The control of global brain dynamics: opposing actions of frontoparietal control and default mode networks on attention

Understanding how dynamic changes in brain activity control behavior is a major challenge of cognitive neuroscience. Here, we consider the brain as a complex dynamic system and define two measures of brain dynamics: the synchrony of brain activity, measured by the spatial coherence of the BOLD signal across regions of the brain; and metastability, which we define as the extent to which synchrony varies over time. We investigate the relationship among brain network activity, metastability, and cognitive state in humans, testing the hypothesis that global metastability is “tuned” by network interactions. We study the following two conditions: (1) an attentionally demanding choice reaction time task (CRT); and (2) an unconstrained “rest” state. Functional MRI demonstrated increased synchrony, and decreased metastability was associated with increased activity within the frontoparietal control/dorsal attention network (FPCN/DAN) activity and decreased default mode network (DMN) activity during the CRT compared with rest. Using a computational model of neural dynamics that is constrained by white matter structure to test whether simulated changes in FPCN/DAN and DMN activity produce similar effects, we demonstate that activation of the FPCN/DAN increases global synchrony and decreases metastability. DMN activation had the opposite effects. These results suggest that the balance of activity in the FPCN/DAN and DMN might control global metastability, providing a mechanistic explanation of how attentional state is shifted between an unfocused/exploratory mode characterized by high metastability, and a focused/constrained mode characterized by low metastability

Severe generalised hypersensitivity reaction to topical neomycin after cataract surgery: a case report

<p>Abstract</p> <p>Introduction</p> <p>Systemic hypersensitivity reactions to topical ophthalmic treatment occur rarely, but when they do they can be severe as highlighted by this case.</p> <p>Case presentation</p> <p>A post-operative cataract surgery patient developed a severe and generalised hypersensitivity reaction following topical treatment with Maxitrol (Dexamethasone and Neomycin) eye drops. The patient reported a previous allergic reaction to Neomycin.</p> <p>Conclusion</p> <p>This case report emphasises the importance of a thorough drug and allergy history when patients are seen at pre-assessment or clerked in for surgery.</p

Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens

There is accumulating evidence that the nucleus accumbens (NAc) has an important role in the pathophysiology of depression. As the NAc is a key component in the neural circuitry of reward, it has been hypothesized that anhedonia, a core symptom of depression, might be related to dysfunction of this brain region. Neuronal morphology and expression of plasticity-related molecules were examined in the NAc of rats displaying anhedonic behavior (measured in the sucrose-consumption test) in response to chronic mild stress. To demonstrate the relevance of our measurements to depression, we tested whether the observed changes were sensitive to reversal with antidepressants (imipramine and fluoxetine). Data show that animals displaying anhedonic behavior display an hypertrophy of medium spiny neurons in the NAc and, in parallel, have increased expression of the genes encoding for brain-derived neurotrophic factor, neural cell adhesion molecule and synaptic protein synapsin 1. Importantly, the reversal of stress-induced anhedonia by antidepressants is linked to a restoration of gene-expression patterns and dendritic morphology in the NAc. Using an animal model of depression, we show that stress induces anhedonic behavior that is associated with specific changes in the neuronal morphology and in the gene-expression profile of the NAc that are effectively reversed after treatment with antidepressants.The present work was funded by the Portuguese Foundation for Technology (FCT), project PTDC/SAU-NEU/105180/2008. FM and PL are recipients of postdoctoral fellowships and MM is recipient of a doctoral fellowship, all from FCT, Portugal

Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology

Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions

Hemispheric Asymmetries in Speech Perception: Sense, Nonsense and Modulations

Background: The well-established left hemisphere specialisation for language processing has long been claimed to be based on a low-level auditory specialization for specific acoustic features in speech, particularly regarding 'rapid temporal processing'.Methodology: A novel analysis/synthesis technique was used to construct a variety of sounds based on simple sentences which could be manipulated in spectro-temporal complexity, and whether they were intelligible or not. All sounds consisted of two noise-excited spectral prominences (based on the lower two formants in the original speech) which could be static or varying in frequency and/or amplitude independently. Dynamically varying both acoustic features based on the same sentence led to intelligible speech but when either or both acoustic features were static, the stimuli were not intelligible. Using the frequency dynamics from one sentence with the amplitude dynamics of another led to unintelligible sounds of comparable spectro-temporal complexity to the intelligible ones. Positron emission tomography (PET) was used to compare which brain regions were active when participants listened to the different sounds.Conclusions: Neural activity to spectral and amplitude modulations sufficient to support speech intelligibility (without actually being intelligible) was seen bilaterally, with a right temporal lobe dominance. A left dominant response was seen only to intelligible sounds. It thus appears that the left hemisphere specialisation for speech is based on the linguistic properties of utterances, not on particular acoustic features

Missing paternal demographics: A novel indicator for identifying high risk population of adverse pregnancy outcomes

BACKGROUND: One of every 6 United Status birth certificates contains no information on fathers. There might be important differences in the pregnancy outcomes between mothers with versus those without partner information. The object of this study was to assess whether and to what extent outcomes in pregnant women who did not have partner information differ from those who had. METHODS: We carried out a population-based retrospective cohort study based on the registry data in the United States for the period of 1995–1997, which was a matched multiple birth file (only twins were included in the current analysis). We divided the study subjects into three groups according to the availability of partner information: available, partly missing, and totally missing. We compared the distribution of maternal characteristics, maternal morbidity, labor and delivery complications, obstetric interventions, preterm birth, fetal growth restriction, low birth weight, congenital anomalies, fetal death, neonatal death, post-neonatal death, and neonatal morbidity among three study groups. RESULTS: There were 304466 twins included in our study. Mothers whose partner's information was partly missing and (especially) totally missing tended to be younger, of black race, unmarried, with less education, smoking cigarette during pregnancy, and with inadequate prenatal care. The rates of preterm birth, fetal growth restriction, low birth weight, Apgar score <7, fetal mortality, neonatal mortality, and post-neonatal mortality were significantly increased in mothers whose partner's information was partly or (especially) totally missing. CONCLUSIONS: Mothers whose partner's information was partly and (especially) totally missing are at higher risk of adverse pregnant outcomes, and clinicians and public health workers should be alerted to this important social factor

Computerized general practice based networks yield comparable performance with sentinel data in monitoring epidemiological time-course of influenza-like illness and acute respiratory illness

<p>Abstract</p> <p>Background</p> <p>Computerized morbidity registration networks might serve as early warning systems in a time where natural epidemics such as the H₁N₁flu can easily spread from one region to another.</p> <p>Methods</p> <p>In this contribution we examine whether general practice based broad-spectrum computerized morbidity registration networks have the potential to act as a valid surveillance instrument of frequently occurring diseases. We compare general practice based computerized data assessing the frequency of influenza-like illness (ILI) and acute respiratory infections (ARI) with data from a well established case-specific sentinel network, the European Influenza Surveillance Scheme (EISS). The overall frequency and trends of weekly ILI and ARI data are compared using both networks.</p> <p>Results</p> <p>Detection of influenza-like illness and acute respiratory illness occurs equally fast in EISS and the computerized network. The overall frequency data for ARI are the same for both networks, the overall trends are similar, but the increases and decreases in frequency do not occur in exactly the same weeks. For ILI, the overall rate was slightly higher for the computerized network population, especially before the increase of ILI, the overall trend was almost identical and the increases and decreases occur in the same weeks for both networks.</p> <p>Conclusions</p> <p>Computerized morbidity registration networks are a valid tool for monitoring frequent occurring respiratory diseases and the detection of sudden outbreaks.</p

COVID-19 and cancer registries: Learning from the first peak of the SARS-CoV-2 pandemic

The SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT-chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care