Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study. Psychiatry Research, 155 : 231-243

Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
Psychiatry Research (Impact Factor: 2.47). 09/2007; 155(3):231-43. DOI: 10.1016/j.pscychresns.2007.03.006
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Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of fronto-limbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HC) viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HC) in the bilateral rostral/subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD.

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Available from: Michael Minzenberg, Oct 09, 2015
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    • "The majority of previous functional magnetic resonance imaging (fMRI) studies in BPD have looked at activation abnormalities in regions understood to be involved in the regulation of stress responses, emotion and affect, amongst others. The most common finding amongst these studies is that of hyperactivity in the amygdala and insula of BPD patients as well as decreased frontal activity, e.g., in the anterior cingulate cortex (ACC), compared with controls during tasks that involve the processing of emotionally aversive stimuli (Donegan et al., 2003; Minzenberg et al., 2007; O'Neill and Frodl, 2012; Krause-Utz et al., 2014). Social cognitive aspects like mentalization and theory of mind (ToM), although relevant to BPD and its therapy, have thus far only been explored at a rudimentary level in BPD research. "
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    ABSTRACT: Individuals with borderline personality disorder (BPD) commonly display deficits in emotion regulation, but findings in the area of social cognitive (e.g., theory of mind, ToM) capacities have been heterogeneous. The aims of the current study were to investigate differences between patients with BPD and controls in functional connectivity (1) between the emotion and ToM network and (2) in the default mode network (DMN). Functional magnetic resonance imaging was used to investigate 19 healthy controls and 17 patients with BPD at rest and during ToM processing. Functional coupling was analysed. Significantly decreased functional connectivity was found for patients compared with controls between the anterior cingulate cortex and three brain areas involved in ToM processes: the left superior temporal lobe, right supramarginal/inferior parietal lobes, and right middle cingulate cortex. Increased functional connectivity was found in patients compared with controls between the precuneus as the DMN seed and the left inferior frontal lobe, left precentral/middle frontal, and left middle occipital/superior parietal lobes during rest. Reduced functional coupling between the emotional and the ToM network during ToM processing is in line with emotion-regulation dysfunctions in BPD. The increased connectivity between the precuneus and frontal regions during rest might be related to extensive processing of internal thoughts and self-referential information in BPD.
    Psychiatry Research: Neuroimaging 11/2014; 231(1). DOI:10.1016/j.pscychresns.2014.11.002 · 2.42 Impact Factor
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    • "Our results conflict with these findings but could be attributed to differences in study design, use of ROI methodology, patient selection including Axis I co-morbidity, hospitalization and/or medication status. For example, the studies reporting amygdala hyperactivity (e.g., Koenigsberg et al., 2009; Minzenberg et al., 2007; Schulze et al., 2011) involved unmedicated BPD patients, while the studies demonstrating diminished amygdala responsivity included participants currently taking psychotropic medications (Smoski et al., 2011). Similarly, Axis I co-morbidities such as PTSD may influence amygdala reactivity, particularly in relation to pain perception (Kraus et al., 2009). "
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    ABSTRACT: Objective: Siever and Davis' (1991) psychobiological framework of borderline personality disorder (BPD) identifies affective instability (AI) as a core dimension characterized by prolonged and intense emotional reactivity. Recently, deficient amygdala habituation, defined as a change in response to repeated relative to novel unpleasant pictures within a session, has emerged as a biological correlate of AI in BPD. Dialectical behavior therapy (DBT), an evidence-based treatment, targets AI by teaching emotion-regulation skills. This study tested the hypothesis that BPD patients would exhibit decreased amygdala activation and improved habituation, as well as improved emotion regulation with standard 12-month DBT. Methods: Event-related fMRI was obtained pre- and post-12-months of standard-DBT in unmedicated BPD patients. Healthy controls (HCs) were studied as a benchmark for normal amygdala activity and change over time (n = 11 per diagnostic-group). During each scan, participants viewed an intermixed series of unpleasant, neutral and pleasant pictures presented twice (novel, repeat). Change in emotion regulation was measured with the Difficulty in Emotion Regulation (DERS) scale. Results: fMRI results showed the predicted Group × Time interaction: compared with HCs, BPD patients exhibited decreased amygdala activation with treatment. This post-treatment amygdala reduction in BPD was observed for all three pictures types, but particularly marked in the left hemisphere and during repeated-emotional pictures. Emotion regulation measured with the DERS significantly improved with DBT in BPD patients. Improved amygdala habituation to repeated-unpleasant pictures in patients was associated with improved overall emotional regulation measured by the DERS (total score and emotion regulation strategy use subscale). Conclusion: These findings have promising treatment implications and support the notion that DBT targets amygdala hyperactivity-part of the disturbed neural circuitry underlying emotional dysregulation in BPD. Future work includes examining how DBT-induced amygdala changes interact with frontal-lobe regions implicated in emotion regulation.
    Journal of Psychiatric Research 10/2014; 57(1). DOI:10.1016/j.jpsychires.2014.06.020 · 3.96 Impact Factor
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    • "Male and female actors were asked to produce emotions of happiness, fear, anger, sad- 105 ness and 'emotional neutrality'. As suggested by previous studies, hair and clothing were removed from the images to show only faces (Blair et al., 2001; Minzenberg et al., 2007). Eighty images were rated by an independent sample of 97 volunteers. "
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    ABSTRACT: Social anxiety disorder (SAD), which is characterized by the fear of being rejected and negatively evaluated, involves altered brain activation during the processing of negative emotions in a social context. Although associated temperament traits, such as shyness or behavioral inhibition, have been studied, there is still insufficient knowledge to support the dimensional approach, which assumes a continuum from subclinical to clinical levels of social anxiety symptoms. This study used functional magnetic resonance imaging (fMRI) to examine the neural bases of individual differences in social anxiety. Our sample included participants with both healthy/subclinical as well as clinical levels of social anxiety. Forty-six participants with a wide range of social anxiety levels performed a gender decision task with emotional facial expressions during fMRI scanning. Activation in the left anterior insula and right lateral prefrontal cortex in response to angry faces was positively correlated with the level of social anxiety in a regression analysis. The results substantiate, with a dimensional approach, those obtained in previous studies that involved SAD patients or healthy and subclinical participants. It may help to refine further therapeutic strategies based on markers of social anxiety.
    Social Cognitive and Affective Neuroscience 06/2014; DOI:10.1093/scan/nst061 · 7.37 Impact Factor
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