Resting state brain dynamics: Associations with childhood sexual abuse and major depressive disorder

Abstract

Early life stress (ELS) and major depressive disorder (MDD) share neural network abnormalities. However, it is unclear how ELS and MDD may separately and/or jointly relate to brain networks, and whether neural differences exist between depressed individuals with vs without ELS. Moreover, prior work evaluated static versus dynamic network properties, a critical gap considering brain networks show changes in coordinated activity over time. Seventy-one unmedicated females with and without childhood sexual abuse (CSA) histories and/or MDD completed a resting state scan and a stress task in which cortisol and affective ratings were collected. Recurring functional network co-activation patterns (CAPs) were examined and time in CAP (number of times each CAP is expressed) and transition frequencies (transitioning between different CAPs) were computed. The effects of MDD and CSA on CAP metrics were examined and CAP metrics were correlated with depression and stress-related variables. Results showed that MDD, but not CSA, related to CAP metrics. Specifically, individuals with MDD (N = 35) relative to HCs (N = 36), spent more time in a posterior default mode (DMN)-frontoparietal network (FPN) CAP and transitioned more frequently between posterior DMN-FPN and prototypical DMN CAPs. Across groups, more time spent in a posterior DMN-FPN CAP and greater DMN-FPN and prototypical DMN CAP transition frequencies were linked to higher rumination. Imbalances between the DMN and the FPN appear central to MDD and might contribute to MDD-related cognitive dysfunction, including rumination. Unexpectedly, CSA did not modulate such dysfunctions, a finding that needs to be replicated by future studies with larger sample sizes.

Keywords: Brain network dynamics; Co-activation pattern analysis; Depression; Early life stress; Resting state fMRI; Rumination.

Fig. 1

Consensus clustering yields K = 8 as an optimal number of clusters. (A) Clustering quality (1 minus the percentage of ambiguously clustered frames, or PAC) across candidate cluster numbers. The color gradient for a given cluster number denotes the assessment of clustering quality with a more or less strict definition of “ambiguous clustering” (darker shades denote a more lenient one). Quality gradually increases until it reaches a plateau for large numbers of clusters. (B) When fitting an exponential function to the data and subtracting it from the actual clustering quality values, the positive-valued peaks denote cluster numbers for which the rise in quality measure exceeds that expected from the trend alone (see Bolton et al., 2020b). K_opt = 8 was selected for further analyses, as it was the global optimum within the investigated range.

Fig. 2

Eight Co-activation Patterns (CAPs). The eight CAPs along with the corresponding brain region activations and deactivations for each CAP. Activations appear in warm colors and deactivations appear in cold colors. Activations and deactivations for each Z-scored CAP were thresholded at 1.5 ≤ Z ≤ 3.6. The eight CAPs included: 1) CAP 1 involving activations in anterior default mode network (DMN) regions, 2) CAP 2 involving activations in salience (SN) regions, 3) CAP 3 involving activations in posterior DMN and frontoparietal (FPN) regions, 4) CAP 4 involving activations in visual system network regions, 5) CAP 5 involving activations in prototypical DMN regions, 6) CAP 6 involving activations in dorsal attention network (DAN) regions, 7) CAP 7 involving activations in somatosensory network regions, and 8) CAP 8 involving prefrontal cortex, anterior cingulate cortex and posterior cingulate cortex regions.

Fig. 3

Individuals with MDD spend more time in CAP 3 (posterior DMN-FPN) and transition more frequently between CAP 3 and CAP 5. Top graph: Individuals with major depressive disorder (MDD) compared to healthy controls (HCs) spent more time in coactivation pattern (CAP) 3 consisting of posterior default mode network (DMN) and frontoparietal (FPN) network regions. Middle and bottom graphs: Relative to healthy controls (HCs), individuals with major depressive disorder (MDD) transitioned more frequently from CAP 3 (posterior DMN-FPN) to CAP 5 (prototypical DMN) and from CAP 5 to CAP 3. All error bars reflect the standard error of the mean.

Fig. 4

Higher levels of rumination are associated with CAP dynamic metrics. Across the groups, higher levels of rumination partially correlated with spending more time in CAP 3 (posterior DMN-FPN) and transitioning more frequently between CAP 3 and CAP 5 (prototypical DMN), when controlling for fMRI motion metrics. RRS Scores and time in CAP are residualized for motion variables in the graphs.