Resting-state functional connectivity and inflexibility of daily emotions in major depression

Abstract

Background: Major Depressive Disorder (MDD) is characterized by aberrant resting-state functional connectivity (FC) in anterior cingulate regions (e.g., subgenual anterior cingulate [sgACC]) and by negative emotional functioning that is inflexible or resistant to change.

Methods: MDD (N = 33) and control (CTL; N = 31) adults completed a resting-state scan, followed by a smartphone-based Experience Sampling Methodology (ESM) protocol surveying 10 positive and negative emotions 5 times per day for 21 days. We used multilevel modeling to assess moment-to-moment emotional inflexibility (i.e., strong temporal connections between emotions). We examined group differences in whole-brain FC analysis of bilateral sgACC, and then examined associations between emotional experiences and the extracted FC values within each group.

Results: As predicted, MDDs had inflexibility in sadness and avoidance (p < .001, FDR-corrected p < .05), indicating that these emotional experiences persist in depression. MDDs showed weaker FC between the right sgACC and pregenual/dorsal anterior cingulate (pg/dACC) than did CTLs (FWE-corrected, voxelwise p = .01). Importantly, sgACC-pg/dACC FC predicted sadness inflexibility in both MDDs (p = .046) and CTLs (p = .033), suggesting that sgACC FC is associated with day-to-day negative emotions.

Limitations: Other maladaptive behaviors likely also affect the flexibility of negative emotions. We cannot generalize our finding of a positive relation between sgACC FC and inflexibility of sadness to individuals with more chronic depression or who have recovered from depression.

Conclusions: Our preliminary findings suggest that connections between portions of the ACC contribute to the persistence of negative emotions and are important in identifying a brain mechanism that may underlie the maintenance of sadness in daily life.

Keywords: Dorsal anterior cingulate cortex; Emotion; Experience sampling methodology; MDD; Resting-state functional connectivity; Subgenual anterior cingulate cortex.

Figure 1.. Emotion-Inflexibility of MDDs and CTLs.

* indicates a significant group difference (p <.001).

Figure 2A,B.

(A) The right sgACC seed (RAI coordinates: x=−5.0, y=−25, z=−10; k=19, 463 mm³) and right cingulate cluster showing reduced connectivity in pregenual anterior cingulate cortex extending to the dorsal anterior cingulate cortex (RAI coordinates: x=−4, y=−40, z=−2; k=345, 8414 mm³) in MDDs compared to CTLs (voxel-wise p=.01). (B) A boxplot showing reduced sgACC connectivity in MDDs compared to CTLs.

Figure 3.

Increased sgACC connectivity associated with increased inflexibility of sadness. Significant association between R sgACC–R pg/dACC connectivity and inflexibility of sadness in MDDs and CTLs, p<.05.