Cerebral Correlates of Abnormal Emotion Conflict Processing in Euthymic Bipolar Patients: A Functional MRI Study

Abstract

Background: Patients with bipolar disorder experience cognitive and emotional impairment that may persist even during the euthymic state of the disease. These persistent symptoms in bipolar patients (BP) may be characterized by disturbances of emotion regulation and related fronto-limbic brain circuitry. The present study aims to investigate the modulation of fronto-limbic activity and connectivity in BP by the processing of emotional conflict.

Methods: Fourteen euthymic BP and 13 matched healthy subjects (HS) underwent functional magnetic resonance imaging (fMRI) while performing a word-face emotional Stroop task designed to dissociate the monitoring/generation of emotional conflict from its resolution. Functional connectivity was determined by means of psychophysiological interaction (PPI) approach.

Results: Relative to HS, BP were slower to process incongruent stimuli, reflecting higher amount of behavioral interference during emotional Stroop. Furthermore, BP showed decreased activation of the right dorsolateral prefrontal cortex (DLPFC) during the monitoring and a lack of bilateral amygdala deactivation during the resolution of the emotional conflict. In addition, during conflict monitoring, BP showed abnormal positive connectivity between the right DLPFC and several regions of the default mode network.

Conclusions: Overall, our results highlighted dysfunctional processing of the emotion conflict in euthymic BP that may be subtended by abnormal activity and connectivity of the DLPFC during the conflict monitoring, which, in turn, leads to failure of amygdala deactivation during the resolution of the conflict. Emotional dysregulation in BP may be underpinned by a lack of top-down cognitive control and a difficulty to focus on the task due to persistent self-oriented attention.

Trial registration: ClinicalTrials.gov NCT01821469.

Fig 1. Example of two successive trials presented in word-face emotional Stroop.

Stimuli were either congruent or incongruent according to the valence of facial expression (i.e., joyful or fearful) and the valence of the word written across them (i.e., joie: happy or peur: fear). High conflict resolution trials consisted of incongruent stimuli preceded by incongruent stimuli; Low conflict resolution trials consisted of incongruent stimuli preceded by congruent stimuli; No conflict trials consisted of congruent stimuli preceded by either congruent (NC1) or by incongruent stimuli (NC2) (not shown in the figure). Pictures were extracted from the “Montreal Set of Facial Display of Emotion” (MSFDE) database [30].

Fig 2. Behavioral performances during word-face emotional Stroop.

Panel A: Illustration of behavioral dissociation between conflict monitoring and conflict resolution. The graph shows the mean response time ± SE according to the congruency of the current trial and the congruency of the previous trial. Panel B: Illustration of the increase emotional interference in euthymic bipolar patients. The graph shows the mean response time ± SE according to the group and the congruency of the current trial. *p<0.05. Abbreviations: LR: Low conflict resolution; HR: High conflict resolution; NC: No conflict.

Fig 3. Results of the within-group analyses at whole-brain level during conflict monitoring in (A) healthy subjects and (B) euthymic bipolar patients.

Identified regions are projected onto 2D anatomical slices in axial, coronal and sagittal orientations (p < 0.001 uncorrected at whole brain level, p _FWE < 0.05 after small volume correction).

Fig 4. Results provided by between-group analyses.

Panel A: Whole-brain comparison in HS vs BP during conflict monitoring (LR > HR) (p < 0.001 uncorrected at whole brain level, p _FWE < 0.05 after small volume correction). Identified regions are projected onto 2D anatomical slices in axial, coronal and sagittal orientations. Panel B: Region of interest analysis focused on bilateral amygdala. The graph shows the mean %MR signal intensity variations ± SE according to the group and the amount of the conflict (LR vs HR). *p<0.05. Abbreviations: BP: Bipolar patients; HS: Healthy subjects; LR: Low conflict resolution; HR: High conflict resolution.

Fig 5. Psychophysiological interaction results.

Panel A: Results provided by “within group” analysis in healthy subjects; Panel B: Results provided by “within group” analysis in bipolar patients; Panel C: Results provided by the “between-group” analysis in Bipolar patients vs. Healthy subjects. Red-scale areas represent regions showing positive connectivity with the right dorsolateral prefrontal cortex; Blue-scale areas represent regions showing negative connectivity with the right dorsolateral prefrontal cortex. Identified regions are projected onto 2D anatomical slices in axial, coronal and sagittal orientations (p < 0.005 uncorrected at whole brain level, p _FWE < 0.05 after small volume correction).