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Neural mechanisms of sensory reactivity and regulation in autism across development

Award Number: R01MH124977
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Neural mechanisms of sensory reactivity and regulation in autism across development - PROJECT SUMMARY/ABSTRACT Sensory over-responsivity (SOR) is an impairing condition manifested as extreme sensitivity to stimuli such as loud noises or being touched. SOR is present across neurodevelopmental disorders, but is particularly prevalent in youth with autism spectrum disorders (ASD) with rates of at least 56-70%. SOR is a fundamental limitation to individuals’ ability to participate in the community, succeed in school, complete daily living tasks, and interact socially. Despite this, there are almost no empirically-based treatments for SOR, in part due to the lack of understanding of its underlying biological mechanisms. Furthermore, while SOR tends to decline across adolescence into adulthood, there is little understanding as to why and for whom it improves. Thus, the primary goals of this study are to identify the developmental course of SOR as well as neurobiological mechanisms through which it can be attenuated, both essential to developing interventions. Our team has conducted some of the first studies identifying key neural mechanisms of SOR across youth with ASD, including 1) over-reactive brain responses/reduced habituation in primary sensory cortices and amygdala, 2) reduced thalamic GABA, and 3) reduced prefrontal cortex (PFC)-amygdala functional connectivity during aversive sensory stimulation. Our prior studies also indicate that the subset of youth with ASD but low SOR show heightened amygdala-prefrontal connectivity during sensory stimulation, suggesting a mechanism for resilience against SOR. Our preliminary data also suggest that amygdala reactivity to aversive sensory stimulation declines with age while PFC activation increases. This proposal seeks to build on this foundation by examining biological mechanisms through which SOR may be attenuated either through natural development or through direct intervention, with the goal of proximate translation to treatment. Using a combined cross-sectional and longitudinal design, we will examine: 1) developmental changes in sensory reactivity in ASD compared to typically developing (TD) children; 2) developmental changes in two candidate neural mechanisms of sensory regulation (thalamic GABA and PFC- amygdala connectivity), and 3) the relative ability of two different emotion regulation strategies (attention cuing vs. reappraisal) in engaging sensory regulation. Based on our prior studies and preliminary data, we expect to see that behavioral and neural markers of SOR decrease with age, but that this decline happens later than is typical for youth with ASD, indicating a developmental delay in sensory regulation. We further expect that of our two candidate top-down mechanisms of sensory regulation that prefrontal-amygdala connectivity but not thalamic GABA will improve with development, which will inform our understanding of why SOR decreases with age and how best to treat it at different stages of development. Finally, we will compare the relative ability of attention cuing vs. reappraisal to engage PFC for youth of different ages and SOR severity. Results will directly inform both behavioral and psychopharmacological personalized interventions for SOR.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	5	11/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $747,382 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	5	9/18/2025	NON-COMPETING CONTINUATION	$112,107
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	5	1/24/2025	NON-COMPETING CONTINUATION	$635,275
														Subtotal = $747,382

Issue Date FY: 2024 ( Subtotal = $763,099 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	4	1/19/2024	NON-COMPETING CONTINUATION	$686,788
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	4	8/14/2024	NON-COMPETING CONTINUATION	$76,311
														Subtotal = $763,099

Issue Date FY: 2023 ( Subtotal = $659,760 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	3	1/20/2023	NON-COMPETING CONTINUATION	$659,760
														Subtotal = $659,760

Issue Date FY: 2022 ( Subtotal = $687,877 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	2	1/20/2022	NON-COMPETING CONTINUATION	$619,090
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	2	6/21/2022	NON-COMPETING CONTINUATION	$68,787
														Subtotal = $687,877

Issue Date FY: 2021 ( Subtotal = $777,916 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	000	1	3/26/2021	NEW	$700,123
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Mental Health Research Grants	001	1	4/28/2021	NEW	$77,793
														Subtotal = $777,916

Grand Total All Awards = $3,636,034

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Neural mechanisms of sensory reactivity and regulation in autism across development

Award Number: R01MH124977

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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