Enhancement of indirect functional connections with shortest path length in the adult autistic brain.

Autism is a neurodevelopmental condition characterized by atypical brain functional organization. Here we investigated the intrinsic indirect (semi-metric) connectivity of the functional connectome associated with autism. Resting-state functional magnetic resonance imaging scans were acquired from 65 neurotypical adults (33 males/32 females) and 61 autistic adults (30 males/31 females). From functional connectivity networks, semi-metric percentages (SMPs) were calculated to assess the proportion of indirect shortest functional pathways at global, hemisphere, network, and node levels. Group comparisons were then conducted to ascertain differences between autism and neurotypical control groups. Finally, the strength and length of edges were examined to explore the patterns of semi-metric connections associated with autism. Compared with neurotypical controls, autistic adults displayed significantly higher SMP at all spatial scales, similar to prior observations in adolescents. Differences were primarily in weaker, longer-distance edges in the majority between networks. However, no significant diagnosis-by-sex interaction effects were observed on global SMP. These findings suggest increased indirect functional connectivity in the autistic brain is persistent from adolescence to adulthood and is indicative of reduced functional network integration.

The distance backbone of complex networks.

Redundancy needs more precise characterization as it is a major factor in the evolution and robustness of networks of multivariate interactions. We investigate the complexity of such interactions by inferring a connection transitivity that includes all possible measures of path length for weighted graphs. The result, without breaking the graph into smaller components, is a distance backbone subgraph sufficient to compute all shortest paths. This is important for understanding the dynamics of spread and communication phenomena in real-world networks. The general methodology we formally derive yields a principled graph reduction technique and provides a finer characterization of the triangular geometry of all edges-those that contribute to shortest paths and those that do not but are involved in other network phenomena. We demonstrate that the distance backbone is very small in large networks across domains ranging from air traffic to the human brain connectome, revealing that network robustness to attacks and failures seems to stem from surprisingly vast amounts of redundancy.

Stochastic model for scale-free networks with cutoffs.

We propose and analyze a stochastic model which explains, analytically, the cutoff behavior of real scale-free networks previously modeled computationally by Amaral [Proc. Natl. Acad. Sci. U.S.A. 97, 11149 (2000)] and others. We present a mathematical model that can explain several existing computational scale-free network generation models. This yields a theoretical basis to understand cutoff behavior in complex networks, previously treated only with simulations using distinct models. Therefore, ours is an integrative approach that unifies the existing literature on cutoff behavior in scale-free networks. Furthermore, our mathematical model allows us to reach conclusions not hitherto possible with computational models: the ability to predict the equilibrium point of active vertices and to relate the growth of networks with the probability of aging. We also discuss how our model introduces a useful way to classify scale free behavior of complex networks.

Cognitive Behavioral Therapy Lowers Elevated Functional Connectivity in Depressed Adolescents.

Imaging studies have implicated altered functional connectivity in adults with major depressive disorder (MDD). Whether similar dysfunction is present in adolescent patients is unclear. The degree of resting-state functional connectivity (rsFC) may reflect abnormalities within emotional ('hot') and cognitive control ('cold') neural systems. Here, we investigate rsFC of these systems in adolescent patients and changes following cognitive behavioral therapy (CBT). Functional Magnetic Resonance Imaging (fMRI) was acquired from adolescent patients before CBT, and 24-weeks later following completed therapy. Similar data were obtained from control participants. Cross-sectional Cohort: From 82 patients and 34 controls at baseline, rsFC of the amygdala, anterior cingulate cortex (ACC), and pre-frontal cortex (PFC) was calculated for comparison. Longitudinal Cohort: From 17 patients and 30 controls with longitudinal data, treatment effects were tested on rsFC. Patients demonstrated significantly greater rsFC to left amygdala, bilateral supragenual ACC, but not with PFC. Treatment effects were observed in right insula connected to left supragenual ACC, with baseline case-control differences reduced. rsFC changes were significantly correlated with changes in depression severity. Depressed adolescents exhibited heightened connectivity in regions of 'hot' emotional processing, known to be associated with depression, where treatment exposure exerted positive effects, without concomitant differences in areas of 'cold' cognition.

Protein annotation as term categorization in the gene ontology using word proximity networks.

BACKGROUND: We participated in the BioCreAtIvE Task 2, which addressed the annotation of proteins into the Gene Ontology (GO) based on the text of a given document and the selection of evidence text from the document justifying that annotation. We approached the task utilizing several combinations of two distinct methods: an unsupervised algorithm for expanding words associated with GO nodes, and an annotation methodology which treats annotation as categorization of terms from a protein's document neighborhood into the GO. RESULTS: The evaluation results indicate that the method for expanding words associated with GO nodes is quite powerful; we were able to successfully select appropriate evidence text for a given annotation in 38% of Task 2.1 queries by building on this method. The term categorization methodology achieved a precision of 16% for annotation within the correct extended family in Task 2.2, though we show through subsequent analysis that this can be improved with a different parameter setting. Our architecture proved not to be very successful on the evidence text component of the task, in the configuration used to generate the submitted results. CONCLUSION: The initial results show promise for both of the methods we explored, and we are planning to integrate the methods more closely to achieve better results overall.

An algebraic topological method for multimodal brain networks comparisons.

Understanding brain connectivity is one of the most important issues in neuroscience. Nonetheless, connectivity data can reflect either functional relationships of brain activities or anatomical connections between brain areas. Although both representations should be related, this relationship is not straightforward. We have devised a powerful method that allows different operations between networks that share the same set of nodes, by embedding them in a common metric space, enforcing transitivity to the graph topology. Here, we apply this method to construct an aggregated network from a set of functional graphs, each one from a different subject. Once this aggregated functional network is constructed, we use again our method to compare it with the structural connectivity to identify particular brain regions that differ in both modalities (anatomical and functional). Remarkably, these brain regions include functional areas that form part of the classical resting state networks. We conclude that our method -based on the comparison of the aggregated functional network- reveals some emerging features that could not be observed when the comparison is performed with the classical averaged functional network.

A Winding Road: Alzheimer's Disease Increases Circuitous Functional Connectivity Pathways.

Neuroimaging has been successful in characterizing the pattern of cerebral atrophy that accompanies the progression of Alzheimer's disease (AD). Examination of functional connectivity, the strength of signal synchronicity between brain regions, has gathered pace as another way of understanding changes to the brain that are associated with AD. It appears to have good sensitivity and detect effects that precede cognitive decline, and thus offers the possibility to understand the neurobiology of the disease in its earliest phases. However, functional connectivity analyzes to date generally consider only the strongest connections, with weaker links ignored. This proof-of-concept study compared patients with mild-to-moderate AD (N = 11) and matched control individuals (N = 12) based on functional connectivities derived from blood-oxygenation level dependent (BOLD) sensitive functional MRI acquired during resting wakefulness. All positive connectivities irrespective of their strength were included. Transitive closures of the resulting connectome were calculated that classified connections as either direct or indirect. Between-group differences in the proportion of indirect paths were observed. In AD, there was broadly increased indirect connectivity across greater spatial distances. Furthermore, the indirect pathways in AD had greater between-subject topological variance than controls. The prevailing characterization of AD as being a disconnection syndrome is refined by the observation that direct links between regions that are impaired are perhaps replaced by an increase in indirect functional pathways that is only detectable through inclusion of connections across the entire range of connection strengths.

Semi-metric analysis of the functional brain network: Relationship with familial risk for psychotic disorder.

BACKGROUND: Dysconnectivity in schizophrenia can be understood in terms of dysfunctional integration of a distributed network of brain regions. Here we propose a new methodology to analyze complex networks based on semi-metric behavior, whereby higher levels of semi-metricity may represent a higher level of redundancy and dispersed communication. It was hypothesized that individuals with (increased risk for) psychotic disorder would have more semi-metric paths compared to controls and that this would be associated with symptoms. METHODS: Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 unaffected siblings and 72 controls. Semi-metric percentages (SMP) at the whole brain, hemispheric and lobar level were the dependent variables in a multilevel random regression analysis to investigate group differences. SMP was further examined in relation to symptomatology (i.e., psychotic/cognitive symptoms). RESULTS: At the whole brain and hemispheric level, patients had a significantly higher SMP compared to siblings and controls, with no difference between the latter. In the combined sibling and control group, individuals with high schizotypy had intermediate SMP values in the left hemisphere with respect to patients and individuals with low schizotypy. Exploratory analyses in patients revealed higher SMP in 12 out of 42 lobar divisions compared to controls, of which some were associated with worse PANSS symptomatology (i.e., positive symptoms, excitement and emotional distress) and worse cognitive performance on attention and emotion processing tasks. In the combined group of patients and controls, working memory, attention and social cognition were associated with higher SMP. DISCUSSION: The results are suggestive of more dispersed network communication in patients with psychotic disorder, with some evidence for trait-based network alterations in high-schizotypy individuals. Dispersed communication may contribute to the clinical phenotype in psychotic disorder. In addition, higher SMP may contribute to neuro- and social cognition, independent of psychosis risk.

Semi-Metric Topology of the Human Connectome: Sensitivity and Specificity to Autism and Major Depressive Disorder.

INTRODUCTION: The human functional connectome is a graphical representation, consisting of nodes connected by edges, of the inter-relationships of blood oxygenation-level dependent (BOLD) time-series measured by MRI from regions encompassing the cerebral cortices and, often, the cerebellum. Semi-metric analysis of the weighted, undirected connectome distinguishes an edge as either direct (metric), such that there is no alternative path that is accumulatively stronger, or indirect (semi-metric), where one or more alternative paths exist that have greater strength than the direct edge. The sensitivity and specificity of this method of analysis is illustrated by two case-control analyses with independent, matched groups of adolescents with autism spectrum conditions (ASC) and major depressive disorder (MDD). RESULTS: Significance differences in the global percentage of semi-metric edges was observed in both groups, with increases in ASC and decreases in MDD relative to controls. Furthermore, MDD was associated with regional differences in left frontal and temporal lobes, the right limbic system and cerebellum. In contrast, ASC had a broadly increased percentage of semi-metric edges with a more generalised distribution of effects and some areas of reduction. In summary, MDD was characterised by localised, large reductions in the percentage of semi-metric edges, whilst ASC is characterised by more generalised, subtle increases. These differences were corroborated in greater detail by inspection of the semi-metric backbone for each group; that is, the sub-graph of semi-metric edges present in >90% of participants, and by nodal degree differences in the semi-metric connectome. CONCLUSION: These encouraging results, in what we believe is the first application of semi-metric analysis to neuroimaging data, raise confidence in the methodology as potentially capable of detection and characterisation of a range of neurodevelopmental and psychiatric disorders.

Adolescents with current major depressive disorder show dissimilar patterns of age-related differences in ACC and thalamus.

OBJECTIVE: There is little understanding of the neural system abnormalities subserving adolescent major depressive disorder (MDD). In a cross-sectional study we compare currently unipolar depressed with healthy adolescents to determine if group differences in grey matter volume (GMV) were influenced by age and illness severity. METHOD: Structural neuroimaging was performed on 109 adolescents with current MDD and 36 healthy controls, matched for age, gender, and handedness. GMV differences were examined within the anterior cingulate cortex (ACC) and across the whole-brain. The effects of age and self-reported depressive symptoms were also examined in regions showing significant main or interaction effects. RESULTS: Whole-brain voxel based morphometry revealed no significant group differences. At the whole-brain level, both groups showed a main effect of age on GMV, although this effect was more pronounced in controls. Significant group-by-age interactions were noted: A significant regional group-by-age interaction was observed in the ACC. GMV in the ACC showed patterns of age-related differences that were dissimilar between adolescents with MDD and healthy controls. GMV in the thalamus showed an opposite pattern of age-related differences in adolescent patients compared to healthy controls. In patients, GMV in the thalamus, but not the ACC, was inversely related with self-reported depressive symptoms. CONCLUSIONS: The depressed adolescent brain shows dissimilar age-related and symptom-sensitive patterns of GMV differences compared with controls. The thalamus and ACC may comprise neural markers for detecting these effects in youth. Further investigations therefore need to take both age and level of current symptoms into account when disaggregating antecedent neural vulnerabilities for MDD from the effects of MDD on the developing brain.

Aesthetic comparison of the ideal nasal radix height in Brazilians.

UNLABELLED: The harmony of the facial profile is widely influenced by the height and form of the nasal dorsum. A few millimeters can make the lateral view aesthetically more or less pleasing and adequate in a subject's face. Professionals working with facial aesthetics should focus not only on the surgical techniques for proposed outcomes, but also with the subtleties and subjectivity that characterize aesthetic concepts and judgment. MATERIAL AND METHODS: A prospective survey to evaluate the preferences of a group of healthcare professionals working with facial aesthetics, a group of fine artists, and lay people about the best nasal radix height; the survey involved comparing 3 different nasal radix heights using computer-altered photographs of women with measurements close to the Caucasian standard. RESULTS AND CONCLUSION: The lowest position of the nasal radix--close to the height of the pupil--was preferred (53%), followed by the middle position (superior crease of the eye). The highest position, resembling classic Greek statues, was considered the worst. The authors evaluated the effect of age, gender, and educational level on the choice of the best and worst female profiles.

Aesthetic comparison of the ideal nasal radix height in brazilians / Comparação estética da altura ideal do radix nasal em uma população brasileira

The harmony of the facial profile is widely influenced by the height and form of the nasal dorsum. A few millimeters can make the lateral view aesthetically more or less pleasing and adequate in a subject's face. Professionals working with facial aesthetics should focus not only on the surgical techniques for proposed outcomes, but also with the subtleties and subjectivity that characterize aesthetic concepts and judgment. MATERIAL AND METHODS: A prospective survey to evaluate the preferences of a group of healthcare professionals working with facial aesthetics, a group of fine artists, and lay people about the best nasal radix height; the survey involved comparing 3 different nasal radix heights using computer-altered photographs of women with measurements close to the Caucasian standard. RESULTS AND CONCLUSION: The lowest position of the nasal radix - close to the height of the pupil - was preferred (53 percent), followed by the middle position (superior crease of the eye). The highest position, resembling classic Greek statues, was considered the worst. The authors aos evaluated the effect of age, gender, and educational level on the choice of the best and worst female profiles.

A harmonia facial da visão de perfil é muito influenciada pela altura e forma do dorso nasal. Poucos milímetros podem determinar as diferenças que tornam o perfil esteticamente agradável e adequado a uma determinada face. Além da discussão a respeito de técnicas cirúrgicas para obter determinados objetivos, os profissionais também precisam se aprofundar nas sutilezas e subjetividades que envolvem o julgamento estético. Com forma de estudo tipo inquérito, o objetivo foi pesquisar a preferência de um grupo de profissionais de saúde que lidam com estética facial, um grupo de artistas e outro de leigos sobre três possíveis variações da altura da raiz do nariz. MATERIAIS E MÉTODOS: Fotografias de mulheres, com medidas muito próximas do modelo caucasiano, foram modificadas com computação gráfica e opiniões sobre estas variações colhidas entre profissionais, artistas e leigos. RESULTADOS E CONCLUSÃO: A população de entrevistados considerou o perfil alto, tipo grego, como indesejável. Tal convicção foi muito evidente em todos os grupos. A preferência foi pelo perfil com raiz nasal próxima da altura da pupila em 53 por cento, seguido do perfil na altura da prega tarsal. Avaliou-se também a influência da idade, sexo e escolaridade dos entrevistados sobre as escolhas dos melhores e piores perfis femininos.

Conduta nos contatos de doenças infecto-contagiosas / Conduct in contacts of infectious diseases

Assunto de suma importância em infectologia na conduta com contatos frente às doenças infecto-contagiosas, faz-se mister enfatizar a ação preventiva do pessoal da área de saúde e as noções ensinadas às comunidades. Algumas doenças infecciosas transmissíveis são causas importantes de morbimortalidade, principalmente ao acometerem pacientes de baixa idade e imunodeprimidos. Poderíamos citar como exemplos a varicela e a tuberculose. Atualmente, nos centros de referência para imunobiológicos especiais disponíveis em todo o terrítório nacional (www.saude.gov.br/rvs e www.saude.gov.br/bvs), são disponibilizadas vacinas especiais como varicela e imunoglobulinas como antivaricela-zóster e anti-hepatite B. A finalidade deste artigo é abordar diversas situações comuns na prática diária e qual conduta adotar com relação aos contatos, não só na comunidade como na infecção hospitalar, principalmente no caso da varicela. É importante considerar a relação das doenças com os agentes etiológicos e os periódos de incubação e de transmissão.

Subjecto of paramount importance in infectology, in front of conduct contacts with infectious diseases, it's extremely necessary to emphasize the preventive action of staff in the areas of health and the concepts taught to communities. Some infectious transmissible diseases are important causes of morbid-mortality, especially when related to young patients and immunodepressed, such as chickenpox and tuberculosis. Currently, the Center of Reference for Special Immunobiologicals available throughout the national territory (www.saude.gov.br/rvs and www.saude.gov.br/bvs), special vaccines such as varicella and anti-varicella zoster immunoglobulins and anti-hepatitis B are available. The purpose of this article is to adress various situations, common in daily practice and which conduct to adopt, regarding contacts, not only in the community and in hospital infection, especially in the case of chickenpox. It is important to consider the relationship of diseases with the etiologic agents and the periods os incubation and transmission.