2011 — 2014 |
Kennedy, Daniel Patrick |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Investigating Brain Connectivity in Autism At the Whole-Brain Level @ California Institute of Technology
DESCRIPTION (provided by applicant): 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.
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2017 — 2021 |
Kennedy, Daniel Patrick |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Using Complex Video Stimuli to Elucidate Atypical Brain Functioning in Asd @ Indiana University Bloomington
ABSTRACT A major gap in our understanding of autism spectrum disorder (ASD) is in knowing how the brain functions during conditions that approximate the complex processing demands of the real world. Instead, almost everything we know about brain functioning in ASD comes from reductionist studies that often use highly simpli?ed stimuli and isolated task demands, or even from studies that lack a stimulus or task altogether, as in the case of resting-state functional connectivity. Yet, successful processing ?in the wild? (i.e., in the real world) relies on the simultaneous engagement and seamless integration of multiple brain regions, brain networks, and cognitive processes. Understanding how these neural systems behave and interact during real-time processing of complex and dynamic stimuli, therefore, is critical for understanding how real-world behavior and cognition emerge from brain activity, and this remains a major gap in our understanding of ASD. The purpose of the current proposal is to ?ll this gap, by using complex video stimuli that sample broadly from the natural world and engage multiple diverse perceptual and cognitive systems simultaneously, thus evoking activity across the entire brain at once. From this data, rich high-dimensional measures can be generated and used in combination with multivariate analytic methods ideally-suited to detect idiosyncratic and heterogeneous patterns of neural responding, which can then be related back to phenotypic variability across individuals. Our proposed studies will take place over 5 years and include 4 speci?c aims. In the ?rst two aims, we will identify neural systems most affected in ASD during the presentation of a complex video stimulus, parse the heterogeneity at the neural level using data-driven approaches and relate it back to heterogeneity at the behavioral level, and explore the stimulus dimensions (social and non-social alike, both sampled broadly) that underlie these neural abnormalities. In a third aim, we will examine video-evoked functional connectivity both within and across brain networks, comparing this directly against resting-state connectivity, and examining both modes of functional connectivity across various timescales (including dynamic coupling). A ?nal exploratory aim will assess the short-term and long-term stability of these measures, as well as their sensitivity in tracking change following experimental perturbation?important characteristics for potential biomarkers and/or predictor and outcome measures for use in intervention studies. Altogether, this work will provide new insight into brain activity and brain connectivity during conditions that more closely re?ect processing demands of the natural world, help to link individual differences in brain functioning with individual differences in behavior (i.e., heterogeneity), and assess whether these neural measures may be viable candidates as biomarkers for use in future studies. This proposal addresses the Interagency Autism Coordinating Committee's Strategic Plan (2013 Update) that includes comprehensive examination of the neural circuitry in individuals with ASD across the lifespan, including throughout adulthood, as well as a focus on heterogeneity.
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