Neural correlates of emotion processing in borderline personality disorder

Abstract

Emotional instability is a hallmark feature of borderline personality disorder (BPD), yet its biological underpinnings are poorly understood. We employed functional magnetic resonance imaging (fMRI) to compare patterns of regional brain activation in BPD patients and healthy volunteers as they process positive and negative social emotional stimuli. fMRI images were acquired while 19 BPD patients and 17 healthy controls (HC) viewed emotion-inducing pictures from the International Affective Pictures System set. Activation data were analyzed with SPM5 ANCOVA models to derive the effects of diagnosis and stimulus type. BPD patients demonstrated greater differences in activation than controls, when viewing negative pictures compared with rest, in the amygdala, fusiform gyrus, primary visual areas, superior temporal gyrus (STG), and premotor areas, while healthy controls showed greater differences than BPD patients in the insula, middle temporal gyrus and dorsolateral prefrontal cortex (BA46). When viewing positive pictures compared with rest, BPD patients showed greater differences in the STG, premotor cortex, and ventrolateral prefrontal cortex. These findings suggest that BPD patients show greater amygdala activity and heightened activity of visual processing regions relative to findings for HC subjects in the processing of negative social emotional pictures compared with rest. The patients activate neural networks in emotion processing that are phylogeneticall older and more reflexive than those activated by HC subjects.

Introduction

Emotional instability is one of the most striking features of borderline personality disorder (BPD) and is central to many of the behavioral and interpersonal symptoms of the disorder (Stone, 1988, Linehan, 1993), including some of the most disabling, even life-threatening, symptoms of BPD, such as suicidality, outbursts of intense anger, stormy relationships, and identity disturbances (Koenigsberg et al., 2001). This emotional instability may be related to a heightened attention or sensitivity to social–emotional cues in interpersonal senarios (Wagner and Linehan, 1999, Meyer et al., 2004, Taylor and Fragopanagos, 2005, Lynch et al., 2006), a tendency to self-referential emotional processing (Schnell et al., 2007), or to dysregulated emotional processing mechanisms (Phillips et al., 2003b). Understanding the nature of the disturbances in emotion processing in BPD may provide important insights into the mechanisms of affective instability, the underlying pathology of the disorder, understanding disorder, and the relationship between BPD and the Axis I mood disorders, as well as helping to identify endophenotypes that could focus genetic studies of BPD, and target biological or psychological treatments to more specifically address affective instability in BPD.

Neuroimaging studies have begun to identify networks that are engaged in emotion processing in healthy individuals and in those with disturbed affect. A number of studies have employed images from the International Affective Pictures System (IAPS; Lang et al., 2001) as emotional stimuli. The IAPS is a set of positive, negative and neutral valence pictures for which normative data for picture valence and arousal level are available. In healthy individuals, viewing of emotional pictures is associated with activation in the visual cortex (Takahashi et al., 2004, Britton et al., 2006), ventromedial prefrontal cortex and medial orbitofrontal cortex (Northoff et al., 2000, Takahashi et al., 2004, Britton et al., 2006, Grimm et al., 2006), anterior cingulate (Takahashi et al., 2004, Grimm et al., 2006), dorsolateral prefrontal cortex (Northoff et al., 2000, Grimm et al., 2006), amygdala-hippocampal region (Takahashi et al., 2004, Britton et al., 2006) and basal ganglia (Takahashi et al., 2004). Differences in activation patterns in these regions have been identified in schizophrenic subjects with and without affective flattening (Takahashi et al., 2004), phobics (Goossens et al., 2007), and individuals high in neuroticism (Britton et al., 2007).

Little is known about the neurobiological underpinnings of the emotional instability in BPD, but the BPD syndrome itself has been associated with regional hypometabolism and deficits in serotonergic activity (De La Fuente et al., 1997, Siever et al., 1999, Soloff et al., 2000, Leyton et al., 2001, New et al., 2002, Juengling et al., 2003). Structural magnetic resonance imaging (MRI) studies have found smaller amygdala, hippocampal (Driessen et al., 2000, Schmahl et al., 2003, Tebartz van Elst et al., 2003), anterior cingulate (Tebartz van Elst et al., 2003, Hazlett et al., 2005) and orbitofrontal cortex (Tebartz van Elst et al., 2003) volumes in BPD patients compared with controls. Two functional neuroimaging studies of borderline patients performing an emotion-relation task have been reported. In the first, BOLD functional MRI (fMRI) was performed in six BPD patients and controls as they viewed negative or neutral pictures (inanimate objects). Compared with healthy controls, the BPD patients showed an increased activation of the amygdala bilaterally and of the medial and inferolateral prefrontal cortex when viewing the negative versus the neutral images (Herpertz et al., 2001). The second study examined the processing of facial expressions of emotion (Donegan et al., 2003). The BPD patients showed increased left amygdala activation to fearful, sad, happy and neutral faces.

The emotional instability in BPD is associated with emotional reactivity to social events (Stiglmayr et al., 2005), yet the neuroimaging studies of emotion processing in BPD have thus far been confined to studies of face perception (Donegan et al., 2003) and to scenes intermixing social and non-social stimuli (e.g. images of attacking animals, offensive insects and reptiles, and disfigured bodies), making it impossible to characterize the processing of social cues in particular. This is a serious limitation since social and non-social emotional stimuli are processed differently in the brain (Britton et al., 2006). The present study represents an important advance because of its focus on social emotional processing in particular.

A network comprising the amygdala, fusiform gyrus, superior temporal sulcus (STS), primary visual regions, and the prefrontal cortex has been implicated in visual social emotional cognition (Allison et al., 2000, Adolphs and Spezio, 2006, Bokde et al., 2006). This model posits that visual social stimuli are processed by the fusiform face area in interaction with the STS, which attributes motivation and social intension. Emotional salience is then assigned by the amygdala, together with other prefrontal areas such as the insula. The amygdala, via feedback loops to the STS and more primary visual areas, may activate attentional amplification (Allison et al., 2000) to relevant features of the stimuli. Building upon this formulation, Satpute and Lieberman (2006) have proposed a dual-process model of social cognition in which there is a division between “reflexive” and “reflective” neural systems. The former, including the amygdala, STS, orbitofrontal (OFC) cortex, dorsal anterior cingulate (dACC) and basal ganglia, provides an automatic, fast operating emotional response, while the latter, incorporating the lateral and medial prefrontal areas, the medial temporal lobe and the rostral anterior cingulate (rACC), provides a more nuanced, experience-based, but slower-responding emotional appraisal. We hypothesize that the increased emotional reactivity characteristic of BPD patients may be a consequence of their inability to adequately engage the reflective system and thus to rely heavily upon the more primitive reflexive system. This model would imply that when processing social emotional stimuli, BPD patients compared with healthy subjects would show greater activation of the amygdala, fusiform gyrus, primary visual areas, STS, dACC and OFC, while healthy subjects would demonstrate greater activation of lateral and medial prefrontal areas and medial temporal regions compared with BPD subjects. To test these hypotheses, we obtained BOLD fMRI in BPD patients and healthy volunteers as they viewed social emotional pictures.