Neural dynamics underlying the persistence of perseverative thought in depression and anxiety

Abstract

Depression and anxiety are characterized by transdiagnostic symptoms, including perseverative thought: a class of thoughts such as rumination and worry that are negative, repetitive, and difficult to control. These thoughts contribute to substantial distress, poor treatment response, and increased risk of relapse. What makes perseverative thoughts persevere? Using task-based fMRI, we compared how adults with no lifetime psychopathology and adults with major depressive disorder, generalized anxiety disorder, or both, engaged top-down control processes to switch from personally-relevant perseverative or neutral thought to a working memory task. For only adults with clinical depression or anxiety, stopping perseverative thought was associated with more probable frontoparietal deactivation and more frequent default-mode activation versus stopping neutral thought. Using network control theory, we identified key control points that lead to these activity dynamics. We found that clinical perseverative thought elicited less controlled activity in the anterior cingulate cortex relative to thoughts in adults with no lifetime psychopathology, and lower control energy correlated with greater depression severity. The occipital-temporal, lateral prefrontal, and insular cortices also used less control energy in clinical perseverative thought. Low energy is characteristic of attractor states in dynamical systems theory, deep channels wherein the flow of activity naturally settles, analogous to how a ball needs little energy to roll to the bottom of a bowl yet more energy to leave it. Entrenchment in attractors provides a computational perspective on why top-down control signals relate to the persistence of clinical perseverative thought. These insights advance our understanding of the dynamic processes of perseverative thought, paving the way for novel interventions for depression and anxiety.