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.
