Resting-State and Task-Based Functional Connectivity Reveal Distinct mPFC and Hippocampal Network Alterations in Major Depressive Disorder

<b>Background:</b> Resting-state functional connectivity (RSFC) is widely used to identify abnormal brain function associated with depression. Resting-state functional magnetic resonance imaging (fMRI) scans have many potential confounds, and task-based FC might provide complementary information leading to better insight on brain function. <b>Methods:</b> We used MATLAB's (version 2024b) CONN toolbox (version 22a) to evaluate FC in 40 adults with and without major depressive disorder (MDD) (n_MDD = 23, n_HC = 17). fMRI acquisition was performed while participants were at rest and while performing the Selves Task, an individualized goal priming task. Seed-based analyses were performed using two seeds: medial prefrontal cortex (mPFC) and left hippocampus. <b>Results:</b> Both groups showed strong positive RSFC between the mPFC and other DMN regions, including the anterior cingulate cortex and precuneus, which had more focal positive FC to the mPFC during the task in both groups. Additionally, the MDD group had significantly lower RSFC between the mPFC and several regions, including the right inferior temporal gyrus. The left hippocampus seed-based analysis revealed a pattern of hypoconnectivity to multiple brain regions in MDD, including the cerebellum, which was present at rest and during the task. <b>Conclusions:</b> Our results indicated multiple FC differences between adults with and without MDD, as well as distinct FC patterns and contrast results in resting state and task-based analyses, including differential FC between mPFC-cerebellum and hippocampus-cerebellum. These results emphasize that resting-state and task-based fMRI capture distinct patterns of brain connectivity. Further investigation into combining resting-state and task-based FC could inform future neuroimaging research.