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

Social Cognitive and Affective Neuroscience, 2017, 81–94 doi: 10.1093/scan/nsw149 Advance Access Publication Date: 19 October 2016 Original article Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder John A. Richey,1 Merage Ghane,1 Andrew Valdespino,1 Marika C. Coffman,1 Marlene V. Strege,1 Susan W. White,1,2 and Thomas H. Ollendick1,2 1 2 Department of Psychology, Virginia Tech., 109 Williams Hall, MC0436 Blacksburg, VA 24061, USA and Virginia Tech Child Study Center, Suite 207, Turner St, Blacksburg, VA 24061, USA Correspondence should be addressed to : John A. Richey, Department of Psychology, Virginia Tech, 109 Williams Hall, MC0436, Blacksburg, VA 24061, USA. Email: . 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 ¼ 21) and age-, sex- and IQ-matched control subjects (N ¼ 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. Key words: social anxiety disorder; fMRI; reward; monetary incentive delay; nucleus accumbens; threat Introduction Social anxiety disorder (SAD) is a common and debilitating psychiatric disorder predominantly characterized by persistent fear of one or more social or performance situations (American Psychiatric Association and American Psychiatric Association and DSM-5 Task Force, 2013). Previous behavioral and neuroimaging studies of SAD have highlighted a central role for negative affects and threat-related neural circuits in symptom expression, primarily including a limbic–medial prefrontal circuit that involves enhanced processing of threat stimuli (Phan et al., 2006; Goldin et al., 2009; Etkin, 2010; Schmidt et al., 2010; Hattingh et al., 2013). Additionally, recent work has also suggested that SAD may be uniquely characterized by diminished positive affect (Brown et al., 1998; Kashdan, 2007; Alden et al., 2008; Morrison and Heimberg, 2013; Weeks, 2015), which may mechanistically relate to its development and maintenance (Caouette and Guyer, 2014; Haller et al., 2015) and cannot be accounted for by depressive symptomatology (Kashdan, 2007; Eisner et al., 2009; Weeks, 2015). Despite the increasing interest in characterizing psychiatric disorders in terms of positively and negatively valenced motivational systems (Insel et al., 2010; Casey et al., 2014; Insel, 2014) and the potential to inform treatment development, few studies have examined the Received: 10 December 2015; Revised: 12 September 2016; Accepted: 4 October 2016 C The Author (2016). Published by Oxford University Press. For Permissions, please email: V 81 82 | Social Cognitive and Affective Neuroscience, 2017, Vol. 12, No. 1 mechanisms of positive affect deficits in SAD within the functional neurobiology of reward. Reward processing in typically developing humans and nonhuman primates is mediated by dense dopaminergic projections originating from the ventral tegmental area (VTA) that project to the striatum, the orbitofrontal cortex (OFC), the ventromedial prefrontal cortex (vmPFC) and the anterior cingulate cortex (Haber and Knutson, 2010). Collectively, these regions form a mesolimbic dopamine pathway that is sensitive to both the magnitude and the probability of reward (Schultz, 1998; Ikemoto and Panksepp, 1999; Schultz, 2000; Berridge et al., 2009; Saddoris et al., 2015). In particular, patterned firing of dopaminergic neurons in the nucleus accumbens (NAc) is thought to encode incentive motivation related to approach behaviors toward salient goals (Knutson et al., 2001; Knutson and Cooper, 2005; Kim et al., 2006; Bjork and Hommer, 2007; Forbes et al., 2009). Comparative research further suggests that dopamine-mediated responses in NAc are increased during anticipation of learned cue-outcome associations (Martin and Ono, 2000; Melendez et al., 2002), which are thought to be broadly reflective of the motivational relevance of upcoming events (Carter et al., 2009) and related to the modulation and planning of complex motivated behavior (Mogenson et al., 1980; Roesch et al., 2009). Social interaction mobilizes the same mesolimbic network that is active while processing non-social rewards such as food, money, sex and drugs of addiction (Koob and LeMoal, 1997; Izuma et al., 2008; Rilling et al., 2008; Spreckelmeyer et al., 2009; Rademacher et al., 2010; Trezza et al., 2011). Such reward network responses toward social information are also present during both anticipatory and outcome periods (Hayden et al., 2007; Winston et al., 2007; Rademacher et al., 2010), suggesting that behavior is strongly guided by both the motivation to attain social rewards and the enjoyment of such rewards once received (Ruff and Fehr, 2014). While convergent evidence suggests that in typically developing individuals, social cohesion and affiliation are associated with increase in striatal responses to social cues, this perspective also suggests that reduced striatal activation during the assignment of values to social stimuli ought to be associated with degraded social affiliation and perceptions of weaker social bond formation, both of which are observed in SAD (Mathew et al., 2001; Fox and Kalin, 2014; Haller et al., 2015). Consistent with this conceptualization, relatively early PET imaging studies demonstrated altered striatal functions in SAD, which may be rooted in abnormal central dopamine function, linked to dopamine D2 receptor and dopamine transporter (DAT) availability i (...truncated)