Waisman Laboratory for Brain Imaging

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Waisman Laboratory for Brain Imaging
Behavior
University of Wisconsin - Madison
Brain function gaze-fixation during facial
emotion processing Comparisons between fragile-X
autism.
Kim Dalton Andrea McDuffie Matthew
Nersesian Andrew Alexander Richard Davidson
Gatlinberg Conference - March 2006, San
Diego, CA
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Acknowledgments

• Thanks to all the participants families for
  their time and support!

NICHD Post-Doctoral Training Grant Waisman Core
Grant Leonard Abbeduto Marsha Seltzer NIH
STAART Grant Helen Tager-Flusberg Richard
Davidson NARSAD Distinguished Investigator Award
Richard Davidson NARSAD Seaver Investigator
Award Kim Dalton NAAR Investigator Award Kim
Dalton
Waisman Laboratory for Brain Imaging
Behavior Andrew Alexander Michael Anderle Ronald
Fisher Laura Holsen Tom Johnstone Daniel
Kelley Emilia McAuliff Brendon
Nacewicz Donna Schaann
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fragile-X syndrome autism

• fragile-X is the most common inherited cause of
  mental retardation with a know genetic etiologly
  (over expansion of the CGG repeat on the X
  chromosome), (Kauffmann Reiss, 1999).
• 2.5 - 6 of the individuals with autism spectrum
  have fragile-X and 15-25 of individuals with
  fragile-X have autism, (Hagerman, 2002).
• approximately 50-90 of individuals with
  fragile-X exhibit at least one core
  characteristic of autism, primarily in
  social/emotional impairments such as poor peer
  relations and social skills, (Hagerman et al,
  1986 Dykens Volkmar, 1997 Rogers et al, 2001
  Kauffmann et al, 2004).

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Theoretical Perspective
Hypothesis autism and autistic symptoms in
fragile-X syndrome reflect a common etiological
or pathophysiological pathway underlying the two
conditions. (NIH PA-05-108) Particularly in
the realm of social/communication deficits.
(Kauffmann et al, 2004)
Specific Aim To investigate the underlying
abnormalities in the neural circuitry of
emotional face processing associated with
fragile-X and relate these differences to autism
characteristics and behavioral phenotype within
fragile-X individuals.
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Face Processing Gaze-Fixation in Autism

• Deficits in attention, learning discrimination
  of human faces, (Osterling, Dawson Munson,
  2002 Joseph Tager-Flusberg, 1997).
• Disproportionate attention to the mouth versus
  eyes, (Klin et al., 2002 Schultz et al., 2002).
• Tendency not to show the face inversion effect,
  (Hobson, Ouston Lee, 1998).
• More detailed, less specialize rather than a
  more specialized configural process, (Joseph
  Tanaka, 2003).

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Emotional Face Processing Task

• 40 human faces each face presented for 3 sec
  with 5, 6 or 7 sec in between faces (average 6
  sec).
• 24 emotional faces (8 each of happy, fear
  anger) 16 neutral faces.
• 20 faces looking straight ahead 20
  quarter-turned (10 to right and 10 to left)
• Responses press the first button if the face is
  neutral or plain (has no emotion) or press the
  second button if the face has any type of
  emotional expression (happy, fear or anger).

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Participant Groups
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Relationship between general IQ Autism
Characteristics in fragile-X
r -.71, p .03
general IQ
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Performance on 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
correct out of 40
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Average face feature fixation time
p.03
ms
p.10
p.02
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Relationship between face eye fixation time
IQ in fragile-X
Face fixations r .72, p .04
Eye fixations r .65, p .055
General IQ
Average fixation (ms)
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Group differences in Brain Activation
Fusiform Gyrus Insula Post
Central Gyrus Superior Temporal
Control Autism fragile-X
signal change
Time from stimulus onset (s)
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Group differences in Brain Activation

significant from Control significant from
Autism


signal change




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Eye-fixation Brain Activation in fragile-X
Right Fusiform Left Fusiform
Right Fusiform r .96, p lt .00001
Average eye-fixation (ms)
Left Fusiform r .98, p lt .00001
signal change
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Autism Characteristics Brain Activation in
fragile-X
Left Amygdala Right Fusiform
Left Amygdala r .82, p .01
Social Communication Questionnaire
Right Fusiform r -.93, p .0001
signal change
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Summary of Findings

• Autism characteristics are negatively correlated
  with general IQ in fragile-X.
• the fragile-X group showed a tendency for
  diminished eye-fixations and both eye and
  face-fixations were positively correlated with
  IQ.
• the fragile-X group showed diminished fusiform
  activation and enhanced activation in insula,
  post-central gyrus and superior temporal sulcus
  during the task.
• fusiform activation was strongly and positively
  correlated with eye-fixation and negatively
  correlated with autism characteristics in
  fragile-X, independent of IQ.
• amygdala activation was positively correlated
  with autism characteristics in fragile-X but this
  was confounded with IQ.

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Future Research Directions

• 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.

Thank You for Your Attention!