Structural and functional brain alterations in anorexia nervosa:A multimodal meta-analysis of neuroimaging studies.

Anorexia nervosa (AN) is a complex psychiatric disorder with poorly understood etiology. Numerous voxel-based morphometry (VBM) and resting-state functional imaging studies have provided strong evidence of abnormal brain structure and intrinsic and functional activities in AN, but with inconsistent conclusions. Herein, a whole-brain meta-analysis was conducted on VBM (660 patients with AN, and 740 controls) and resting-state functional imaging (425 patients with AN, and 461 controls) studies that measured differences in the gray matter volume (GMV) and intrinsic functional activity between patients with AN and healthy controls (HCs). Overall, patients with AN displayed decreased GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex), and left middle occipital gyrus (extending to the left inferior parietal lobe). In resting-state functional imaging studies, patients with AN displayed decreased resting-state functional activity in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increased resting-state functional activity in the right parahippocampal gyrus. This multimodal meta-analysis identified reductions of gray matter and functional activity in the anterior and median cingulate in patients with AN, which contributes to further understanding of the pathophysiology of AN.

Common and distinct patterns of intrinsic brain activity alterations in major depression and bipolar disorder: voxel-based meta-analysis.

Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded consistent conclusions. A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) was conducted using seed-based d mapping software. Systematic literature search identified 50 studies comparing 1399 MDD patients and 1332 HCs, and 15 studies comparing 494 BD patients and 593 HCs. MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC]), bilateral insula extending into the striatum and left supramarginal gyrus and decreased ALFF in the bilateral cerebellum, bilateral precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus, bilateral insula extending into the striatum, right SFG, and right superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum (extending to the occipital cortex), left ACC, and left STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus, and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Our comprehensive meta-analysis suggests that MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system and occipital cortex may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies.

Abnormalities of aquaporin-4 in the cerebellum in bipolar II disorder: An ultra-high b-values diffusion weighted imaging study.

BACKGROUND: Cumulative evidence indicated the cerebellum is involved in the pathophysiology of bipolar disorder (BD). It was reported that the apparent diffusion coefficient from ultra-high b-values (ADCuh) could reflect the function of aquaporin-4 (AQP4) which was involved in neurological disorders. However, no studies have reported the AQP4 alteration in the cerebellum in BD. Therefore, this study aimed to investigate the ADCuh and AQP4 in the cerebellum in BD-II. METHODS: Fifty patients with BD-II as well as 43 healthy controls underwent enhance diffusion weighted imaging (eDWI) with ultra-high b-values. The eDWI parameters including ADCuh , pure water diffusion (D) and pseudodiffusion (D*) was measured using regions-of-interest analysis in the superior cerebellar peduncles (SCP), middle cerebellar peduncles (MCP) , cerebellar hemisphere, dentate nuclei, tonsil and vermis of the cerebellum. RESULTS: BD-II exhibited increased ADCuh values in the bilateral SCP, cerebellar hemisphere, tonsil and right dentate nuclei, and increased D* and D in the bilateral SCP, and decreased D* in the tonsil. Additionally, there were positive correlations between Hamilton Rating Scale for Depression-24 scores and bilateral ADCuh values in the SCP and cerebellar hemisphere. CONCLUSIONS: The alteration of the ADCuh values in the cerebellum may reflect the changes of the AQP4, especially the abnormality of eDWI parameters in the SCP may be a key neurobiological feature of BD-II. The current results provide a novel insight to look into the pathophysiology mechanisms underlying BD-II.

Abnormal resting-state regional homogeneity in unmedicated bipolar II disorder.

BACKGROUND: Previous studies demonstrated that patients with bipolar disorder (BD) exhibited abnormal neural activity in multiple brain regions. However, no study has been conducted to identify regional intrinsic neural activity changes in BD II. In the present study, we used the regional homogeneity (ReHo) approach to explore the regional abnormal neural activity in bipolar II disorder METHODS: One hundred unmedicated patients with BD II depression and 100 healthy controls (HC) underwent the resting-state functional magnetic resonance imaging. The ReHo values of each voxel was calculated in the whole brain. The two-sample t-test and threshold-free cluster enhancement (TFCE) correction were applied for the ReHo analysis. RESULTS: Compared with the HC group, the BD II group showed significantly decreased ReHo in the left orbitofrontal cortex, and increased ReHo in the right precentral gyrus, right supplementary motor area and bilateral middle occipital gyrus (P < .05, TFCE corrected). LIMITATIONS: This study lacks the evidence of brain structural changes, and used the cross-sectional design which did not explore local alterations of remitted and manic patients. CONCLUSION: Our findings revealed abnormal local intrinsic neural activity during resting state which may contribute to the pathophysiology of bipolar II disorder. Particularly the disrupted balance between the prefrontal cortex and primary sensorimotor regions provides evidence for the unique pathological mechanism underlying BD.

Disrupted functional connectivity within the default mode network and salience network in unmedicated bipolar II disorder.

BACKGROUND: Recent studies demonstrate that functional disruption in resting-state networks contributes to cognitive and affective symptoms of bipolar disorder (BD), however, the functional connectivity (FC) pattern underlying BD II depression within the default mode network (DMN), salience network (SN), and frontoparietal network (FPN) is still not well understood. The primary aim of this study was to explore whether the pathophysiology of BD II derived from the pattern of FC within the DMN, SN, and FPN by using seed-based FC approach of resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Ninety-six BD II patients and 100 HCs underwent rs-fMRI and three-dimensional structural data acquisition. All patients were either drug naive or unmedicated for at least 6 months. The following four regions of interest were used to conduct seed-based FC: the left posterior cingulate cortex (PCC) seed to probe the DMN, the left subgenual anterior cingulate cortex (sgACC) and amygdala seeds to probe the SN, the left dorsal lateral prefrontal cortex (dlPFC) seed to probe the FPN. RESULTS: Compared with HCs, patients with BD II demonstrated hypoconnectivity of the left PCC to the bilateral medial prefrontal cortex (mPFC) and bilateral precuneus/PCC, and of the left sgACC to the right inferior temporal gyrus (ITG); nevertheless, the left amygdala and dlPFC had no within-network hypo- or hyperconnectivity to any other SN and FPN regions. CONCLUSION: Our findings suggest that disrupted FC is located in the DMN and SN, especially in the PCC-mPFC and precuneus/PCC, and sgACC-ITG connectivity in BD II patients.

Abnormal cerebellum-DMN regions connectivity in unmedicated bipolar II disorder.

OBJECTIVE: Bipolar disorder (BD) is a common psychiatric disease. Previous studies have found abnormalities in structural and functional brain connectivity in BD patients. However, few studies have focused on the functional connectivity (FC) of the cerebellum and its sub-regions in patients with BD. The present study aimed to examine the FC of cerebellum-default mode network (DMN) regions in patients with BD II. METHOD: Ninety patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We selected three pairs of subregions of the cerebellum that are DMN-related (the bilateral Crus I, Crus II, and lobule IX) as seed regions and calculated the whole brain FC for each subregion. RESULTS: Compared with the HCs, the patients with BD II depression showed increased connectivity between the right Crus I and bilateral precuneus and decreased connectivity between the left Crus II and bilateral medial prefrontal cortex (mPFC) and between the left Crus II and right medial frontal gyrus (MFG). There was no significant difference in the whole FC of the left Crus I and bilateral lobule IX between the BD II depression group and the HCs group. LIMITATIONS: This study was cross-sectional and did not examine data from euthymic BD patients. CONCLUSIONS: The findings showed impaired FC of cerebellum-DMN regions in BD; partial FC between the Crus I and precuneus and the Crus II and prefrontal cortex suggests the importance of abnormal cerebellum-DMN regions FC in the pathophysiology of BD.

Disruption of superficial white matter in the emotion regulation network in bipolar disorder.

Bipolar disorder (BD) is characterized by emotion dysregulation and involves changes in the gray matter (GM) and white matter (WM). Although previous diffusion tensor imaging (DTI) studies reported changes in the diffusion properties of the deep WM (DWM) in BD patients, the diffusion properties of the superficial WM (SWM) are rarely investigated. In this study, we tried to determine whether the diffusion parameters of the SWM were altered in BD patients compared to controls and whether the changes were associated with the disrupted emotion regulation of the BD patients. We collected DTI data from 37 BD patients and 42 gender- and age-matched healthy controls (HC). Using probabilistic tractography, we defined a population-based SWM mask based on all the subjects. After performing the tract-based spatial statistical (TBSS) analyses, we identified the SWM areas in which the BD patients differed from the controls. This study showed significantly reduced fractional anisotropy in the SWM (FASWM) in the BD patients compared to the HC in the bilateral dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), medial prefrontal cortex (mPFC), and the left parietal cortex. Moreover, compared to the controls, the BD patients showed significantly increased mean diffusivity (MDSWM) and radial diffusivity (RDSWM) in the SWM in the right frontal cortex. This study presents altered cortico-cortical connections proximal to the regions related to the emotion dysregulation of BD patients, which indicated that the SWM may serve as the brain's structural basis underlying the disrupted emotion regulation of BD patients. The disrupted FASWM in the parietal cortex may indicate that the emotion dysregulation in BD patients is related to the cognitive control network.

Disrupted Cerebellar Connectivity With the Central Executive Network and the Default-Mode Network in Unmedicated Bipolar II Disorder.

Objective: Bipolar disorder (BD) is a common psychiatric disease. Although structural and functional abnormalities of the cerebellum in BD patients have been reported by recent neuroimaging studies, the cerebellar-cerebral functional connectivity (FC) has not yet been examined. The present study aims to investigate the FC between the cerebellum and cerebrum, particularly the central executive network (CEN) and the default-mode network (DMN) in bipolar II disorder (BD II). Methods: Ninety-four patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging. Seed-based connectivity analyses were performed using cerebellar seeds previously identified as being involved in the CEN (bilateral Crus Ia) and DMN (bilateral Crus Ib). Results: Compared with HCs, BD II depression patients appeared decreased FC in the right Crus Ia-left dorsal lateral prefrontal cortex (dlPFC) and -left anterior cingulate cortex (ACC), the right Crus Ib-left medial prefrontal cortex (mPFC), -left middle temporal gyrus (MTG), and -left inferior temporal gyrus (ITG). No altered FC between the left Crus Ia or Crus Ib and the cerebral regions was found. Conclusions: Patients with BD II depression showed disrupted FC between the cerebellum and the CEN (mainly in the left dlPFC and ACC) and DMN (mainly in the left mPFC and temporal lobe), suggesting the significant role of the cerebellum-CEN and -DMN connectivity in the pathogenesis of BD.