needed. decoding 40%60% fluency Decoding & Fluency Training (DeFT) Combination of CR and GRR in alternation by the same tutor. The Three Approaches to Intervention Students and tutors are randomly assigned to a program.

55 N=13 N pre/post training scans (across training method) T2 > T1 changes

56 Outline of talk 1) Neurobiological research must be grounded by solid cognitive/behavioral knowledge of typical and atypical strengths and weaknesses. 2) Mapping the reading circuit in typically developing readers: Basic taxonomy and developmental trajectories. 3) Mapping the reading circuit in typically developing readers:Sub- specialization across the reading circuitry. 4) Mapping the reading circuit in typically developing readers: Tradeoffs and dynamic changes with adaptive learning. 5) Remediation and plasticity in struggling (RD) readers. 6) New directions: multiple levels of analysis, cross linguistic accounts, early identification of risk factors.

57 Next steps: Going beyond description. A mediating level of analysis in linking behavioral variation to the genetic variation (sub-group identification is critical). Functional imaging is descriptive of brain state, not inherently explanatory. (note new developments in genetics, sMRI, DTI, spectroscopy, etc. to get closer to mechanism).

58 New NIH funded projects ( ; Ken Pugh,PI) 1) Longitudinal tracking study (ages ) Focus is on identifying genetic, neuroanatomic, neurochemistry, neurociruitry, behavioral relations over the course of reading development in typically developing and high risk childen. The primary goal is to develop a better understanding of brain building mechanisms in RD (why RD readers develop a poorly structured LH system for reading).

59 Next steps: Cross Linguistic research Cross-linguistic developmental studies will allow us to: 1) Identify language specific and language invariant aspects of typical development. Does the relative weighting of different regions at different stages vary systematically as a function of factors such as orthographic depth? 2) Identify language invariant bio-markers of risk for RD (e.g., ventral pathway).

60 New NIH-funded project ( ; Haskins PO, Pr. 3 Pugh PI) 2) Longitudinal tracking (ages and ages ). Comparable data will be acquired over this critical developmental period for children learning to read in very different languages (English, Finnish, Chinese). We seek to understand language invariant factors in typical and atypical reading development. Different writing systems result in somewhat different profiles in RD, yet in all RD kids are reading in a non-fluent manner.

61 Why study brain? 1) A mediating level of analysis between genes and behavior. 2) Better computational models: neural constraints. 3) A potentially better account of individual differences in either typical or atypical development. 4) A potentially better account of individual differences in response to intervention for at-risk children. What works for whom.

62 Adolescent RD learning and plasticity: Repetition Effects We compared NI and RD readers on the linear effects on words seen 6 times over the course of a scanning run. Given the previous tradeoff data we anticipated linear decrease in NI (replicating Katz et al., 2005) but linear increase in RD.

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64 Implications of NI/RD differences on effects of facilitatory variables 1) The phonologically-tuned subsystem in adolescent RD appears to be poorly trained but not fundamentally disrupted. 2) Factors that facilitate performance, such as semantic support or repetition can increase the coherence of processing in this subsystem. Ideal training in this population will strengthen phonological coherence and generalize to new items.