Discussion
The objective of the present study was to examine neural responses to negative social and non-social reinforcement in children and adolescents with ASD by using an incentive delay task. We found that children with ASD demonstrated reduced activation of the right caudate nucleus while anticipating monetary reward loss and reduced activation of several mesolimbic (amygdala, caudate nucleus, NAc, and putamen) and prefrontal cortical regions (ACC, frontal pole, inferior frontal gyrus, and insula) while anticipating sad faces presented in the context of a reward task. Across both groups, reduced activation of the right caudate nucleus while anticipating negative non-social reinforcement was negatively associated with SRS social motivation scores (that is, reduced responsivity to monetary loss cues was associated with greater impairment in social motivation).
This study extends the existing body of literature addressing the processing of social and non-social positive reinforcers in ASD and provides evidence that individuals with ASD may be hyporesponsive in canonical reward processing regions to the anticipation of potential social and non-social negative reinforcement. These findings complement previous studies of neural responses to reward gains in ASD, which have found attenuated activation of mesolimbic brain regions in response to social and monetary reward gains in ASD [
8-
11]. This study also supports previous research that the motivation to avoid failure or punishment is associated with different physiological responses in ASD and is differentially related to personality and clinical measures [
13]. In addition, this study found evidence that the anticipation of negative social reinforcers is associated with hypoactivation of a more extensive network of frontostriatal regions than the anticipation of monetary reward loss in ASD, which corroborates several studies demonstrating greater deficits in social versus non-social reward processing in ASD [
9,
10].
When considered alongside the extant literature on reward processing in ASD, these results provide evidence that impaired social motivation in this population may involve attenuated responsivity to cues for both positive social reinforcement
and negative social reinforcement. Reduced responsivity to negative social cues may contribute to the tendency of individuals with ASD to be less attuned to social exclusion [
67] and thus less likely to engage in prosocial behaviors that build social relationships. This attenuated response to negative social reinforcement may be a particularly powerful factor in reduced social motivation since the motivation to avoid negative social reinforcement may be greater than the drive to seek out social rewards in individuals without ASD [
46].
In particular, our finding of reduced NAc activation while anticipating a sad face suggests that negative social reinforcement may be less salient for individuals with ASD, given the critical role of the NAc in incentive salience [
21,
22]. Reduced activation of the dorsal striatum in the ASD group while anticipating negative social reinforcement is also notable given the role of the dorsal striatum in instrumental learning [
30]. This finding suggests that children with ASD may be impaired in learning to anticipate negative social situations. For example, children with ASD may not learn which actions are associated with social rejection or how to apply this knowledge to modify their behavior. Accordingly, children with ASD may continue to act in a way that may be considered awkward or inappropriate by their peers even after experiencing negative social consequences for these behaviors - a conceptualization that is consistent with the literature indicating deficits in social reward learning in ASD [
9,
68].
The finding of reduced activation in both the ventral striatum and dorsal striatum for social negative reinforcement and reduced activation only in the dorsal striatum for non-social negative reinforcement is notable in light of models that delineate distinct functional roles for these regions in reward processing [
30,
69]. According to these models, the NAc serves as the ‘director’ or ‘critic’, which evaluates reward outcomes in order to learn how to predict future rewards. On the other hand, the dorsal striatum serves as the ‘actor,’ which codes for the action used to obtain a reward in order to guide future reward-related behavior. Although both the ventral striatum and dorsal striatum may code for motivational salience [
21,
22], the dorsal striatum in particular plays an important role in linking behavior to reward information [
29,
30] and is critical to instrumental learning [
70]. The dorsal striatum is also critically involved in the development of habits, which are ritualized behaviors that are initiated based on positive and negative reinforcers yet persist even after reward devaluation or omission [
12,
71]. Therefore, hypoactivation of the dorsal striatum while anticipating negative social reinforcement may ultimately result in an inability to develop and maintain ritualized social behavior and other habitual behaviors in the absence of consistent reward feedback.
Atypical responding to cues predicting potential negative social reinforcement in ASD has important implications for reward learning, which occurs when there is a mismatch between an expected and an actual event. This mismatch is referred to as a prediction error [
72-
76], and it reflects the integration of information about current and predicted rewards. Learning occurs during both positive prediction errors (‘better than predicted’) and negative prediction errors (‘worse than predicted’) [
77]. Therefore, atypical processing of cues for negative reinforcement would likely impact the ability to learn from prediction errors during reward feedback, and future studies that model outcome prediction errors will be needed to confirm the role of atypical striatal activation during outcome violations in the context of reward learning in ASD.
More broadly, the present findings provide further support that ASD may be characterized by domain-general dysfunction of brain reward circuitry. The present study, along with previous studies on this topic [
8-
11], have consistently found evidence for atypical reward circuit activation across a range of different study methodologies involving both reward loss and gain and both social and non-social stimuli. However, these domain-general findings raise the possibility that this atypicality may reflect a more basic neural dysfunction in ASD. For instance, ASD is characterized by atypical brain connectivity [
78], including atypical connectivity of reward circuitry [
79]. Thus, atypical reward circuitry activation may be a reflection of more widespread atypicalities of network connectivity in ASD. Alternatively, these results may be attributable to impairments in processing complex or abstract tasks as in the present study, as individuals with ASD may show atypicalities in processing complex stimuli [
80,
81] or in maintaining abstract internal representations [
82,
83].
The present study also found negative correlations between SRS social motivation scores and the magnitude of activation in the right caudate nucleus during monetary loss anticipation. These results indicate that the children and adolescents with ASD who were least sensitive to non-social negative reinforcers were characterized by greater impairments in social motivation. These findings highlight the clinical relevance of neural responses to negative reinforcers for social functioning in children and adolescents with ASD.
Limitations of the present study include the modest sample size, although it is commensurate with previous neuroimaging studies of reward processing in children with ASD [
9,
10]. Another limitation is the exploratory nature of the correlational analyses, which were not corrected for multiple comparisons. In addition, images of sad faces served as proxies for negative reinforcement in naturalistic social interactions - a complex and dynamic process that may involve facial expressions of anger, frustration, or social disapproval rather than sadness.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
CRD and GSD were involved in the study design, coordinating the study, data collection, analysis and interpretation of the data and drafting the manuscript. DCC, KD, EKH, SM, LTB, and MK were involved in the collection and analysis of data and drafting the manuscript. JB, JS, and JK were involved in the data analysis and drafting the manuscript. All authors read and approved the final manuscript.