The orbitofrontal cortex extends into the laterally adjacent inferior frontal gyrus. We analyzed how voxel-level functional connectivity of the inferior frontal gyrus and orbitofrontal cortex is related to depression in 282 people with major depressive disorder (125 were unmedicated) and 254 controls, using FDR correction P < 0.05 for pairs of voxels. In the unmedicated group, higher functional connectivity was found of the right inferior frontal gyrus with voxels in the lateral and medial orbitofrontal cortex, cingulate cortex, temporal lobe, angular gyrus, precuneus, hippocampus and frontal gyri. In medicated patients, these functional connectivities were lower and toward those in controls. Functional connectivities between the lateral orbitofrontal cortex and the precuneus, posterior cingulate cortex, inferior frontal gyrus, ventromedial prefrontal cortex and the angular and middle frontal gyri were higher in unmedicated patients, and closer to controls in medicated patients. Medial orbitofrontal cortex voxels had lower functional connectivity with temporal cortex areas, the parahippocampal gyrus and fusiform gyrus, and medication did not result in these being closer to controls. These findings are consistent with the hypothesis that the orbitofrontal cortex is involved in depression, and can influence mood and behavior via the right inferior frontal gyrus, which projects to premotor cortical areas.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain‐age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain‐age has highlighted the need for robust and publicly available brain‐age models pre‐trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain‐age model. Here we expand this work to develop, empirically validate, and disseminate a pre‐trained brain‐age model to cover most of the human lifespan. To achieve this, we selected the best‐performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain‐age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5–90 years; 53.59% female). The pre‐trained models were tested for cross‐dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8–80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9–25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age‐bins (5–40 and 40–90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain‐age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open‐science, web‐based platform for individualized neuroimaging metrics.

Background: Many emotional experiences such as anxiety and depression are influenced by negative affect (NA). NA has both trait and state features, which play different roles in physiological and mental health. Attending to NA common to various emotional experiences and their trait-state features might help deepen the understanding of the shared foundation of related emotional disorders.Methods: The principal component of five measures was calculated to indicate individuals' NA level. Applying the connectivity-based correlation analysis, we first identified resting-state functional connectives (FCs) relating to NA in sample 1 (n = 367), which were validated through an independent sample (n = 232; sample 2). Next, based on the variability of FCs across large timescale, we further divided the NA-related FCs into high- and low-variability groups. Finally, FCs in different variability groups were separately applied to predict individuals' neuroticism level (which is assumed to be the core trait-related factor underlying NA), and the change of NA level (which represents the state-related fluctuation of NA).Results: The low-variability FCs were primarily within the default mode network (DMN) and between the DMN and dorsal attention network/sensory system and significantly predicted trait rather than state NA. The high-variability FCs were primarily between the DMN and ventral attention network, the fronto-parietal network and DMN/sensory system, and significantly predicted the change of NA level.Conclusions: The trait and state NA can be separately predicted by stable and variable spontaneous FCs with different attentional processes and emotion regulatory mechanisms, which could deepen our understanding of NA.

Although many studies have explored the neural mechanism of the feeling of stress, to date, no effort has been made to establish a model capable of predicting the feeling of stress at the individual level using the resting-state functional connectome. Although individuals may be confronted with multidimensional stressors during the coronavirus disease 2019 (COVID-19) pandemic, their appraisal of the impact and severity of these events might vary. In this study, connectome-based predictive modeling (CPM) with leave-one-out cross-validation was conducted to predict individual perceived stress (PS) from whole-brain functional connectivity data from 817 participants. The results showed that the feeling of stress could be predicted by the interaction between the default model network and salience network, which are involved in emotion regulation and salience attribution, respectively. Key nodes that contributed to the prediction model comprised regions mainly located in the limbic systems and temporal lobe. Critically, the CPM model of PS based on regular days can be generalized to predict individual PS levels during the COVID-19 pandemic, which is a multidimensional, uncontrollable stressful situation. The stability of the results was demonstrated by two independent datasets. The present work not only expands existing knowledge regarding the neural mechanism of PS but also may help identify high-risk individuals in healthy populations.