Neuroticism modulates amygdala—prefrontal connectivity in response to negative emotional facial expressions

Abstract

Neuroticism is associated with the experience of negative affect and the development of affective disorders. While evidence exists for a modulatory role of neuroticism on task induced brain activity, it is unknown how neuroticism affects brain connectivity, especially the crucial coupling between the amygdala and the prefrontal cortex. Here we investigate this relation between functional connectivity and personality in response to negative facial expressions. Sixty healthy control participants, from the Netherlands Study on Depression and Anxiety (NESDA), were scanned during an emotional faces gender decision task. Activity and functional amygdala connectivity (psycho–physiological interaction [PPI]) related to faces of negative emotional valence (angry, fearful and sad) was compared to neutral facial expressions, while neuroticism scores were entered as a regressor. Activity for fearful compared to neutral faces in the dorsomedial prefrontal (dmPFC) cortex was positively correlated with neuroticism scores. PPI analyses revealed that right amygdala–dmPFC connectivity for angry and fearful compared to neutral faces was positively correlated with neuroticism scores. In contrast, left amygdala–anterior cingulate cortex (ACC) connectivity for angry, fearful and sad compared to neutral faces was negatively related to neuroticism levels. DmPFC activity has frequently been associated with self-referential processing in social cognitive tasks. Our results therefore suggest that high neurotic participants display stronger self-referential processing in response to negative emotional faces. Second, in line with previous reports on ACC function, the negative correlation between amygdala–ACC connectivity and neuroticism scores might indicate that those high in neuroticism display diminished control function of the ACC over the amygdala. These connectivity patterns might be associated with vulnerability to developing affective disorders such as depression and anxiety.

Introduction

Neuroticism is a widely recognized trait in various theoretical approaches to human personality (Smits and Boeck, 2006, Zelenski and Larsen, 1999). Characteristics of this trait include a tendency to worry and to be anxious (Canli et al., 2001), and is related to the experience of negative affect (Larsen and Ketelaar, 1991, Robinson et al., 2007a, Zelenski and Larsen, 1999). Neuroticism is also associated with affective disorders such as social anxiety disorder (SAD) and depression (Bienvenu et al., 2001, Bienvenu et al., 2004, Clark et al., 1994).

Functional magnetic resonance imaging (fMRI) studies have provided substantial evidence for the modulatory role of individual differences in neuroticism on neural activity related to emotion processing (Canli, 2004, Hamann and Canli, 2004). Regions where activity is associated with neuroticism (and related personality traits) include the amygdala (Haas et al., 2007, Reuter et al., 2004, Stein et al., 2007b), the anterior cingulate cortex (ACC) (Eisenberger et al., 2005, Reuter et al., 2004) and the medial prefrontal cortex (Britton et al., 2007, Haas et al., 2007, Rubino et al., 2007). However, these regions are functionally coupled, and such connectivity, especially between the amygdala and prefrontal regions, is crucial for the integration between emotion and cognition (Pessoa, 2008; Stein et al., 2007a). To gain a better understanding of the neural basis of individual differences in emotion processing related to neuroticism, a focus on functional connectivity between limbic and prefrontal regions is therefore required.

Neuroticism is associated with alterations in cognitive–emotional functions such as affect regulation (Tamir, 2005), self-consciousness (Trapnell and Campbell, 1999) and self-regulation (Robinson et al., 2007b). Thus, dysfunctional interactions between the amygdala and regions related to these functions, such as ventrolateral PFC (vlPFC), dorsolateral PFC (dlPFC) and ACC (Ochsner & Gross, 2005; Pessoa, 2008) (cognitive control of emotion), and dorsomedial prefrontal cortex (dmPFC) (Amodio & Frith, 2006; Northoff & Bermpohl, 2004) (self-regulation and self-referential processing) are likely to be specifically associated with individual differences in neuroticism.

Only recently, fMRI studies have started to investigate personality-associated differences in functional connectivity during emotion processing. Whereas some of these studies focused on traits related to positive affect (Haas et al., 2006; Passamonti et al., 2008), one study reported trait anxiety differences in amygdala–ACC coupling (Kienast et al., 2008). A mood induction study during positron emission tomography (PET) showed that neuroticism is associated with changes in subgenual cingulate coupling with prefrontal regions during mood induction, possibly reflecting a susceptibility marker for depression (Keightley et al., 2003). Despite these initial findings, to the best of our knowledge, no study has systematically addressed the question on how individual differences in neuroticism are associated with amygdala–prefrontal cortex connectivity for various negative emotional facial expressions.

To investigate the modulatory role of neuroticism on amygdala–prefrontal cortex connectivity during emotion processing, we applied a standardized face paradigm with different negative emotional facial expressions (angry, fearful and sad) in a large subject sample. This sample represented the healthy control subjects as part of the Netherlands Study on Depression and Anxiety (NESDA) (Penninx et al., 2008). We hypothesize that activity in the medial PFC, ACC and the amygdala is associated with neuroticism scores when processing negative as compared to neutral facial expressions. We also hypothesize that connectivity, between the amygdala on one hand and the lateral and medial prefrontal regions and the ACC on the other, should vary with individual differences in neuroticism.