1. Different patterns of improvement in phonological dyslexia evidence from two ERP studies Michel Habib, M.D. University Hospital La Timone Marseilles

2. Phonological impairment Grapheme phoneme conversion Reading impairment Impaired phonological representations Low level auditory defect Phonological awareness Verbal short-term memory Rapid automatized naming Clinical evidence Experimental evid. electrophysiological

3. Two auditory evoked potential studies Study 1 : early auditory evoked potentials in adults listening to voiced/unvoiced pairs : study of the time course of the EEG scalp response according to a method developed from intracranial cortical recordings (Liégeois-Chauvel et al.) Study 2 : late potentials obtained in children before and after specific phonological training using stimuli previously used to explore the neural events accompanying cognitive integration of prosodic variations (Besson et al.)

4. Study 1 : auditory evoked potenitals (AEP) following perception of ba/pa contrasts ba/ stimulus recorded from a female native French speaker ; /pa/ stimulus created by extracting the initial low frequency activity five 8-minute blocks of 450 trials of one of two stimuli, followed by the same number of blocks and presentations of the other stimulus. 14 male French-speaking adult dyslexics (23-49, mean 32.7) and 10 adult male controls (20-38, mean 26,5) All dyslexics with a long history of difficulties in academic achievement, needs for specific speech therapist intervention, and persistent spelling difficulties Raven PM38 ; normal intellectual function

5. 100 260 240 370 100 /BA/ /PA/ Patterns of auditory dysfunction in compensated and persistent dyslexic adults K. Giraud, C. Liégeois-Chauvel, M. Habib (In press)

6. 14 dyslexic adults : reading, phonological, and spelling performances

7. ba Non-dyslexics A B C Figure 1 80 240 180 120 Off resp.

8. Primary auditory cortex (A1) Voiced/unvoiced discrimination is represented by synchronized responses in A1 neuronal populations Secondary auditory areas : integration of activity emanating from multiple frequency-specific areas in A1 Neural representation of VOT is determined by the tonotopic organization of A1, with response peaks time-locked to voicing onset being observed in low- frequency regions (Steinschneider et al.,2003). ? ? ? V Voicing perception is specific of anterior Heschl’s gyrus, whereas more posterior cortex, near PT, show no response to voicing onset (Steinschneider et al.,2004).

9. Results of AEP study (adult dyslexics) In the auditory cortex of normal subjects, voiced and voiceless stop CV syllables are coded in a temporal fashion according to the sequential phonetic markers constituting the voiced- voiceless contrast. After the N1/P2 complex, a negative component peaking at approximately 240 ms for non-dyslexics and 226 ms for Moderate dyslexics was observed for /ba/, but not /pa/, Moderate dyslexics had AEP patterns not different from that of normals, except for absence of lateralization of the ba additional component Severe dyslexics displayed two different AEP patterns :

10. Figure 2 C * 350 280 220 170 80 Off resp. ? B Moderate dyslexics A * 70 228 180 120 Off resp. Severe Profile I dyslexicsSevere Profile II dyslexics * 80 257 177

11. Two patterns of abnormal AEP in severe dyslexics –AEP Pattern I) is characterized by several additional peaks following the component at 230 ms. AEPs from these subjects did not clearly terminate before 400 ms and identification of an off-response was difficult. – AEP Pattern II) did not demonstrate a clear negative component at or near 240 ms for /ba/. –Although a more pronounced off-response was observed for /ba/, /ba/ and /pa/ AEPs were not distinguishable on the basis of the supplementary voiced-CV-specific N240 component for these subjects.

13. Conclusion study 1 Adult outcome of childhood phonological dyslexia seems to depend on the presence or absence of auditory perceptual impairments, moderate dyslexics having normal temporal coding of speech signal more than one dysfunctional mechanism may be implicated in severe persistent dyslexia: –one related to the processing of extraneous acoustic cues in the speech signal or to a “sluggishness” in auditory processing (AEP Pattern I); –another to an inability to code crucial, sequentially-occurring cues differentiating voiced/voiceless speech sounds (AEP Pattern II).

14. Conclusion study 1 At least 3 neural auditory correlates of dyslexia –Normal cortical anatomo-functional organization, but less lateralized to the LH – abnormally synchronized recruitment of otherwise normal neuronal populations –Abnormal spatio-temporal organization

15. Unmodified ending Small incongruity Large incongruity ERP protocol : « proso » Incongruity resulting from F0 manipulation of the last word of sentences Possible effect on semantic/prosodic integration of linguistic stimuli

16. forêt solitaire Un loupsefaufileentre les troncsde la grande + 35% + 120%

18. Dyslexics (12 children, 9-11 y-old) RT and error percentage data

19. controls (11 children, 7-8 y-old) RT and error percentage data

20. PRE- POST-training ** *** n.s. %errors %errors normal small incongruity large incongruity Significant improvement of prosodic integration after phonological auditory training

21. CONTROLS (N=11) -10 µV -150 ms 1500ms __ normal (206 trials) __ small (135 trials) __ large (200 trials) N400 P600 incongruency

22. PRE-TRAINING (N=11) P600 __ normal (169 trials) __ small (103 trials) __ large (138 trials) -10 µV -150 ms 1500ms N400 P600 artéfacts

23. -10 µV -150 ms 1500ms POST-TRAINING (N=11) __ normal (213 trials) __ small (119 trials) __ large (241 trials)

24. Comparison pre / post training LARGE INCONGRUENCY (N=10) -10 µV -150 ms 1500ms __ pre-training (138 trials) __ post-training (241 trials) P600

25. Comparaison pré / post entraînement MOT CONGRUENT (N=10) -10 µV -150 ms 1500ms __ pré-entraînement (169 essais) __ post-entraînement (213 essais) N400 P600 FIGURE 14

26. Theoretical background Dyslexia in the context of developmental neuroscience ; abnormal neuronal organization, connectivity or plasticity? Dyslexia and neuroimaging ; morphological (mMRI), neurocognitive (PET and fMRI), neurofunctional (early ERP - auditory/visual) Dyslexia and recovery of function : combining clinical evidence of improvement with repeated neuroimaging

27. neuroimaging and recovery of dyslexia (1) Functional imaging before and after specific training : Areas of greater activation in controls Beforeafter training Simos et al., 2002 Aylward et al., 2003 Temple et al., 2003 pre post Areas non activated before training

28. neuroimaging and recovery of dyslexia (2) Long-term neural correlates of recovery (Shaywitz et al., 2003) compensated (AIR) vs persistent (PPR)

29. neuroimaging and recovery of dyslexia (3) Auditory ERP correlates of reading improvement (Kujala et al., 2001)

30. Heterogeneity of temporal processing of speech in developmental dyslexia revealed by Auditory Evoked Potentials