The social brain through the eyes of autism

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The social brain through the eyes of autism

• Kim M. Dalton
• Medical Home Autism Summit,
• November 10th 2006

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Research Support

• NICHD T32 Training Grant Waisman Center Core
  Grant Leonard
  Abbeduto Marsha Seltzer
• NIH STAART Grant
  Helen Tager-Flusberg Richard Davidson
• NARSAD Grants
  Richard Davidson Distinguished Investigator
• Kim Dalton Seaver Investigator
• NAAR Grant Kim Dalton

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Autism from the Greek word auto, meaning self.

• Eugen Bleuler (Zurich, 1911) - ...the narrowing
  of relationships to people and to the outside
  world so extreme that it seems to exclude
  everything except the persons own self.
• Leo Kanner (Baltimore, 1943) - Autism
• Hans Asperger (Vienna, 1944) - Aspergers

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Pervasive Developmental Disabilities

• Autism
• Aspergers
• Childhood Degenerative Disorder
• Pervasive Developmental Disorder - Not Otherwise
  Specified (PDD_NOS)
• Retts

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Pervasive Developmental Disabilities

• Autism
• Aspergers
• Social/Emotional Deficits
• Deficits in Communication Language.
• Repetitive Stereotypical Behaviors

fragile X syndrome The most common form of
inherited mental retardation.
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Social/ Emotional Deficits in Autism

• Lack or diminished affinity for human faces, even
  as infants
• Diminished gaze-fixation through-out development
• Impaired emotional regulation
• Poor peer relations/social skills social
  withdrawal

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Theoretical Perspective Autism the Brain
It is proposed that these social/emotional
deficits arise very early on in development and
are associated with abnormal function and/or
structure in neural circuitry implicated in
affective and social processes.
Main Goal Understand the underlying central and
peripheral nervous system correlates of these
social/emotional deficits by focusing on brain
function and structure using functional magnetic
resonance imaging (fMRI).
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Epistemology of Autism Chaos the Brain

• Epigenesis Development as a cumulative process
  in which species-typical development proceeds
  cumulatively based on a partly completed
  phenotype requiring specific gene products and
  environmental conditions. Hendriks-Jansen
• Experience and the passage of time inevitably
  mold our DNA, silencing some genes and promoting
  the expression of others, thereby facilitating
  the cognitive, emotional, and behavioral changes
  that either improve or detract from our quality
  of life. Roy-Burn, on 2005 PNAS articles.

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Brain Development Chaos Theory

• Neither completely periodic nor random
• Extremely sensitive to initial condition
• Unstable but bounded
• Unpredictable behavior of a deterministic system

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Growth Dysregulation Hypothesis
Abnormal chronicity of neural growth in autism,
including enlarged cerebral volume during the
toddler years and decreased cerebellar volume
followed by wide spread hypoplasia as individuals
with autism reach adulthood. (Akshoomoff,
Pierce Courchesne, 2002)
Experience-expectant information storage
(Greenough et al., 1987)
(Redcay Courchesne, 2005)
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Possible Effects of Abnormal Neural Growth
Chronicity

• The window for experience-expectant learning may
  be shortened.
• Neural networks normally set-up during this
  critical period may be compromised.
• Distinct compensatory mechanisms with unique and
  potentially sub-optimal neural networks may be
  set-up leading to specific strengths (e.g. local
  processes) and/or deficits (global processes).

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Theoretical Perspective Autism the Brain

• Relate brain based functional differences/deficits
  in social/emotional processes to current
  behavior by focusing on individual differences
  within autism.
• Investigate the relationship between autism
  characteristics in fragile X syndrome and brain
  functional differences during social/emotional
  processes and compare these to differences in
  brain function and behavior in individuals with
  idiopathic autism.

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GE 3-Tesla Signa Scanner
Waisman Laboratory for Brain Imaging
Behaviors Director Richard J. Davidson
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Visual Stimulus Presentation Eye-Tracking
Location of the pupillary light reflex on a
callibrated grid tracks gaze.
Avotec goggles with SilentVision infra-red
eye-tracking
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Human Face Processing in Autism

• Deficits in attention, learning discrimination
  of human faces.
• Decreased fixation on the eyes relative to other
  facial features.
• Tendency not to show the face inversion effect.

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Gaze-fixation and the neural circuitry of face
processing in autism.
Dalton, K.M., Nacewicz, B.M., Johnstone, T.,
Schaefer, H.S., Gernsbacher, M.A., Goldsmith,
H.H., Alexander, A.L. Davidson, R.J.
(2005), Nature Neuroscience, 8, 19-525.
Two independent studies were conducted with
adolescent and adult males with autism/Aspergers
and typically developing control males.
Study I
Study II Control Autism Control
Autism n12 n11 n16
n16 age17 age16.1 age14.5
age14.5
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Study Designs Facial Emotion Discrimination
Facial Recognition
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Behavioral Measures How they performed the tasks
looked at the faces.
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Task Performance Reaction Time
Study I
Study II
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Eye-Tracking Gaze-Fixation
Control
Autism
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Gaze-fixation in Response to the Faces
Study I
Study II
ms
ms
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Brain Activation What areas of the brain were
active when they performed the task ?
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Study I Control - Autism Differences in Brain
Function during Facial Emotion
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Study II Control - Autism Differences in Brain
Function during Facial Recognition
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Does where they are looking on the face effect
how the brain is working?
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Brain Activation Associated with Eye-Fixation
Study I
Study II
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Can we predict brain activity based on
gaze-fixation?
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Rather than predicting a specific amount of
brain activation in a given region based on when
a face appears - an all-or-none stick function...
we can use the amount of gaze-fixation during a
given trial to predict brain activation in a
given region during that trial - a fixation based
relative function.
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Amygdala Activation Predicted by Relative Amount
of Eye-Fixation per Trial
Study I
Study II
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Gaze-fixation the Brain in Autism.
Proposed functional relevance of decreased
gaze-fixation in autism
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Follow-Up Future Research

• Whole vs. Part-Base Face Processing
• Multisensory Integration of Emotional Faces
  Voices
• Analyses of Skin Conductance, Pupillometry
  Heart Rate Variability
• Inclusion of Genetic Behavioral Comparison
  Groups
• Morphometric Connectivity Analyses

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Follow-Up Future Research

• Whole vs. Part-Base Face Processing
• Multisensory Integration of Emotional Faces
  Voices
• Analyses of Skin Conductance, Pupillometry
  Heart Rate Variability
• Inclusion of Genetic Behavioral Comparison
  Groups
• Morphometric Connectivity Analyses

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Genetic Behavioral Comparison Groups the
example of fragile X syndrome.
Main Goal To relate social/emotional deficits
and related brain function in autism to other
developmental disabilities with known genetic
etiologies and overlapping or obverse behavioral
phenotypes - specifically, fragile X syndrome.
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fragile X Syndrome Autism
Behavioral Phenotype

• Mild (female) to serve (male) mental retardation
• 15-25 also have a diagnosis of autism
• As many as 50-90 have at least one core autism
  feature
• Commonly seen characteristics include
  gaze-aversion and social withdrawal

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fragile X Group Study I
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Performance during emotional face processing
t(1,22) 2.42, p .02
t(1,18) 2.93, p .01
correct out of 40
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Relationship between performance IQ
General IQ
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Average feature fixation time.
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Relationship between face eye fixation time
IQ in fragile X.
Eye fixations r .65, p .055
Face fixations r .72, p .04
General IQ
Average fixation (ms)
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Group differences in Brain Activation during Face
Processing.
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Group differences in Brain Activation during Face
Processing (cont).
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Eye-fixation Brain Activation in fragile X.
Right Fusiform r .96, p lt .00001
Right Fusiform Left Fusiform
Average eye-fixation (ms)
Left Fusiform r .98, p lt .00001
signal change
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Brain Activation Predicted by Autism Severity
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Follow-Up Future Research

• Focus on objectively delineating the
  heterogeneity inherent in autism and fragile-X
  syndrome with and without autism (e.g. IQ,
  specific autism characteristics, fMR1 level).
• Relate differences in behavioral phenotypes
  outlined above to brain structure and function.
• Eventually draw ties between specific
  endophenotypes and underlying genotypes.
• Develop/hone endophenotypic specific treatments
  and interventions.

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Morphometric Connectivity Analyses
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Voxel Based Morphometry
Less white matter concentration in autism 2D
voxel-based morphometry. Chung, M.K., Dalton,
K.M., Alexander, A.L. Davidson, R.J. (2004),
NeuroImage, 23, 242-251.
Decrease white matter concentration in regions of
the -rostrum -genu -splenium
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Cortical Thickness Analyses
Cortical thickness analyses in autism with heat
kernel smoothing. Chung, M.K., Robbins, S.M.,
Dalton, K.M., Davidson. R.J., Alexander, A.L.
Evans, A.C. (2005) NeuroImage, 25, 1256-1265.
Regions of cortical thickness decrease in
autism -Right inferior orbital prefrontal
cortex -Left superior temporal sulcus -Left
occipito-temporal gyrus
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Regional Volume of Interest
Amygdala Pathology Predicts Autistic Social
Impairment. Nacewicz, B.M., Dalton, K.M.,
Johnstone, T., Long, M.T., McAuliff, E.A., Oakes,
T., Alexander, A.L. Davidson. R.J. (2005).
Submitted for Review.
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Functional Connectivity
Altered Functional Connectivity in Amygdala
Emotional Face Processing Circuitry in Autism.
Kelley, D., Dalton, K.M., Nacewicz, B.M.,
Johnstone, T., Chung, M.K., Schaeffer, H.S.,
Oakes, T., Alexander, A.L. Davidson. R.J.
(2005). Presentation at Society for Neuroscience.
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Diffusion Tensor Imaging (DTI)
-Indexes the random orientation dependent thermal
displacement of molecules (e.g. water) in
tissues. -Color-coded DTI image maps superimposed
on high resolution anatomical images depicts the
local fiber orientation. -Can be used to detect
differences in local fiber tracks or
neurocognitive nets.
DaSilva et al., 2003
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Thanks to Participants Parents!
Waisman Center
Marsha Seltzer Leonard Abbeduto Morton Ann
Gernsbacher H. Hill Goldsmith
Waisman Laboratory for Brain Imaging Behavior
Richard J. Davidson Andrew L. Alexander
Michael Anderle Lisa Angelos Moo Chung Donna
Cole Ronald Fisher Andrew Fox Larry
Greischar Laura Holsen Tom Johnstone Daniel
Kelley Micah Long Emelia McAuliff Andrea
McDuffie Brendon Nacewicz Matthew
Nersesian Terrance Oakes Hillary
Schaefer Zachary Zugin
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Contact Information
Web page brainimaging.waisman.wisc.edu/AutismWeb
email kmdalton_at_wisc.edu