Neural mechanism of critical self-judgment as a trans-diagnostic therapeutic target: a secondary data analysis study from the RDoC perspective - Project Summary Critical self-judgment is a common phenomenon underlying a wide range of psychological disorders. The proposed project aims to investigate the neural mechanism of critical self-judgment by analyzing fMRI and questionnaire data from a total of 203 subjects collected from 5 previous projects that all included mindfulness or compassion-based interventions for various conditions, e.g., depression, anxiety, trauma, stress and chronic pain. The analyses will particularly evaluate the effective and functional connectivity among the amygdala, the hippocampus, inferior frontal gyrus and precuneus, to test the central hypothesis that critical self-judgment is characterized by excessive influence from negative valence on the left Inferior Frontal Gyrus-Pars Triangularis (IFGPT), a key area for internal speech and self-awareness, which further influences the precuneus (PCu) of the default mode network (DMN), a neural circuitry that supports self-referential processes. Aim 1: To elucidate the effective connectivity in the neural circuitry during critical self-judgment. Using fMRI data from a self-reappraisal task that included self-critical vs. self-reassurance conditions, Granger Causality analysis will be conducted with fMRI time series from regions of interest of the hypothesized neural circuitry to test whether there is significant effective connectivity in the directions of amygdala→IFGPT and IFGPT→PCu during self-critical condition. Similar analyses with the self-reassurance condition will test whether there is significant effective connectivity in the direction of MPFC→amygdala and IFGPT→amygdala, reflecting frontal inhibition of negative affect. Aim 2: To identify features from resting state fMRI that are associated with trait critical self-judgment. Through analyzing resting state fMRI data with the CONN toolbox, we will extract Resting State Functional Connectivity (RSFC) from regions of interest in the proposed neural circuitry, then use linear mixed effects models to test whether the severity of trait critical self-judgment is collectively predicted by RSFC of hippocampus-IFGPT, amygdala-IFGPT, IFGPT-PCu, hippocampus-PCu and amygdala-PCu. Aim 3: To investigate whether post-intervention changes in trait critical self-judgment are predicted by changes in the proposed neural circuitry. By analyzing post-intervention changes in fMRI metrics and trait critical self-judgment severity, we will test whether post-intervention changes in trait critical self-judgment are predicted by post-intervention changes in RSFC of hippocampal-IFGPT, amygdala-IFGPT, IFGPT-PCu, hippocampus-PCu and amygdala-PCu.