Dimensional Affective Processing in BD

Abstract

Bipolar Disorder (BD) involves altered neural affective processing, but studies comparing BD patients to controls have yielded inconsistent results. This might relate to substantial variability in the nature and severity of mood symptoms among individuals with BD. Hence, we dimensionally examined the relationship between depressive and manic symptom severity and neural responses to positive and negative affective stimuli. 39 Participants with BD completed measures of depression and mania severity prior to completing a cognitive-affective processing task during fMRI. A multiple regression model was run in SPM to identify brain regions correlated with depressive and manic symptoms during positive-neutral and negative-neutral contrasts. A-priori anatomical ROIs were defined bilaterally in frontal, parietal and limbic regions. Results showed that depression severity was associated with increased activation in frontal, parietal, and limbic ROIs, regardless of valence. Mania severity was correlated with both increased and decreased activation, particularly within frontal subdivisions and during the processing of positively valenced images. In conclusion, dimensional modeling of symptom severity captures variance in neural responses to affect, which may have been previously undetected due to heterogeneity when examined at the group level. Future fMRI studies comparing BD patients and controls should account for symptom variability in BD.

Keywords: Affective processing; Bipolar disorder; Depression; Mania; fMRI.

Figure 1:

Illustration of MSIT-IAPS task trials, which consist of the Multisource Interference Task (MSIT) overlaid on images from the International Affective Picture Scale (IAPS). A) Example of a negatively valenced “Non-Interference” trial. The target number “2” is in the same position as the second finger on the number pad. B) Example of a positively valenced “Interference” trial. The target number “2” is in a different position than the second finger on the number pad. In the “Interference” trial, the prepotent response to press the first finger (matching the position of the target number) is inhibited in order to make the correct selection with the second finger. Trials not shown are “Positive Non-Interference,” “Neutral Non-Interference,” “Negative Interference,” “Neutral Interference.”

Figure 2:

Pearson’s r correlation coefficients between symptom severity and activation for Positive-Neutral contrast. Pearson’s r of zero reflects non-significance per the established SPM corrected threshold, but does not necessarily represent a true correlation of zero. Superscripts are to designate BAs where there are both positive and negative correlations within different subdivisions of the ROI ^aBrodmann area 44; ^bBrodmann area 6. ^cBrodmann area 46; ^dBrodmann area 44.

Figure 3:

Pearson’s r correlation coefficients between symptom severity and activation for Negative-Neutral contrast. Pearson’s r of zero reflects non-significance per the established SPM corrected threshold, but does not necessarily represent a true zero-order uncorrected bivariate association. Superscripts are to designate BAs where there are both positive and negative correlations within different subdivisions of the ROI ^aBrodmann area 9; ^bBrodmann area 10. ^cBrodmann area 6; ^dBrodmann area 10.