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Research studies based on tractography have revealed a prominent reduction of asymmetry in some key white-matter tracts in schizophrenia (SCZ). However, we know little about the influence of common genetic risk factors for SCZ on the efficiency of routing on structural brain networks (SBNs). Here, we use a novel recall-by-genotype approach, where we sample young adults from a population-based cohort (ALSPAC:N genotyped = 8,365) based on their burden of common SCZ risk alleles as defined by polygenic risk score (PRS). We compared 181 individuals at extremes of low (N = 91) or high (N = 90) SCZ-PRS under a robust diffusion MRI-based graph theoretical SBN framework. We applied a semi-metric analysis revealing higher SMR values for the high SCZ-PRS group compared with the low SCZ-PRS group in the left hemisphere. Furthermore, a hemispheric asymmetry index showed a higher leftward preponderance of indirect connections for the high SCZ-PRS group compared with the low SCZ-PRS group (PFDR

Group comparisons of individuals with psychotic disorder and controls have shown alterations in white matter microstructure. Whether white matter microstructure and network connectivity is altered in adolescents with subclinical psychotic experiences (PE) at the lowest end of the psychosis severity spectrum is less clear. DWI scan were acquired in 48 individuals with PE and 43 healthy controls (HC). Traditional tensor-derived indices: Fractional Anisotropy, Axial Diffusivity, Mean Diffusivity and Radial Diffusivity, as well as network connectivity measures (global/local efficiency and clustering coefficient) were compared between the groups. Subclinical psychopathology was assessed with the Community Assessment of Psychic Experiences (CAPE) and Montgomery–Åsberg Depression Rating Scale (MADRS) questionnaires and, in order to capture momentary subclinical expression of psychosis, the Experience Sampling Method (ESM) questionnaires. Within the PE-group, interactions between subclinical (momentary) symptoms and brain regions in the model of tensor-derived indices and network connectivity measures were investigated in a hypothesis-generating fashion. Whole brain analyses showed no group differences in tensor-derived indices and network connectivity measures. In the PE-group, a higher positive symptom distress score was associated with both higher local efficiency and clustering coefficient in the right middle temporal pole. The findings indicate absence of microstructural white matter differences between emerging adults with subclinical PE and controls. In the PE-group, attenuated symptoms were positively associated with network efficiency/cohesion, which requires replication and may indicate network alterations in emerging mild psychopathology. Electronic supplementary material The online version of this article (10.1007/s11682-019-00129-0) contains supplementary material, which is available to authorized users.

Understanding sex-related differences across the human cerebral cortex is an important step in elucidating the basis of psychological, behavioural and clinical differences between the sexes. Prior structural neuroimaging studies primarily focused on regional sex differences using univariate analyses. Here we focus on sex differences in cortical morphological networks (CMNs) derived using multivariate modelling of regional cortical measures of volume and surface from high-quality structural MRI scans from healthy participants in the Human Connectome Project (HCP) (n = 1,063) and the Southwest University Longitudinal Imaging Multimodal (SLIM) study (n = 549). The functional relevance of the CMNs was inferred using the NeuroSynth decoding function. Sex differences were widespread but not uniform. In general, females had higher volume, thickness and cortical folding in networks that involve prefrontal (both ventral and dorsal regions including the anterior cingulate) and parietal regions while males had higher volume, thickness and cortical folding in networks that primarily include temporal and posterior cortical regions. CMN loading coefficients were used as input features to linear discriminant analyses that were performed separately in the HCP and SLIM; sex was predicted with a high degree of accuracy (81%–85%) across datasets. The availability of behavioral data in the HCP enabled us to show that male-biased surface-based CMNs were associated with externalizing behaviors. These results extend previous literature on regional sex-differences by identifying CMNs that can reliably predict sex, are relevant to the expression of psychopathology and provide the foundation for the future investigation of their functional significance in clinical populations.

Structural brain networks constructed from diffusion MRI are important biomarkers for understanding human brain structure and its relation to cognitive functioning. There is increasing interest in learning differences in structural brain networks between groups of subjects in neuroimaging studies, leading to a variable selection problem in network classification. Traditional methods often use independent edgewise tests or unstructured generalized linear model (GLM) with regularization on vectorized networks to select edges distinguishing the groups, which ignore the network structure and make the results hard to interpret. In this paper, we develop a symmetric bilinear logistic regression (SBLR) with elastic-net penalty to identify a set of small clique subgraphs in network classification. Clique subgraphs, consisting of all the interconnections among a subset of brain regions, have appealing neurological interpretations as they may correspond to some anatomical circuits in the brain related to the outcome. We apply this method to study differences in the structural connectome between adolescents with high and low crystallized cognitive ability, using the crystallized cognition composite score, picture vocabulary and oral reading recognition tests from NIH Toolbox. A few clique subgraphs containing several small sets of brain regions are identified between different levels of functioning, indicating their importance in crystallized cognition.

Cerebral small vessel disease is a common finding in the elderly and associated with various clinical sequelae. Previous studies suggest disturbances in the integration capabilities of structural brain networks as a mediating link between imaging and clinical presentations. To what extent cerebral small vessel disease might interfere with other measures of global network topology is not well understood. Connectomes were reconstructed via diffusion weighted imaging in a sample of 930 participants from a population based epidemiologic study. Linear models were fitted testing for an association of graph‐theoretical measures reflecting integration and segregation with both the Peak width of Skeletonized Mean Diffusivity (PSMD) and the load of white matter hyperintensities of presumed vascular origin (WMH). The latter were subdivided in periventricular and deep for an analysis of localisation‐dependent correlations of cerebral small vessel disease. The median WMH volume was 0.6 mL (1.4) and the median PSMD 2.18 mm2/s x 10−4 (0.5). The connectomes showed a median density of 0.880 (0.030), the median values for normalised global efficiency, normalised clustering coefficient, modularity Q and small‐world propensity were 0.780 (0.045), 1.182 (0.034), 0.593 (0.026) and 0.876 (0.040) respectively. An increasing burden of cerebral small vessel disease was significantly associated with a decreased integration and increased segregation and thus decreased small‐worldness of structural brain networks. Even in rather healthy subjects increased cerebral small vessel disease burden is accompanied by topological brain network disturbances. Segregation parameters and small‐worldness might as well contribute to the understanding of the known clinical sequelae of cerebral small vessel disease., Even in rather healthy subjects increased cerebral small vessel disease burden is accompanied by topological brain network disturbances. Besides the known mediation effect of integration parameters, the segregation parameters might as well contribute to the understanding of the known clinical sequelae of cerebral small vessel disease.

Background Altered structural network-connectivity has been reported in psychotic disorder but whether these alterations are associated with genetic vulnerability, and/or with phenotypic variation, has been less well examined. This study examined i) whether differences in network-connectivity exist between patients with psychotic disorder, siblings of patients with psychotic disorder and controls, and ii) whether network-connectivity alterations vary with (subclinical) symptomatology. Methods Network-connectivity measures (global efficiency (GE), density, local efficiency (LE), clustering coefficient (CC)) were derived from diffusion weighted imaging (DWI) and were compared between 85 patients with psychotic disorder, 93 siblings without psychotic disorder and 80 healthy comparison subjects using multilevel regression models. In patients, associations between Positive and Negative Syndrome Scale (PANSS) symptoms and topological measures were examined. In addition, interactions between subclinical psychopathology and sibling/healthy comparison subject status were examined in models of topological measures. Results While there was no main effect of group with respect to GE, density, LE and CC, siblings had a significantly higher CC compared to patients (B = 0.0039, p = .002). In patients, none of the PANSS symptom domains were significantly associated with any of the four network-connectivity measures. The two-way interaction between group and SIR-r positive score in the model of LE was significant (χ2 = 6.24, p = .01, df = 1). In the model of CC, the interactions between group and respectively SIS-r positive (χ2 = 5.59, p = .02, df = 1) and negative symptom scores (χ2 = 4.71, p = .03, df = 1) were significant. Stratified analysis showed that, in siblings, decreased LE and CC was significantly associated with increased SIS-r positive scores (LE: B = −0.0049, p = .003, CC: B = −0.0066, p = .01) and that decreased CC was significantly associated with increased SIS-r negative scores (B = −0.012, p = .003). There were no significant interactions between group and SIS-r scores in the models of GE and density. Conclusion The findings indicate absence of structural network-connectivity alterations in individuals with psychotic disorder and in individuals at higher than average genetic risk for psychotic disorder, in comparison with healthy subjects. The differential subclinical symptom-network connectivity associations in siblings with respect to controls may be a sign of psychosis vulnerability in the siblings., Highlights • Patients with psychotic disorder had unchanged network efficiency and clustering. • Siblings of patients had higher clustering coefficient compared to patients. • Lower clustering/efficiency was associated with higher positive symptoms in siblings. • Decreased clustering was associated with increased negative symptoms in siblings.

BACKGROUND: Graph theory applied to brain networks is an emerging approach to understanding the brain's topological associations with human cognitive ability. Despite well-documented cognitive impairments in bipolar disorder (BD) and recent reports of altered anatomical network organization, the association between connectivity and cognitive impairments in BD remains unclear.METHODS: We examined the role of anatomical network connectivity derived from Ti - and diffusion-weighted magnetic resonance imaging in impaired cognitive performance in individuals with BD (n = 32) compared with healthy control individuals (n = 38). Fractional anisotropy- and number of streamlines-weighted anatomical brain networks were generated by mapping constrained spherical deconvolution-reconstructed white matter among 86 cortical/subcortical bilateral brain regions delineated in the individual's own coordinate space. Intelligence and executive function were investigated as distributed functions using measures of global, rich-club, and interhemispheric connectivity, while memory and social cognition were examined in relation to subnetwork connectivity.RESULTS: Lower executive functioning related to higher global clustering coefficient in participants with BD, and lower IQ performance may present with a differential relationship between global and interhemispheric efficiency in individuals with BD relative to control individuals. Spatial recognition memory accuracy and response times were similar between diagnostic groups and associated with basal ganglia and thalamus interconnectivity and connectivity within extended anatomical subnetworks in all participants. No anatomical subnetworks related to episodic memory, short-term memory, or social cognition generally or differently in BD.CONCLUSIONS: Results demonstrate selective influence of subnetwork patterns of connectivity in underlying cognitive performance generally and abnormal global topology underlying discrete cognitive impairments in BD. We gratefully acknowledge the participants, the support of the Welcome-Trust HRB Clinical Research Facility, the Centre for Advanced Medical Imaging at St. James Hospital Dublin and funding support from the Irish Research Council Government of Ireland Postgraduate Scholarship. We would also like to thank Andrew Hoopes, Research Technician I, MGH/HST Martinos Center for Biomedical Imaging for Freesurfer software support, Christopher Grogan, MSc, for his contribution to data processing and Jenna Pittman, BSc and Fiona Martyn, BA for their contribution to data handling. This research was funded by the Health Research Board (HRA-POR324) awarded to Dara M. Cannon, PhD. peer-reviewed 2020-09-18

Background: Focal dystonias are severe and disabling movement disorders of a still unclear origin. The structural brain networks associated with focal dystonia have not been well characterized. Here, we investigated structural brain network fingerprints in patients with blepharospasm (BSP) compared with those with hemifacial spasm (HFS), and healthy controls (HC). The patients were also examined following treatment with botulinum neurotoxin (BoNT). Methods: This study included matched groups of 13 BSP patients, 13 HFS patients, and 13 HC. We measured patients using structural-magnetic resonance imaging (MRI) at baseline and after one month BoNT treatment, at time points of maximal and minimal clinical symptom representation, and HC at baseline. Group regional cross-correlation matrices calculated based on grey matter volume were included in graph-based network analysis. We used these to quantify global network measures of segregation and integration, and also looked at local connectivity properties of different brain regions. Results: The networks in patients with BSP were more segregated than in patients with HFS and HC ( p

Over the last two decades the field of network science has been evolving fast. Many useful applications in a wide variety of disciplines have been found. The application of network science to the brain initiated the interdisciplinary field of complex brain networks. On a macroscopic level, brain regions are taken as nodes in a network. The analysis of pairwise connections between the brain regions as links has provided a new perspective on many problems. The application of network science to neuroscience data helped, for example, to identify the disruptions due to different neurological disorders when comparing healthy and abnormal brain networks. In this dissertation, we focus on the macroscopic level of brain regions and analyze their pairwise connections from a network science perspective. We address different general research questions from network science and exploit their application possibilities towards brain networks. Due to different measurement techniques, one can construct many different representations of brain networks. We thereby distinguish between the structural and functional brain network. Structural brain networks map the anatomical connections between the regions, which we could interpret as the ’streets’ of the brain. On top of these streets, we can measure the traffic with techniques like e.g. magnetoencephalography (MEG) or functional Magnetic Resonance Imaging (fMRI) resulting in so-called functional brain networks. However, the relation between the structural and the functional brain networks is still insufficiently understood. The first main research question of this dissertation focuses on the functional network layer and tries to identify the most important links and motifs of these networks. For this purpose, we propose the union of shortest path trees (USPT) as a new sampling method extracting all the shortest paths of a network (Chapter 2 and 3). After constructing the USPT, we compare the individual functional brain networks of multiple sclerosis patients and healthy controls (Chapter 2). Furthermore, we generalize this sampling method and present a new ranking of all the links based on the USPT (Chapter 3). Regarding the higher-order building blocks of the functional brain networks, we analyze the so-called information flow motifs based on MEG data from different frequency bands (Chapter 4). After researching the local properties of the functional brain networks, we analyze the influence of the underlying structural connections on the emerging information flow. Thus, the second main research question concerns the relationship between the functional and the underlying structural connectivity. Specifically, we analyze which topological properties of the structural networks drive the functional interactions. First, this question is approached in a mathematical and straightforward manner by assuming that an analytic function between the two networks exists (Chapter 5). We investigate this mapping function and its reverse by evaluating empirical individual and group-averaged multimodal data sets. A second approach towards the structure-function relationship employs a simple model of activity spread. The epidemic spreading model is applied on the human connectome to investigate the global patterns of directional information flow in brain networks (Chapter 6). The main focus here lies on the pairwise measure of transfer entropy to investigate the influence of one brain region on another. We present the results for the local and global outcomes of the dynamic spreading process aiming to identify the driving structural properties behind the observed global patterns.

International audience; The three-volume set LNCS 8149, 8150, and 8151 constitutes the refereed proceedings of the 16th International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 2013, held in Nagoya, Japan, in September 2013. Based on rigorous peer reviews, the program committee carefully selected 262 revised papers from 789 submissions for presentation in three volumes. The 81 papers included in the third volume have been organized in the following topical sections: image reconstruction and motion modeling; machine learning in medical image computing; imaging, reconstruction, and enhancement; segmentation; physiological modeling, simulation, and planning; intraoperative guidance and robotics; microscope, optical imaging, and histology; diffusion MRI; brain segmentation and atlases; and functional MRI and neuroscience applications.

International audience; The three-volume set LNCS 8149, 8150, and 8151 constitutes the refereed proceedings of the 16th International Conference on Medical Image Computing and Computer-Assisted Intervention, MICCAI 2013, held in Nagoya, Japan, in September 2013. Based on rigorous peer reviews, the program committee carefully selected 262 revised papers from 789 submissions for presentation in three volumes. The 95 papers included in the first volume have been organized in the following topical sections: physiological modeling and computer-assisted intervention; imaging, reconstruction, and enhancement; registration; machine learning, statistical modeling, and atlases; computer-aided diagnosis and imaging biomarkers; intraoperative guidance and robotics; microscope, optical imaging, and histology; cardiology, vasculatures and tubular structures; brain imaging and basic techniques; diffusion MRI; and brain segmentation and atlases.