Disentangling the effects of stimulus context on auditory responses using electroencephalography

A ubiquitous feature of neural responses is their dependence on stimulus context. One prominent contextual effect is the reduction in neural response size with stimulus repetition, known as “adaptation”. As adaptation is often stimulus-specific, it has been used in visual neuroimaging studies to probe mechanisms of stimulus representation that would otherwise be hidden due to the limited spatial resolution of the available measurement techniques. However, work on the visual system has suggested that stimulus-specific adaptation may not only reflect stimulus representations, but may itself also modify representational information. The four studies described in this report examined the effects of stimulus context on auditory cortical responses using electroencephalography (EEG). The first study used adaptation to examine the neural representation of musical pitch in auditory cortex. Whilst pitch is often treated as a single dimension, namely, the repetition rate of the stimulus waveform, in music, pitch actually has two dimensions: pitch height (the octave in which a note resides) and pitch chroma (the position of the note within an octave). The current study provided evidence for an explicit representation of pitch chroma in an anterolateral region of non-primary auditory cortex. The second, third and fourth studies examined the auditory “mismatch response” (MMR). The MMR refers to the increase in response size to a stimulus when it is presented infrequently (as a “deviant”) compared to when it is presented frequently (as a “standard”). The second study found that the MMR could not be fully accounted for by a passive release from adaptation. Instead, the MMR seemed to reflect a sharpening of the neural representation of the adaptor stimulus with repeated presentation. This suggests that the MMR may be involved in perceptual learning. The third study examined the time courses of the contextual effects on neural responses. Both short- and longer-term effects were observed, with the effects differing between the different components of the auditory evoked response. Notably, the N1 component was influenced by complex effects that seemed to partially reflect the longer-term probabilities of certain short segments of the stimulus sequence, whereas the P2 was influenced by a strong suppressive effect with a remarkably short time course. The fourth study examined whether the contextual effects on auditory-evoked transient and sustained responses are sensitive to the absolute, or the relative, stimulus probabilities. For the transient N1 response, the most striking finding was that adaptation was broadly tuned for deviant stimuli, but sharply tuned for stimuli that were, in terms of their relative probabilities, standards. In contrast, the sustained response appeared to be influenced by a different effect, which facilitated responses to deviant stimuli. The current results suggest that contextual effects differ vastly between different deflections of the auditory-evoked responses, that they include effects that are both complex and long-lasting (of the order of ten seconds or longer), and that they involve not only suppressive, but also facilitatory effects

A role for glycolipid biosynthesis in severe fever with thrombocytopenia syndrome virus entry

A novel bunyavirus was recently found to cause severe febrile illness with high mortality in agricultural regions of China, Japan, and South Korea. This virus, named severe fever with thrombocytopenia syndrome virus (SFTSV), represents a new group within the Phlebovirus genus of the Bunyaviridae. Little is known about the viral entry requirements beyond showing dependence on dynamin and endosomal acidification. A haploid forward genetic screen was performed to identify host cell requirements for SFTSV entry. The screen identified dependence on glucosylceramide synthase (ugcg), the enzyme responsible for initiating de novo glycosphingolipid biosynthesis. Genetic and pharmacological approaches confirmed that UGCG expression and enzymatic activity were required for efficient SFTSV entry. Furthermore, inhibition of UGCG affected a post-internalization stage of SFTSV entry, leading to the accumulation of virus particles in enlarged cytoplasmic structures, suggesting impaired trafficking and/or fusion of viral and host membranes. These findings specify a role for glucosylceramide in SFTSV entry and provide a novel target for antiviral therapies

Physiological Evidence for a Midline Spatial Channel in Human Auditory Cortex

Studies with humans and other mammals have provided support for a two-channel representation of horizontal (“azimuthal”) space in the auditory system. In this representation, location-sensitive neurons contribute activity to one of two broadly tuned channels whose responses are compared to derive an estimate of sound-source location. One channel is maximally responsive to sounds towards the left and the other to sounds towards the right. However, recent psychophysical studies of humans, and physiological studies of other mammals, point to the presence of an additional channel, maximally responsive to the midline. In this study, we used electroencephalography to seek physiological evidence for such a midline channel in humans. We measured neural responses to probe stimuli presented from straight ahead (0 °) or towards the right (+30 ° or +90 °). Probes were preceded by adapter stimuli to temporarily suppress channel activity. Adapters came from 0 ° or alternated between left and right (−30 ° and +30 ° or −90 ° and +90 °). For the +90 ° probe, to which the right-tuned channel would respond most strongly, both accounts predict greatest adaptation when the adapters are at ±90 °. For the 0 ° probe, the two-channel account predicts greatest adaptation from the ±90 ° adapters, while the three-channel account predicts greatest adaptation when the adapters are at 0 ° because these adapters stimulate the midline-tuned channel which responds most strongly to the 0 ° probe. The results were consistent with the three-channel account. In addition, a computational implementation of the three-channel account fitted the probe response sizes well, explaining 93 % of the variance about the mean, whereas a two-channel implementation produced a poor fit and explained only 61 % of the variance

Early antenatal prediction of gestational diabetes in obese women: development of prediction tools for targeted intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most

The effect of a lifestyle intervention in obese pregnant women on gestational metabolic profiles: findings from the UK Pregnancies Better Eating and Activity Trial (UPBEAT) randomised controlled trial

Background: Pregnancy is associated with widespread change in metabolism, which may be more marked in obese women. Whether lifestyle interventions in obese pregnant women improve pregnancy metabolic profiles remains unknown. Our objectives were to determine the magnitude of change in metabolic measures during obese pregnancy, to indirectly compare these to similar profiles in a general pregnant population, and to determine the impact of a lifestyle intervention on change in metabolic measures in obese pregnant women. Methods: Data from a randomised controlled trial of 1158 obese (BMI ≥ 30 kg/m2) pregnant women recruited from six UK inner-city obstetric departments were used. Women were randomised to either the UPBEAT intervention, a tailored complex lifestyle intervention focused on improving diet and physical activity, or standard antenatal care (control group). UPBEAT has been shown to improve diet and physical activity during pregnancy and up to 6-months postnatally in obese women and to reduce offspring adiposity at 6-months; it did not affect risk of gestational diabetes (the primary outcome). Change in the concentrations of 158 metabolic measures (129 lipids, 9 glycerides and phospholipids, and 20 low-molecular weight metabolites), quantified three times during pregnancy, were compared using multilevel models. The role of chance was assessed with a false discovery rate of 5% adjusted p values. Results: All very low-density lipoprotein (VLDL) particles increased by 1.5–3 standard deviation units (SD) whereas intermediate density lipoprotein and specific (large, medium and small) LDL particles increased by 1–2 SD, between 16 and 36 weeks’ gestation. Triglycerides increased by 2–3 SD, with more modest changes in other metabolites. Indirect comparisons suggest that the magnitudes of change across pregnancy in these obese women were 2- to 3-fold larger than in unselected women (n = 4260 in cross-sectional and 583 in longitudinal analyses) from an independent, previously published, study. The intervention reduced the rate of increase in extremely large, very large, large and medium VLDL particles, particularly those containing triglycerides. Conclusion: There are marked changes in lipids and lipoproteins and more modest changes in other metabolites across pregnancy in obese women, with some evidence that this is more marked than in unselected pregnant women. The UPBEAT lifestyle intervention may contribute to a healthier metabolic profile in obese pregnant women, but our results require replication. Trial Registration: UPBEAT was registered with Current Controlled Trials, ISRCTN89971375, on July 23, 2008 (prior to recruitment)

Beta-frequency electrophysiological bursts: BOLD correlates and relationships with psychotic illness

AIMS: To identify the BOLD (blood oxygenation level dependent) correlates of bursts of beta frequency band electrophysiological activity, and to compare BOLD responses between healthy controls and patients with psychotic illness. The post movement beta rebound (PMBR) is a transient increase in power in the beta frequency band (13-30 Hz), recorded with methods such as electroencephalography (EEG), following the completion of a movement. PMBR size is reduced in patients with schizophrenia and inversely correlated with severity of illness. PMBR size is inversely correlated with measures of schizotypy in non-clinical groups. Therefore, beta-band activity may reflect a fundamental neural process whose disruption plays an important role in the pathophysiology of schizophrenia. Recent work has found that changes in beta power reflect changes in the probability-of-occurrence of transient bursts of beta-frequency activity. Understanding the generators of beta bursts could help unravel the pathophysiology of psychotic illness and thus identify novel treatment targets. METHOD: EEG data were recorded simultaneously with BOLD data measured with 3T functional magnetic resonance imaging (fMRI), whilst participants performed an n-back working memory task. We included seventy-eight participants – 32 patients with schizophrenia, 16 with bipolar disorder and 30 healthy controls. Beta bursts were identified in the EEG data using a thresholding method and burst timings were used as markers in an event-related fMRI design convolved with a conventional haemodynamic response function. A region of interest analysis compared beta-event-related BOLD activity between patients and controls. RESULT: Beta bursts phasically activated brain regions implicated in coding task-relevant content (specifically, regions involved in the phonological representation of letter stimuli, as well as areas representing motor responses). Further, bursts were associated with suppression of tonically-active regions. In the EEG, PMBR was greater in controls than patients, and, in patients, PMBR size was positively correlated with Global Assessment of Functioning scores, and negatively correlated with persisting symptoms of disorganisation and performance on a digit symbol substition test. Despite this, patients showed greater, more extensive, burst-related BOLD activation than controls. CONCLUSION: Our findings are consistent with a recent model in which beta bursts serve to reactivate latently-maintained, task-relevant, sensorimotor information. The increased BOLD response associated with bursts in patients, despite reduced PMBR, could reflect inefficiency of burst-mediated cortical synchrony, or it may suggest that the sensorimotor information reactivated by beta bursts is less precisely specified in psychosis. We propose that dysfunction of the mechanisms by which beta bursts reactivate task-relevant content can manifest as disorganisation and working memory deficits, and may contribute to persisting symptoms and impairment in psychosis

Adiposity and cardiovascular outcomes in three-year-old children of participants in UPBEAT, an RCT of a complex intervention in pregnant women with obesity

Background: Maternal obesity is associated with offspring cardiometabolic risk. UPBEAT was a randomised controlled trial of an antenatal diet and physical activity intervention in 1555 women with obesity. The intervention was associated with lower gestational weight gain, healthier diet and metabolic profile in pregnancy, and reduced infant adiposity at six months. Objective: We have investigated whether the UPBEAT intervention influenced childhood cardiometabolic outcomes or was associated with sustained improvements in maternal lifestyle 3-years after delivery. Methods: In UPBEAT mother-child dyads at the 3-year follow-up, we assessed childhood blood pressure, resting pulse rate, and adiposity (body mass index, skinfold thicknesses, body fat, waist and arm circumferences) and maternal diet, physical activity, and anthropometry. Results: 514 three-year-old children attended the appointment (49% intervention, 51% standard care). There was no difference in the main outcome of interest, subscapular skinfold thickness, between the trial arms (−0.30 mm, 95% confidence interval: −0.92, 0.31). However, the intervention was associated with a lower resting pulse rate (−5 bpm [−8.41, −1.07]). There was also a non-significant lower odds of overweight/obesity (OR 0.73; 0.50, 1.08). Maternal dietary improvements observed in the UPBEAT trial, including glycaemic load and saturated fat were maintained 3-years postpartum. Conclusion: This study has demonstrated that an antenatal dietary and physical activity intervention in women with obesity is associated with lower offspring pulse rate and sustained improvement in maternal diet. Whilst larger than previous cohorts, there remains potential for bias from attrition and these findings require validation in future cohorts

Prediction of uncomplicated pregnancies in obese women:a prospective multicentre study

Background: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. Methods: Data form obese women (BMI ≥ 30 kg/m2) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15+0 to 18+6 weeks’ gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. Results: Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m2), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68–0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65–0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. Conclusion: Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth

Regional Brain Correlates of Beta Bursts in Health and Psychosis: A Concurrent Electroencephalography and Functional Magnetic Resonance Imaging Study

Background: There is emerging evidence for abnormal beta oscillations in psychosis. Beta-oscillations are likely to play a key role in the coordination of sensorimotor information, crucial to healthy mental function. Growing evidence suggests that beta oscillations typically manifest as transient “beta-bursts” that increase in probability following a motor response, observable as Post-Movement Beta Rebound (PMBR). Evidence indicates that PMBR is attenuated in psychosis, with greater attenuation associated with greater symptom severity and impairment. Delineating the functional role of beta-bursts may therefore be key to understanding the mechanisms underlying persistent psychotic illness.Methods: We used concurrent EEG and fMRI to identify BOLD correlates of beta-bursts during the N-back working memory task and intervening rest periods in healthy participants (N = 30) and patients with psychosis (N = 48). Results: During both task-blocks and intervening rest periods, beta-bursts phasically activated regions implicated in task-relevant content, while suppressing currently tonically active regions. Patients showed attenuated PMBR that was associated with persisting Disorganisation symptoms, as well as impairments in cognition and role function. Patients also showed greater task-related reductions in overall beta-burst rate, and greater, more extensive, beta-burst-related BOLD activation.Conclusions: Our evidence supports a model in which beta-bursts reactivate latently maintained sensorimotor information and are dysregulated and inefficient in psychosis. We propose that abnormalities in the mechanisms by which beta-bursts coordinate reactivation of contextually appropriate content can manifest as Disorganisation, working memory deficits and inaccurate forward models, and may underlie a “core deficit” associated with persisting symptoms and impairment

Los lenguajes controlados y la documentación técnica : mejorando la traducibilidad

Los lenguajes controlados pueden suponer una estrategia efectiva para mejorar los procesos de traducción, modificando el texto origen para que se adapte a una serie de reglas que mejoran su traducibilidad. El artículo analiza el concepto de lenguaje controlado y revisa las diferentes áreas de control y su tipología, para después realizar un breve repaso al origen y evolución de estos si stemas lingüísticos. A continuación explora qué papel representan los lenguajes controlados en el proceso de redacción y traducción de documentación técnica. Por último, se centra en la relación entre lenguajes controlados y traducción y, más en concreto, la traducción automática, haciendo especial hincapié en las reglas más efectivas para la mejora de la traducibilidad.Els llenguatges controlats poden suposar una estratègia efectiva per a millorar els processos de traducció, modificant el text origen perquè s'adapte a una sèrie de regles que milloren la seua traduïbilitat. L'article analitza el concepte de llenguatge controlat i revisa les diferents àrees de control i la seua tipologia, per a després realitzar un breu repàs a l'origen i evolució d'estos sistemes lingüístics. A continuació explora quin paper representen els llenguatges controlats en el procés de redacció i traducció de documentació tècnica. Finalment, es centra en la relació entre llenguatges controlats i traducció i, més concretament, traducció autom àtica, fent especial insistència en les regles més efectives per a la millora de la traduïbilitat.Controlled languages can be an effective strategy to improve translation processes, pre-editing the source text to conform to a set of rules to improve its translatability. This article analyses the concept of controlled language and reviews the different control areas and their typology. Further, it reviews the origin and evolution of these linguistic systems and explores the role controlled languages play in the process of writing and translating technical documentation. Finally, it focuses on the relationship between controlled language and translation and, more specifically, machine translation, with particular emphasis on the rules aimed at improving translatability