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Brain network analysis reveals affected connectome structure in bipolar I disorder.

ABSTRACT: The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections--i.e., the connectome--suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (-4.4%, P =0.002) and that this deficit relates (r = 0.56, P < 0.001) to reduced connectivity strength of interhemispheric connections (-13.0%, P = 0.001). Bipolar disorder patients were found not to show predominant alterations in the strength of brain hub connections in general, or of connections spanning brain hubs (i.e., "rich club" connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central "rich club" system appears not to be particularly affected.

SUBMITTER: Collin G

PROVIDER: S-EPMC5597048 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Brain network analysis reveals affected connectome structure in bipolar I disorder.

Collin Guusje G van den Heuvel Martijn P MP Abramovic Lucija L Vreeker Annabel A de Reus Marcel A MA van Haren Neeltje E M NE Boks Marco P M MP Ophoff Roel A RA Kahn René S RS

Human brain mapping 20151010 1

The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections--i.e., the connectome--suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar defic ...[more]

PMID: 26454006

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Project description:BackgroundAttention-deficit/hyperactivity disorder (ADHD) is highly prevalent among youth with or at familial risk for bipolar-I disorder (BD-I), and ADHD symptoms commonly precede and may increase the risk for BD-I; however, associated neuropathophysiological mechanisms are not known. In this cross-sectional study, we sought to investigate brain structural network topology among youth with ADHD, with and without familial risk of BD-I.MethodsWe recruited 3 groups of psychostimulant-free youth (aged 10-18 yr), namely youth with ADHD and at least 1 biological parent or sibling with BD-I (high-risk group), youth with ADHD who did not have a first- or second-degree relative with a mood or psychotic disorder (low-risk group) and healthy controls. We used graph-based network analysis of structural magnetic resonance imaging data to investigate topological properties of brain networks. We also evaluated relationships between topological metrics and mood and ADHD symptom ratings.ResultsA total of 149 youth were included in the analysis (49 healthy controls, 50 low-risk youth, 50 high-risk youth). Low-risk and high-risk ADHD groups exhibited similar differences from healthy controls, mainly in the default mode network and central executive network. We found topological alterations in the salience network of the high-risk group, relative to both low-risk and control groups. We found significant abnormalities in global network properties in the high-risk group only, compared with healthy controls. Among both low-risk and high-risk ADHD groups, nodal metrics in the right triangular inferior frontal gyrus correlated positively with ADHD total and hyperactivity/impulsivity subscale scores.LimitationsThe cross-sectional design of this study could not determine the relevance of these findings to BD-I risk progression.ConclusionYouth with ADHD, with and without familial risk for BD-I, exhibit common regional abnormalities in the brain connectome compared with healthy youth, whereas alterations in the salience network distinguish these groups and may represent a prodromal feature relevant to BD-I risk.

Project description:Background:Bipolar disorder (BD) is a serious psychiatric disorder that is associated with a high suicide rate, and for which no clinical biomarker has yet been identified. To address this issue, we investigated the use of magnetoencephalography (MEG) as a new prospective tool. MEG has been used to evaluate frequency-specific connectivity between brain regions; however, no previous study has investigated the frequency-specific resting-state connectome in patients with BD. This resting-state MEG study explored the oscillatory representations of clinical symptoms of BD via graph analysis. Methods:In this prospective case-control study, 17 patients with BD and 22 healthy controls (HCs) underwent resting-state MEG and evaluations for depressive and manic symptoms. After estimating the source current distribution, orthogonalized envelope correlations between multiple brain regions were evaluated for each frequency band. We separated regions-of-interest into seven left and right network modules, including the frontoparietal network (FPN), limbic network (LM), salience network (SAL), and default mode network (DMN), to compare the intra- and inter-community edges between the two groups. Results:In the BD group, we found significantly increased inter-community edges of the right LM-right DMN at the gamma band, and decreased inter-community edges of the right SAL-right FPN at the delta band and the left SAL-right SAL at the theta band. Intra-community edges in the left LM at the high beta band were significantly higher in the BD group than in the HC group. The number of connections in the left LM at the high beta band showed positive correlations with the subjective and objective depressive symptoms in the BD group. Conclusion:We introduced graph theory into resting-state MEG studies to investigate the functional connectivity in patients with BD. To the best of our knowledge, this is a novel approach that may be beneficial in the diagnosis of BD. This study describes the spontaneous oscillatory brain networks that compensate for the time-domain issues associated with functional magnetic resonance imaging. These findings suggest that the connectivity of the LM at the beta band may be a good objective biological biomarker of the depressive symptoms associated with BD.

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Brain network analysis reveals affected connectome structure in bipolar I disorder.

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Brain network analysis reveals affected connectome structure in bipolar I disorder.

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