Shared and distinct patterns of dynamic functional connectivity variability of thalamo-cortical circuit in bipolar depression and major depressive disorder.

Evidence has indicated abnormalities of thalamo-cortical functional connectivity (FC) in bipolar disorder during a depressive episode (BDD) and major depressive disorder (MDD). However, the dynamic FC (dFC) within this system is poorly understood. We explored the thalamo-cortical dFC pattern by dividing thalamus into 16 subregions and combining with a sliding-window approach. Correlation analysis was performed between altered dFC variability and clinical data. Classification analysis with a linear support vector machine model was conducted. Compared with healthy controls (HCs), both patients revealed increased dFC variability between thalamus subregions with hippocampus (HIP), angular gyrus and caudate, and only BDD showed increased dFC variability of the thalamus with superior frontal gyrus (SFG), HIP, insula, middle cingulate gyrus, and postcentral gyrus. Compared with MDD and HCs, only BDD exhibited enhanced dFC variability of the thalamus with SFG and superior temporal gyrus. Furthermore, the number of depressive episodes in MDD was significantly positively associated with altered dFC variability. Finally, the disrupted dFC variability could distinguish BDD from MDD with 83.44% classification accuracy. BDD and MDD shared common disrupted dFC variability in the thalamo-limbic and striatal-thalamic circuitries, whereas BDD exhibited more extensive and broader aberrant dFC variability, which may facilitate distinguish between these 2 mood disorders.

Individual variation in brain network topology is linked to course of illness in major depressive disorder.

Major depressive disorder (MDD) is a chronic and highly recurrent disorder. The functional connectivity in depression is affected by the cumulative effect of course of illness. However, previous neuroimaging studies on abnormal functional connection have not mainly focused on the disease duration, which is seen as a secondary factor. Here, we used a data-driven analysis (multivariate distance matrix regression) to examine the relationship between the course of illness and resting-state functional dysconnectivity in MDD. This method identified a region in the anterior cingulate cortex, which is most linked to course of illness. Specifically, follow-up seed analyses show this phenomenon resulted from the individual differences in the topological distribution of three networks. In individuals with short-duration MDD, the connection to the default mode network was strong. By contrast, individuals with long-duration MDD showed hyperconnectivity to the ventral attention network and the frontoparietal network. These results emphasized the centrality of the anterior cingulate cortex in the pathophysiology of the increased course of illness and implied critical links between network topography and pathological duration. Thus, dissociable patterns of connectivity of the anterior cingulate cortex is an important dimension feature of the disease process of depression.

Neural mechanisms of aberrant self-referential processing in patients with generalized anxiety disorder.

Massive theoretical studies in clinical psychology have implicated the self in understanding internalizing disorders (i.e., anxiety and mood disorders), in which self-related tasks were frequently used to investigate internalizing psychopathology. As one of the most frequently seen internalizing disorder in primary care, patients with generalized anxiety disorder (GAD) are characterized by inappropriate self-related processing such as negative self-referential thinking. However, relevant neural mechanisms remain unknown. In this study, participants underwent a self-related task which they were presented with several positive and negative trait words and were required to judge the extent to which these traits matched themselves when compared to their average peers. Aberrant brain activation and functional connectivity of GAD were detected during processing positive and negative traits. Compared to healthy controls (HCs), patients with GAD exhibited abnormal self-processing which manifested as lower biased self-rating scores particularly for negative traits and weaker brain activity in the left dorsomedial prefrontal cortex, inferior frontal gyrus, superior temporal sulcus (STS), and bilateral lingual gyrus when processing trait words. Abnormal functional connections between these hypoactive regions and regions associated with reward, emotion, and theory of mind were observed in subsequent psychophysiological interaction analysis. An attenuation of connectivity between the left insula and left STS was associated with greater severity of anxiety symptom in GAD patients. These findings provide insight into the abnormal neurocognitive mechanisms of biased self-related processing in GAD patients, which involves distorted self-schema accompanied by abnormal activation and functional connections of regions implicated in self-related and social cognition processing.

Shared and distinct changes in local dynamic functional connectivity patterns in major depressive and bipolar depressive disorders.

BACKGROUND: Distinguishing bipolar depressive disorder (BDD) from major depressive disorder (MDD) solely relying on clinical clues is a challenge. Evidence in neuroimaging have revealed potential neurological markers for the differential diagnosis. METHODS: We aimed to characterize common and specific alterations in the dynamic local functional connectivity pattern in BDD and MDD by using the dynamic regional phase synchrony (DRePS), a newly developed method for assessing intrinsic dynamic local functional connectivity. A total of 98 patients with MDD and 56 patients with BDD patients, and 97 age-, gender-, and education-matched healthy controls (HC) were included and underwent the resting-state functional magnetic resonance imaging. RESULTS: Compared with HC, patients with two disorders shared decreased DRePS value in the bilateral orbitofrontal cortex (OFC) extends to insula, the right insula extends to hippocampus, the left hippocampus, the right inferior frontal gyrus (IFG), the left thalamus extends to caudate, the right caudate, the bilateral superior frontal gyrus (SFG), and the right medial frontal gyrus (MFG). Furthermore, patients with MDD exhibited specific decreased DRePS value in the left caudate. Moreover, voxel signals in these regions during the support vector machine analysis contributed to the classification of the two diagnoses. CONCLUSIONS: Our findings provided new insight into the neural mechanism of patients with MDD and BDD and could potentially inform the diagnosis and the treatment of this disease.