Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder

Abstract

Social anxiety disorder (SAD) involves abnormalities in social motivation, which may be independent of well-documented differences in fear and arousal systems. Yet, the neurobiology underlying motivational difficulties in SAD is not well understood. The aim of the current study was to spatiotemporally dissociate reward circuitry dysfunction from alterations in fear and arousal-related neural activity during anticipation and notification of social and non-social reward and punishment. During fMRI acquisition, non-depressed adults with social anxiety disorder (SAD; N = 21) and age-, sex- and IQ-matched control subjects (N = 22) completed eight runs of an incentive delay task, alternating between social and monetary outcomes and interleaved in alternating order between gain and loss outcomes. Adults with SAD demonstrated significantly reduced neural activity in ventral striatum during the anticipation of positive but not negative social outcomes. No differences between the SAD and control groups were observed during anticipation of monetary gain or loss outcomes or during anticipation of negative social images. However, consistent with previous work, the SAD group demonstrated amygdala hyper-activity upon notification of negative social outcomes. Degraded anticipatory processing in bilateral ventral striatum in SAD was constrained exclusively to anticipation of positive social information and dissociable from the effects of negative social outcomes previously observed in the amygdala. Alterations in anticipation-related neural signals may represent a promising target for treatment that is not addressed by available evidence-based interventions, which focus primarily on fear extinction and habituation processes.

Impaired generalization of reward but not loss in obsessive-compulsive disorder

“…Conversely, gain learning in OCD is associated with “hypoactivation” of neural circuits associated with reward learning, including the nucleus accumbens (Figee et al, 2011; Jung et al, 2013; Kaufmann et al, 2013). For the SAD group, the lack of impaired reward generalization in in this study is consistent with suggestions that aberrant reward processing in SAD may be specific to social reward cues (Richey et al, 2017). …”

Nuclear Neuroimaging in Social Anxiety Disorder: A Review

“…The observation that people with SAD tend to avoid social interactions (and the rewards they may confer) has led some investigators to hypothesize that disrupted reward processing may be a feature of the condition (51). There is emerging evidence from fMRI work that this is indeed the case (27,38), although exactly which components of reward processing are involved is still unclear. In this context, the as yet limited and inconsistent results from nuclear imaging studies that have investigated dopaminergic targets (DAT and the inhibitory D 2 /D 3 family of receptors) in SAD are difficult to reconcile.…”

“…The dopaminergic system has an established role in reward processing. Social interaction activates the reward system in ways similar to nonsocial rewards such as money, food, or addictive substances (27). The rewards achieved through personal interactions are thought to drive social affiliation.…”

“…Conflicting results from these few nuclear imaging studies emphasize the need for further research to establish the role (if any) of dopamine in the disorder. Continued interest in dopamine is supported by several recent fMRI studies of the reward system in SAD (27,38).…”

Reward Circuitry and Motivational Deficits in Social Anxiety Disorder: What Can Be Learned From Mouse Models?

“…One potentially promising avenue has identified dysfunction in the mesolimbic dopamine (DA) system, which has been linked to observations of motivational deficits in SAD, and consistent with a social anhedonic phenotype, which has been linked as a correlate of SAD (Tiihonen et al, 1997;Schneier et al, 2000Schneier et al, , 2008Cremers et al, 2015;Richey et al, 2013Richey et al, , 2017Richey et al, , 2019; but see also Schneier et al, 2009), but not other anxiety disorders such as generalized anxiety disorder (Brown et al, 1998). Dysfunction in the ventral striatum (VS) is central to this model, with a number of studies demonstrating reduced activity in the VS in relation to social but not non-social incentives (Richey et al, 2013(Richey et al, , 2017Maresh et al, 2014). Yet, despite the potential promise of this approach, remarkably little is known about the details and neurobiological relevance of DAergic neurocircuitry in SAD.…”