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Numerous studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed differences in specific brain regions of patients with bipolar disorder (BD), but the results have been inconsistent.
A whole-brain voxel-wise meta-analysis was conducted on resting-state functional imaging and VBM studies that compared differences between patients with BD and healthy controls using Seed-based d Mapping with Permutation of Subject Images software.
A systematic literature search identified 51 functional imaging studies (1842 BD and 2190 controls) and 83 VBM studies (2790 BD and 3690 controls). Overall, patients with BD displayed increased resting-state functional activity in the left middle frontal gyrus, right inferior frontal gyrus (IFG) extending to the right insula, right superior frontal gyrus and bilateral striatum, as well as decreased resting-state functional activity in the left middle temporal gyrus extending to the left superior temporal gyrus and post-central gyrus, left cerebellum, and bilateral precuneus. The meta-analysis of VBM showed that patients with BD displayed decreased VBM in the right IFG extending to the right insula, temporal pole and superior temporal gyrus, left superior temporal gyrus extending to the left insula, temporal pole, and IFG, anterior cingulate cortex, left superior frontal gyrus (medial prefrontal cortex), left thalamus, and right fusiform gyrus.
The multimodal meta-analyses suggested that BD showed similar patterns of aberrant brain activity and structure in the insula extending to the temporal cortex, fronto-striatal-thalamic, and default-mode network regions, which provide useful insights for understanding the underlying pathophysiology of BD.
Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA).
Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality.
Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group.
Our findings indicated that the dysfunction of insula–cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.
Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.
In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.
Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = −0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.
Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.
Accumulating studies have found structural and functional abnormalities of the striatum in bipolar disorder (BD) and major depressive disorder (MDD). However, changes in intrinsic brain functional connectivity dynamics of striato-cortical circuitry have not been investigated in BD and MDD. This study aimed to investigate the shared and specific patterns of dynamic functional connectivity (dFC) variability of striato-cortical circuitry in BD and MDD.
Brain resting-state functional magnetic resonance imaging data were acquired from 128 patients with unmedicated BD II (current episode depressed), 140 patients with unmedicated MDD, and 132 healthy controls (HCs). Six pairs of striatum seed regions were selected: the ventral striatum inferior (VSi) and the ventral striatum superior (VSs), the dorsal-caudal putamen (DCP), the dorsal-rostral putamen (DRP), and the dorsal caudate and the ventral-rostral putamen (VRP). The sliding-window analysis was used to evaluate dFC for each seed.
Both BD II and MDD exhibited increased dFC variability between the left DRP and the left supplementary motor area, and between the right VRP and the right inferior parietal lobule. The BD II had specific increased dFC variability between the right DCP and the left precentral gyrus compared with MDD and HCs. The MDD had increased dFC variability between the left VSi and the left medial prefrontal cortex compared with BD II and HCs.
The patients with BD and MDD shared common dFC alteration in the dorsal striatal-sensorimotor and ventral striatal-cognitive circuitries. The patients with MDD had specific dFC alteration in the ventral striatal-affective circuitry.
Previous studies have analyzed brain functional connectivity to reveal the neural physiopathology of bipolar disorder (BD) and major depressive disorder (MDD) based on the triple-network model [involving the salience network, default mode network (DMN), and central executive network (CEN)]. However, most studies assumed that the brain intrinsic fluctuations throughout the entire scan are static. Thus, we aimed to reveal the dynamic functional network connectivity (dFNC) in the triple networks of BD and MDD.
We collected resting state fMRI data from 51 unmedicated depressed BD II patients, 51 unmedicated depressed MDD patients, and 52 healthy controls. We analyzed the dFNC by using an independent component analysis, sliding window correlation and k-means clustering, and used the parameters of dFNC state properties and dFNC variability for group comparisons.
The dFNC within the triple networks could be clustered into four configuration states, three of them showing dense connections (States 1, 2, and 4) and the other one showing sparse connections (State 3). Both BD and MDD patients spent more time in State 3 and showed decreased dFNC variability between posterior DMN and right CEN (rCEN) compared with controls. The MDD patients showed specific decreased dFNC variability between anterior DMN and rCEN compared with controls.
This study revealed more common but less specific dFNC alterations within the triple networks in unmedicated depressed BD II and MDD patients, which indicated their decreased information processing and communication ability and may help us to understand their abnormal affective and cognitive functions clinically.
Bipolar disorder (BD) has been associated with altered brain structural and functional connectivity. However, little is known regarding alterations of the structural brain connectome in BD. The present study aimed to use diffusion-tensor imaging (DTI) and graph theory approaches to investigate the rich club organization and white matter structural connectome in BD.
Forty-two patients with unmedicated BD depression and 59 age-, sex- and handedness-matched healthy control participants underwent DTI. The whole-brain structural connectome was constructed by a deterministic fiber tracking approach. Graph theory analysis was used to examine the group-specific global and nodal topological properties, and rich club organizations, and then nonparametric permutation tests were used for group comparisons of network parameters.
Compared with healthy control participants, the patients with BD showed abnormal global properties, including increased characteristic path length, and decreased global efficiency and local efficiency. Locally, the patients with BD showed abnormal nodal parameters (nodal strength, nodal efficiency, and nodal betweenness) predominantly in the parietal, orbitofrontal, occipital, and cerebellar regions. Moreover, the patients with BD showed decreased rich club and feeder connectivity density.
Our results may reflect the disrupted white matter topological organization in the whole-brain, and abnormal regional connectivity supporting cognitive and affective functioning in depressed BD, which, in part, be due to impaired rich club connectivity.
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