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8/12/2012
1
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
8/12/2012
2
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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3
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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4
Tracts mature at different rates
Lebel et al., 2008
Inferior Longitudinal Fasciculus
– links vision to sound
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5
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
8/12/2012
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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.
8/12/2012
7
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.
8/12/2012
8
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.’’
8/12/2012
9
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
8/12/2012
10
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
8/12/2012
11
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
8/12/2012
12
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
8/12/2012
14
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
8/12/2012
15
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
8/12/2012
16
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?
8/12/2012
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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.
8/12/2012
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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
8/12/2012
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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.
8/12/2012
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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)
8/12/2012
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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
8/12/2012
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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
8/12/2012
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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
8/12/2012
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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.
8/12/2012
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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
8/12/2012
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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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8/12/2012
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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