Impaired Resting-State Functional Integrations within Default Mode Network of Generalized Tonic-Clonic Seizures Epilepsy

Generalized tonic-clonic seizures (GTCS) are characterized by unresponsiveness and convulsions, which cause complete loss of consciousness. Many recent studies have found that the ictal alterations in brain activity of the GTCS epilepsy patients are focally involved in some brain regions, including thalamus, upper brainstem, medial prefrontal cortex, posterior midbrain regions, and lateral parietal cortex. Notably, many of these affected brain regions are the same and overlap considerably with the components of the so-called default mode network (DMN). Here, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients are different from normal controls, even in the resting state. To test this hypothesis, we compared the DMN of the GTCS epilepsy patients and the controls using the resting state functional magnetic resonance imaging. Thirteen brain areas in the DMN were extracted, and a complete undirected weighted graph was used to model the DMN for each participant. When directly comparing the edges of the graph, we found significant decreased functional connectivities within the DMN of the GTCS epilepsy patients comparing to the controls. As for the nodes of the graph, we found that the degree of some brain areas within the DMN was significantly reduced in the GTCS epilepsy patients, including the anterior medial prefrontal cortex, the bilateral superior frontal cortex, and the posterior cingulate cortex. Then we investigated into possible mechanisms of how GTCS epilepsy could cause the reduction of the functional integrations of DMN. We suggested the damaged functional integrations of the DMN in the GTCS epilepsy patients even during the resting state, which could help to understand the neural correlations of the impaired consciousness of GTCS epilepsy patients

Functional Brain Networks Develop from a “Local to Distributed” Organization

The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MRI (rs-fcMRI), graph analysis, community detection, and spring-embedding visualization techniques to analyze four separate networks defined in earlier studies. As we have previously reported, we find, across development, a trend toward ‘segregation’ (a general decrease in correlation strength) between regions close in anatomical space and ‘integration’ (an increased correlation strength) between selected regions distant in space. The generalization of these earlier trends across multiple networks suggests that this is a general developmental principle for changes in functional connectivity that would extend to large-scale graph theoretic analyses of large-scale brain networks. Communities in children are predominantly arranged by anatomical proximity, while communities in adults predominantly reflect functional relationships, as defined from adult fMRI studies. In sum, over development, the organization of multiple functional networks shifts from a local anatomical emphasis in children to a more “distributed” architecture in young adults. We argue that this “local to distributed” developmental characterization has important implications for understanding the development of neural systems underlying cognition. Further, graph metrics (e.g., clustering coefficients and average path lengths) are similar in child and adult graphs, with both showing “small-world”-like properties, while community detection by modularity optimization reveals stable communities within the graphs that are clearly different between young children and young adults. These observations suggest that early school age children and adults both have relatively efficient systems that may solve similar information processing problems in divergent ways

Maturation of the Language Network: From Inter- to Intrahemispheric Connectivities

Language development must go hand-in-hand with brain maturation. Little is known about how the brain develops to serve language processing, in particular, the processing of complex syntax, a capacity unique to humans. Behavioral reports indicate that the ability to process complex syntax is not yet adult-like by the age of seven years. Here, we apply a novel method to demonstrate that the basic neural basis of language, as revealed by low frequency fluctuation stemming from functional MRI data, differs between six-year-old children and adults in crucial aspects. Although the classical language regions are actively in place by the age of six, the functional connectivity between these regions clearly is not. In contrast to adults who show strong connectivities between frontal and temporal language regions within the left hemisphere, children's default language network is characterized by a strong functional interhemispheric connectivity, mainly between the superior temporal regions. These data indicate a functional reorganization of the neural network underlying language development towards a system that allows a close interplay between frontal and temporal regions within the left hemisphere

A parsimonious explanation for intersecting perinatal mortality curves: understanding the effect of plurality and of parity

BACKGROUND: Birth weight- and gestational age-specific perinatal mortality curves intersect when compared across categories of maternal smoking, plurality, race and other factors. No simple explanation exists for this paradoxical observation. METHODS: We used data on all live births, stillbirths and infant deaths in Canada (1991–1997) to compare perinatal mortality rates among singleton and twin births, and among singleton births to nulliparous and parous women. Birth weight- and gestational age-specific perinatal mortality rates were first calculated by dividing the number of perinatal deaths at any given birth weight or gestational age by the number of total births at that birth weight or gestational age (conventional calculation). Gestational age-specific perinatal mortality rates were also calculated using the number of fetuses at risk of perinatal death at any given gestational age. RESULTS: Conventional perinatal mortality rates among twin births were lower than those among singletons at lower birth weights and earlier gestation ages, while the reverse was true at higher birth weights and later gestational ages. When perinatal mortality rates were based on fetuses at risk, however, twin births had consistently higher mortality rates than singletons at all gestational ages. A similar pattern emerged in contrasts of gestational age-specific perinatal mortality among singleton births to nulliparous and parous women. Increases in gestational age-specific rates of growth-restriction with advancing gestational age presaged rising rates of gestational age-specific perinatal mortality in both contrasts. CONCLUSIONS: The proper conceptualization of perinatal risk eliminates the mortality crossover paradox and provides new insights into perinatal health issues

Functional Brain Network Modularity Captures Inter- and Intra-Individual Variation in Working Memory Capacity

Cognitive abilities, such as working memory, differ among people; however, individuals also vary in their own day-to-day cognitive performance. One potential source of cognitive variability may be fluctuations in the functional organization of neural systems. The degree to which the organization of these functional networks is optimized may relate to the effective cognitive functioning of the individual. Here we specifically examine how changes in the organization of large-scale networks measured via resting state functional connectivity MRI and graph theory track changes in working memory capacity.Twenty-two participants performed a test of working memory capacity and then underwent resting-state fMRI. Seventeen subjects repeated the protocol three weeks later. We applied graph theoretic techniques to measure network organization on 34 brain regions of interest (ROI). Network modularity, which measures the level of integration and segregation across sub-networks, and small-worldness, which measures global network connection efficiency, both predicted individual differences in memory capacity; however, only modularity predicted intra-individual variation across the two sessions. Partial correlations controlling for the component of working memory that was stable across sessions revealed that modularity was almost entirely associated with the variability of working memory at each session. Analyses of specific sub-networks and individual circuits were unable to consistently account for working memory capacity variability.The results suggest that the intrinsic functional organization of an a priori defined cognitive control network measured at rest provides substantial information about actual cognitive performance. The association of network modularity to the variability in an individual's working memory capacity suggests that the organization of this network into high connectivity within modules and sparse connections between modules may reflect effective signaling across brain regions, perhaps through the modulation of signal or the suppression of the propagation of noise

Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis

Tissue factor (TF) is an initiator of the extrinsic cascade of blood coagulation. Although recent studies have revealed a relationship between metastatic properties and TF expression in some neoplastic cells, the significance of TF in lung cancer, especially in non-small-cell lung cancer (NSCLC), is still unclear. In this study, TF was detected in NSCLC cell lines by functional study, Western blot analysis and immunocytochemical staining. TF levels in eight NSCLC cell lines were also quantitated by enzyme-linked immunosorbent assay (ELISA), and TF expression was evaluated in 55 specimens of surgically resected NSCLCs. NSCLC cell lines derived from metastatic lesions produced high levels of TF (48.3 ± 23.5 ng 10−6 cells, mean ± s.e.m.), whereas those derived from primary lesions produced low levels of TF (0.2 ± 0.1 ng 10−6 cells). Immunohistochemical studies disclosed significantly stronger staining for TF in cells from NSCLC patients with metastasis than in those without metastasis. Among the 28 patients with metastasis, ten were strongly positive, 16 were moderately positive and two were negative for TF. In contrast, among the 27 patients without metastasis, only two were strongly positive, 18 were moderately positive and seven were negative for TF. Therefore, malignant cells from patients with lung cancer produce various levels of TF, and TF may play an important role in the metastatic process. © 1999 Cancer Research Campaig

Default Network Deactivations Are Correlated with Psychopathic Personality Traits

Background: The posteromedial cortex (PMC) and medial prefrontal cortex (mPFC) are part of a network of brain regions that has been found to exhibit decreased activity during goal-oriented tasks. This network is thought to support a baseline of brain activity, and is commonly referred to as the ‘‘default network’’. Although recent reports suggest that the PMC and mPFC are associated with affective, social, and self-referential processes, the relationship between these default network components and personality traits, especially those pertaining to social context, is poorly understood. Methodology/Principal Findings: In the current investigation, we assessed the relationship between PMC and mPFC deactivations and psychopathic personality traits using fMRI and a self-report measure. We found that PMC deactivations predicted traits related to egocentricity and mPFC deactivations predicted traits related to decision-making. Conclusions/Significance: These results suggest that the PMC and mPFC are associated with processes involving selfrelevancy and affective decision-making, consistent with previous reports. More generally, these findings suggest a link between default network activity and personality traits

The effect of hypertensive disorders in pregnancy on small for gestational age and stillbirth: a population based study

BACKGROUND: Hypertensive disorders in pregnancy are leading causes of maternal, fetal and neonatal morbidity and mortality worldwide. However, studies attempting to quantify the effect of hypertension on adverse perinatal outcomes have been mostly conducted in tertiary centres. This population-based study explored the frequency of hypertensive disorders in pregnancy and the associated increase in small for gestational age (SGA) and stillbirth. METHODS: We used information on all pregnant women and births, in the Canadian province of Nova Scotia, between 1988 and 2000. Pregnancies were excluded if delivery occurred < 20 weeks, if birthweight was < 500 grams, if there was a high-order multiple pregnancy (greater than twin gestation), or a major fetal anomaly. RESULTS: The study population included 135,466 pregnancies. Of these, 7.7% had mild pregnancy-induced hypertension (PIH), 1.3% had severe PIH, 0.2% had HELLP (hemolysis, elevated liver enzymes, low platelets), 0.02% had eclampsia, 0.6% had chronic hypertension, and 0.4% had chronic hypertension with superimposed PIH. Women with any hypertension in pregnancy were 1.6 (95% CI 1.5–1.6) times more likely to have a live birth with SGA and 1.4 (95% CI 1.1–1.8) times more likely to have a stillbirth as compared with normotensive women. Adjusted analyses showed that women with gestational hypertension without proteinuria (mild PIH) and with proteinuria (severe PIH, HELLP, or eclampsia) were more likely to have infants with SGA (RR 1.5, 95% CI 1.4–1.6 and RR 3.2, 95% CI 2.8–3.6, respectively). Women with pre-existing hypertension were also more likely to give birth to an infant with SGA (RR 2.5, 95% CI 2.2–3.0) or to have a stillbirth (RR 3.2, 95% CI 1.9–5.4). CONCLUSIONS: This large, population-based study confirms and quantifies the magnitude of the excess risk of small for gestational age and stillbirth among births to women with hypertensive disease in pregnancy

A survey of health professions students for knowledge, attitudes, and confidence about tuberculosis, 2005

<p>Abstract</p> <p>Background</p> <p>In 2003 the NIH perceived a need to strengthen teaching about tuberculosis (TB) to health professions students. The National Tuberculosis Curriculum Consortium (NTCC) was funded to meet this need. The purpose of this study was to survey students enrolled in NTCC schools prior to NTCC-developed educational materials being made available to faculty.</p> <p>Methods</p> <p>A self-administered survey for students in NTCC schools to establish a baseline level of knowledge, attitudes, and confidence about tuberculosis.</p> <p>Results</p> <p>1480/2965 (50%) students in 28 programs in 20 NTCC schools completed the survey. If public health students are eliminated from totals (only 61 respondents of 765 public health students), the overall response proportion for the seven clinically-related disciplines was 64.5%. The majority (74%) were in schools of medicine (MD/DO), undergraduate nursing (BSN), and pharmacy (PharmD); others were in programs for physician assistants (PA), advanced practice nursing (NP/APN), respiratory therapy (RT), clinical laboratory sciences (MT/CLS), and public health (MPH). Almost 90% had attended at least one lecture about TB. Although 91.4% knew TB was transmitted via aerosols, about one-third did not know the method for administering tuberculin, or that Bacillus Calmette-Guerin (BCG) vaccine was not a contraindication to TB skin testing. Fewer than two-thirds knew that about 10% of people in the U.S.A. who have latent tuberculosis infection (LTBI) and a normal immune system will develop TB disease, or that BCG is not part of the routine vaccination program in the U.S.A. because it complicates surveillance for new TB infection.</p> <p>Conclusion</p> <p>There is room for improvement in knowledge, attitudes, and confidence about TB by health professions students surveyed. The NTCC-developed educational products may be used by faculty to improve student performance to be assessed with future surveys.</p