Resting State and Task-Evoked Neural Bases of Rumination and Affective Dysfunction

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

? DESCRIPTION (provided by applicant): [Depression is a common disorder with a major public health impact.] Recent research has linked [depression with abnormal function] in the default-mode network (DMN), a network of regions that is typically active at rest, and deactivates during cognitive tasks. [Depression has been linked with increased DMN connectivity] during resting-state fMRI, and a relative failure to suppress DMN when individuals view negative images. In addition, depressed individuals demonstrate enhanced and prolonged amygdala responses to negative images. [This has led to the theory that DMN abnormalities might interfere with recruitment of brain regions to regulate amygdala in depressed individuals.] [These neural markers in depressed individuals have also been related to brooding rumination, a type of maladaptive coping involving repetitive negative thoughts.] This work proposes to test this model using cross-modal comparison of fMRI data in individuals during a resting-state scan and while participants are viewing negative images. Two main hypotheses will be tested: 1) resting-state DMN [function] will predict decreased top-down regulation of emotion during viewing of negative images, and 2) increased resting-state DMN [function], and decreased top-down emotion regulation during negative-image-viewing, will be predicted by increased trait [brooding]. Assessment of top-down emotion regulation during negative-image-viewing will be multimodal and will focus on the time period 6-12s after image offset, capturing recovery from the negative image, while controlling for initial 6 s of activity in response to the image (reactivity). Measures will include amygdala activity, amygdala-prefrontal connectivity, and electromyography of the corrugator supercilii, a muscle that is a reliable indicator of the experience of negative emotion. [In addition, multivariate pattern analysis (MVPA) will be used to classify negative vs. neutral images as an alternative measure of neural responses.] DMN [function] will be assessed in two ways. First, functional connectivity between two major nodes of the DMN (medial prefrontal cortex and posterior cingulate cortex) will be calculated using correlation-based methods. Second, [a metric of DMN dominance over a cognitive control network will be calculated following methods used previously by other researchers. In order to assess how resting-state DMN function predicts top-down emotion regulation, these DMN metrics will be regressed onto all of the above metrics of emotion regulation. In order to assess how these measures correspond to trait brooding, brooding will be assessed using a standardized measure (the Ruminative Responses Scale; RRS) [and also regressed onto the outcome measures above]. This work will elucidate the relationship of DMN activity, [neural correlates of] emotion regulation and [brooding] with implications for risk and treatment of affective disorders.