Association between reward-related functional connectivity and tri-level mood and anxiety symptoms

Depression and anxiety are associated with abnormalities in brain regions that process rewards including the medial orbitofrontal cortex (mOFC), the ventral striatum (VS), and the amygdala. However, there are in-consistencies in these findings. This may be due to past reliance on categorical diagnoses that, while valuable, provide less precision than may be required to understand subtle neural changes associated with symptoms of depression and anxiety. In contrast, the tri-level model defines symptom dimensions that are common (General Distress) or relatively specific (Anhedonia-Apprehension, Fears) to depression and anxiety related disorders, which provide increased precision. In the current study, eligibility was assessed by quasi-orthogonal screening questionnaires measuring reward and threat sensitivity (Behavioral Activation Scale; Eysenck Personality Questionnaire-Neuroticism). These participants were assessed on tri-level symptom severity and completed the Monetary Incentive Delay task during fMRI scanning. VS-mOFC and VS-amygdala connectivity were estimated during reward anticipation and reward outcome. Heightened General Distress was associated with lower VS-mOFC connectivity during reward anticipation (b =-0.064, p = 0.021) and reward outcome (b =-0.102, p = 0.014). Heightened Anhedonia-Apprehension was associated with greater VS-amygdala connectivity during reward anticipation (b = 0.065, p = 0.004). The present work has important implications for understanding the coupling between the mOFC and vS and the amygdala and the vS during reward processing in the pathophys-iology of mood and anxiety symptoms and for developing targeted behavioral, pharmacological, and neuro-modulatory interventions to help manage these symptoms.