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Aberrant affective neural processing and negative emotional bias are trait-marks of major depression disorders (MDDs). However, most research on biased emotional perception in depression has only focused on unimodal experimental stimuli, the neural basis of potentially biased emotional processing of multimodal inputs remains unclear. Here, we addressed this issue by implementing an audiovisual emotional task during functional MRI scanning sessions with 37 patients with MDD and 37 gender-, age-and education-matched healthy controls. Participants were asked to distinguish laughing and crying sounds while being exposed to faces with different emotional valences as background. We combined general linear model and psychophysiological interaction analyses to identify abnormal local functional activity and integrative processes during audiovisual emotional processing in MDD patients. At the local neural level, MDD patients showed increased bias activity in the ventromedial prefrontal cortex (vmPFC) while listening to negative auditory stimuli and concurrently processing visual facial expressions, along with decreased dorsolateral prefrontal cortex (dlPFC) activity in both the positive and negative visual facial conditions. At the network level, MDD exhibited significantly decreased connectivity in areas involved in automatic emotional processes and voluntary control systems during perception of negative stimuli, including the vmPFC, dlPFC, insula, as well as the subcortical regions of posterior cingulate cortex and striatum. These findings support a multimodal emotion dysregulation hypothesis for MDD by demonstrating that negative bias effects may be facilitated by the excessive ventral bottom-up negative emotional influences along with incapability in dorsal prefrontal top-down control system.

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Generalized anxiety disorder (GAD) is characterized by a chronic, continuous symptom of worry and exaggerated startle response. Although functional abnormality in GAD has been widely studied using functional magnetic resonance imaging (fMRI), the dynamic signatures of GAD are not fully understood. As a vital index of brain function, brain signal variability (BSV) reflects the capacity of state transition of neural activities. In this study, we recruited 47 patients with GAD and 38 healthy controls (HCs) to investigate whether or not BSV is altered in patients with GAD by measuring the standard deviation of fMRI signal of each voxel. We found that patients with GAD exhibited decreased BSV in widespread regions including the visual network, sensorimotor network, frontoparietal network, limbic system, and thalamus, indicating an inflexible brain state transfer pattern in these systems. Furthermore, the correlation between BSV and trait anxiety score was prone to be positive in patients with GAD but negative in HCs. The opposite relationships between BSV and anxiety level in the two groups indicate that the brain with moderate anxiety level may stay in the most stable rather than in the flexible state. As the first study of BSV in GAD, we revealed extensively decreased BSV in patients with GAD similar to that in other mental disorders but with a non-linear relationship between BSV and anxiety level indicating a novel neurodynamic mechanism of the anxious brain.