Studying the Developmental Neurobiology of Reading Using fMRI

1. Studying the Developmental Neurobiology of Reading Using fMRI Bradley L. Schlaggar MD PhD John Merck Fund Summer Institute, July 23, 2003

2. B.L.S. is a Scholar of the Child Health Research Center of Excellence in Developmental Biology at Washington University School of Medicine (HD33688). Acknowledgements Steven E Petersen PhD Tim Brown BS Kristina Visscher BS Kristin Wenger BS Erica Palmer MS Christine Kang MD Darcy Burgund PhD Jim Kelly BS Randy Buckner PhD Avi Snyder MD PhD David Van Essen PhD Fran Miezin MS Mark McAvoy PhD Heather Lugar BS Becky Coalson BS Tara Spevack PhD NIH NINDS NICHDMcDonnell Center for Higher Brain Function Charles A Dana Foundation Burroughs-Wellcome Fund John Merck Scholars Fund

3. Cytoarchitectonic Map of Human Cerebral Cortex From Brodmann,1909

4. How and when does the mature organization emerge?What are the rules?

5. Gross Development of Human Cerebrum From Cowan,1979

6. Why study typical and atypical brain development? • Informs normal function • Developmental disabilities and consequences of brain injury • Generate rational interventions and assay their effects

7. A developmental context “our real teacher has been and still is the embryo ---who is, incidentally, the only teacher who is always right…” Viktor Hamburger (1900-2001)

8. Importance of Reading • Straightforward predictor of success in school and later in life. • Understanding how skilled reading is carried out and acquired… • critical to improving strategies for reading education and • for identifying reading disabled for early and effective remediation

9. Reading… • Taught • Not evolutionarily driven • Disabled reading entirely consistent with normal intelligence (dyslexia).

10. Shaywitz et al 2001 In general… Reading is sub-served by a left hemisphere network of cortical regions for mapping visual (orthographic) information onto auditory (phonological) and conceptual (semantic) representations. • frontal • articulation/word analysis • parieto-temporal • orthographic-phonological word analysis, • occipitotemporal • word form

11. Shaywitz et al 2001 In general… Reading is sub-served by a left hemisphere network of cortical regions for mapping visual (orthographic) information onto auditory (phonological) and conceptual (semantic) representations. • Transition to expertise • Early: parieto-temporal word analysis “dorsal system” • Skilled: occipito-temporal word form “ventral system”

12. Approaches/Tools • Cognitive Psychology • Behavioral Neurology • Cognitive Neuroscience/Functional Neuroimaging

13. Semantic Lexicon Phonological lexicon Object Representation Visual Representation Sub-lexical phonological Representation Acoustic Representation Articulatory Representation Object Text Initial State: Logographic Readingfrom Ramus Speech

14. Semantic Lexicon Phonological lexicon Object Representation Visual Representation Sub-lexical phonological Representation Acoustic Representation Articulatory Representation Object Text Intermediate State: Alphabetic Readingfrom Ramus Sub-lexical Alphabetic Representation Phonological awareness Speech

15. Sub-lexical Alphabetic Representation Semantic Lexicon Phonological lexicon Object Representation Visual Representation Orthographic Lexicon Sub-lexical phonological Representation Acoustic Representation Articulatory Representation Object Text Final State: Orthographic Readingfrom Ramus Speech

16. Approaches/Tools • Cognitive Psychology • Behavioral Neurology • Lesion/behavior • Alexia without agraphia (dom. medial occipital and inferior fibers of splenium of corpus callosum) • Alexia with agraphia (dominant angular gyrus); Gerstman • Cognitive Neuroscience/Functional Neuroimaging

17. Approaches/Tools • Cognitive Psychology • Behavioral Neurology • Cognitive Neuroscience/Functional Neuroimaging

18. Functional MRI • Safe • FDA approved sequences • Non-ionizing • PET, SPECT • Non-invasive 8 year old volunteer in mock scanner

19. The basis of fMRI is the BOLD Effect (blood oxygen level dependent) BOLD Hemodynamic Response Function • deoxyHg paramagnetic; oxyHg not • Neural activity->“luxury perfusion” • [deoxyHg]/ [oxyHg] decreases • Given volume less magnetic • T2 relaxation in given volume slows • T2 change is the “BOLD effect” TIME (SEC) 0 4 14 32 From Josephs, Turner, & Friston 1997

20. Conceptualization of the developing neocortex • Conceptual framework/pendulum • “Nature”: neocortex is entirely hard-wired at birth. • “Nurture”: neocortex is entirely equipotent. • Softer versions of these models emerged in the 1980’s • Rakic: “protomap” (i.e. not a fatemap) • O’Leary: “protocortex” (i.e. not a tabula rasa) • Analogy with the cognitive development literature • Chomsky, Fodor, Pinker,(Kanwisher?): nativist, “modularist” • Elman et al, Quartz & Sejnowski, Johnson, Karmiloff-Smith: connectionist, selectionist, neuro-constructivist

21. Potential Developmental Scenarios • Activation of a nascent adult organization • nativist • Intially “diffuse” organization becomes “specialized” • selectionist • Acquisition and skilled performance are sub-served by different neural mechanisms • Neuro-constructivist/scaffolding

22. Progressive Cell proliferation Migration to definitive locations Selective aggregation Establishment of phenotypic diversity Establishment of complex connections Neuropil expansion Myelination Regressive Restriction of phenotypic potential Cell death Pruning of synapses Elimination of exuberant connections/processes “Cowanian” model of brain development Deprivation of trophic factors W. Maxwell Cowan 1931-2002 Regressive (and Progressive) Events in Building a Brain Cowan et al Science 1984

23. Potential Developmental Scenarios • Activation of a nascent adult organization • nativist • Intially “diffuse” organization becomes “specialized” • selectionist • Acquisition and skilled performance are subserved by different neural mechanisms • Neuro-constructivist/scaffolding

32. Where to begin to study reading development? • Even automatic/expert reading is very complex • Requires the coordination of multiple visual, oculomotor, and linguistic mechanisms. • Start with reading words aloud • Orthography to phonology • Easy to manipulate experimentally

33. Functional neuroimaging and single word reading • A wide variety of lexical tasks examined requiring not only word reading, but also performance of complex operations on single words. • But, relatively little work has been specifically dedicated to the functional neuroanatomy of single word reading.

34. Neuroimaging studies of skilled word reading • Variables manipulated: • frequency, regularity, lexicality, letter case, word length, stimulus degradation, rate, duration • Context: • lexical decision, verb & past tense generation, object naming, simple reading. • Control tasks (for “baseline comparison”): • resting with eyes closed, visual fixation, passive viewing of words, silent reading of words , uttering a pre-determined word in response to consonant strings, false fonts. • Responses: • vocalization, “silent” mouthing, silent reading.

35. Common brain regions for skilled word reading • Encouragingly, despite these experimental differences, a set of brain regions common to single word reading has emerged (Fiez and Petersen 1998, Turkeltaub et al 2002, Palmer et al, in press) 12 published PET and fMRI studies involving reading single words aloud; adapted and updated from Fiez and Petersen 1998

36. Digression; What is the goal of functional imaging? • “In contrast to a localist assumption of a one-to-one mapping between cortical regions and cognitive operations, an alternative view is that cognitive task performance is subserved by large-scale cortical networks that consist of spatially separate computational components, each with its own set of relative specializations, that collaborate extensively to accomplish cognitive functions.” Carpenter et al 2001

37. Localization of Cognitive Operations in the Human BrainPosner, Petersen, Fox, and Raichle 1988 Science • “The hypothesis is that elementary operations forming the basis of cognitive analyses of human tasks are strictlylocalized. Many such local operations are involved in any cognitive task. A set of distributed brain areas must be orchestrated in the performance of even simple cognitive tasks. The task itself is not performed by any single area of the brain, but the operations that underlie the performance are strictly localized…

38. Localization of Cognitive Operations in the Human BrainPosner, Petersen, Fox, and Raichle 1988 Science • “…This form of localization of function differs from the idea that cognitive tasks are performed by a particular brain area. Visual imagery, word reading, and even shifting visual attention from one location to another are not performed by any single brain area. Each of them involves a large number of component computations that must be orchestrated to perform the cognitive task.

39. What is an area? How about a region? • A neocortical area is defined by its afferents, efferents, architecture (cyto-, chemo-, myelo-) and function (e.g. primary motor cortex versus primary somatosensory cortex). • FMRI does not (necessarily) show activation in “areas”. • Check out “The anatomical basis of functional localization in the cortex” by Passingham et al, Nat Rev Neuro 2002

40. What does diffuse/distributed look like? ? ?

41. Methodological Issues in Studying the Development of Reading with fMRI

42. Perceived Barriers • Variability of child brain • too variable to be compared directly with the adult brain. • Performance mismatch on cognitive tasks; children will not perform as well as adults on most tasks. • performance versus processing • These issues are relevant to any group-wise comparison • Adults versus Children • Princeton versus Yale

43. Issues • Anatomical variability across development • Physiological variability across development • Performance differences between adults and children • “Task B problem” • choosing appropriate comparison tasks

44. Strategy • Child-friendly (yet adult-challenging) tasks • lexical processing tasks with overt responding • Event-related design • Relate performance to fMRI measures on trial-by-trial basis. • Code and analyze only correct responses. • Compatible with overt verbal responding.

45. Strategy • Child-friendly (yet adult-challenging) tasks • lexical processing tasks with overt responding • Event-related design • Relate performance to fMRI measures on trial-by-trial basis. • Code and analyze only correct responses. • Compatible with overt verbal responding. • Voxel- and Region-wise (ANOVA) direct statistical comparison in a common stereotactic space • Main effect of time image • Group x time interaction image • Performance-matching • Maturation versus performance • In scanner behavioral data

46. Transformation of adult and pediatric brains into a common stereotactic space 1. Anatomical Variability 2. Functional Variability

47. Comparison of primary sulcus location and general brain shape in children and adultsBurgund et al Neuroimage 2002 • 20 adults, 20 children ages 7 and 8 • Brains placed in adult stereotactic space • Measured: • parts of 10 sulci, distributed across the cortex in both hemispheres • outer surface in transverse, sagittal and coronal planes at selected slice locations

48. There are only small differences between adults and children in sulcus location Burgund et al Neuroimage 2002

49. This is true for variability as well Burgund et al Neuroimage 2002

50. Transformation of adult and pediatric brains into a common stereotactic space 1. Anatomical Variability 2. Functional Variability