Exponential Random Graph Modeling for Complex Brain Networks

Exponential random graph models (ERGMs), also known as p* models, have been utilized extensively in the social science literature to study complex networks and how their global structure depends on underlying structural components. However, the literature on their use in biological networks (especially brain networks) has remained sparse. Descriptive models based on a specific feature of the graph (clustering coefficient, degree distribution, etc.) have dominated connectivity research in neuroscience. Corresponding generative models have been developed to reproduce one of these features. However, the complexity inherent in whole-brain network data necessitates the development and use of tools that allow the systematic exploration of several features simultaneously and how they interact to form the global network architecture. ERGMs provide a statistically principled approach to the assessment of how a set of interacting local brain network features gives rise to the global structure. We illustrate the utility of ERGMs for modeling, analyzing, and simulating complex whole-brain networks with network data from normal subjects. We also provide a foundation for the selection of important local features through the implementation and assessment of three selection approaches: a traditional p-value based backward selection approach, an information criterion approach (AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF approach serves as the best method given the scientific interest in being able to capture and reproduce the structure of fitted brain networks

Spontaneous Prediction Error Generation in Schizophrenia

Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks

Effects of Different Correlation Metrics and Preprocessing Factors on Small-World Brain Functional Networks: A Resting-State Functional MRI Study

Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01–0.027 Hz) versus slow-4 (0.027–0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the “best” network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027–0.073 Hz band exhibited greater reliability than those in the 0.01–0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific preprocessing choices on both the global and nodal topological properties of functional brain networks. This study also has important implications for how to choose reliable analytical schemes in brain network studies

Identification and Classification of Hubs in Brain Networks

Brain regions in the mammalian cerebral cortex are linked by a complex network of fiber bundles. These inter-regional networks have previously been analyzed in terms of their node degree, structural motif, path length and clustering coefficient distributions. In this paper we focus on the identification and classification of hub regions, which are thought to play pivotal roles in the coordination of information flow. We identify hubs and characterize their network contributions by examining motif fingerprints and centrality indices for all regions within the cerebral cortices of both the cat and the macaque. Motif fingerprints capture the statistics of local connection patterns, while measures of centrality identify regions that lie on many of the shortest paths between parts of the network. Within both cat and macaque networks, we find that a combination of degree, motif participation, betweenness centrality and closeness centrality allows for reliable identification of hub regions, many of which have previously been functionally classified as polysensory or multimodal. We then classify hubs as either provincial (intra-cluster) hubs or connector (inter-cluster) hubs, and proceed to show that lesioning hubs of each type from the network produces opposite effects on the small-world index. Our study presents an approach to the identification and classification of putative hub regions in brain networks on the basis of multiple network attributes and charts potential links between the structural embedding of such regions and their functional roles

New Zealand Blackcurrant Extract Improves Cycling Performance and Fat Oxidation in Cyclists

PURPOSE: Blackcurrant intake increases peripheral blood flow in humans, potentially by anthocyanin-induced vasodilation which may affect substrate delivery and exercise performance. We examined the effects of New Zealand blackcurrant (NZBC) extract on substrate oxidation, cycling time-trial performance and plasma lactate responses following the time-trial in trained cyclists. METHODS: Using a randomized, double-blind, crossover design, fourteen healthy men (age: 38 ± 13 years, height: 178 ± 4 cm, body mass: 77 ± 9 kg, V?O2max: 53 ± 6 ml·kg-1·min-1, mean ± SD) ingested NZBC extract (300 mg?day-1 CurraNZ™ containing 105 mg anthocyanin) or placebo (PL, 300 mg microcrystalline cellulose M102) for 7-days (washout 14-days). On day 7, participants performed 30 min of cycling (3x10 min at 45, 55 and 65% V?O2max), followed by a 16.1 km time-trial with lactate sampling during a 20-minute passive recovery. RESULTS: NZBC extract increased fat oxidation at 65% V?O2max by 27% (P < 0.05) and improved 16.1 km time-trial performance by 2.4% (NZBC: 1678 ± 108 s, PL: 1722 ± 131 s, P < 0.05). Plasma lactate was higher with NZBC extract immediately following the time-trial (NZBC: 7.06 ± 1.73 mmol?L-1, PL: 5.92 ± 1.58 mmol?L-1 P < 0.01). CONCLUSIONS: Seven days intake of New Zealand blackcurrant extract improves 16.1 km cycling time-trial performance and increases fat oxidation during moderate intensity cycling

Impact of severity, duration, and etiology of hyperthyroidism on bone turnover markers and bone mineral density in men

<p>Abstract</p> <p>Background</p> <p>Hyperthyroidism is accompanied by osteoporosis with higher incidence of fracture rates. The present work aimed to study bone status in hyperthyroidism and to elucidate the impact of severity, duration, and etiology of hyperthyroidism on biochemical markers of bone turnover and bone mineral density (BMD).</p> <p>Methods</p> <p>Fifty-two male patients with hyperthyroidism, 31 with Graves' disease (GD) and 21 with toxic multinodular goiter (TNG), with an age ranging from 23 to 65 years were included, together with 25 healthy euthyroid men with matched age as a control group. In addition to full clinical examination, patients and controls were subjected to measurement of BMD using dual-energy X-ray absorptiometery scanning of the lower half of the left radius. Also, some biochemical markers of bone turnover were done for all patients and controls.</p> <p>Results</p> <p>Biochemical markers of bone turnover: included serum bone specific alkaline phosphatase, osteocalcin, carboxy terminal telopeptide of type l collagen also, urinary deoxypyridinoline cross-links (DXP), urinary DXP/urinary creatinine ratio and urinary calcium/urinary creatinine ratio were significantly higher in patients with GD and TNG compared to controls (P < 0.01). However, there was non-significant difference in these parameters between GD and TNG patients (P > 0.05). BMD was significantly lower in GD and TNG compared to controls, but the Z-score of BMD at the lower half of the left radius in patients with GD (-1.7 ± 0.5 SD) was not significantly different from those with TNG (-1.6 ± 0.6 SD) (>0.05). There was significant positive correlation between free T3 and free T4 with biochemical markers of bone turnover, but negative correlation between TSH and those biochemical markers of bone turnover. The duration of the thyrotoxic state positively correlated with the assessed bone turnover markers, but it is negatively correlated with the Z-score of BMD in the studied hyperthyroid patients (r = -0.68, P < 0.0001).</p> <p>Conclusion</p> <p>Men with hyperthyroidism have significant bone loss with higher biochemical markers of bone turnover. The severity and the duration of the thyrotoxic state are directly related to the derangement of biochemical markers of bone turnover and bone loss.</p

Stainable hepatic iron in 341 African American adults at coroner/medical examiner autopsy

BACKGROUND: Results of previous autopsy studies indicate that increased hepatic iron stores or hepatic iron overload is common in African Americans dying in hospitals, but there are no reports of hepatic iron content in other cohorts of African Americans. METHODS: We investigated the prevalence of heavy liver iron deposition in African American adults. Using established histochemical criteria, we graded Perls' acid ferrocyanide-reactive iron in the hepatocytes and Kupffer cells of 341 consecutive African American adults who were autopsied in the coroner/medical examiner office. Heavy staining was defined as grade 3 or 4 hepatocyte iron or grade 3 Kupffer cell iron. RESULTS: There were 254 men and 85 women (mean age ± 1 SD: 44 ± 13 y vs. 48 ± 14 y, respectively; p = 0.0255); gender was unstated or unknown in two subjects. Approximately one-third of subjects died of natural causes. Heavy staining was observed in 10.2% of men and 4.7% of women. 23 subjects had heavy hepatocyte staining only, six had heavy Kupffer cell staining only, and one had a mixed pattern of heavy staining. 15 subjects had histories of chronic alcoholism; three had heavy staining confined to hepatocytes. We analyzed the relationships of three continuous variables (age at death in years, hepatocyte iron grade, Kupffer cell iron grade) and two categorical variables (sex, cause of death (natural and non-natural causes)) in all 341 subjects using a correlation matrix with Bonferroni correction. This revealed two positive correlations: hepatocyte with Kupffer cell iron grades (p < 0.01), and male sex with hepatocyte iron grade (p < 0.05). We also analyzed the relationship of steatosis, inflammation, and fibrosis/cirrhosis in 30 subjects with heavy iron staining using a correlation matrix with Bonferroni correction. There were significant positive correlations of steatosis with inflammation (r = 0.5641; p < 0.01), and of inflammation with fibrosis/cirrhosis (r = 0.6124; p < 0.01). CONCLUSIONS: The present results confirm and extend previous observations that heavy liver iron staining is relatively common in African Americans. The pertinence of these observations to genetic and acquired causes of iron overload in African Americans is discussed

Screen-based media use clusters are related to other activity behaviours and health indicators in adolescents

Background: Screen-based media (SBM) occupy a considerable portion of young peoples’ discretionary leisure time. The aim of this paper was to investigate whether distinct clusters of SBM use exist, and if so, to examine the relationship of any identified clusters with other activity/sedentary behaviours and physical and mental health indicators.Methods: The data for this study come from 643 adolescents, aged 14 years, who were participating in the longitudinal Western Australian Pregnancy Cohort (Raine) Study through May 2003 to June 2006. Time spent on SBM, phone use and reading was assessed using the Multimedia Activity Recall for Children and Adults. Height, weight, muscle strength were measured at a clinic visit and the adolescents also completed questionnaires on their physical activity and psychosocial health. Latent class analysis (LCA) was used to analyse groupings of SBM use.Results: Three clusters of SBM use were found; C1 ‘instrumental computer users’ (high email use, general computer use), C2 ‘multi-modal e-gamers’ (both high console and computer game use) and C3 ‘computer e-gamers’ (high computer game use only). Television viewing was moderately high amongst all the clusters. C2 males took fewer steps than their male peers in C1 and C3 (-13,787/week, 95% CI: -4619 to -22957, p = 0.003 and -14,806, 95% CI: -5,306 to -24,305, p = 0.002) and recorded less MVPA than the C1 males (-3.5 h, 95% CI: -1.0 to -5.9, p = 0.005). There was no difference in activity levels between females in clusters C1 and C3.Conclusion: SBM use by adolescents did cluster and these clusters related differently to activity/sedentary behaviours and both physical and psychosocial health indicators. It is clear that SBM use is not a single construct and future research needs to take consideration of this if it intends to understand the impact SBM has on health

Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

Background. Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design. A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion. This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration. Netherlands Trial Register (NTR1636)

Disturbed functional brain networks and neurocognitive function in low-grade glioma patients: a graph theoretical analysis of resting-state MEG

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