Functional Connectivity In Bipolar Disorder Research Articles

Person-based similarity in brain structure and functional connectivity in bipolar disorder

BACKGROUNDBipolar disorder shows significant variability in clinical presentation. Here we adopt a personalized approach to quantify the brain structural and functional similarity of each individual patient to other patients and to healthy individuals. METHODSBrain morphometric and resting-state functional connectivity measures from two independent samples of patients with bipolar disorder and healthy individuals (total number of participants=215) were modeled as single vectors to generated individualized morphometric and connectivity profiles. These profiles were then used to compute a person-based similarity indices which quantified the similarity in neuroimaging profiles amongst patients and between patients and health individuals. RESULTSThe morphometric and connectivity profiles of patients showed within-diagnosis similarity which was comparable to that observed in healthy individuals. They also showed minimal deviance from those of healthy individuals; the correlation between the profiles of patients and healthy individuals was high (range: 0.71–0.94, p<10−5). The degree of similarity between imaging profiles was associated with IQ (for cortical thickness) and age (functional integration) rather than clinical variables. Patients who were prescribed lithium, compared to those who were not, showed greater similarity to healthy individuals in terms of network integration (t = 2.2, p = 0.03). LIMITATIONSWe focused on patients with Bipolar disorder, type I only. CONCLUSIONSHigh inter-individual similarity in neuroimaging profiles was observed amongst patients with bipolar disorder and between patients and healthy individuals. We infer that brain alterations associated with bipolar disorder may be nested within the normal biological diversity consistent with the high prevalence of mood symptoms in the general population.

Altered functional connectivity of right inferior frontal gyrus subregions in bipolar disorder: a resting state fMRI study

The right inferior frontal gyrus (rIFG) is a key cortical node in the circuits of emotion and cognitive control, and it has been frequently associated with bipolar disorder (BP); however, a reliable pattern of aberrant rIFG activation and connectivity in bipolar disorder has yet to be established. To further elucidate rIFG abnormalities in different states of bipolar disorder, we examined activation and functional connectivity (FC) in five subregions of rIFG in bipolar disorder. A total of 83 participants, including those with bipolar depression (BPD; n = 25) and bipolar mania (BPM; n = 37) along with healthy control (HC) subjects (n = 26), were examined by resting state functional magnetic resonance imaging (rs-fMRI). Both BPD and BPM groups showed higher values of amplitude of low-frequency fluctuations (ALFF) than healthy control in four of the five rIFG subregions except cluster 2(posterior-ventral rIFG). Using five subregions of rIFG as seeds, the decreased FC in bipolar disorder was mainly between posterior-ventral rIFG(cluster 2) and multiple brain regions including the postcentral gyrus, the precentral gyrus, paracentral lobule, lingual Gyrus, fusiform and cerebellum posterior lobe. These results indicated that local activity and FC were altered within specific subregions of the rIFG in BP. These findings may provide the distinct functional connectivity of rIFG subregions in BP and suggest that the cluster2 (posterior-ventral rIFG) circuitry plays a crucial role in BP. Also, such abnormalities might help define a more precise intervention targets.

F115. Common and Dissociable Disruptions in Reward Circuit Functional Connectivity in Bipolar Disorder and Obesity

F115. Common and Dissociable Disruptions in Reward Circuit Functional Connectivity in Bipolar Disorder and Obesity

Resting-state functional connectivity in individuals with bipolar disorder during clinical remission: a systematic review.

Bipolar disorder is chronic and debilitating. Studies investigating resting-state functional connectivity in individuals with bipolar disorder may help to inform neurobiological models of illness. We conducted a systematic review with the following goals: to summarize the literature on resting-state functional connectivity in bipolar disorder during clinical remission (euthymia) compared with healthy controls; to critically appraise the literature and research gaps; and to propose directions for future research. We searched PubMed/MEDLINE, Embase, PsycINFO, CINAHL and grey literature up to April 2017. Twenty-three studies were included. The most consistent finding was the absence of differences in resting-state functional connectivity of the default mode network (DMN), frontoparietal network (FPN) and salience network (SN) between people with bipolar disorder and controls, using independent component analysis. However, 2 studies in people with bipolar disorder who were positive for psychosis history reported DMN hypoconnectivity. Studies using seed-based analysis largely reported aberrant resting-state functional connectivity with the amygdala, ventrolateral prefrontal cortex, cingulate cortex and medial prefrontal cortex in people with bipolar disorder compared with controls. Few studies used regional homogeneity or amplitude of low-frequency fluctuations. We found heterogeneity in the analysis methods used. Stability of the DMN, FPN and SN may reflect a state of remission. Further, DMN hypoconnectivity may reflect a positive history of psychosis in patients with bipolar disorder compared with controls, highlighting a potentially different neural phenotype of psychosis in people with bipolar disorder. Resting-state functional connectivity changes between the amygdala, prefrontal cortex and cingulate cortex may reflect a neural correlate of subthreshold symptoms experienced in bipolar disorder euthymia, the trait-based pathophysiology of bipolar disorder and/or a compensatory mechanism to maintain a state of euthymia.

Aberrant Brain Structural-Functional Connectivity Coupling in Euthymic Bipolar Disorder

Aberrant structural (diffusion tensor imaging, DTI) and resting-state functional (rsfMRI) connectivity are core features of bipolar disorder (BD). However, few studies have explored the integrity agreement between structural and functional connectivity in BD (SC-FC coupling). Such SC-FC coupling index could potentially provide additional clinical predictive value for BD spectrum disorders besides the intra-modality network measures. Thus, we examined the structural (DTI) and resting-state functional network properties, as well as their coupling index, among 57 euthymic BD patients (age 13-28 years, 18 females) and 42 age- and gender-matched healthy controls (age 13-28 years, 16 females). We found that compared to controls, BD patients showed increased structural rich club connectivity as well as decreased functional modularity. Importantly, the coupling strength between structural and functional connectome was decreased in BD patients compared to controls, which emerged as the most powerful feature discriminating the two groups. Our findings suggest that structural-functional coupling strength could serve as a valuable biological trait marker for bipolar disorder over and above the intra-modality network measures. Such measure can have important clinical implications for early identification of BD individuals, and inform strategies for prevention of BD onset and relapse. Funding: This study was funded by the National Natural Science Foundation of China (NSFC: 81471375,81671347), Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders (201805010009), and Guangzhou Municipal Psychiatric Disease Clinical Transformation Laboratory (201805010009), which had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. Declaration of Interest: We declare no competing interests. Ethical Approval: This study was approved by the Institutional Review Board of the Guangzhou Brain Hospital.

F87. Rostral Anterior Cingulate Glutamate Levels are Linked to Abnormal High-Frequency Resting-State Functional Connectivity in Bipolar Disorder

F87. Rostral Anterior Cingulate Glutamate Levels are Linked to Abnormal High-Frequency Resting-State Functional Connectivity in Bipolar Disorder

Altered cerebellar functional connectivity in remitted bipolar disorder: A resting-state functional magnetic resonance imaging study.

Several recent studies have reported a strong association between the cerebellar structural and functional abnormalities and psychiatric disorders. However, there are no studies to investigate possible changes in cerebellar functional connectivity in bipolar disorder. This study aimed to examine the whole-brain functional connectivity pattern of patients with remitted bipolar disorder II, in particular in the cerebellum. A total of 25 patients with remitted bipolar disorder II and 25 controls underwent resting-state functional magnetic resonance imaging and neuropsychological tests. Voxel-wise whole-brain connectivity was analyzed using a graph theory approach: functional connectivity strength. A seed-based resting-state functional connectivity analysis was further performed to investigate abnormal functional connectivity pattern of those regions with changed functional connectivity strength. Remitted bipolar disorder II patients had significantly decreased functional connectivity strength in the bilateral posterior lobes of cerebellum (mainly lobules VIIb/VIIIa). The seed-based functional connectivity analyses revealed decreased functional connectivity between the right posterior cerebellum and the default mode network (i.e. right posterior cingulate cortex/precuneus and right superior temporal gyrus), bilateral hippocampus, right putamen, left paracentral lobule and bilateral posterior cerebellum and decreased functional connectivity between the left posterior cerebellum and the right inferior parietal lobule and bilateral posterior cerebellum in patients with remitted bipolar disorder II. Our results suggest that cerebellar dysconnectivity, in particular distributed cerebellar-cerebral functional connectivity, might be associated with the pathogenesis of bipolar disorder.

Night sleep influences white matter microstructure in bipolar depression

BackgroundAlteration of circadian rhythms and sleep disruption are prominent trait-like features of bipolar disorder (BD). Diffusion tensor imaging (DTI) measures suggest a widespread alteration of white matter (WM) microstructure in patients with BD. Sleep promotes myelination and oligodendrocyte precursor cells proliferation. We hypothesized a possible association between DTI measures of WM microstructure and sleep quantity measures in BD. MethodsWe studied 69 inpatients affected by a depressive episode in course of type I BD. We used whole brain tract-based spatial statistics on DTI measures of WM microstructure: axial, radial, and mean diffusivity (AD, RD, MD), and fractional anisotropy (FA). Self-assessed measures of time asleep (TA) and total sleep time (TST) were extracted from the Pittsburgh Sleep Quality Index (PSQI). Actigraphic recordings were performed on a subsample of 23 patients. ResultsWe observed a positive correlation of DTI measures of FA with actigraphic measures of TA and TST, and with PSQI measure of TA. DTI measures of RD inversely associated with actigraphic measure of TA, and with PSQI measures of TA and TST. Several WM tracts were involved, including corpus callosum, cyngulate gyrus, uncinate fasciculus, left superior and inferior longitudinal and fronto-occipital fasciculi, thalamic radiation, corona radiata, retrolenticular part of internal capsule and corticospinal tract. LimitationsThe study is correlational in nature, and no conclusion about a causal connection can be drawn. ConclusionsReduced FA with increased RD and MD indicate higher water diffusivity associated with less organized myelin and/or axonal structures. Our findings suggest an association between sleep disruption and these measures of brain microstructure in specific tracts contributing to the functional connectivity in BD.

822. Abnormal Resting State Functional Connectivity in Bipolar Disorder with and without Psychosis

822. Abnormal Resting State Functional Connectivity in Bipolar Disorder with and without Psychosis

Dynamic functional connectivity in bipolar disorder is associated with executive function and processing speed: A preliminary study.

Disturbances in functional connectivity have been suggested to contribute to cognitive and emotion processing deficits observed in bipolar disorder (BD). Functional connectivity between medial prefrontal cortex (mPFC) and other brain regions may be particularly abnormal. The goal of the present study was to characterize the temporal dynamics of the default mode network (DMN) connectivity in BD and examine its association with cognition. In a preliminary study, euthymic BD (n = 15) and healthy comparison (HC, n = 19) participants underwent resting-state functional MRI, using high-resolution sequences adapted from the Human Connectome Project, and completed neuropsychological measures of processing speed and executive function. A seed-based approach was used to measure DMN correlations in each participant, with regions of interest in the mPFC, posterior cingulate cortex (PCC), and lateral parietal cortex. Subsequently, to characterize temporal dynamics, correlational analyses between the mPFC and other DMN nodes were repeated using a sliding-window correlational analysis with subsets of the time series. When averaged across the entire scan, there were no group differences in overall connectivity strength between the mPFC and other regions of the DMN. However, dynamic connectivity between the mPFC and PCC was altered in BD, such that connectivity was less variable (i.e., more rigid) over time. Decreased connectivity variability was associated with slower processing speed and reduced cognitive set-shifting in BD patients. Variability in resting-state functional connectivity may be an index of internetwork flexibility that is reduced in BD and a correlate of ongoing cognitive impairment during periods of euthymia. (PsycINFO Database Record

Supplemental Material for Dynamic Functional Connectivity in Bipolar Disorder Is Associated With Executive Function and Processing Speed: A Preliminary Study

Supplemental Material for Dynamic Functional Connectivity in Bipolar Disorder Is Associated With Executive Function and Processing Speed: A Preliminary Study

Altered functional connectivity during self- and close other-reflection in patients with bipolar disorder with past psychosis and patients with schizophrenia

Disturbances in implicit self-processing have been reported both in psychotic patients with bipolar disorder (BD) and schizophrenia. It remains unclear whether these two psychotic disorders show disturbed functional connectivity during explicit self-reflection, which is associated with social functioning and illness symptoms. Therefore, we investigated functional connectivity during explicit self-reflection in BD with past psychosis and schizophrenia. Twenty-three BD-patients, 17 schizophrenia-patients and 21 health controls (HC) performed a self-reflection task, including the conditions self-reflection, close other-reflection and semantic control. Functional connectivity was investigated with generalized psycho-physiological interaction (gPPI). During self-reflection compared to semantic, BD-patients had decreased connectivity between several cortical-midline structures (CMS) nodes (i.e., anterior cingulate cortex, ventromedial prefrontal cortex), the insula and the head of the caudate while HC showed increased connectivities. Schizophrenia-patients, during close other-reflection compared to semantic, demonstrated reduced ventral-anterior insula-precuneus/posterior cingulate cortex (PCC) functional connectivity, whereas this was increased in HC. There were no differences between BD and schizophrenia during self- and close other-reflection. We propose that decreased functional connectivity between the CMS nodes/insula and head of the caudate in BD-patients may imply a reduced involvement of the motivational system during self-reflection; and the reduced functional connectivity between the ventral-anterior insula and precuneus/PCC during close other-reflection in schizophrenia-patients may subserve difficulties in information integration of autobiographical memory and emotional awareness in relation to close others. These distinctive impaired patterns of functional connectivity in BD and schizophrenia (compared to HC) deserve further investigation to determine their robustness and associations with differences in clinical presentation.

Aberrant intrinsic functional connectivity within and between corticostriatal and temporal-parietal networks in adults and youth with bipolar disorder.

Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas. We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10-50 years) with BD (n = 39) and healthy volunteers (HV; n = 78). We identified brain regions with aberrant intrinsic functional connectivity in BD by first comparing voxel-wise mean global connectivity and then conducting correlation analyses. We used k-means clustering and multidimensional scaling to organize all detected regions into networks. Across the brain, we detected areas of dysconnectivity in both youths and adults with BD relative to HV. There were no significant age-group × diagnosis interactions. When organized by interregional connectivity, the areas of dysconnectivity in patients with BD comprised two networks: one of temporal and parietal areas involved in late stages of visual processing, and one of corticostriatal areas involved in attention, cognitive control and response generation. These data suggest that two networks show abnormal intrinsic functional connectivity in BD. Regions in these networks have been implicated previously in BD. We observed similar dysconnectivity in youths and adults with BD. These findings provide guidance for refining models of network-based dysfunction in BD.