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Neural mechanism of reward processing in autistic adolescents

Award Number: R21MH137759
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/08/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Neural mechanism of reward processing in autistic adolescents - PROJECT SUMMARY Social deficits are a primary characteristic of autism spectrum disorder (ASD). The social motivation hypothesis posits that these deficits reflect alterations in social information processing, including a blunted reward response to social stimuli. Neuroimaging research suggests this blunting may generalize beyond the social domain. Given the considerable resources devoted to motivation and reinforcement-based interventions, it is essential to identify the extent that blunted reward processing influences the entire spectrum of autism (i.e., beyond social motivation) and to identify the neural mechanisms that contribute to said blunting. Proposed aims make substantive progress towards answering these questions in neurotypical (NT; N=50) vs. autistic (N=50) youths. We focus on emerging adolescence (10-15 years; 20% female reflecting autism prevalence) as it is a critical phase of development when peer feedback gains salience in NT youth and social deficits increase in autistic youth. Significance is derived from three factors. First, we address two shortcomings in fMRI study design that have hindered progress towards isolating ASD-related differences in reward processing: A) Most studies fail to directly compare neural response to social (e.g., viewing a smiling face) and non-social (e.g., winning money) outcomes. B) Social stimuli typically used to study reward fail to model the experience of actually being liked by peers (i.e., direct social reward). To overcome these shortcomings, we developed an fMRI-based feedback paradigm that quantifies neural response to reward in social (being liked) and non-social (winning money) domains. Aim 1 uses this paradigm to isolate differences in neural response to social and non-social reward. This will be the first fMRI study to test ASD-related neural response to direct social reward. Second, we address a major knowledge gap in the social motivation hypothesis - the extent to which ASD symptoms relate to dopamine (DA) system function in brain. Animal models of autism suggest that DA system dysfunction contributes to blunted reward processing. However, testing human correlates has proved challenging because it requires invasive techniques involving radioactivity. Recent advances have demonstrated that neuromelanin-MRI (NM-MRI) can be used as a non- invasive proxy for measuring DA system function. Aim 2 quantifies differences in midbrain DA system function via NM-MRI. If awarded, this study will be the first to apply NM-MRI in ASD research. Third, in Aim 3, we lay the foundation for a novel approach to individualized treatment by testing the extent to which DA system function influences relations between ASD and blunted reward response. Gold standard interventions (e.g., Applied Behavioral Analysis, ABA) rely on intact reward processing for maximal effect. If DA system deficits diminish neural response to reward, this may explain variation in treatment outcomes. NM-MRI could identify those who may benefit most (or least) from ABA, and identify novel pharmacological targets to treat core symptoms of ASD.


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	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Mental Health Research Grants	000	2	5/20/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $185,787 )
2025	2025	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Mental Health Research Grants	000	2	8/5/2025	NON-COMPETING CONTINUATION	$185,787
														Subtotal = $185,787

Issue Date FY: 2024 ( Subtotal = $255,362 )
2024	2024	TEMPLE UNIVERSITY-OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	1805 N BROAD ST	PHILADELPHIA	PA	19122	PHILADELPHIA	USA	Mental Health Research Grants	000	1	7/8/2024	NEW	$255,362
														Subtotal = $255,362

Grand Total All Awards = $441,149

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Neural mechanism of reward processing in autistic adolescents

Award Number: R21MH137759

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/08/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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