1. School readiness and brain development: insights from neuroimaging research on early language development and language remediation. Kenneth R. Pugh, PhD President and Director of Research, Haskins Laboratories, and Associate Professor, Yale University School of Medicine

2. Connections between early experience and later language and reading development The focus of this conference is on factors that allow children to realize their fullest abilities and talents. Pre- and post natal environment is crucial to later language and reading development. Major risk factors include: 1) Mother/infant nutrition. 2) Pre-natal drug, nicotine, and alcohol exposure. 3) Neglect and abuse. 4) early stimulation of language and learning.

3. Neglect: Evidence from adoption studies Early neglect can have profound negative consequences on later development. Recent studies have focused on children adopted at different ages from orphanages where neglect was prevalent.

4. http://www.olderchildadoption.com/rad/3-year-old.gif A normally developing brain at 6 and 12 months. Lombroso, P. J. Development of the Cerebral Context: VI. Growth Factors. 1998 Brain images of a normally developing 3 year old and a child suffering from extreme neglect.

5. Participants CT sample n = 54 children (23 boys), 4 - 12 years Time in orphanage: 2 - 75 mos n = 32: E. Europe (Lithuania, Romania, Russia, Ukraine) n = 10: N. Asia (China, Korea) n = 6: Central/S. America (Peru, Columbia, Guatemala and Mexico) n = 6: S.E. Asia (Cambodia, Vietnam). n = 24 (17 boys) non-adopted controls Matched on age, gender, SES Time in U.S.: 15 - 127 mos.

6. Emotional regulation

7. Language results CELF subscales and mos. in institution, r ’s = -.30* to -.40** Receptive Vocabulary (PPVT) and 20-min memory delay: r (43) =.50*** Note: all are in average range; SES as a factor ….

8. 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: Enriched pre-school exposure to phonological (spoken language) and simple orthographic experience is very important in potentially preventing later reading difficulties.

9. 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.

10. 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).

11. 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. Behavioral phenotype in reading disability

12. Brain and Language: Central Sulcus Lateral Sulcus Functions Frontal: Executive, Motor Parietal: Sensation, Spatial representation Temporal: Hearing/Language Occipital: Vision

13. 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

14. 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.

15. 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?

16. MRI: Magnetic Resonance Imaging

17. MRI Brain: axial parallel to floor Brain: sagittal Through the midline Knee Spine

18. Slice Locations

19. Auditory vs Visual Sentence Task Constable, Pugh et al. (2004) common print(red) speech(blue) RH on left side

20. The Reading Circuit (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

21. 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 Disability Occipitotemporal Anterior Temporoparietal Left Hemisphere

22. Normal Readers Dyslexic Readers TD & RD Reading Children (Temple et al., 2003) Frontal & Temporo- parietal Frontal but NO Temporo- parietal

23. Plasticity in Reading Development Anterior Occipitotemporal Temporoparietal Increases in reading skill are associated with increased specialization of ventral LH areas for print

24. 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?

26. P <.0005 FDR >Print >Speech Modality Effect

27. Correlation of PA with BOLD Modality Effect P <.005 FDR

28. Correlation of PA with BOLD Modality Effect P <.005 FDR

29. Correlation of PA with BOLD Modality Effect

30. 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.

31. Plasticity and Remediation in Reading Development Anterior Occipitotemporal Temporoparietal Increases in reading skill are associated with increased specialization of ventral LH areas for print

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

33. 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.

34. 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 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)

35. 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

36. 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.

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

38. 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

39. 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.

40. 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.

41. Conclusions Neuroimaging Good teaching can develop LH reading system

42. 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, Inge Marie Eigstie 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