Automated multi-subject fiber clustering of mouse brain using dominant sets

Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra- and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups.Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra-and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups

Differential Effects of Brain Disorders on Structural and Functional Connectivity

Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate

Traces Of Human Functional Activity: Moment-To-Moment Fluctuations In Fmri Data

Dynamic functional connectivity (dFC) measured by functional magnetic resonance imaging (fMRI) shows evidence of large-scale networks with highly dynamic (re) configurations. We propose a novel approach to extract traces of human brain function by the construction of a trajectory in a meaningful low-dimensional space. This allows studying dFC in more detail and identify possible meaningful brain states from the moment-to-moment fluctuations of the brain signals during resting state or naturalistic conditions such as passive movie watching. Specifically, we explored dynamic organization of sub-networks derived from the time-dependent graph Laplacian in combination with Riemannian manifold distance to measure dissimilarity over time of dFC and to subsequently build the trajectory of brain activity. As a proof-of-principle, we show results for an fMRI dataset containing both rest and movie epochs in 15 healthy participants. The movie condition varied (i.e., fearful, joyful, and neutral movie excerpts) and clearly influenced the subsequent resting-state period in terms of FC brain state

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features

The recent identification of multiple dominant mutations in the gene encoding β-catenin in both humans and mice has enabled exploration of the molecular and cellular basis of β-catenin function in cognitive impairment. In humans, β-catenin mutations that cause a spectrum of neurodevelopmental disorders have been identified. We identified de novo β-catenin mutations in patients with intellectual disability, carefully characterized their phenotypes, and were able to define a recognizable intellectual disability syndrome. In parallel, characterization of a chemically mutagenized mouse line that displays features similar to those of human patients with β-catenin mutations enabled us to investigate the consequences of β-catenin dysfunction through development and into adulthood. The mouse mutant, designated batface (Bfc), carries a Thr653Lys substitution in the C-terminal armadillo repeat of β-catenin and displayed a reduced affinity for membrane-associated cadherins. In association with this decreased cadherin interaction, we found that the mutation results in decreased intrahemispheric connections, with deficits in dendritic branching, long-term potentiation, and cognitive function. Our study provides in vivo evidence that dominant mutations in β-catenin underlie losses in its adhesion-related functions, which leads to severe consequences, including intellectual disability, childhood hypotonia, progressive spasticity of lower limbs, and abnormal craniofacial features in adult

Laudes de Sevilla

La Sevilla del siglo XVI / Santiago Montoto - El Parque de María Luisa / José María Pemán - Sevilla en automóvil / Pedro Salinas - La catedral y las callejuelas / Azorín - La ciudad fragante / Juan Ignacio Luca de Ten

The Bostrichidae of the Maltese Islands (Coleoptera)

The Bostrichidae of the Maltese Islands are reviewed. Ten species are recorded with certainty from this Archipelago, of which 6 namely, Trogoxylon impressum (Comolli, 1837), Amphicerus bimaculatus (A.G. Olivier, 1790), Heterobostrychus aequalis (Waterhouse, 1884), Sinoxylon unidentatum (Fabricius, 1801), Xyloperthella picea (A.G. Olivier, 1790) and Apate monachus Fabricius, 1775 are recorded for the first time. Two of the mentioned species (H. aequalis and S. unidentatum) are alien and recorded only on the basis of single captures and the possible establishment of these species is discussed. Earlier records of Scobicia pustulata (Fabricius, 1801) from Malta are incorrect and should be attributed to S. chevrieri (A. Villa & J.B. Villa, 1835). A zoogeographical analysis and an updated checklist of the 12 species of Bostrichidae recorded from the Maltese Islands and neighbouring Sicilian islands (Pantelleria, Linosa and Lampedusa) are also provided. Rhizopertha dominica (Fabricius, 1792) form granulipennis Lesne in Beeson & Bhatia, 1937 from Uttarakhand (northern India) was overlooked by almost all subsequent authors. Its history is summarized and the following new synonymy is established: Rhizopertha dominica (Fabricius, 1792) form granulipennis Lesne in Beeson & Bhatia, 1937 = Rhyzopertha dominica (Fabricius, 1792), syn. n. Finally, records of Amphicerus bimaculatus from Azerbaijan, of Bostrichus capucinus (Linnaeus, 1758) from Jordan and Syria, of Scobicia chevrieri from Jordan and Italy, of Xyloperthella picea from Italy, and of Apate monachus from Corsica (France) and Italy, are also provided.peer-reviewe

Neurobiology of rodent self-grooming and its value for translational neuroscience

Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders-including models of autism spectrum disorder and obsessive compulsive disorder-that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.National Institutes of Health (U.S.) (Grant NS025529)National Institutes of Health (U.S.) (Grant HD028341)National Institutes of Health (U.S.) (Grant MH060379

The Use of Tutomesh for a Tension-Free and Tridimensional Repair of Uterovaginal and Vaginal Vault Prolapse: Preliminary Report

Objective. To evaluate efficacy in terms of vaginal capacity, coital function, and recurrence prevention of a new biological mesh of bovine pericardium (Tutomesh) in the repair of severe POP. Methods. Thirty cases of patients suffering from stage III uterine or apical prolapse undergone surgical repair by means of a modified sacrospinous ligament suspension combined with mesh attachment to both the cardinal ligaments, posterior and anterior colporrhaphy, and perineal body fixation. The mesh was replaced inside the pelvis with the goal of reconstructing the tridimensional fascial disposition of the structures sustaining the correct axis of vagina. Follow-up was done at 12 months with POPIQ analysis. Results. One total mesh failure occurred early after surgery due to marked deficiency of anatomy. Two cystoceles were observed at 12 months in two patients treated for apical prolapse where anterior repair was not performed. Two other patients developed a de novo SUI at 12 months. No reported abnormalities of coital function or dyspareunia were ever found after surgery. Conclusions. It is possible that the utilization of a tension-free and tridimensional placement of Tutomesh might favor a more physiologic reconstruction of the vaginal axis as compared with traditional sacrospinous ligament suspension