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Impaired inter-hemispheric integration in bipolar disorder revealed with brain network analyses.

ABSTRACT: This represents the first graph theory-based brain network analysis study in bipolar disorder, a chronic and disabling psychiatric disorder characterized by severe mood swings. Many imaging studies have investigated white matter in bipolar disorder, with results suggesting abnormal white matter structural integrity, particularly in the fronto-limbic and callosal systems. However, many inconsistencies remain in the literature, and no study to date has conducted brain network analyses with a graph-theoretic approach.We acquired 64-direction diffusion-weighted magnetic resonance imaging on 25 euthymic bipolar I disorder subjects and 24 gender- and age-equivalent healthy subjects. White matter integrity measures including fractional anisotropy and mean diffusivity were compared in the whole brain. Additionally, structural connectivity matrices based on whole-brain deterministic tractography were constructed, followed by the computation of both global and local brain network measures. We also designed novel metrics to further probe inter-hemispheric integration.Network analyses revealed that the bipolar brain networks exhibited significantly longer characteristic path length, lower clustering coefficient, and lower global efficiency relative to those of control subjects. Further analyses revealed impaired inter-hemispheric but relatively preserved intra-hemispheric integration. These findings were supported by whole-brain white matter analyses that revealed significantly lower integrity in the corpus callosum in bipolar subjects. There were also abnormalities in nodal network measures in structures within the limbic system, especially the left hippocampus, the left lateral orbitofrontal cortex, and the bilateral isthmus cingulate.These results suggest abnormalities in structural network organization in bipolar disorder, particularly in inter-hemispheric integration and within the limbic system.

SUBMITTER: Leow A

PROVIDER: S-EPMC4113030 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Impaired inter-hemispheric integration in bipolar disorder revealed with brain network analyses.

Leow Alex A Ajilore Olusola O Zhan Liang L Arienzo Donatello D GadElkarim Johnson J Zhang Aifeng A Moody Teena T Van Horn John J Feusner Jamie J Kumar Anand A Thompson Paul P Altshuler Lori L

Biological psychiatry 20121031 2

<h4>Background</h4>This represents the first graph theory-based brain network analysis study in bipolar disorder, a chronic and disabling psychiatric disorder characterized by severe mood swings. Many imaging studies have investigated white matter in bipolar disorder, with results suggesting abnormal white matter structural integrity, particularly in the fronto-limbic and callosal systems. However, many inconsistencies remain in the literature, and no study to date has conducted brain network an ...[more]

PMID: 23122540

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Project description:Recent investigations have used diffusion-weighted imaging to reveal disturbances in the neurocircuitry that underlie cognitive-emotional control in bipolar disorder (BD) and in unaffected siblings or children at high genetic risk (HR). It has been difficult to quantify the mechanism by which structural changes disrupt the superimposed brain dynamics, leading to the emotional lability that is characteristic of BD. Average controllability is a concept from network control theory that extends structural connectivity data to estimate the manner in which local neuronal fluctuations spread from a node or subnetwork to alter the state of the rest of the brain. We used this theory to ask whether structural connectivity deficits previously observed in HR individuals (n?=?84, mean age 22.4), patients with BD (n?=?38, mean age 23.9), and age- and gender-matched controls (n?=?96, mean age 22.6) translate to differences in the ability of brain systems to be manipulated between states. Localized impairments in network controllability were seen in the left parahippocampal, left middle occipital, left superior frontal, right inferior frontal, and right precentral gyri in BD and HR groups. Subjects with BD had distributed deficits in a subnetwork containing the left superior and inferior frontal gyri, postcentral gyrus, and insula (p?=?0.004). HR participants had controllability deficits in a right-lateralized subnetwork involving connections between the dorsomedial and ventrolateral prefrontal cortex, the superior temporal pole, putamen, and caudate nucleus (p?=?0.008). Between-group controllability differences were attenuated after removal of topological factors by network randomization. Some previously reported differences in network connectivity were not associated with controllability-differences, likely reflecting the contribution of more complex brain network properties. These analyses highlight the potential functional consequences of altered brain networks in BD, and may guide future clinical interventions.

Dataset Information

Impaired inter-hemispheric integration in bipolar disorder revealed with brain network analyses.

Publications

Impaired inter-hemispheric integration in bipolar disorder revealed with brain network analyses.

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