Atypical Visual Processing in Infant Siblings of Children with

Autism Spectrum Disorders (ASD)

Karen DobkinsLeslie Carver

Joseph McCleery

Funded by NAAR / Autism Speaks

Psychology DepartmentUniversity of California, San Diego

& the M.I.N.D. Institute (UC Davis)

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. Unaffected2) Endophenotype analysis: High-Risk vs. Controls2) Endophenotype analysis: High-Risk vs. Controls

TWO TYPE OF TESTS

ASD Screening/Diagnogstics: M-CHAT, PDDST, ADOS, ADI

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

Face Component: N170

Occipito-temporal cortex

Am

plit

ud

e(m

icro

volt

s)

200 400 600

10

Latency (msec)

0

20

-20

-10

-100

StimulusOnset

0

-

-

McPartland, Dawson, Webb, Panagiotides, Carver (2004)

Study of Adults with ASD

N17

0 L

aten

cy (

mse

c)

N17

0 L

ate

nc

y (m

sec )

150

160

170

180

190

200

210

220

Controls ASD

N17

0 L

ate

nc

y (m

sec )

150

160

170

180

190

200

210

220

Controls ASDN

170

Lat

ency

Dif

fere

nce

(Ob

ject

s -

Fac

es)

Fac

eA

dva

nta

ge

Ob

ject

Ad

van

tag

e

-20

-15

-10

-5

0

5

10

15

20 Difference Scores

150

160

170

180

190

200

210

220

Controls

F0

N = 14 N = 9ASD

F0

*

Controls

N = 9

N = 14

10-month-olds

High-Risk InfantsVs.

Low-Risk Control Infants

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

Testing Set-up

Am

plit

ud

e(m

icro

volt

s)

200 400 600

10

Latency (msec)

0

20

-20

-10

-100

StimulusOnset

0

-

-

In adults: N170

N170

In infants: N290 + P400

N290

P400

P400

Latency Differences(Objects - Faces)

Mea

n L

aten

cy D

iffe

ren

ce (

mse

c)(O

bje

cts

- F

aces

)

N290

ControlInfants

High-RiskInfants

-40

-20

0

20

40

60* p = 0.038

High-RiskInfants

High-Risk (n = 10)

FaceAdvantage

ObjectAdvantage

Mea

n L

aten

cy D

iffe

ren

ce (

mse

c)(O

bje

cts

- F

aces

)

ControlInfants

-40

-20

0

20

40

60

Controls (n = 20)

* p = 0.003

2) Group difference for Amplitude of P400 and N290

Let me know if you want to see:

1) RAW Latency Data for P400 and N290

Our results in High-Risk 10-month-olds look likeresults 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)

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 faceprocessing 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

MAGNO = Luminance(Light/Dark)

PARVO = Chromatic(Red/Green)

Forced-Choice Preferential Looking

6-month old infants

T h r e s h o l d =

6 . 5 %

S e n s i t i v i t y = 1 /t h r * 1 0 0

= 1 5 .4

Luminance Contrast (%)

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

Magnocellular vs. Parvocellular Pathway Processing in 6 month olds

High-Risk (n = 13)

Lo

g C

on

tras

t S

ensi

tiv i

ty

Controls (n = 26)

Luminance(Magnocellular)

1.3

1.4

1.5

1.6

1.7

1.8

1.9

Chromatic(Parvocellullar)

-0.3

-0.2

-0.1

0

0.1

0.2

High-RiskInfants

ControlInfants

Lo

g D

iffe

ren

ce S

core

(L

um

- C

hr)

* p = 0.011 * p = 0.011

Thank you

Magnocellular vs. Parvocellular Pathway Processing

High-Risk (n = 13)

Lo

g C

on

tras

t S

ensi

tiv i

ty

Controls (n = 26)

Luminance(Magnocellular)

1.3

1.4

1.5

1.6

1.7

1.8

1.9

Chromatic(Parvocellullar)

-0.3

-0.2

-0.1

0

0.1

0.2

High-RiskInfants

ControlInfants

Lo

g D

iffe

ren

ce S

core

(L

um

- C

hr)

* p = 0.011

Lat

ency

Dif

fer e

nce

(m

sec)

(Ob

ject

s -

Fac

es)

Controls

-40

-20

0

20

40

60

High-Risk

Controls

High-Risk-40

-20

0

20

40

60

Lat

ency

Dif

fer e

nce

(m

sec)

(Ob

ject

s -

Fac

es)

Controls

ASDAdults

-20

-15

-10

-5

0

5

10

15

20

3-4 year olds with ASDWebb et al (2006)

N290

Lat

ency

Dif

fere

nce

Adults with ASDMcPartland et al (2004)

N170

-20

-15

-10

-5

0

5

10

15

20

Controls

ASD(3-4 years)

Parents of ASDDawson et al (2005)

N170

Controls Parentsof

ASD

-20

-15

-10

-5

0

5

10

15

20

10-month-old InfantsN290

10-month-old InfantsP400

FaceAdvantage

ObjectAdvantage

Lat

ency

Dif

fere

nce Controls

-40

-20

0

20

40

60

High-Risk

Controls

High-Risk-40

-20

0

20

40

60

Lat

ency

Dif

fere

nce

N290 P400

* p = 0.004*

p = 0.047

P40

0 L

aten

cy (

mse

c)

Controls High-Risk

410

420

430

440

450

460

470

F F

N29

0 L

aten

cy (

mse

c)

Controls High-Risk220

230

240

250

260

270

280

290

FF

O

OO

O

Controls (n = 20)

High-Risk (n = 10)

Amplitude Differences(Faces - Objects)

* p = 0.021

-15

-10

-5

0

5

10

15

ControlsHigh-Risk

Mea

n A

mp

l itu

de

Dif

fere

nce

(Fac

es -

Ob

ject

s)

N290

Very similar to children with ASD(Webb et al., 2006)

P400

FaceAdvantage

ObjectAdvantage

Mea

n A

mp

l itu

de

Dif

fere

nce

(Fac

es -

Ob

ject

s)

Controls

-15

-10

-5

0

5

10

15

High-Risk

* p = 0.035

Controls (n = 20)

High-Risk (n = 10)

Familiarity Effects (N290)(Unfamiliar - Familiar)

FamiliarAdvantage

UnfamiliarAdvantageM

ean

Lat

ency

Dif

fere

nce

(Un

fam

i lia

r -

Fam

i lia

r)

Controls (n = 20)

High-Risk (n = 10)

Controls ASD-20

-10

0

10

20

* MS

Lat

ency

Dif

fere

nce

(Ob

ject

s -

Fac

es)

Fac

eA

dva

nta

ge

Ob

ject

Ad

van

tag

e

Adults with ASDMcPartland et al (2004)

Controls

ASDAdults

-20

-15

-10

-5

0

5

10

15

20

Lat

ency

Dif

fere

nce

(Ob

ject

s -

Fac

es)

Fac

eA

dva

nta

ge

Ob

ject

Ad

van

tag

e

3-4 year olds with ASD Webb et al (2006)

-20

-15

-10

-5

0

5

10

15

20

Controls

ASD(3-4 years)

Lat

ency

Dif

fere

nce

(Ob

ject

s -

Fac

es)

Fac

eA

dva

nta

ge

Ob

ject

Ad

van

tag

e

Parents of Children with ASD Dawson et al (2005)

ControlsParentsof

ASD

-20

-15

-10

-5

0

5

10

15

20

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

Baseline(100 ms)

Stimulus(500 ms)

Post-Stimulus(700 ms)

-100 0 500 ms 1200 ms

Single Trial Timeline

Data Recording

Continuous EEG, 250 Hz sampling

Impedance: 80 kOhms

0.1 - 100 Hz bandpass filter

Cz reference

Data Analysis

40 Hz low-pass filter

Automated artifact rejection and individual trial inspection

Data average over Occipito-Temporal electrodes (16 channels)

TODAY’S TALK: Data averaged over RH and LH

3) SOCIAL REFERENCING PARADIGM:

- Behavior & ERPs - 18-month-olds

Controls (n = 23)

High-Risk (n = 21)

Me

an

# R

ef e

ren

ce

s

Component 1:Seeking Emotional Info

0

0.5

1.5

2.0

1.0

*p = 0.05

P50

0 L

aten

cy D

iffe

ren

ceP

OS

- N

EG

Toy

(m

sec)

POS Toy

Advantage

NEG Toy Advantage

-40

-20

0

20

40

60

80

100

120

p = 0.06MS

Component 2:Associate Emotion

with Object

Component 3:Regulate Behavior in

Response to EmotionallyTagged Object

0

0.01

0.02

0.03

0.04

0.05

0.06 **p = 0.017

Log

(PO

Sp

ost/

NE

Gp

ost)

-

Log

(PO

Sp

re/N

EG

pre

)