Oxytocin Modulates Amygdala Reactivity to Masked Fearful Eyes

Abstract

The amygdala reveals enhanced reactivity to fearful eye whites, even when they are backwardly masked by a neutral face and therefore processed with limited visual awareness. In our fMRI study, we investigated whether this effect is indeed associated with fear detection within the eyes of the neutral face mask, or more generally, with reactivity to any salient increase in eye white area. In addition, we examined whether a single dose of intranasal oxytocin would modulate amygdala responses to masked fearful eye whites via a doubleblind, placebo-controlled pharmacological protocol. We found that increased amygdala responses to salient changes within a face's eye region occurred specifically for masked fearful eyes but not for similar increases in white area as induced by nonsocial control stimuli. Administration of oxytocin attenuated amygdala responses to masked fearful eye whites. Our results suggest that the amygdala is particularly tuned to potential threat signals from the eye region. The dampening effects of oxytocin on early amygdala reactivity may reflect reduced vigilance for facial threat cues at a preconscious level. Future studies may investigate whether this early modulation accounts for the beneficial effects of oxytocin on social cognition in anxiety-related disorders, as suggested by previous studies.

A face versus non-face context influences amygdala responses to masked fearful eye whites

“…Increased amygdala activity to face-masked fearful eye whites is consistent with findings from previous studies (Whalen et al , 2004; Straube et al , 2010; Kanat et al , 2015) and further supports the notion that the amygdala is sensitive to crude, low-level representations of threat-related stimuli even when the level of awareness is restricted (LeDoux, 1996). By showing an increase in amygdala activity to face-masked fearful eye whites that are comparable to other reports of increased amygdala activity to face-masked fearful faces (Morris et al , 1998; Whalen et al , 1998; Rauch et al , 2000; Etkin et al , 2004; Pessoa et al , 2006; Williams et al , 2006; Kim et al , 2010), the present findings further support the idea that the eyes—especially the eye whites (i.e., sclera)—are a face region from which meaningful predictive information is extracted (Whalen, 1998; Morris et al , 2002; Sekuler et al , 2004; Adolphs et al , 2005).…”

“…These effects are observed even when the level of awareness or attention is restricted (Mogg and Bradley, 1999; Ohman et al , 2001). In order to investigate this automaticity, numerous laboratories have used the backward masking paradigm (Morris et al , 1998; Whalen et al , 1998; Etkin et al , 2004; Armony et al , 2005; Pessoa et al , 2006; Williams et al , 2006; Ohman et al , 2007; Jessen and Grossman, 2014; Kanat et al , 2015). In a typical backward masking experiment using emotional facial expressions, a target stimulus (e.g., a fearful face) is presented briefly, then immediately replaced by a mask stimulus (e.g.…”

A Precision Medicine Approach to Oxytocin Trials

“…In early studies, researchers documented the anxiolytic effect of IN-OT (24 IU) and showed that subjects who received both OT and social support exhibited the lowest cortisol concentrations and displayed decreased anxiety during the Trier Social Stress Test (Heinrichs et al 2003). This reduction in anxiety and fear is in line with an increasing body of evidence showing that IN-OT reduces the BOLD activity of the amygdala region in response to faces (Domes et al 2007a; Kanat et al 2015a, b; Kirsch et al 2005). Importantly, IN-OT attenuates heightened amygdala reactivity to fearful faces in patients with generalized social anxiety disorder (GSAD) (Labuschagne et al 2010).…”

Effects of route of administration on oxytocin-induced changes in regional cerebral blood flow in humans

“…The suppression of amygdala's activity constitutes one of the most robust findings in animal studies and intranasal OT studies in men (37,(41)(42)(43). For instance, the dampening of the amygdala BOLD response to negative affective stimuli after intranasal OT administration has been consistently shown in several studies using task-based fMRI (37,44,45). Similarly, human BOLD fMRI studies have implicated intranasal OT-induced decreases in BOLD in the anterior cingulate cortex in the modulation of social cognition (46), emotion (47) or fear consolidation (48) effects.…”