Large-scale network abnormality in behavioral addiction.

BACKGROUND: Researchers have endeavored to ascertain the network dysfunction associated with behavioral addiction (BA) through the utilization of resting-state functional connectivity (rsFC). Nevertheless, the identification of aberrant patterns within large-scale networks pertaining to BA has proven to be challenging. METHODS: Whole-brain seed-based rsFC studies comparing subjects with BA and healthy controls (HC) were collected from multiple databases. Multilevel kernel density analysis was employed to ascertain brain networks in which BA was linked to hyper-connectivity or hypo-connectivity with each prior network. RESULTS: Fifty-six seed-based rsFC publications (1755 individuals with BA and 1828 HC) were included in the meta-analysis. The present study indicate that individuals with BAs exhibit (1) hypo-connectivity within the fronto-parietal network (FN) and hypo- and hyper-connectivity within the ventral attention network (VAN); (2) hypo-connectivity between the FN and regions of the VAN, hypo-connectivity between the VAN and regions of the FN and default mode network (DMN), hyper-connectivity between the DMN and regions of the FN; (3) hypo-connectivity between the reward system and regions of the sensorimotor network (SS), DMN and VAN; (4) hypo-connectivity between the FN and regions of the SS, hyper-connectivity between the VAN and regions of the SS. CONCLUSIONS: These findings provide impetus for a conceptual framework positing a model of BA characterized by disconnected functional coordination among large-scale networks.

A Multimodal Meta-Analytical Evidence of Functional and Structural Brain Abnormalities Across Alzheimer's Disease Spectrum.

BACKGROUND: Numerous neuroimaging studies have reported that Alzheimer's disease (AD) spectrum have been linked to alterations in intrinsic functional activity and cortical thickness (CT) of some brain areas. However, the findings have been inconsistent and the correlation with the transcriptional profile and neurotransmitter systems remain largely unknown. METHODS: We conducted a meta-analysis to identify multimodal differences in the amplitude of low-frequency fluctuation (ALFF)/fractional ALFF (fALFF) and CT in patients with AD and preclinical AD compared to healthy controls (HCs), using the Seed-based d Mapping with Permutation of Subject Images software. Transcriptional data were retrieved from the Allen Human Brain Atlas. The atlas-based nuclear imaging-derived neurotransmitter maps were investigated by JuSpace toolbox. RESULTS: We included 26 ALFF/fALFF studies comprising 884 patients with AD and 1,020 controls, along with 52 studies comprising 2,046 patients with preclinical AD and 2,336 controls. For CT, we included 11 studies comprising 353 patients with AD and 330 controls. Overall, compared to HCs, patients with AD showed decreased ALFF/fALFF in the bilateral posterior cingulate gyrus (PCC)/precuneus and right angular gyrus, as well as increased ALFF/fALFF in the bilateral parahippocampal gyrus (PHG). Patients with peclinical AD showed decreased ALFF/fALFF in the left precuneus. Additionally, patients with AD displayed decreased CT in the bilateral PHG, left PCC, bilateral orbitofrontal cortex, sensorimotor areas and temporal lobe. Furthermore, gene sets related to brain structural and functional changes in AD and preclincal AD were enriched for G protein-coupled receptor signaling pathway, ion gated channel activity, and components of biological membrane. Functional and structural alterations in AD and preclinical AD were spatially associated with dopaminergic, serotonergic, and GABAergic neurotransmitter systems. CONCLUSIONS: The multimodal meta-analysis demonstrated that patients with AD exhibited convergent functional and structural alterations in the PCC/precuneus and PHG, as well as cortical thinning in the primary sensory and motor areas. Furthermore, patients with preclinical AD showed reduced functional activity in the precuneus. AD and preclinical AD showed genetic modulations/neurotransmitter deficits of brain functional and structural impairments. These findings may provide new insights into the pathophysiology of the AD spectrum.

A multimodal meta-analysis of regional functional and structural brain abnormalities in obsessive-compulsive disorder.

Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed abnormalities in specific brain regions in obsessive-compulsive disorder (OCD), but results have been inconsistent. We conducted a whole-brain voxel-wise meta-analysis on resting-state functional imaging and VBM studies that investigated differences of functional activity and gray matter volume (GMV) between patients with OCD and healthy controls (HCs) using seed-based d mapping (SDM) software. A total of 41 independent studies (51 datasets) for resting-state functional imaging and 42 studies (46 datasets) for VBM were included by a systematic literature search. Overall, patients with OCD displayed increased spontaneous functional activity in the bilateral inferior frontal gyrus (IFG) (extending to the bilateral insula) and bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), as well as decreased spontaneous functional activity in the bilateral paracentral lobule, bilateral cerebellum, left caudate nucleus, left inferior parietal gyri, and right precuneus cortex. For the VBM meta-analysis, patients with OCD displayed increased GMV in the bilateral thalamus (extending to the bilateral cerebellum), right striatum, and decreased GMV in the bilateral mPFC/ACC and left IFG (extending to the left insula). The conjunction analyses found that the bilateral mPFC/ACC, left IFG (extending to the left insula) showed decreased GMV with increased intrinsic function in OCD patients compared to HCs. This meta-analysis demonstrated that OCD exhibits abnormalities in both function and structure in the bilateral mPFC/ACC, insula, and IFG. A few regions exhibited only functional or only structural abnormalities in OCD, such as the default mode network, striatum, sensorimotor areas, and cerebellum. It may provide useful insights for understanding the underlying pathophysiology of OCD and developing more targeted and efficacious treatment and intervention strategies.

Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt.

INTRODUCTION: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. METHODS: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). RESULTS: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. CONCLUSION: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

Meta-analysis of cortical thickness reduction in adult schizophrenia.

BACKGROUND: Numerous neuroimaging studies using surface-based morphometry analyses have reported altered cortical thickness among patients with schizophrenia, but the results have been inconsistent. We sought to provide a whole-brain meta-analysis, which may help enhance the spatial accuracy of identification. METHODS: We conducted a meta-analysis of whole-brain studies that explored cortical thickness alteration among adult patients with schizophrenia, including first-episode patients with schizophrenia, and patients with chronic schizophrenia, compared with healthy controls by using the seed-based d mapping with permutation of subject images (SDM-PSI) software. RESULTS: A systematic literature search identified 25 studies (33 data sets) of cortical thickness, including 2008 patients with schizophrenia and 2004 healthy controls. Overall, patients with schizophrenia showed decreased cortical thickness in the right inferior frontal gyrus (IFG) and bilateral insula extending to the superior temporal gyrus (STG). Subgroup meta-analysis reported that patients with chronic schizophrenia showed decreased cortical thickness in the right insula extending to the right IFG. There was no significant cortical thickness difference between first-episode patients with schizophrenia and healthy controls. LIMITATIONS: The results of meta-regression analyses should be viewed cautiously since they were driven by a small number of studies or did not overlap with the between-group differences found in the primary analyses. CONCLUSION: The meta-analysis suggested robust cortical thickness reduction in the IFG, insula and STG among adult patients with schizophrenia, particularly in those with chronic schizophrenia. The results provide useful insights to understanding the underlying pathophysiology of schizophrenia.

Functional and structural brain abnormalities in substance use disorder: A multimodal meta-analysis of neuroimaging studies.

INTRODUCTION: Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed that patients with substance use disorder (SUD) may present brain abnormalities, but their results were inconsistent. This multimodal neuroimaging meta-analysis aimed to estimate common and specific alterations in SUD patients by combining information from all available studies of spontaneous functional activity and gray matter volume (GMV). METHODS: A whole-brain meta-analysis on resting-state functional imaging and VBM studies was conducted using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software, followed by multimodal overlapping to comprehensively investigate function and structure of the brain in SUD. RESULTS: In this meta-analysis, 39 independent studies with 47 datasets related to resting-state functional brain activity (1444 SUD patients; 1446 healthy controls [HCs]) were included, as well as 77 studies with 89 datasets for GMV (3457 SUD patients; 3774 HCs). Patients with SUD showed the decreased resting-state functional brain activity in the bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC). For the VBM meta-analysis, patients with SUD showed the reduced GMV in the bilateral ACC/mPFC, insula, thalamus extending to striatum, and left sensorimotor cortex. CONCLUSIONS: This multimodal meta-analysis exhibited that SUD shows common impairment in both function and structure in the ACC/mPFC, suggesting that the deficits in functional and structural domains could be correlated together. In addition, a few regions exhibited only structural impairment in SUD, including the insula, thalamus, striatum, and sensorimotor areas.

Abnormal dynamic functional connectivity of hippocampal subregions associated with working memory impairment in melancholic depression.

BACKGROUND: Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions - including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD. METHODS: Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships. RESULTS: Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD. CONCLUSIONS: These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.

Aberrant dynamic functional connectivity in corticostriatal circuitry in depressed bipolar II disorder with recent suicide attempt.

BACKGROUND: The underlying neurobiological mechanisms on suicidal behavior in bipolar disorder remain unclear. We aim to explore the mechanisms of suicide by detecting dynamic functional connectivity (dFC) of corticostriatal circuitry and cognition in depressed bipolar II disorder (BD II) with recent suicide attempt (SA). METHODS: We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 68 depressed patients with BD-II (30 with SA and 38 without SA) and 35 healthy controls (HCs). The whole-brain dFC variability of corticostriatal circuitry was calculated using a sliding-window analysis. Their correlations with cognitive dysfunction were further detected. Support vector machine (SVM) classification tested the potential of dFC to differentiate BD-II with SA from HCs. RESULTS: Increased dFC variability between the right vCa and the right insula was found in SA compared to non-SA and HCs, and negatively correlated with speed of processing. Decreased dFC variability between the left dlPu and the right postcentral gyrus was found in non-SA compared to SA and HCs, and positively correlated with reasoning problem-solving. Both SA and non-SA exhibited decreased dFC variability between the right dCa and the left MTG, and between the right dlPu and the right calcarine when compared to HCs. SVM classification achieved an accuracy of 75.24 % and AUC of 0.835 to differentiate SA from non-SA, while combining the abnormal dFC features between SA and non-SA. CONCLUSIONS: Aberrant dFC variability of corticostriatal circuitry may serve as potential neuromarker for SA in BD-II, which might help to discriminate suicidal BD-II patients from non-suicidal patients and HCs.

Functional and structural brain differences in bipolar disorder: a multimodal meta-analysis of neuroimaging studies.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Shared and specific characteristics of regional cerebral blood flow and functional connectivity in unmedicated bipolar and major depressive disorders.

BACKGROUND: Identifying brain similarities and differences between bipolar disorder (BD) and major depressive disorder (MDD) can help us better understand their pathophysiological mechanisms and develop more effective treatments. However, the features of whole-brain regional cerebral blood flow (CBF) and intrinsic functional connectivity (FC) underlying BD and MDD have not been directly compared. METHODS: Eighty-eight unmedicated BD II depression patients, 95 unmedicated MDD patients, and 96 healthy controls (HCs) underwent three-dimensional arterial spin labeling (3D ASL) and resting-state functional MRI (rs-fMRI). The functional properties of whole brain CBF and seed-based resting-state FC further performed based on those regions with changed CBF were analyzed between the three groups. RESULTS: The patients with BD and MDD showed commonly increased CBF in the left posterior lobe of the cerebellum and the left middle temporal gyrus (MTG) compared with HCs. The CBF of the left MTG was positively associated with 24-items Hamilton Depression Rating Scale scores in MDD patients. Decreased FC between the left posterior lobe of the cerebellum and the left inferior frontal gyrus (IFG) was observed only in patients with BD compared with HCs. CONCLUSION: Patients with BD and those with MDD shared common features of CBF in the posterior lobe of the cerebellum and the MTG. The altered posterior lobe of the cerebellum-IFG FC can be considered as a potential biomarker for the differentiation of patients with BD from those with MDD.

Thyroid hormones disturbances, cognitive deficits and abnormal dynamic functional connectivity variability of the amygdala in unmedicated bipolar disorder.

OBJECTIVE: Accumulating evidence suggests that hypothalamus-pituitary-thyroid (HPT) axis dysfunction is relevant to the neuropsychological and pathophysiology functions of bipolar disorder (BD). However, no research has investigated the inter-relationships among thyroid hormones disturbance, neurocognitive deficits, and aberrant brain function (particularly in the amygdala) in patients with BD. MATERIALS AND METHODS: Data of dynamic resting-state functional connectivity (rs-dFC) were gathered from 59 patients with unmedicated BD II during depressive episodes and 52 healthy controls (HCs). Four seeds were selected (the bilateral lateral amygdala and the bilateral medial amygdala). The sliding-window analysis was applied to investigate dynamic functional connectivity (dFC). Additionally, the serum thyroid hormone (free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4) and thyroid-stimulating hormone (TSH)) levels, and cognitive scores on the MATRICS Consensus Cognitive Battery (MCCB) in patients and HCs were detected. RESULTS: The BD group exhibited increased dFC variability between the left medial amygdala and right medial prefrontal cortex (mPFC) when compared with the HC group. Additionally, the BD group showed lower FT3, TT3, and TSH level, higher FT4 level, and poorer cognitive score. Moreover, a significant negative correlation was observed between the dFC variability of the left medial amygdala-right mPFC and TSH level, or reasoning and problem solving of MCCB score in BD group. Multiple regression analysis showed that the TSH level × dFC variability of the medial amygdala-mPFC was an independent predictor for cognitive processing speed in BD group. CONCLUSIONS: This study revealed patients with BD II depression had excessive variability in dFC between the medial amygdala and mPFC. Moreover, both HPT axis dysfunction and abnormal dFC of the amygdala-mPFC might be implicated in cognitive impairment in the early stages of BD.

Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder.

The pathophysiological mechanisms of bipolar disorder (BD) are not completely known, and systemic inflammation and immune dysregulation are considered as risk factors. Previous neuroimaging studies have proved metabolic, structural and functional abnormalities of the amygdala in BD, suggesting the vital role of amygdala in BD patients. This study aimed to test the underlying neural mechanism of inflammation-induced functional connectivity (FC) in the amygdala subregions of BD patients. Resting-state functional MRI (rs-fMRI) was used to delineate the amygdala FC from two pairs of amygdala seed regions (the bilateral lateral and medial amygdala) in 51 unmedicated BD patients and 69 healthy controls (HCs). The levels of pro-inflammatory cytokines including interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α were measured in the serum. The correlation between abnormal levels of pro-inflammatory cytokines and FC values were calculated in BD patients. The BD group exhibited decreased FC between the right medial amygdala and bilateral medial frontal cortex (MFC), and decreased FC between the left medial amygdala and the left temporal pole (TP), right orbital inferior frontal gyrus compared with HCs. The BD patients had higher levels of TNF-α than HCs. Correlation analysis showed negative correlation between the TNF-α level and abnormal FC of the right medial amygdala-bilateral MFC; and negative correlation between TNF-α levels and abnormal FC of the left medial amygdala-left TP in BD group. These findings suggest that dysfunctional and immune dysregulation between the amygdala and the frontotemporal circuitry might play a critical role in the pathogenesis of BD.

Reduced myelin density in unmedicated major depressive disorder: An inhomogeneous magnetization transfer MRI study.

OBJECTIVES: To detect the whole-brain reduced myelin density in unmedicated patients with major depressive disorder (MDD) using the inhomogeneous magnetization transfer (ihMT) imaging technology. Compared to other technologies, the ihMT provides high specificity and sensitivity to detect myelin. METHOD: In this prospective study, fifty unmedicated patients (mean age 25.36 years, 40% men) with MDD and 57 age- and sex-matched healthy controls (HCs) (mean age 25.02 years, 53% men) were recruited between January 2019 and December 2019. All participants underwent ihMT imaging, and pseudo-quantitative ihMT (qihMT) and ihMT ratio (ihMTR) were obtained. The mean values of qihMT and ihMTR extracted from the 50 WM masks (extracted from the International Consortium for Brain Mapping, ICBM-152) in each participant were compared between participants in the MDD and HCs groups. The symptoms of patients were evaluated using the 24-item Hamilton Depression Rating scale (HDRS). RESULTS: Compared with the HC group, the MDD group showed significantly decreased qihMT and ihMTR values in the left inferior fronto-occipital fasciculus (IFOF) (t = -4.057, p < 0.001; t = -3.662, p < 0.001) and the left uncinate fasciculus (UF) (t = -4.776, p < 0.001; t = -3.800, p < 0.001) after Bonferroni correction. The correlation analysis displayed a significant negative correlation between qihMT values of the left IFOF and HDRS total scores in patients with MDD (r = -0.390, p = 0.012). LIMITATIONS: This was a cross-sectional study with a relative small sample. CONCLUSIONS: These findings suggest the reduced myelin density in the IFOF and UF in patients with MDD, which might be associated with the pathophysiology of MDD.

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.

Inflammation is correlated with abnormal functional connectivity in unmedicated bipolar depression: an independent component analysis study of resting-state fMRI.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder.

BACKGROUND: Systemic inflammation and immune dysregulation have been considered as risk factors in the pathophysiology of mood disorders including bipolar disorder (BD). Previous neuroimaging studies have demonstrated metabolic, structural and functional abnormalities in the insula in BD, proposed that the insula played an important role in BD. We herein aimed to explore neural mechanisms underlying inflammation-induced in the insular subregions functional connectivity (FC) in patients with BD. METHODS: Brain resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 41 patients with unmedicated BD II (current episode depressed), 68 healthy controls (HCs). Three pairs of insular seed regions were selected: the bilateral anterior insula (AI), the bilateral middle insula (MI) and the bilateral posterior insula (PI), and calculated the whole-brain FC for each subregion. Additionally, the serum levels of pro-inflammatory cytokines in patients and HCs, including IL-6 and TNF-α, were detected. Then the partial correlation coefficients between the abnormal insular subregions FC values and pro-inflammatory cytokines levels in patients with BD II depression were calculated. RESULTS: The BD II depression group exhibited decreased FC between the right PI and the left postcentral gyrus, and increased FC between the left AI and the bilateral insula (extended to the right putamen) when compared with the HC group. Moreover, the patients with BD II depression showed higher IL-6 and TNF-α levels than HCs, and IL-6 level was negatively correlated with FC of the right PI to the left postcentral gyrus. CONCLUSIONS: Our results demonstrated that abnormal FC between the bilateral insula, and between the insula and sensorimotor areas in BD. Moreover, disrupted FC between the insula and sensorimotor areas was associated with elevated pro-inflammatory cytokine levels of IL-6 in BD.