Attention Bias Test Differentiates Anxiety and Depression in Sheep

Negative affective states such as anxiety and depression pose a risk to animal welfare, however, practical tests for assessing these states in animals are limited. In humans, anxious individuals are shown to pay more attention toward threatening information than non-anxious individuals, known as an attention bias. Previously, an attention bias test was developed and validated as a measure of anxious states in sheep, where more anxious sheep showed increased attention toward a threat (dog) and were more vigilant than Control animals. Studies in humans suggest that attention biases also occur in depressed individuals, with observations of attention biases toward threats, as well as biases away from positive stimuli. Given these findings, we hypothesized that an attention bias test for sheep could also be used to assess states of depression. We predicted that Merino ewes in pharmacologically induced Depressed (para-chlorophenylalanine) and Anxious (m-chlorophenylpiperazine) states would show greater attention toward a threat than Control animals (saline), but that the Depressed sheep would show relatively less interest in a positive stimulus (photograph of a conspecific). During testing, Depressed sheep paid more attention toward the threat and less toward the photograph than Control animals as predicted (Analyses of Variance, P < 0.05, n = 16 per treatment). Interestingly, Anxious sheep showed an attention bias in the opposite direction, paying more attention toward the photograph and less toward the threat than Control animals (P < 0.05). Both Anxious and Depressed sheep were more vigilant than Control animals (P = 0.002). These results suggest the attention bias test can be used to measure and differentiate states of depression and anxiety in livestock. The bidirectional nature of the attention bias identified between treatments highlights the importance of measuring multiple behaviors in the test and considering the context in which the test is applied. This will enable a clearer characterization of the affective state of an animal, as an aspect of its welfare

Associations between immune competence phenotype and stress response in sheep

Immune competence in domestic sheep is gaining more attention in genetic selection programs that seek to enhance flock immunity and animal welfare. A goal of many programs is to identify behavioral phenotypes that indicate stress-coping strength, as well as disease resilience. The current study set out to explore the relationship between immune responsiveness, physiological stress, and behavioral response among sheep that had been selected for ‘low’ (LR) or ‘high’ (HR) response to cell-mediated and antibody-mediate reactivity to a clostridial vaccine. Multiparous ewes were placed in four experiments which exposed the animals to various threats including, dog presence, human proximity, visual isolation from flock, and physical restraint. To evaluate the consistency of behavioral phenotypes, all ewes were placed in the test circuit one year later. Basal body temperature (via iButton) and serum cortisol concentrations were collected prior to and after the circuit each year. Immune group (HR vs. LR) was not found to be related to behavioral performance during the dog, human, isolation, or restraint challenge. Immune group categorization was also unrelated to pre- and post-cortisol concentrations, and the change in cortisol concentrations during testing. There was a negative relationship identified between response to visual isolation and change in cortisol response during testing, indicating that sheep which were more active or agitated during visual isolation from the flock experienced less of an increase in serum cortisol levels and were perhaps experiencing a negative, high arousal state compared to less reactive sheep (e.g., freeze behavior) (χ2(4, N=99) = 42.72, P <0.0001). There was also a post hoc, positive relationship identified between weight measurements and immune group, such that individuals with greater body weight were more likely to be in the high immune responsiveness group (P= 0.01). Specifically, for every unit increase in weight, there was a ~49% chance of being categorized in the HR group. This is relevant for selection programs because producers that seek to enhance immune responsiveness and performance may be able to select sheep that carry a greater body mass, and while not found in the present study, could lead to greater flock immunity

Gpr126/Adgrg6 has Schwann cell autonomous and nonautonomous functions in peripheral nerve injury and repair

Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model. Here, we show that remyelination is severely delayed after nerve-crush injury. Moreover, we also observe noncell-autonomous defects in macrophage recruitment and axon regeneration in injured nerves following loss of Gpr126 in SCs. This work demonstrates that Gpr126 has critical SC-autonomous and SC-nonautonomous functions in remyelination and peripheral nerve repair. SIGNIFICANCE STATEMENT Lack of robust remyelination represents one of the major barriers to recovery of neurological functions in disease or following injury in many disorders of the nervous system. Here we show that the adhesion class G protein-coupled receptor (GPCR) Gpr126/Adgrg6 is required for remyelination, macrophage recruitment, and axon regeneration following nerve injury. At least 30% of all approved drugs target GPCRs; thus, Gpr126 represents an attractive potential target to stimulate repair in myelin disease or following nerve injury

Repeatability of an attention bias test for sheep suggests variable influence of state and trait affect on behaviour

Understanding the effects of repeated testing on behaviour is essential for behavioural tests that are re-applied to the same individuals for research and welfare assessment purposes. Assessing the repeatability of behaviour can also help us understand the influence of persistent traits vs transient states on animal responses during testing. This study examined the repeatability of behavioural responses in an attention bias test developed for sheep as a measure of affective state. Sheep were assessed in the attention bias test three times (n = 81 sheep), with testing occurring at intervals of 1 year then 2 weeks. During testing, individual sheep were exposed to a dog located behind a window for 3 s in a 4 × 4 m arena, then the dog was obscured from view, removed and sheep behaviours were recorded for 180 s. We hypothesised that behaviours in the test would have moderate-high repeatability but that the mean behavioural responses would change over consecutive trials as sheep habituated to the test environment. To estimate repeatability, data were modelled using restricted maximum likelihood linear mixed-effects models, fitting animal ID as a random effect. Vigilance behaviour, defined as having the head at or above shoulder height, was moderately repeatable (r = 0.58). Latency to eat (r = 0.20) and duration spent looking towards the previous location of the dog (attention to the dog wall) (r = 0.08) had low repeatability. Mean latency to eat did not differ significantly between trials (P = 0.2) and mean vigilance behaviour tended to decrease over the trials (P = 0.07). Mean duration of attention to the dog wall significantly decreased across the trials (P

Sex impacts pain behaviour but not emotional reactivity of lambs following ring tail docking

Studies in humans have shown sex differences in response to painful events, however, little is known in relation to sex differences in sheep. Understanding sex differences would enable improved experimental design and interpretation of studies of painful procedures in sheep. To examine sex differences in response to pain, 80 lambs were tested across five cohorts of 16. The lambs were penned in groups containing two male and two female lambs with their respective mothers. Lambs were randomly allocated from within each block to one of four treatment groups" FRing–Female lamb, ring tail docked without analgesia, MRing–Male lamb, ring tail docked without analgesia, FSham–Female lamb, tail manipulated and MSham–Male lamb, tail manipulated. Following treatment, lambs were returned to their pen and were video recorded for 45 mins for behavioural observations of acute pain and posture. An hour after treatment, lambs then underwent an emotional reactivity test that consisted of three phases: Isolation, Novelty and Startle. Following treatment, Ring lambs displayed more abnormal postures (mean = 2.5 ± 0.5) compared to Sham lambs (mean = 0.05 ± 0.4, P = 0.0001). There was an effect of sex on the display of acute pain-related behaviours in lambs that were tail docked (P P = 0.99). During the Novelty and Startle phase of the emotional reactivity test, Ring lambs tended to (P = 0.084) or did (P = 0.018) show more fear related behaviours, respectively. However, no effect of sex was observed. The results of this study indicate that a pain state may alter the emotional response of lambs to novel objects and potential fearful situations. It was also demonstrated that female lambs display increased sensitivity to the acute pain caused by tail docking compared to males

Abnormal Attention Modulation of Fear Circuit Function in Pediatric Generalized Anxiety Disorder

1. Context. Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. 2. Objective. To determine whether attention modulates amygdala and cortical responses to facial threat cues differentially in adolescents with generalized anxiety disorder (GAD) and healthy adolescents. 3. Design. Case-control study. 4. Setting. Government clinical research institute. 5. Participants. Adolescent volunteers, 15 with GAD and 20 diagnosis-free. 6. Main Outcome Measure(s). Blood oxygenation level-dependent (BOLD) signal, as measured via functional magnetic resonance imaging (fMRI). During fMRI scans, participants completed a face-emotion rating task that systematically manipulated attention. 7. Results. While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful than to happy faces (small volume corrected p’s \u3c .05) in a distributed network including the amygdala, ventral PFC (vPFC), and anterior cingulate cortex (ACC). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, vPFC, and cingulate. 8. Conclusions. Findings provide the first evidence in juveniles that GAD-associated patterns of pathological fear-circuit activation are particularly evident during certain attention states. Specifically, fear-circuit hyperactivation occurred in an attention state involving focus on subjectively-experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping function of the adolescent human fear circuit

Beef Cattle Preference and Usage of Environmental Enrichments Provided Simultaneously in a Pasture-Based Environment

Environmental enrichment can improve livestock welfare through increasing environmental complexity to promote a greater range of natural behaviours. However, there is limited understanding of the need for and impacts of enrichments for extensively managed beef cattle that can sometimes be kept in grassed paddocks devoid of additional natural and artificial features, i.e., 'barren pastures'. This trial assessed which enrichments beef cattle preferred and utilised in a barren paddock environment. Eight groups of seven Angus steers housed on pastured paddocks devoid of natural or artificial features were observed during daylight hours for two days a week over a period of three weeks, after being presented with four enrichments simultaneously: a cattle brush, a piece of hanging rope, a tree stump, and a woodchip pile. Although enrichment use generally decreased over time, the brush, stump, and woodchip maintained a higher level of use than the rope, based on the frequency of interactions and number of displacements around the enrichments (both

What Is a Representative Brain? Neuroscience Meets Population Science

The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain–behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective—population neuroscience—that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4