1. Atypical Visual Processing in Infant Siblings of Children with Autism Spectrum Disorders (ASD) Karen Dobkins Leslie Carver Joseph McCleery Funded by NAAR / Autism Speaks Psychology Department University of California, San Diego & the M.I.N.D. Institute (UC Davis)

2. 1)COGNITIVE/BEHAVIORAL ASSESSMENTS (6 - 36 months) 2) EXPERIMENTAL MEASURES Ages and Stages Questionnaire, MacArthur-Bates Communicative Development Inventory (CDI), Mullen Scales of Early Learning A) Low-Level Visual Processing: 6 months B) Face Processing: 10 months C) Social Referencing: 18 months B) Face Processing: 10 months A) Low-Level Visual Processing: 6 months TWO ANALYSES: 1) ASD analysis: High-Risk, Affected vs. Unaffected 2) Endophenotype analysis: High-Risk vs. Controls TWO TYPE OF TESTS ASD Screening/Diagnogstics: M-CHAT, PDDST, ADOS, ADI

3. OBJECTSFACES 1) FACE PROCESSING PARADIGM: Adults: Bentin et al., 1996. Infants: de Haan et al, 2002, Halit, et al, 2003, 2004; de Haan & Nelson, 1999 - Event Related Potentials (ERPs) - Faces vs. Objects OBJECTS

4. Averaged electrical response time-locked to repeated picture presentations Face Component: N170 Occipito-temporal cortex Amplitude (microvolts) - -

5. McPartland, Dawson, Webb, Panagiotides, Carver (2004) Study of Adults with ASD N170 Latency (msec) N170 Latency Difference (Objects - Faces) Face Advantage Object Advantage Difference Scores F 0 N = 14 N = 9 F 0 * N = 14

6. 10-month-olds Electrical Geodesics, Inc. 124 Electrodes Fast Application EEG Sensor Net High-Risk Infants Vs. Low-Risk Control Infants

7. Subjects Diagnosis of Their Older Sibling: - 5 Autistic Disorder - 1 Aspergers Syndrome - 4 PDD-NOS 10 High-Risk infants Controls: 20 Low-Risk infants Two Groups Matched: - overall cognitive development Ages and Stages Questionnaire, MacArthur-Bates Communicative Development Inventory (CDI), Mullen Scales of Early Learning - gender, age, number of days born pre/post due date

8. Stimulus Monitor CCTV Camera Speakers Testing Set-up

9. Amplitude (microvolts) - - In adults: N170 N170 In infants: N290 + P400 N290 P400

10. Latency Differences (Objects - Faces) Mean Latency Difference (msec) (Objects - Faces) N290 * p = 0.038 High-Risk (n = 10) Face Advantage Object Advantage Mean Latency Difference (msec) (Objects - Faces) Controls (n = 20) * p = 0.003

11. 2) Group difference for Amplitude of P400 and N290 3) Group differences in the effects of Familiarity Let me know if you want to see: 1) RAW Latency Data for P400 and N290

12. Our results in High-Risk 10-month-olds look like results from previous studies: 1)Adults with ASD: McPartland et al. (2004) 2) Toddlers (3-4 yrs) with ASD: Webb et al. (2006) 3) Parents of Children w/ ASD: Dawson et al. (2005)

13. 2) LOW-LEVEL VISUAL PROCESSING PARADIGM: - Visual Psychophysics - Subcortical Magnocellular (M) vs. Parvocellular (P) Pathway Processing - 6-month-olds A test of the hypothesis that atypicalities in face processing in ASD arise from abnormal development of the subcortical face processing pathway, i.e., the “amygdala” pathway (Schultz, 2005) ….. which originates in the M pathway

14. MAGNO = Luminance (Light/Dark) PARVO = Chromatic (Red/Green)

15. Forced-Choice Preferential Looking 6-month old infants

17. Luminance Contrast (%)

18. Subjects Diagnosis of Their Older Sibling: - 6 Autistic Disorder - 1 Aspergers Syndrome - 6 PDD-NOS 13 High-Risk infants Controls: 26 Low-Risk infants Two Groups Matched: - overall cognitive development - gender, age, number of days born pre/post due date

19. Magnocellular vs. Parvocellular Pathway Processing in 6 month olds High-Risk (n = 13) Log Contrast Sensitivity Controls (n = 26) Log Difference Score (Lum - Chr) * p = 0.011

20. Thank you

21. Magnocellular vs. Parvocellular Pathway Processing High-Risk (n = 13) Log Contrast Sensitivity Controls (n = 26) Log Difference Score (Lum - Chr) * p = 0.011

23. Latency Difference (msec) (Objects - Faces) Latency Difference (msec) (Objects - Faces) 3-4 year olds with ASD Webb et al (2006) N290 Latency Difference Adults with ASD McPartland et al (2004) N170 Parents of ASD Dawson et al (2005) N170 10-month-old Infants N290 10-month-old Infants P400 Face Advantage Object Advantage

24. Latency Difference N290 P400 * p = 0.004 * p = 0.047 P400 Latency (msec) F F N290 Latency (msec) F F O O O O Controls (n = 20) High-Risk (n = 10)

25. Amplitude Differences (Faces - Objects) * p = 0.021 Mean Amplitude Difference (Faces - Objects) N290 Very similar to children with ASD (Webb et al., 2006) P400 Face Advantage Object Advantage Mean Amplitude Difference (Faces - Objects) * p = 0.035 Controls (n = 20) High-Risk (n = 10)

26. Familiarity Effects (N290) (Unfamiliar - Familiar) Familiar Advantage Unfamiliar Advantage Mean Latency Difference (Unfamiliar - Familiar) Controls (n = 20) High-Risk (n = 10) * MS

27. 60% scale Latency Difference (Objects - Faces) Face Advantage Object Advantage Adults with ASD McPartland et al (2004) Latency Difference (Objects - Faces) Face Advantage Object Advantage 3-4 year olds with ASD Webb et al (2006) Latency Difference (Objects - Faces) Face Advantage Object Advantage Parents of Children with ASD Dawson et al (2005)

28. Familiar (mother)Unfamiliar (stranger) Familiar (favorite toy)Unfamiliar (novel toy) FACES OBJECTS Stimuli TODAY’S TALK: Data averaged over Familiar and Unfamiliar Data averaged over Right and Left Hemispheres

29. Baseline (100 ms) Stimulus (500 ms) Post-Stimulus (700 ms) -1000 500 ms 1200 ms Single Trial Timeline Data Recording Continuous EEG, 250 Hz sampling Impedance: 80 kOhms 0.1 - 100 Hz bandpass filter Cz reference

30. Data Analysis 40 Hz low-pass filter Automated artifact rejection and individual trial inspection Replace up to 10 channels Data average over Occipito-Temporal electrodes (16 channels) TODAY’S TALK: Data averaged over RH and LH

31. 3) SOCIAL REFERENCING PARADIGM: - Behavior & ERPs - 18-month-olds Controls (n = 23) High-Risk (n = 21) Mean # References P500 Latency Difference POS - NEG Toy (msec) POS Toy Advantage NEG Toy Advantage Log(POSpost/NEGpost) - Log(POSpre/NEGpre)