Subgenual Cingulum Microstructure Supports Control of Emotional Conflict

This is the final version of the article. Available from Oxford University Press via the DOI in this record.Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r= -0.53;P= 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimuli.P.A.K. was funded by the Higher Education Funding Council for Wales (HEFCW) and an Academy of Medical Sciences and Wellcome Trust Starter Grant (AJ17102004). M.M. received an EPSRC Doctoral Training Grant. This work was also supported by a Marie Curie fellowship to Marcel Meyer and received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 267171. D.K.J. was funded by HEFCW and received grants from the MS Society, a Wellcome Trust New Investigator Award, a Wellcome Trust Multi User Equipment Grant and Medical Research Council, and Wellcome Trust project grants. A.N.D. was supported by the Wellcome Trust PhD schemes. N.L. was funded by HEFCW. A.D.L. was funded by HEFCW. He also received grants from the ESRC, Wellcome Trust, and NISCHR. Funding to pay the Open Access publication charges for this article was provided by The Wellcome Trust

Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Diffusion tensor image segmentation of the cerebrum provides a single measure of cerebral small vessel disease severity related to cognitive change.

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS). Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline. Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity. Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period. 98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years. DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue. By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain. Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters. The impact of brain change on cognition was explored using linear mixed-effects models. Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials. Changes in brain structure described by DSEG θ were related to change in EF and IPS (p < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ. Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models (p = 0.002). Change in DSEG θ was also related to change in all other MRI markers (p < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum. Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity. DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for. DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change. Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials. As such it may provide a marker of SVD severity from a single imaging modality (i.e. DTIs)

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Gaseous emissions during concurrent combustion of biomass and non-recyclable municipal solid waste

Background: Biomass and municipal solid waste offer sustainable sources of energy; for example to meet heat and electricity demand in the form of combined cooling, heat and power. Combustion of biomass has a lesser impact than solid fossil fuels (e. g. coal) upon gas pollutant emissions, whilst energy recovery from municipal solid waste is a beneficial component of an integrated, sustainable waste management programme. Concurrent combustion of these fuels using a fluidised bed combustor may be a successful method of overcoming some of the disadvantages of biomass (high fuel supply and distribution costs, combustion characteristics) and characteristics of municipal solid waste (heterogeneous content, conflict with materials recycling). It should be considered that combustion of municipal solid waste may be a financially attractive disposal route if a 'gate fee' value exists for accepting waste for combustion, which will reduce the net cost of utilising relatively more expensive biomass fuels. Results: Emissions of nitrogen monoxide and sulphur dioxide for combustion of biomass are suppressed after substitution of biomass for municipal solid waste materials as the input fuel mixture. Interactions between these and other pollutants such as hydrogen chloride, nitrous oxide and carbon monoxide indicate complex, competing reactions occur between intermediates of these compounds to determine final resultant emissions. Conclusions: Fluidised bed concurrent combustion is an appropriate technique to exploit biomass and municipal solid waste resources, without the use of fossil fuels. The addition of municipal solid waste to biomass combustion has the effect of reducing emissions of some gaseous pollutants

Can modern infrared analyzers replace gas chromatography to measure anesthetic vapor concentrations?

<p>Abstract</p> <p>Background</p> <p>Gas chromatography (GC) has often been considered the most accurate method to measure the concentration of inhaled anesthetic vapors. However, infrared (IR) gas analysis has become the clinically preferred monitoring technique because it provides continuous data, is less expensive and more practical, and is readily available. We examined the accuracy of a modern IR analyzer (M-CAiOV compact gas IR analyzer (General Electric, Helsinki, Finland) by comparing its performance with GC.</p> <p>Methods</p> <p>To examine linearity, we analyzed 3 different concentrations of 3 different agents in O₂: 0.3, 0.7, and 1.2% isoflurane; 0.5, 1, and 2% sevoflurane; and 1, 3, and 6% desflurane. To examine the effect of carrier gas composition, we prepared mixtures of 1% isoflurane, 1 or 2% sevoflurane, or 6% desflurane in 100% O₂(= O₂group); 30%O₂+ 70%N₂O (= N₂O group), 28%O₂+ 66%N₂O + 5%CO₂(= CO₂group), or air. To examine consistency between analyzers, four different M-CAiOV analyzers were tested.</p> <p>Results</p> <p>The IR analyzer response in O₂is linear over the concentration range studied: IR isoflurane % = -0.0256 + (1.006 * GC %), R = 0.998; IR sevoflurane % = -0.008 + (0.946 * GC %), R = 0.993; and IR desflurane % = 0.256 + (0.919 * GC %), R = 0.998. The deviation from GC calculated as (100*(IR-GC)/GC), in %) ranged from -11 to 11% for the medium and higher concentrations, and from -20 to +20% for the lowest concentrations. No carrier gas effect could be detected. Individual modules differed in their accuracy (p = 0.004), with differences between analyzers mounting up to 12% of the medium and highest concentrations and up to 25% of the lowest agent concentrations.</p> <p>Conclusion</p> <p>M-CAiOV compact gas IR analyzers are well compensated for carrier gas cross-sensitivity and are linear over the range of concentrations studied. IR and GC cannot be used interchangeably, because the deviations between GC and IR mount up to ± 20%, and because individual analyzers differ unpredictably in their performance.</p