The hemodynamic impulse response to a single neural event

This article investigates the relation between stimulus-evoked neural activity and cerebral hemodynamics. Specifically, the hypothesis is tested that hemodynamic responses can be modeled as a linear convolution of experimentally obtained measures of neural activity with a suitable hemodynamic impulse response function. To obtain a range of neural and hemodynamic responses, rat whisker pad was stimulated using brief (less than or equal to2 seconds) electrical stimuli consisting of single pulses (0.3 millisecond, 1.2 mA) combined both at different frequencies and in a paired-pulse design. Hemodynamic responses were measured using concurrent optical imaging spectroscopy and laser Doppler flowmetry, whereas neural responses were assessed through current source density analysis of multielectrode recordings from a single barrel. General linear modeling was used to deconvolve the hemodynamic impulse response to a single "neural event" from the hemodynamic and neural responses to stimulation. The model provided an excellent fit to the empirical data. The implications of these results for modeling schemes and for physiologic systems coupling neural and hemodynamic activity are discussed.

Species-specific responses of Late Quaternary megafauna to climate and humans

Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.

Using QR codes to aid accessibility in a museum

Purpose – This paper describes visitors' reactions to using an Apple iPad or smartphone to follow trails in a museum by scanning QR codes and draws conclusions on the potential for this technology to help improve accessibility at low-cost. Design/methodology/approach – Activities were devised which involved visitors following trails around museum objects, each labelled with a QR code and symbolised text. Visitors scanned the QR codes using a mobile device which then showed more information about an object. Project-team members acted as participant-observers, engaging with visitors and noting how they used the system. Experiences from each activity fed into the design of the next. Findings – Some physical and technical problems with using QR codes can be overcome with the introduction of simple aids, particularly using movable object labels. A layered approach to information access is possible with the first layer comprising a label, the second a mobile-web enabled screen and the third choices of text, pictures, video and audio. Video was especially appealing to young people. The ability to repeatedly watch video or listen to audio seemed to be appreciated by visitors with learning disabilities. This approach can have low equipment-cost. However, maintaining the information behind labels and keeping-up with technological changes are on-going processes. Originality/value – Using QR codes on movable, symbolised object labels as part of a layered information system might help modestly-funded museums enhance their accessibility, particularly as visitors increasingly arrive with their own smartphones or tablets.

First human hNT astrocytes patterned to single cell resolution on parylene-C/Silicon dioxide substrates

In our previous work we developed a successful protocol to pattern the human hNT neuron (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/SiO2 substrates. This communication, reports how we have successfully managed to pattern the supportive cell to the neuron, the hNT astrocyte, on such substrates. Here we disseminate the nanofabrication, cell differentiation and cell culturing protocols necessary to successfully pattern the first human hNT astrocytes to single cell resolution on parylene-C/SiO2 substrates. This is performed for varying parylene strip widths providing excellent contrast to the SiO2 substrate and elegant single cell isolation at 10μm strip widths. The breakthrough in patterning human cells on a silicon chip has widespread implications and is valuable as a platform technology as it enables a detailed study of the human brain at the cellular and network level.

Resting state cortico-thalamic-striatal connectivity predicts pesponse to dorsomedial prefrontal rTMS in major depressive disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for Major Depressive Disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting state functional connectivity predicted response to treatment with rapid transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased sgACC-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.

Changes in reactive stratospheric gases due to a change in Brewer–Dobson circulation: results from a simple model

Amounts of source gases with stratospheric sinks (CFCs, N2O, CH4) are affected by changes in Brewer–Dobson circulation. Source gases and their degradation products are important for atmospheric chemistry and climate. With a simple model, we examine how amounts and lifetimes of source gases and products depend on speed of the circulation. Transient results differ from steady-state and stratospheric results differ from those for stratosphere plus troposphere. Increases in speed increase the stratospheric burden of source gases, but reduce products and reduce total burdens and lifetimes of source gases

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.

How to apologise in Latin: a case study

Recent years have seen an increase in sociolinguistic studies of the Latin language devoted to aspects and forms of politeness as part of general linguistic behaviour, and considerable progress has been made overall. One area, albeit central to the notion of politeness, has been conspicuously neglected so far, and this area is best summarised by the term ‘apologies’. This paper aims to remedy this situation and to provide a first extensive case study, based on the textual corpus of Terence.

Making an effort to feel positive: insecure attachment in infancy predicts the neural underpinnings of emotion regulation in adulthood

Background: Animal research indicates that the neural substrates of emotion regulation may be persistently altered by early environmental exposures. If similar processes operate in human development then this is significant, as the capacity to regulate emotional states is fundamental to human adaptation. Methods: We utilised a 22-year longitudinal study to examine the influence of early infant attachment to the mother, a key marker of early experience, on neural regulation of emotional states in young adults. Infant attachment status was measured via objective assessment at 18-months, and the neural underpinnings of the active regulation of affect were studied using fMRI at age 22 years. Results: Infant attachment status at 18-months predicted neural responding during the regulation of positive affect 20-years later. Specifically, while attempting to up-regulate positive emotions, adults who had been insecurely versus securely attached as infants showed greater activation in prefrontal regions involved in cognitive control and reduced co-activation of prefrontal cortex and nucleus accumbens, consistent with relative inefficiency in the neural regulation of positive affect. Conclusions: Disturbances in the mother-infant relationship may persistently alter the neural circuitry of emotion regulation, with potential implications for adjustment in adulthood.

A longitudinal study of child sleep in high and low risk families: relationship to early maternal settling strategies and child psychological functioning

Objectives To investigate whether sleep disturbances previously found to characterise high risk infants: (a) persist into childhood; (b) are influenced by early maternal settling strategies and (c) predict cognitive and emotional/behavioural functioning. Methods Mothers experiencing high and low levels of psychosocial adversity (risk) were recruited antenatally and longitudinally assessed with their children. Mothers completed measures of settling strategies and infant sleep postnatally, and at 12 and 18 months, infant age. At five years, child sleep characteristics were measured via an actigraphy and maternal report; IQ and child adjustment were also assessed. Results Sleep disturbances observed in high-risk infants persisted at five years. Maternal involvement in infant settling was greater in high risk mothers, and predicted less optimal sleep at five years. Poorer five year sleep was associated with concurrent child anxiety/depression and aggression, but there was limited evidence for an influence of early sleep problems. Associations between infant/child sleep characteristics and IQ were also limited. Conclusions Early maternal over-involvement in infant settling is associated with less optimal sleep in children, which in turn, is related to child adjustment. The findings highlight the importance of supporting parents in the early development of good settling practices, particularly in high-risk populations.

Socially anxious mothers’ narratives to their children, and their relation to child representations and adjustment

Anxious mothers’ parenting, particularly transfer of threat information, has been considered important in their children’s risk for social anxiety disorder (SAnxD), and maternal narratives concerning potential social threat could elucidate this contribution. Maternal narratives to their pre-school 4-5 year-old children, via a picture book about starting school, were assessed in socially anxious (N=73), and non-anxious (N=63) mothers. Child representations of school were assessed via Doll Play (DP). After one school term, mothers (CBCL) and teachers (TRF) reported on child internalizing problems, and child SAnxD was assessed via maternal interview. Relations between these variables, infant behavioral inhibition, and attachment, were examined. Socially anxious mothers showed more negative (higher threat attribution), and less supportive (lower encouragement) narratives, than controls, and their children’s DP representations, SAnxD and CBCL scores were more adverse. High narrative threat predicted child SAnxD; lower encouragement predicted negative child CBCL scores and, particularly for behaviorally inhibited children, TRF scores and DP representations. In securely attached children, CBCL scores and risk for SAnxD were affected by maternal anxiety and threat attributions, respectively. Low encouragement mediated the effects of maternal anxiety on child DP representations, and CBCL scores. Maternal narratives are affected by social anxiety, and contribute to adverse child outcome.

Humans use predictive kinematic models to calibrate visual cues to three-dimensional surface slant

When the sensory consequences of an action are systematically altered our brain can recalibrate the mappings between sensory cues and properties of our environment. This recalibration can be driven by both cue conflicts and altered sensory statistics, but neither mechanism offers a way for cues to be calibrated so they provide accurate information about the world, as sensory cues carry no information as to their own accuracy. Here, we explored whether sensory predictions based on internal physical models could be used to accurately calibrate visual cues to 3D surface slant. Human observers played a 3D kinematic game in which they adjusted the slant of a surface so that a moving ball would bounce off the surface and through a target hoop. In one group, the ball’s bounce was manipulated so that the surface behaved as if it had a different slant to that signaled by visual cues. With experience of this altered bounce, observers recalibrated their perception of slant so that it was more consistent with the assumed laws of kinematics and physical behavior of the surface. In another group, making the ball spin in a way that could physically explain its altered bounce eliminated this pattern of recalibration. Importantly, both groups adjusted their behavior in the kinematic game in the same way, experienced the same set of slants and were not presented with low-level cue conflicts that could drive the recalibration. We conclude that observers use predictive kinematic models to accurately calibrate visual cues to 3D properties of world.

Drivers of change in mountain farming in Slovakia: from socialist collectivisation to the Common Agricultural Policy

The transformations in Slovak agriculture from the 1950s to the present day, considering both the generic (National and EU) and site-specific (local) drivers of landscape change, were analysed in five mountain study areas in the country. An interdisciplinary approach included analysis of population trends, evaluation of land use and landscape change combined with exploration of the perceptions of local stakeholders and results of previous biodiversity studies. The generic processes active from the 1950s to 1970s were critical for all study areas with impacts lasting right up until the present day. Agricultural collectivisation, agricultural intensification and land abandonment had negative effects in all study areas. However, the precise impacts on the landscape were different in the different study areas due to site-specific attributes (e.g. population trends, geographic localisation and local attitudes and opportunities), and these played a decisive role in determining the trajectory of change. Regional contrasts in rural development between these territories have increased in the last two decades, also due to the imperfect preconditions of governmental support. The recent Common Agricultural Policy developments are focused on maintenance of intensive large-scale farming rather than direct enhancement of agro-biodiversity and rural development at the local scale. In this context, local, site-specific attributes can and must form an essential part of rural development plans, to meet the demands for management of the diversity of agricultural mountain landscapes and facilitate the multifunctional role of agriculture.

Does bacterial density in cystic fibrosis sputum increase prior to pulmonary exacerbation?

These findings strongly suggest that CFPE do not generally result from increased bacterial density within the airways. Instead, data presented here are consistent with alternative models of pulmonary exacerbation.