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The Neurobiology of Autism

Spectrum Disorders and What

That Means for Special

Education

Part 1

Martha S. Burns, Ph.D.

September 20, 2012

Selected New References

• Buie, T., et al. (2010) Evaluation, Diagnosis, and Treatment of

Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report Evaluation, Diagnosis, and Treatment of Gastrointestinal

Disorders. Pediatrics 2010;125

• Durkin, S. et al (2008) Advanced Parental Age and the Risk of Autism Spectrum Disorder. American Journal of Epidemiology, Vol.

168, No. 11

• Nordahl, C. et al (2007) Cortical Folding Abnormalities in Autism Revealed by Surface-Based Morphometry. The Journal of

Neuroscience, 27(43):11725–11735

• Landa, R. et al (2007) Archives of General Psychiatry, 64 (NO. 7)

• Haladay, A. et al (2011) Animal models of autism spectrum disorders:

Information for neurotoxicologists. Neurotoxicology. Author manuscript;

available in PMC 2011 January 4

Newer references (continued)

• Minshew, N. & Williams, D. (2007) The

New Neurobiology of Autism: Cortex,

Connectivity, and Neuronal Organization.

Arch Neurol. 64(7): 945–950

Autism Spectrum Disorders

• Autism spectrum disorders (ASDs) are a

group of developmental disorders

characterized by impairments in:

– social interaction;

– varying degrees of verbal and nonverbal

communication deficits; and

– restricted, repetitive, and stereotyped patterns of behavior and interests.

• ASD’s are neurodevelopmental disorders

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ASD’s

• The term includes:

– autistic disorder,

– Asperger disorder, and

– Pervasive developmental disorder, not otherwise

specified (PDD-NOS)

• The incidence of ASD’s is now 1 in every 110

children

– 1 in 70 males

• autism is a polygenetic disorder with a

heritability index of 0.90. DeHaene, 2009

Neuronal communication system Early fMRI studies of networks: Neurons that fire together

wire together in networks

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Neurological Development

• Critical “optimal” Periods – Huttenlocher, 2002

• Four major divisions:

– Neuron formation (neurogenesis) –between

post-ovulary day (POD) 52-140

• Supported by increased sensitivity to ionizing radiation

– reduced neuronal number in cerebral forebrain causes

microcephaly and mental retardation

– Neuronal Migration – Second trimester

– Dendritic and Synaptic development –third

trimester and first two postnatal years

Diffusion Tensor Imaging

• Measures diffusion (motion) of protons in water molecules.

• Direction of proton motion within a voxel can be described by a “tensor”.

• Proton diffusion tends to be relatively isotropic in gray matter.

• The linear structure of fiber tracts constrains proton diffusion

and produces anisotropy.

Fiber Tract Development

Observable with DTI (from Hermoye et al., 2006)

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Tracts mature at different rates

Lebel et al., 2008

Inferior Longitudinal Fasciculus

– links vision to sound

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Autism Spectrum Disorder is

Partially Genetic

• Autism spectrum disorders have a strong

genetic bases

– autism susceptibility genes

– Copy number variations ( insertion or deletion of large

DNA fragments) – both inherited and idiosyncratic –

and other mutations

– Genetic syndromes

• But linking genes to specific language, social

skill and repetitive behaviors will help drive

interventions

Abrahams and Geschwind (2008)

Advances in autism genetics: on the

threshold of a new neurobiology

• Figure 1 | Loci implicated in ASD etiology.

• Green bars correspond to genes that are

observed to modulate autism spectrum disorder

– light green and dark green bars represent promising or probable candidate genes, respectively

• Red and yellow bars correspond to de novo

losses and gains, respectively, that are observed

in cases but not in controls

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Some of the genes regulate brain

development

• Common genetic variants on 5p14.1

associate with autism spectrum

disorders Wang et al, Nature 2009

• For example - CDH9 and CDH10

– Are very important for the development

of the obito-frontal cortex

Stereotypical. Girls

with Rett syndrome

often

exhibit repetitive

handwringing.

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Stunted branches.

Mouse hippocampal

neurons (green) grow

dendrites

with fewer branches

when MeCP2 is

blocked (right)

compared to when

the protein is active

(left).

UC Davis M.I.N.D. Institute

• M.I.N.D. (Medical Investigation of Neurodevelopmental Disorders)

• Study Shows California Autism Increase Not Due to Better Counting,

Diagnosis - By U C Davis Health System, January 06, 2009

– The incidence of autism by age six in California has increased from fewer than nine in 10,000 for children born in 1990 to more

than 44 in 10,000 for children born in 2000.

– Some have argued that this change could have been due to migration into California, inclusion of children with milder forms

of autism and earlier ages of diagnosis.

– Hertz-Picciotto and her colleagues two large studies aimed at discovering the causes of autism. Hertz-Picciotto is the principal

investigator on the CHARGE (Childhood Autism Risk from

Genetics and the Environment) and MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) studies

M.I.N.D. Institute (U.C. Davis)

C.H.A.R.G.E

• CHARGE is the largest epidemiologic

study of reliably confirmed cases of autism

to date.

– the first major investigation of environmental

factors and gene-environment interactions in the disorder.

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Halladay, A. et al (2011) Animal models of autism

spectrum disorders: Information for

neurotoxicologists. Neurotoxicology 30(5): 811–

821 • In October, 2009 a symposium was organized in conjunction with

the International Neurotoxicology Conference Meeting which included: – Autism Speaks

– M.I.N.D. Institute

– Vanderbilt University

– Wadsworth Center, New York State Department of Health, Albany, NY

– Robert Wood Johnson Medical School

– Golisano Childrens' Hospital at

– University of Rochester School of Medicine and Dentistry, Rochester, NY

– Lab of Developmental Neuroscience, Università Campus Bio-Medico, Roma, Italy

– Department of Neurobiology, University of Arizona

– Department of Genetics, North Carolina State University, Raleigh, NC,

Neurotoxicology in autism

(Halladay et al., 2011 continued) • Amaral - Evidence has been accumulating for over 20

years suggesting that immune factors may playa role in the etiology of some forms of autism (Warren et al., 1986, 1996; Ashwood and Vande Water, 2004).

• Judy Van de Water, Paul Ashwood and colleagues at the M.I.N.D. Institute have conducted comprehensive evaluations of children with autism and their parents to determine what, if any, perturbations of immune function are characteristic of the disorder.

• Part of this effort has been to evaluate these individuals for evidence of autoimmunity.

Pamela Yein, U.C. Davis

• Have identified three different classes of environmental factors that modulate neuronal connectivity in primary cultures of hippocampal neurons – identify non-coplanar PCBs as candidate

environmental risk factors in ASD and suggest the possibility that exposure even to very low PCB levels could amplify adverse effects in genetically susceptible individuals

• May be a factor in perceptual problems (see next section) and birth order findings (see Newschaffer, 2008)

Autism increases with maternal and

paternal age (Newschaffer, 2008)

• The results of this study provide the most compelling evidence to date that ASD risk increases with both maternal and paternal age and decreases with birth order

• The observation in this and at least 2 previous studies (2, 4) that the risk of developing ASD was highest for firstborn children and declined with increasing birth order is a pattern also observed for other childhood disorders, including type I diabetes and atopy, and is cited as support for the ‘‘hygiene hypothesis.’’

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Hygiene Hypothesis

• First born children are exposed to fewer

infections from other children early in

childhood and, because of delayed

immunologic challenge, may be more

likely to develop autoimmune responses

including those that may adversely affect

neurodevelopment

Incidence in first born children

• Another possible factor that could lead to the observed birth order effect is exposure to potentially neurotoxic, fat-soluble chemicals accumulated in maternal tissue that have been passed to offspring transplacentally or through breast milk.

• Because of accumulation over a lifetime, the load ofsuch neurotoxins transmitted might be expected to be highest for firstborn children, particularly when combined with advanced maternal age

Pamela Yein, U.C. Davis

– the second class of environmental factors we

are studying, the pro-inflammatory cytokines,

interferon-γ and interleukin (IL)-6 decrease

dendritic arborization and synapse formation

in cultured hippocampal neurons (Kim et al., 2002).

• Our preliminary data suggest that at least

interferon-γ modulates dendritic growth and synaptic density similarly in situ. Interestingly,

these cytokines are elevated in the serum and

cerebrospinal fluid of ASD patients (Ciaranello and

Ciaranello,1995).

M.A.R.B.L.E.S

• MARBLES is a prospective investigation

that follows women who already have had

one child with autism, beginning early in or

even before a subsequent pregnancy, to

search for early markers that predict

autism in the younger sibling

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M.I.N.D. biomarker research

• Patent number: 7604948 Filing date: May 5, 2006 Issue date: Oct 20, 2009 Application number: 11/381,976

• A method for diagnosing an autism spectrum disorder in an individual, said method comprising: – a) determining the level of complement factor H-related protein (FHR1)

in a blood or serum sample from a first individual exhibiting symptoms of an autism spectrum disorder; and

– b) comparing the level of the FHR1 determined in step a) with the level of the FHR1 in a control sample from a second individual or a population of individuals who do not have an autism spectrum disorder;

• wherein levels of increased complement factor H-related protein (FHR1) in the sample from the first individual in comparison to the control sample from the second individual or population of individuals is indicative of an autism spectrum disorder.

Amaral, D. 2009 U.S.

Patent

Amaral, D (2009) U.S. Patent

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Pamela Yein, continued

– Third, we are investigating organophosphorus

pesticides (OPs), which we have shown

inhibit axonal growth in developing neurons

by interfering with the morphogenic activity of

acetylcholinesterase (Yang et al., 2008)

Status of research on other

potential causes of autism?

“Leaky Gut” theory of autism –

Belief, based on a paper he wrote about 12

children, is that the three vaccines, given

together, can alter a child’s immune system,

allowing the measles virus in the vaccine to

infiltrate the intestines; certain proteins,

escaping from the intestines, could then

reach and harm neurons in the brain.

Gave parents a hope that autism is caused

by a real medical issue and can be “treated”

and perhaps cured through dietary changes Dr. Andrew Wakefield

Repercussions

Evidence that Wakefield fabricated some research, with no other

evidence that MMR leads to autism and physicians worry that separating

vaccines will result in many children under-immuninized – but… Parents

need to be taken seriously and gastrointestinal problems studied

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Buie, T. et al. (2010) Evaluation, Diagnosis, and

Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report PEDIATRICS

Volume 125, Supplement 1, January 2010

• Statement 12 – Available research data do not support the use of a casein-free

diet, a gluten-free diet, or combined gluten-free, casein-free (GFCF) diet as a primary treatment for individuals with ASDs.

– only 1 double-blind placebo controlled study has been published to date (Elder JH, Shankar M, Shuster J, Theriaque D, Burns S, Sherrill L. The gluten-free casein-free diet in autism: results of a preliminary double blind clinical trial. J Autism Dev Disord. 2006;36(3):413– 420)

• In this double-blind crossover trial of GFCF or typical diet in 15 children

with ASDs, there were no differences in measures of severity of ASD

symptoms, communication, social responsiveness, and urinary peptide

levels after 12 weeks.46

• Nevertheless, after being informed of the results 9/15 parents wanted to

continue the diet and reported positive subjective clinical changes while

their child was on the GFCF diet.

Buie, et al 2010 -- GFCF diet (continued)

• Parents need information to help plan a balanced diet within the restrictions imposed by any chosen diet

• Given the real hardships associated with implementation of a strict GFCF diet, additional studies are needed to assess risk factors and possible markers that identify individuals who might benefit from these diets.

Structural Architecture of the Human Cortex pre-natal to 16 years

ASD’s are developmental neuropathologies

(Minshew & Williams, 2007)

• Autism is characterized by abnormalities in

complex behavior, language, and cognition

• mental retardation in 70% of cases and seizures

in 30% of cases,

• and the absence of blindness, and deafness,

• and long tract signs in 90% to 95% of cases

without any cause for brain dysfunction other

than autism.

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Behavioral neurology perspective

2007: (Minshew and Williams,)

• From a behavioral neurology perspective, this

constellation suggests generalized dysfunction of the association cortex, with sparing of primary sensory and

motor cortex and of white matter.

• The absence of clinical signs of focal brain dysfunction

common in children with hypoxic ischemic injury, such as

visuospatial deficits and cerebral palsy, further suggests

a distributed neural systems abnormality

• it was not until the past 10 years that a neurobiology for

autism matching this behavioral neurology emerged

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Iacoboni and Dapretto Redgrave Nature Reviews Neuroscience 7, 942–951 (December 2006) | doi:10.1038/

nrn2024

Mirror neuron

system (MNS)

(red) and its

main visual

input (yellow) in

the human

brain. anterior

area located in

the inferior

frontal cortex, A

posterior area

in the rostral

part of the

inferior parietal

lobule (IPL),

Together, these

three areas

form a 'core

circuit' for

imitation

Iacoboni and Dapretto Redgrave Nature Reviews Neuroscience 7, 942–951 (December 2006) | doi:10.1038/

nrn2024

children with

and w/o

autism on

fMRI while

they

observed or

imitated facial

emotional

expressions

(a). children

with autism

show

reduced

activity in

(MNS) lin the

pars

opercularis of

the inferior frontal gyrus.

Thix

correlated

with the

severity of

disorder

Turken, Whitfield-Gabrieli,

Bammer, Baldo, Dronkers,

Gabrieli

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Turken, et al. Turken and Dronkers (2010 in press)

speech, fluency and grammar pathways

Turken and Dronkers (2010) in press – White

Matter tracts underlying auditory speech

processing

Decreased Interhemispheric

Functional Connectivity in Autism – Jeffrey S. Anderson, T. Jason Druzgal, Alyson Froehlich, Molly B. DuBray,

Nicholas Lange, Andrew L. Alexander, Tracy Abildskov, Jared A. Nielsen,

Annahir N. Cariello, Jason R. Cooperrider, Erin D. Bigler and Janet E. Lainhart

– Cerebral Cortex Advance Access published October 12, 2010

• Examined resting-state blood oxygen level--dependent

interhemispheric correlation in 53 males with high functioning autism and 39 typically developing males from late childhood through early

adulthood

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Anderson, et al., 2010

• found significantly reduced interhemispheric correlation specific to regions with functional relevance to autism: – sensorimotor cortex,

– anterior insula,

– fusiform gyrus,

– superior temporal gyrus, and

– superior parietal lobule

• Observed interhemispheric connectivity differences were better explained by diagnosis of autism than by potentially confounding neuropsychological metrics of language, IQ, or handedness.

Distortions and disconnections:

disrupted brain connectivity in autism

(Wass, 2011) • Point to evidence that there is local over-

connectivity

– Perhaps leading to repetitive behaviors and savant characteristics

• Long Distance underconnectivity

– Leading to problems with long fiber track

networks for:

• Language and problem solving

• MNS and TOM (see tomorrow’s discussion)

Wass, 2011

• Review DTI studies that reveal inter-hemispheric structural under-connectivity in mature subjects with ASD

– With younger subjects the results are more mixed

• Also evidence showing disruptions to and from frontal and temporal cortices may be most heavily disrupted in ASD

– This is consistent with early relatively intact development becoming progressively more disrupted during the first two years of life

Wass, 2011

• fMRI and EEG studies show evidence of functional over-connectivity but with this regard DTI is more mixed – Strongest evidence of local over-connectivity comes from the

micro-level from a small number of post-mortem studies

• Tantalizing evidence that increased short-range connectivity and decreased long-range may resemble that found in immature vs. mature typically developing children

• ASD may be partially due to failure to undergo typical developmental process

• SO – is this the primary pathogeneis or does it develop over time?

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N.Y.Times November 1, 2010

A camera operator observed Carmen and Saul Aguilar during a therapy session with

their son Emilio at 7 months old. Emilio showed signs of autism, and his older brother,

Diego, received a diagnosis at age 2.

By APRIL DEMBOSKY

Published: November 1, 2010

SACRAMENTO — In the three years since her son Diego was given a diagnosis of

autism at age 2, Carmen Aguilar has made countless contributions to research on

this perplexing disorder.

So if some genes affect frontal

lobe development, other factors

interfere with long fibre tract

development what does the pre-

frontal lobe (the farthest area for

long tracts and last to develop in

typcial brains) do?

Pre-frontal Lobes

• Ventromedial – connected to limbic

system

– Important in delayed gratification

– Empathy

• Dorsolateral –

– Organization, planning, flexibility

– Working memory

– Processing speed

Meeting of minds: the medial frontal

cortex and social cognition.

Amodio, DM and Frith, CD. (2006)

Nature Reviews Neuroscience 7,

268-277.

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Amodio et al. Nature Reviews Neuroscience 7, 268–277 (April 2006) | doi:10.1038/nrn1884 Amodio et al. Nature Reviews Neuroscience 7, 268–277 (April 2006) | doi:10.1038/nrn1884

Mindblind Eyes: An Absence of

Spontaneous Theory of Mind in

Asperger Syndrome

• Atsushi Senju,Victoria Southgate, Sarah

White, Uta Frith

• SCIENCE VOL 325 14 AUGUST 2009

.

Sally-Anne False Belief Task (FBT)

• (Sally) places a marble in a basket and leaves the room. In her absence, another character (Anne) moves the marble to a box. When Sally returns, children are asked where she will look for her marble.

• If children understand that Sally’s actions will be based on what she believes to be true, rather than the actual state of affairs, they should answer that she will look in the basket, rather than the box.

• This correct answer requires the child to predict Sally’s behavior based on her now false belief

• Children with autism fail the verbally instructed Sally-Anne false-belief task (FBT), whereas 4-year-old neurotypical children pass, as do children with Down syndrome of similar verbal mental age

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Asperger Syndrome

• Despite still exhibiting atypical social features characteristic of autism, individuals of higher verbal ability, in particular those with Asperger syndrome, can pass such false-belief attribution tasks

• This has prompted the proposal that these high-ability individuals have acquired the ability to reason explicitly about false beliefs by compensatory learning, whereas difficulties in spontaneous mental-state attribution may nevertheless persist

Limbic System

• Channeling emotion and motivation

– To behaviorally relevant motor acts, mental

content and extrapersonal event

– Is accomplished through the paralimbic

regions

Eye-tracking task that has revealed the spontaneous ability to mentalize in

typically developing infants

In familiarization trials,

participants were familiarized to an event in which (A) the

puppet placed a ball in one of two boxes,

(B) both windows were illuminated and chime

sounded, and (C) an actor reached through

the window above the box in which the ball was placed

and retrieved the ball. The participants were familiarized to the

contingency between (B) and (C).

In (D), the puppet moves the ball while the actor is looking

away. This operation induces a false belief in the actor

about the location of the ball. Published by AAAS

A. Senju et al., Science 325, 883 -885 (2009)

Fig. 2 (A) Mean ({+/-} SEM) DLS (19) and (B) the ratio of the number of participants who made correct

first saccades in each group AS, participants with Asperger syndrome (n = 19); NT,

neurotypical participants (n = 17). *P < 0.05; **P < 0.01. Dotted lines indicate

chance level. Statistical test used: (A), t test; (B), binominal test.

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Conclusions

• results confirm indirect indications that individuals with Asperger syndrome have a persistent impairment in spontaneous mentalizing

• are also consistent with a previous finding that children with autism are more likely to give a correct verbal answer than a correct anticipatory look when asked to infer someone’s preference.

The Limbic System

• Regulates emotions

• Through the frontal lobe connections as we mature: – We become conscious of our own emotions

– Then are able to interpret the emotions of others

– Perhaps largely through the mirror neuron system which leads to: • Compassion

• Empathy

Emotional

circuits

Tuning the developing brain

to social signals of emotions

• Jukka M. Leppänen and Charles A.

Nelson

• NRNS 1.09

• The importance of the limbic system for

processing of emotions

• The importance of the right hemisphere for

Theory of Mind (Saxe, 2006)

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b | Results showing that

discrimination of

emotional expressions in bimodal

(audiovisual) stimuli

emerges earlier than discrimination of

emotional expressions in

unimodal auditory or visual stimuli. c | After

habituation to

happy expressions on different faces, 7-month-

old infants could

discriminate this expression from fearful

and angry expressions

when the stimuli were presented upright

but not when they were

inverted

Emotion-related

neural

systems (the

amygdala and the

orbitofrontal

cortex

(OFC)) receive

visual information

from cortical

regions

that are involved

in the visual

analysis of

invariant and

changeable

aspects of faces

(face-sensitive regions in the

fusiform gyrus

and the posterior

superior temporal

sulcus

(pSTS)).

What is the social cognitive

network? Right Parietal Junction

• Research of Rebecca Saxe on the importance of the Right Parietal Junction in thinking about another person’s thoughts – We have been attributing theory of mind to pre-frontal

lobe function but…….

– Saxe’s research points to the importance of the RPJ in Theory of Mind and Social Cognition in general

• Since children develop social skills early – see new research on intention and affiliation as early as nine months old (Bloom, Wynn, etc.) – this may be the precursor to full TOM skills that later emerge with other areas

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Saxe, 2006

• The developmental trajectory from attending to:

– Human faces and bodies (infants),

– to understanding goal-directed actions (toddlers),

– to the uniquely human representational theory of mind

(preschoolers),

• is reflected in the functional profiles of three

regions in lateral occipitotemporo-parietal cortex

Social awareness network

• Right extrastriate body – detects a person’s presence • Posterior right superior temporal sulcus -perceives intentional action

[note new research showing autistic infants are not interested in biological motion and show RSTS impairments]

• Right Temporal-parietal –reasoning about others’ representation of mental states

• [ note however - Two regions of medial prefrontal cortex, -, – Ventral MPFC associated with attributing emotion and

– Dorsal MPFC, possibly linked to reasoning about triadic relations

– dMRFC takes a really long time to reach maturity]

Chang, et al, 2010

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Categorical Perception /ba/ /ga/ /da/

/pa/ /ba/

Time (msec)

Time (msec)

Fre

qu

ency

(H

z)

Fre

qu

ency

(k

Hz)

English Phonemic Cortical Representation

da ga

ba

da ga

ba

A) Proficient English B) English Language Learners

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Four ways to degrade sensory cortex

(aural language and somatosensory cortex)

development

• structured noise Zhang et al (2004) PNAS

• continuous, unmodulated noise

Chang et al (2003) Nature Neurosci; Chang et al (2005) PNAS

• perinatal anoxia Strata et al (2005) PNAS

• non-coplanar PCBs (PBDEs?) Kenet et

al (2006) submitted, Nature Medicine

A1 does not mature in infants

raised in continuous noise

• In continuous noise reared rats, the critical

period remains open indefinitely

Chang et al. (2003) ms submitted for publication

A1 does NOT

mature in

rats raised in

CONTINUOUS

noise.

A1 processing is

“specialized”

as the infant rat

is exposed to

specific sound

stimuli

Zhang, Bao & Merzenich, Nature Neuroscience, 2001

A learning

context is

NOT required

--- as it is after

the end of

the critical

period.

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Perinatally

generated

representational

distortions in

A1 tonotopy and

input selectivity

persist into

adulthood.

Zhang, Bao & Merzenich, Nature Neuroscience, 2001

PCB poisoning radically alters cortical map development

Normal PCB exposed animals

Exactly the same bizarre typography seen in autism

PCB exposure in pregnant mothers .87 correlation with % of autism – some regions of Texas – Merzenich, 2006

There are also perceptual deficits

• That interfere with ability to perceive pitch

variations in voice that signal emotion,

Russo and Kraus, 2008

• And perceive facial cues, Dalton et al

• And perceive human bodily movement

The Speed of Sound Syllable-initial ‘d’ vs ‘g’

100

dee dih deh dah doe due

gee gih geh gah go gue

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Try taking vowels dee and gee….

101

d d d d d d ??

g g g g g g ??

Methods

• 12 children diagnosed with an Autism Spectrum Disorder

– 6 trained, 6 control

– Age matched (Trained=9.17±1.47 years; Control= 9.0±1.47 years, n.s.)

• Brainstem neurophysiology tests

– /da/ in quiet and background noise

– rising and falling /ya/ in quiet

Pitch tracking and phase locking of F0 improved

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Pre Post

Kim M Dalton, Brendon M Nacewicz, Tom Johnstone,

Hillary S Schaefer, Morton Ann Gernsbacher, H H

Goldsmith, Andrew L Alexander & Richard J Davidson

• Published online: 6 March 2005; |

doi:10.1038/nn1421

• Gaze fixation and the neural circuitry of

face processing in autism

Figure 1. Study designs and exemplar stimuli. (a) Study I: 2 (Emotion) 2 (Orientation) repeated-measures design.

Twenty-four emotional faces and 16 neutral faces were used, half with eyes

and face oriented straight ahead, and half with face and eyes averted 45 degrees (equal toward the right and left). (b) Study II: examples of matched

familiar versus unfamiliar photographs. Photographs of participants' family and friends were matched for gender, age, facial expression and orientation

as closely as possible to photographs taken by other study participants.

Two-year-olds with autism orient to non-

social

contingencies rather than biological motion

• Ami Klin, David J. Lin, Phillip Gorrindo,

Gordon Ramsay & Warren Jones

• Nature Vol 459| 14 May 2009

• Video demonstration

8/12/2012

28

A Klin et al. Nature 000, 1-5 (2009) doi:10.1038/nature07868

Two-year-olds with autism show no preferential attention to

biological motion, whereas control children show significant preferences.

A Klin et al. Nature 000, 1-5 (2009) doi:10.1038/nature07868

When the animation contains a physical contingency,

two-year-olds with autism do show significant viewing preferences.

Conclusions

• Autism is genetic – new research will point to:

– What each of the genes does

– What causes the genes to be expressed and/or

corrupted (epigenetics – eg. environmental factors)

• In general the genes affect brain development

of:

– Prefrontal lobe functions – TOM and Mirror neuron system

– Perceptual functions related to preferences for human faces, biological motion and human vocal intonation