Intensity of repetitive negative thinking in depression is associated with greater functional connectivity between semantic processing and emotion regulation areas

Abstract

Background Repetitive negative thinking (RNT), a cognitive process that encompasses past (rumination) and future (worry) directed thoughts focusing on negative experiences and the self, is a transdiagnostic construct that is especially relevant for major depressive disorder (MDD). Severe RNT often occurs in individuals with severe levels of MDD, which makes it challenging to disambiguate the neural circuitry underlying RNT from depression severity. Methods We used a propensity score, i.e., a conditional probability of having high RNT given observed covariates to match high and low RNT individuals who are similar in the severity of depression, anxiety, and demographic characteristics. Of 148 MDD individuals, we matched high and low RNT groups (n = 50/group) and used a data-driven whole-brain voxel-to-voxel connectivity pattern analysis to investigate the resting-state functional connectivity differences between the groups. Results There was an association between RNT and connectivity in the bilateral superior temporal sulcus (STS), an important region for speech processing including inner speech. High relative to low RNT individuals showed greater connectivity between right STS and bilateral anterior insular cortex (AI), and between bilateral STS and left dorsolateral prefrontal cortex (DLPFC). Greater connectivity in those regions was specifically related to RNT but not to depression severity. Conclusions RNT intensity is directly related to connectivity between STS and AI/DLPFC. This might be a mechanism underlying the role of RNT in perceptive, cognitive, speech, and emotional processing. Future investigations will need to determine whether modifying these connectivities could be a treatment target to reduce RNT.

Emotion dysregulation in bipolar disorder compared to other mental illnesses: a systematic review and meta-analysis

“…In addition, acutely depressed patients with MDD scored significantly higher than acutely depressed BD patients when looking at more absorbing and negative emotion-focused form of ruminations, although this comparison was not significant after conducting a sensitivity analysis. A study comparing MDD patients presenting different levels of rumination (Tsuchiyagaito et al, 2022) observed that higher degrees of rumination were associated with greater connectivity between brain areas dedicated to language processing and areas involved in ER: the heterogeneity found at the level of brain connectivity may further influence the differences observed in our analyses.…”

Clinical Response to Neurofeedback in Major Depression Relates to Subtypes of Whole-Brain Activation Patterns During Training

“…Changes in SMA and middle cingulate activation were also observed in MDD during reward anticipation in a meta-analysis 72 . In addition, increased connectivity in the auditory cortex, associated with repetitive negative thinking 73 , and increased activity or connectivity in the visual cortex 48,74 have also been reported in MDD.…”

Trait repetitive negative thinking in depression is associated with functional connectivity in negative thinking state rather than resting state

“…Connectivity outside of the DMN (i.e., language and emotional salience regions) has also been suggested to differentiate individuals with high and low RNT (Tsuchiyagaito et al, 2022). Furthermore, rumination severity is not correlated with RSFC after controlling for other clinical measures of worry, whereas a worry-specific association was found after controlling for rumination (Andreescu et al, 2015), suggesting that RSFC is more closely associated with worry than rumination.…”

“…However, in contrast to the RSFC findings of increased connectivity within the DMN and between the DMN and other regions, meta- and mega-analysis studies of large cohort data have reported decreased or no difference in DMN RSFC in depressed individuals (Goldstein-Piekarski et al, 2022; Tozzi et al, 2021; Yan et al, 2019; Zhang et al, 2020). Connectivity outside of the DMN (i.e., language and emotional salience regions) has also been suggested to differentiate individuals with high and low RNT (Tsuchiyagaito et al, 2022). Furthermore, rumination severity is not correlated with RSFC after controlling for other clinical measures of worry, whereas a worry-specific association was found after controlling for rumination (Andreescu et al, 2015), suggesting that RSFC is more closely associated with worry than rumination.…”