This proposal aims to elucidate the functional organization of the whole brain in Autism Spectrum Disorders (hereafter referred to as autism), a group of neurodevelopmental disorders that affect roughly 1 in 110 individuals born today. I will test the overarching hypothesis that functional coupling between different regions of the brain in autism is generally reduced. Moreover, I will explore the prediction that such reduced connectivity is associated with abnormal behavior. While anatomical and functional evidence support reduced brain connectivity in autism, this has never been tested at the whole-brain level. In this application, I propose to acquire resting-state and stimulus-evoked Blood Oxygenation Level Dependent (BOLD) activity across the entire brain in high-functioning adults with autism and matched healthy control participants. A measure of functional connectivity will be derived from the resting-state BOLD activity, by examining the functional coupling across all regions of the brain in a pairwise manner. In each of 4 specific aims, I will test the following hypotheses: (1) that the autistic brain is generally less connected than normal, but that there is anatomical specificity to this reduction, (2) that the functional responsivity of the entire brain can be examined simultaneously in autism using complex naturalistic stimuli, and can be used to reveal which regions function abnormally in autism, (3) that abnormal resting-state functional connectivity is associated with reduced evoked activity in those same regions, and (4) that the functional properties of broadly distributed brain regions contain information that can be used to predict a diagnosis of autism.
Aims 1 &2 will be carried out during the training phase (K99) of the grant, while Aims 3 &4 will be completed during the independent phase (R00). The training component will consist of learning state-of-the-art functional imaging methods at the Caltech Brain Imaging Center, together with statistical techniques for pattern classification. Together, these studies will provide the first comprehensive picture of brain connectivity and brain activity in autism, and set the direction for my future career.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Career Transition Award (K99)
Project #
5K99MH094409-02
Application #
8293058
Study Section
Special Emphasis Panel (ZMH1-ERB-L (02))
Program Officer
Anderson, Kathleen C
Project Start
2011-07-01
Project End
2012-09-05
Budget Start
2012-07-01
Budget End
2012-09-05
Support Year
2
Fiscal Year
2012
Total Cost
$88,508
Indirect Cost
$6,556
Name
California Institute of Technology
Department
None
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Pantelis, Peter C; Kennedy, Daniel P (2016) Prior expectations about where other people are likely to direct their attention systematically influence gaze perception. J Vis 16:7
Byrge, Lisa; Dubois, Julien; Tyszka, J Michael et al. (2015) Idiosyncratic brain activation patterns are associated with poor social comprehension in autism. J Neurosci 35:5837-50
Wang, Shuo; Jiang, Ming; Duchesne, Xavier Morin et al. (2015) Atypical Visual Saliency in Autism Spectrum Disorder Quantified through Model-Based Eye Tracking. Neuron 88:604-16
Kennedy, Daniel P; Paul, Lynn K; Adolphs, Ralph (2015) Brain Connectivity in Autism: The Significance of Null Findings. Biol Psychiatry 78:81-2
Pantelis, Peter C; Byrge, Lisa; Tyszka, J Michael et al. (2015) A specific hypoactivation of right temporo-parietal junction/posterior superior temporal sulcus in response to socially awkward situations in autism. Soc Cogn Affect Neurosci 10:1348-56
Paul, Lynn K; Corsello, Christina; Kennedy, Daniel P et al. (2014) Agenesis of the corpus callosum and autism: a comprehensive comparison. Brain 137:1813-29
Tyszka, J Michael; Kennedy, Daniel P; Paul, Lynn K et al. (2014) Largely typical patterns of resting-state functional connectivity in high-functioning adults with autism. Cereb Cortex 24:1894-905
Di Martino, A; Yan, C-G; Li, Q et al. (2014) The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism. Mol Psychiatry 19:659-67
Kennedy, Daniel P; Adolphs, Ralph (2012) The social brain in psychiatric and neurological disorders. Trends Cogn Sci 16:559-72
Kennedy, Daniel P; Adolphs, Ralph (2012) Perception of emotions from facial expressions in high-functioning adults with autism. Neuropsychologia 50:3313-9