To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Irritability and anxiety frequently co-occur in pediatric populations. Studies separately looking at the neural correlates of these symptoms have identified engagement of similar neural systems – particularly those implicated in emotional processing. Both irritability and anxiety can be considered negative valence emotional states that might relate to emotion dysregulation. However, previous work has not examined the neural responding during the performance of an emotion regulation task as a function of interaction between irritability and anxiety simultaneously.
This fMRI study involved 155 participants (90 with significant psychopathologies and 92 male) who performed the Affective Stroop Task, designed to engage emotion regulation as a function of task demands. The Affective Reactivity Index (ARI) was used to index irritability and the Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to index anxiety.
Levels of irritability, but not anxiety, was positively correlated with responses to visual images within the right rostro-medial prefrontal cortex and left anterior cingulate cortex during view trials. The second region of ventral anterior cingulate cortex showed a condition-by-emotion-by-ARI score-by-SCARED score interaction. Specifically, anxiety level was significantly correlated with a decreased differential BOLD response to negative relative to neutral view trials but only in the presence of relatively high irritability.
Atypical maintenance of emotional stimuli within the rostro-medial prefrontal cortex may exacerbate the difficulties faced by adolescents with irritability. Moreover, increased anxiety combined with significant irritability may disrupt an automatic emotional conflict-based form of emotion regulation that is particularly associated with the ventral anterior cingulate cortex.
As the primary risk factor for cardiovascular disease (CVD), hypertension is the leading cause of preventable, premature mortality globally. Hypertension, or elevated blood pressure (BP), has a number of well-established risk factors, including genetics. A common C677T polymorphism in the gene encoding the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) affects 10–12% of UK and Irish populations and has been linked with 24–87% increased risk of hypertension globally. Evidence from randomised controlled trials (RCTs) conducted at this Centre has shown BP to be highly responsive (by 5–13 mmHg) to supplementation with riboflavin (MTHFR co-factor), an effect confined to homozygous individuals (TT genotype). To date, our trials have focused on peripheral BP; however, additional measures of vascular health such as central pressure are reported to be more closely correlated with CVD risk. Investigation of central BP, augmentation index (AIx) and pulse pressure amplification (PPA) may thus offer further insight into the role of this gene-nutrient interaction in blood pressure. The present study aims to investigate BP, and measures of vascular health in healthy adults stratified by MTHFR 677 genotype. Apparently healthy adults aged 18–60 years were recruited from workplaces across Northern Ireland and screened for MTHFR genotype via buccal swab. Clinic BP, anthropometry and blood sample were measured in TT individuals (n 209) and age and sex-matched CC (n 98) and CT (n 102) controls. AIx and central BP were assessed using SphygmoCor® (AtCor Medical, Australia). Preliminary results demonstrate higher BP in individuals with the MTHFR 677TT genotype compared to non-TT controls (systolic BP 134.7 ± 13.8 mmHg vs 129.7 ± 12.4 mmHg, P < 0.001; diastolic BP 81.6 ± 9.5 mmHg vs 79.7 mmHg ± 8.9 mmHg, P = 0.023, respectively). The MTHFR 677TT genotype group had significantly higher central systolic BP (119.4 ± 11.8 vs 116.7 ± 10.9 mmHg, P = 0.018), central pulse pressure (P = 0.006) and central mean pressure (P = 0.011) compared to the non-TT group. No significant differences for central diastolic BP, pulse pressure amplification, pulse pressure ratio and augmentation index were observed. This study confirms the phenotype of elevated BP in individuals with the C677T polymorphism in the gene encoding MTHFR. For the first time, this study reports that individuals with the MTHFR 677TT genotype have higher central systolic BP, central mean pressure and pulse pressure. Further investigations through RCTs investigating the effect of the MTHFR cofactor, riboflavin, on central blood pressure in these genetically at-risk adults are warranted.
Gut microbiota data obtained by DNA sequencing are not only complex because of the number of taxa that may be detected within human cohorts, but also compositional because characteristics of the microbiota are described in relative terms (e.g., “relative abundance” of particular bacterial taxa expressed as a proportion of the total abundance of taxa). Nutrition researchers often use standard principal component analysis (PCA) to derive dietary patterns from complex food data, enabling each participant's diet to be described in terms of the extent to which it fits their cohort's dietary patterns. However, compositional PCA methods are not commonly used to describe patterns of microbiota in the way that dietary patterns are used to describe diets. This approach would be useful for identifying microbiota patterns that are associated with diet and body composition. The aim of this study is to use compositional PCA to describe gut microbiota profiles in 5 year old children and explore associations between microbiota profiles, diet, body mass index (BMI) z-score, and fat mass index (FMI) z-score. This study uses a cross-sectional data for 319 children who provided a faecal sample at 5 year of age. Their primary caregiver completed a 123-item quantitative food frequency questionnaire validated for foods of relevance to the gut microbiota. Body composition was determined using dual-energy x-ray absorptiometry, and BMI and FMI z-scores calculated. Compositional PCA identified and described gut microbiota profiles at the genus level, and profiles were examined in relation to diet and body size. Three gut microbiota profiles were found. Profile 1 (positive loadings on Blautia and Bifidobacterium; negative loadings on Bacteroides) was not related to diet or body size. Profile 2 (positive loadings on Bacteroides; negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was associated with a lower BMI z-score (r = -0.16, P = 0.003). Profile 3 (positive loadings on Faecalibacterium, Eubacterium and Roseburia) was associated with higher intakes of fibre (r = 0.15, P = 0.007); total (r = 0.15, P = 0.009), and insoluble (r = 0.13, P = 0.021) non-starch polysaccharides; protein (r = 0.12, P = 0.036); meat (r = 0.15, P = 0.010); and nuts, seeds and legumes (r = 0.11, P = 0.047). Further regression analyses found that profile 2 and profile 3 were independently associated with BMI z-score and diet respectively. We encourage fellow researchers to use compositional PCA as a method for identifying further links between the gut, diet and obesity, and for developing the next generation of research in which the impact on body composition of dietary interventions that modify the gut microbiota is determined.
Alterations in reinforcement-based decision making may be associated with increased psychiatric vulnerability in children who have experienced maltreatment. A probabilistic passive avoidance task and a model-based functional magnetic resonance imaging analytic approach were implemented to assess the neurocomputational components underlying decision making: (a) reinforcement expectancies (the representation of the outcomes associated with a stimulus) and (b) prediction error signaling (the ability to detect the differences between expected and actual outcomes). There were three main findings. First, the maltreated group (n = 18; mean age = 13), relative to nonmaltreated peers (n = 19; mean age = 13), showed decreased activity during expected value processing in a widespread network commonly associated with reinforcement expectancies representation, including the striatum (especially the caudate), the orbitofrontal cortex, and medial temporal structures including the hippocampus and insula. Second, consistent with previously reported hyperresponsiveness to negative cues in the context of childhood abuse, the maltreated group showed increased prediction error signaling in the middle cingulate gyrus, somatosensory cortex, superior temporal gyrus, and thalamus. Third, the maltreated group showed increased activity in frontodorsal regions and in the putamen during expected value representation. These findings suggest that early adverse environments disrupt the development of decision-making processes, which in turn may compromise psychosocial functioning in ways that increase latent vulnerability to psychiatric disorder.
Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder.
Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future.
As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both).
The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.
The foetal mammary gland is sensitive to maternal weight and nutrition during gestation, which could affect offspring milk production. It has previously been shown that ewes born to dams offered maintenance nutrition during pregnancy (day 21 to 140 of gestation) produced greater milk, lactose and CP yields in their first lactation when compared with ewes born to dams offered ad libitum nutrition. In addition, ewes born to heavier dams produced greater milk and lactose yields when compared with ewes born to lighter dams. The objective of this study was to analyse and compare the 5-year lactation performance of the previously mentioned ewes, born to heavy or light dams that were offered maintenance or ad libitum pregnancy nutrition. Ewes were milked once per week, for the first 6 weeks of their lactation, for 5 years. Using milk yield and composition data, accumulated yields were calculated over a 42-day period for each year for milk, milk fat, CP, true protein, casein and lactose using a Legendre orthogonal polynomial model. Over the 5-year period, ewes born to heavy dams produced greater average milk (P=0.04), lactose (P=0.01) and CP (P=0.04) yields than offspring born to light dams. In contrast, over the 5-year period dam nutrition during pregnancy did not affect average (P>0.05) offspring milk yields or composition, but did increase milk and lactose accumulated yield (P=0.03 and 0.01, respectively) in the first lactation. These results indicate that maternal gestational nutrition appears to only affect the first lactational performance of ewe offspring. Neither dam nutrition nor size affected grand-offspring live weight gain to, or live weight at weaning (P>0.05). Combined these data indicate that under the conditions of the present study, manipulating dam weight or nutrition in pregnancy can have some effects of offspring lactational performance, however, these effects are not large enough to alter grand-offspring growth to weaning. Therefore, such manipulations are not a viable management tool for farmers to influence lamb growth to weaning.
Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people's negative reactions?
A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions.
During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions.
These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments.
Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)
The Perth Astronomy Research Group (PARG), consisting of members from Curtin University of Technology, Perth Observatory and the University of Western Australia, is in the process of developing an automated supernova search system, using the 61-cm Lowell-Perth reflector, a CCD camera and an 80386-based computer for image analysis. Computer control of the telescope and dome, a liquid-nitrogen-cooled CCD camera, and modified VISTA image analysis software will be completed in late 1990, allowing initial semi-automatic searching of external galaxies, together with CCD photometry of flare stars and newly discovered supernovae. Full-scale automation will be introduced subsequently, in collaboration with the Berkeley group. This paper describes the project, and reports on its current status.
To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10–18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits.
Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group×emotion by task) was conducted on the BOLD response data.
Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD.
These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology.
The new 1 m f/4 fast-slew Zadko Telescope was installed in June 2008 about 70 km north of Perth, Western Australia. It is the only metre-class optical facility at this southern latitude between the east coast of Australia and South Africa, and can rapidly image optical transients at a longitude not monitored by other similar facilities. We report on first imaging tests of a pilot program of minor planet searches, and Target of Opportunity observations triggered by the Swift satellite. In 12 months, 6 gamma-ray burst afterglows were detected, with estimated magnitudes; two of them, GRB 090205 (z = 4.65) and GRB 090516 (z = 4.11), are among the most distant optical transients imaged by an Australian telescope. Many asteroids were observed in a systematic 3-month search. In September 2009, an automatic telescope control system was installed, which will be used to link the facility to a global robotic telescope network; future targets will include fast optical transients triggered by high-energy satellites, radio transient detections, and LIGO gravitational wave candidate events. We also outline the importance of the facility as a potential tool for education, training, and public outreach.
Using behavioral and blood oxygen level dependent (BOLD) response indices through functional magnetic resonance imaging (fMRI), the current study investigated whether youths with disruptive behavior disorders (conduct disorder and oppositional defiant disorder) plus psychopathic traits (DBD + PT) show aberrant sensitivity to eye gaze information generally and/or whether they show particular insensitivity to eye gaze information in the context of fearful expressions. The participants were 36 children and adolescents (ages 10–17 years); 17 had DBD + PT and 19 were healthy comparison subjects. Participants performed a spatial attention paradigm where spatial attention was cued by eye gaze in faces displaying fearful, angry, or neutral affect. Eye gaze sensitivity was indexed both behaviorally and as BOLD response. There were no group differences in behavioral response: both groups showed significantly faster responses if the target was in the congruent spatial direction indicated by eye gaze. Neither group showed a Congruence × Emotion interaction; neither group showed an advantage from the displayer's emotional expression behaviorally. However, the BOLD response revealed a significant Group × Congruence × Emotion interaction. The comparison youth showed increased activity within the dorsal endogenous orienting network (superior parietal lobule and inferior parietal sulcus) for fearful congruent relative to incongruent trials relative to the youth with DBD + PT. The results are discussed with reference to current models of DBD + PT and possible treatment innovations.
This study aimed to determine whether patients with post-traumatic stress disorder (PTSD) show difficulty in recruitment of the regions of the frontal and parietal cortex implicated in top-down attentional control in the presence and absence of emotional distracters.
Unmedicated individuals with PTSD (n = 14), and age-, IQ- and gender-matched individuals exposed to trauma (n = 15) and healthy controls (n = 19) were tested on the affective number Stroop task. In addition, blood oxygen level-dependent responses, as measured via functional magnetic resonance imaging, were recorded.
Patients with PTSD showed disrupted recruitment of lateral regions of the superior and inferior frontal cortex as well as the parietal cortex in the presence of negative distracters. Trauma-comparison individuals showed indications of a heightened ability to recruit fronto-parietal regions implicated in top-down attentional control across distracter conditions.
These results are consistent with suggestions that emotional responsiveness can interfere with the recruitment of regions implicated in top-down attentional control; the heightened emotional responding of patients with PTSD may lead to the heightened interference in the recruitment of these regions.
From an affective neuroscience perspective, our understanding of psychiatric illness may be advanced by neuropsychological test paradigms probing emotional processes. Reversal learning is one such process, whereby subjects must first acquire stimulus/reward and stimulus/punishment associations through trial and error and then reverse them. We sought to determine the specificity of previously demonstrated reversal learning impairments in youths with bipolar disorder (BD) by now comparing BD youths to those with severe mood dysregulation (SMD), major depressive disorder (MDD), anxiety (ANX), and healthy controls.
We administered the probabilistic response reversal (PRR) task to 165 pediatric participants aged 7–17 years with BD (n=35), SMD (n=35), ANX (n=42), MDD (n=18) and normal controls (NC; n=35). Our primary analysis compared PRR performance across all five groups matched for age, sex and IQ.
Compared to typically developing controls, probabilistic reversal learning was impaired in BD youths, with a trend in those with MDD (p=0.07).
Our results suggest that reversal learning deficits are present in youths with BD and possibly those with MDD. Further work is necessary to elucidate the specificity of neural mechanisms underlying such behavioral deficits.
The epidemiology, symptomology, and viral aetiology of endemic influenza remain largely uncharacterized in Cambodia. In December 2006, we established passive hospital-based surveillance to identify the causes of acute undifferentiated fever in patients seeking healthcare. Fever was defined as tympanic membrane temperature >38°C. From December 2006 to December 2008, 4233 patients were screened for influenza virus by real-time reverse-transcriptase polymerase chain reaction (rRT–PCR). Of these patients, 1151 (27·2%) were positive for influenza. Cough (68·8% vs. 50·5%, P<0·0001) and sore throat (55·0% vs. 41·9%, P<0·0001) were more often associated with laboratory-confirmed influenza-infected patients compared to influenza-negative enrollees. A clear influenza season was evident between July and December with a peak during the rainy season. Influenza A and B viruses were identified in 768 (66·3%) and 388 (33·7%) of the influenza-positive population (n=1153), respectively. In December 2008, passive surveillance identified infection of the avian influenza virus H5N1 in a 19-year-old farmer from Kandal province who subsequently recovered. From a subset of diagnostic samples submitted in 2007, 15 A(H1N1), seven A(H3N2) and seven B viruses were isolated. The predominant subtype tested was influenza A(H1N1), with the majority antigenically related to the A/Solomon Island/03/2006 vaccine strain. The influenza A(H3N2) isolates and influenza B viruses analysed were closely related to A/Brisbane/10/2007 or B/Ohio/01/2005 (B/Victoria/2/87-lineage) vaccine strains, respectively. Phylogenetic analysis of the HA1 region of the HA gene of influenza A(H1N1) viruses demonstrated that the Cambodian isolates belonged to clade 2C along with representative H1N1 viruses circulating in SE Asia at the time. These viruses remained sensitive to oseltamivir. In total, our data suggest that viral influenza infections contribute to nearly one-fifth of acute febrile illnesses and demonstrate the importance of influenza surveillance in Cambodia.