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.

Distorted empathic processing has been observed across multiple psychiatric disorders. Simulation theory provides a theoretical framework that proposes a mechanism through which empathy difficulties may arise. Specifically, introspection-centric simulation theory (IST) predicts that an inability to accurately interpret and describe internal affective states may lead to empathy difficulties. The purpose of this review is to synthesize and summarize an empirical literature suggesting that simulation theory provides insights into a cognitive and neurobiological mechanism (i.e., alexithymia and insula pathology) that negatively impacts empathic processing, in addition to how disruptions in these processes manifest across psychiatric disorders. Specifically, we review an emerging non-clinical literature suggesting that consistent with IST, alexithymia and associated insula pathology leads to empathy deficits. Subsequently, we highlight clinical research suggesting that a large number of disorders characterized by empathy pathology also feature alexithymia. Collectively, these findings motivate the importance for future work to establish the role of alexithymia in contributing to empathy deficits across clinical symptoms and disorders. The current review suggests that simulation theory provides a tractable conceptual platform for identifying a potential common cognitive and neural marker that is associated with empathy deficits across a wide array of diagnostic classes.

Sustaining attention to the task at hand is a crucial part of everyday life, from following a lecture at school to maintaining focus while driving. Lapses in sustained attention are frequent and often problematic, with conditions such as attention deficit hyperactivity disorder affecting millions of people worldwide. Recent work has had some success in finding signatures of sustained attention in whole-brain functional connectivity (FC) measures during basic tasks, but since FC can be dynamic and task-dependent, it remains unclear how fully these signatures would generalize to a more complex and naturalistic scenario. To this end, we used a previously defined whole-brain FC network - a marker of attention that was derived from a sustained attention task - to predict the ability of participants to recall material during a free-viewing reading task. Though the predictive network was trained on a different task and set of participants, the strength of FC in the sustained attention network predicted reading recall significantly better than permutation tests where behavior was scrambled to simulate chance performance. To test the generalization of the method used to derive the sustained attention network, we applied the same method to our reading task data to find a new FC network whose strength specifically predicts reading recall. Even though the sustained attention network provided significant prediction of recall, the reading network was more predictive of recall accuracy. The new reading network's spatial distribution indicates that reading recall is highest when temporal pole regions have higher FC with left occipital regions and lower FC with bilateral supramarginal gyrus. Right cerebellar to right frontal connectivity is also indicative of poor reading recall. We examine these and other differences between the two predictive FC networks, providing new insight into the task-dependent nature of FC-based performance metrics.

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Only a portion of individuals experiencing chronic stress and associated increases in inflammation go on to develop pathological elevations in mood and anxiety symptoms. Some prevailing models suggest that the outcomes of chronic stress may largely depend on individual differences in perceived control. In the current study, we used this theoretical framework to disambiguate the influence of autonomic arousal and perceived control on inflammatory and psychological outcomes in a large sample of adults from the Midlife in the United States dataset (wave 2; MIDUS-2) (Final N ​= ​1030), and further replicated our approach in a second (MIDUS-Refresher) cohort (Final N ​= ​728). Using k-means clustering we created subgroups systematically differing in subjective arousal (high/low) and perceived control (low/high) and compared these subgroups on inflammatory markers and psychological outcomes. Overall results showed that individuals in the high subjective arousal subgroups had higher levels of IL-6, CRP, and FIB, independent of level of CNTL. However, distinctive, and pathological psychological symptom patterns became more apparent when individuals were characterized by both subjective arousal and perceived control. These findings suggest that subtyping individuals based on subjective arousal and perceived control can help us disentangle pathological versus adaptive mental health outcomes in those with co-occurring inflammation and may help identify those vulnerable to psychopathology in the context of physical or psychological stressor exposure.

Overactivation of proinflammatory pathways in response to stress may play an important role in the pathophysiology of psychiatric disorders such as major depressive disorder. Autonomic arousal in response to chronic stress has been mechanistically linked to the activation of proinflammatory pathways. However, not all individuals who experience chronic stress or increased inflammation develop pathological elevations in symptoms of mood and anxiety disorders. This heterogeneity poses a challenge in using inflammation as a marker of individual risk or vulnerability for related psychiatric conditions. Rodent models of pathological stress suggest that the outcomes of chronic stress may largely depend on individual differences in perceived control. In the current study, we used this theoretical framework to disambiguate the influence of autonomic arousal and perceived control on inflammatory and psychological outcomes in a large sample of adults from the Midlife in the United States dataset (wave 2; MIDUS-2) (Final N=1030), and further replicated our approach in a second (MIDUS-Refresher) cohort (Final N=728). Using k-means clustering we created subgroups systematically differing in subjective arousal (high/low) and perceived control (low/high) and compared these subgroups on inflammatory markers and psychological outcomes. Overall results showed that high subjective arousal uniquely and reliably predicted higher levels of Interleukin-6, C-Reactive Protein, and Fibrinogen. However, domain specific heterogeneity in pathological and adaptive affective outcomes, depended on both subjective arousal and perceived control. These results further extend and expand upon basic work in rodent models of stressor controllability and illustrate a useful way to probe mechanistic phenotypes in humans.