The neural correlates of regulating another person's emotions: an exploratory fMRI study

Studies investigating the neurophysiological basis of intrapersonal emotion regulation (control of one's own emotional experience) report that the frontal cortex exerts a modulatory effect on limbic structures such as the amygdala and insula. However, no imaging study to date has examined the neurophysiological processes involved in interpersonal emotion regulation, where the goal is explicitly to regulate another person's emotion. Twenty healthy participants (10 males) underwent fMRI while regulating their own or another person's emotions. Intrapersonal and interpersonal emotion regulation tasks recruited an overlapping network of brain regions including bilateral lateral frontal cortex, pre-supplementary motor area, and left temporo-parietal junction. Activations unique to the interpersonal condition suggest that both affective (emotional simulation) and cognitive (mentalizing) aspects of empathy may be involved in the process of interpersonal emotion regulation. These findings provide an initial insight into the neural correlates of regulating another person's emotions and may be relevant to understanding mental health issues that involve problems with social interaction

The neural correlates of emotion regulation by implementation intentions

Several studies have investigated the neural basis of effortful emotion regulation (ER) but the neural basis of automatic ER has been less comprehensively explored. The present study investigated the neural basis of automatic ER supported by ‘implementation intentions’. 40 healthy participants underwent fMRI while viewing emotion-eliciting images and used either a previously-taught effortful ER strategy, in the form of a goal intention (e.g., try to take a detached perspective), or a more automatic ER strategy, in the form of an implementation intention (e.g., “If I see something disgusting, then I will think these are just pixels on the screen!”), to regulate their emotional response. Whereas goal intention ER strategies were associated with activation of brain areas previously reported to be involved in effortful ER (including dorsolateral prefrontal cortex), ER strategies based on an implementation intention strategy were associated with activation of right inferior frontal gyrus and ventro-parietal cortex, which may reflect the attentional control processes automatically captured by the cue for action contained within the implementation intention. Goal intentions were also associated with less effective modulation of left amygdala, supporting the increased efficacy of ER under implementation intention instructions, which showed coupling of orbitofrontal cortex and amygdala. The findings support previous behavioural studies in suggesting that forming an implementation intention enables people to enact goal-directed responses with less effort and more efficiency

The electronic structure of the aqueous permanganate ion: aqueous-phase energetics and molecular bonding studied using liquid jet photoelectron spectroscopy

Permanganate aqueous solutions, MnO4(aq.)-, were studied using liquid-micro-jet-based soft X-ray non-resonant and resonant photoelectron spectroscopy to determine valence and core-level binding energies. To identify possible differences in the energetics between the aqueous bulk and the solution-gas interface, non-resonant spectra were recorded at two different probing depths. Similar experiments were performed with different counter ions, Na(+)and K+, with the two solutions yielding indistinguishable anion electron binding energies. Our resonant photoelectron spectroscopy measurements, performed near the Mn L-II,L-III- and O K-edges, selectively probed valence charge distributions between the Mn metal center, O ligands, and first solvation shell in the aqueous bulk. Associated resonantly-enhanced solute ionisation signals revealed hybridisation of the solute constituents' atomic orbitals, including the inner valence Mn 3p and O 2s. We identified intermolecular coulombic decay relaxation processes following resonant X-ray excitation of the solute that highlight valence MnO4(aq.)--H(2)O((l))electronic couplings. Furthermore, our results allowed us to infer oxidative reorganisation energies of MnO(4)((aq.))and adiabatic valence ionisation energies of MnO4(aq.)-, revealing the Gibbs free energy of oxidation and permitting estimation of the vertical electron affinity of MnO4(aq.). Finally, the Gibbs free energy of hydration of isolated MnO(4)(-)was determined. Our results and analysis allowed a near-complete binding-energy-scaled MnO(4)((aq.))(-)molecular orbital and a valence energy level diagram to be produced for the MnO4(aq.)-/MnO(4)((aq.))system. Cumulatively, our mapping of the aqueous-phase electronic structure of MnO(4)(-)is expected to contribute to a deeper understanding of the exceptional redox properties of this widely applied aqueous transition-metal complex ion

Microvascular Perfusion Abnormalities of the Thalamus in Painful but Not Painless Diabetic Polyneuropathy: A clue to the pathogenesis of pain in type 1 diabetes

OBJECTIVE The pathogenesis of painful diabetic neuropathy (DN) remains undetermined, with both central and peripheral mechanisms implicated. This study investigates whether thalamic perfusion abnormalities occur in painful DN. RESEARCH DESIGN AND METHODS Eighteen subjects with type 1 diabetes (no DN = 6, painful DN = 5, painless DN = 7) and six healthy volunteers (HV) were recruited. Microvascular perfusion characteristics (relative cerebral blood volume [rCBV], flow [rCBF], and transit time [ttFM]) of the thalamus and caudate nucleus were assessed using magnetic resonance perfusion imaging. The caudate nucleus was chosen to serve as an in vivo control region. RESULTS Subjects with painful DN had significantly greater thalamic rCBV (means [SD]; painful DN, 228.7 [19.5]; no DN, 202.3 [25.8]; painless DN, 216.5 [65.5]; HV, 181.9 [51.7]; P = 0.04) and the longest ttFM(s) (painful DN, 38.4 [3.6]; no DN, 35.3 [13.2]; painless DN, 35.9 [13.7]; HV, 33.7 [14.9]; P = 0.07). There was no significant difference in markers of caudate nucleus perfusion. CONCLUSIONS Painful DN is associated with increased thalamic vascularity. This may provide an important clue to the pathogenesis of pain in DN

A Neuroanatomical Basis for the Frequency of Discrete Spontaneous Activities in Schizophrenia

Limited behavioural repertoire impacts quality of life in chronic schizophrenia. We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. However, increased movement in itself may be of limited clinical significance. Hence, we sought to analyse the ‘structure’ of spontaneous movement in patients with schizophrenia and to examine whether the chunking of spontaneous activity has a neuroanatomical basis. ‘Actiwatches’ were used to record spontaneous motor activity over a 20 hour period in sixteen male patients with schizophrenia. Time-series data were analysed for the number of discrete spontaneous activities, which might indicate a degree of structure to ongoing activity. Subjects underwent a whole-brain structural MRI scan. The ‘number of discrete movement epochs’ correlated with volumes of regions within bilateral rostro-ventral putamen and temporal poles. These data suggest that in people with schizophrenia the volume of bilateral putamen may influence the complexity of their behaviours, as distinct from the overall amount of behaviour. The results are presented in the context of a large body of previous research examining the role of the basal ganglia in motor and cognitive pattern generation

Alcohol Induces Sensitization to Gluten in Genetically Susceptible Individuals: A Case Control Study

Background: The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1) to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2) to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias. Materials & Methods: Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data. Results: Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia. Conclusions: Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar insult

Potentially toxic metals in historic landfill sites: Implications for grazing animals

Municipal waste disposal is an increasing global problem, frequently solved by the use of landfill sites. Following closure, such sites contain a legacy of pollutants and must be managed to provide a safe and useful end life. The soils and vegetation from four historic landfill sites were analysed to determine the extent of pollution by potentially toxic metals (PTMs). Data were subsequently assessed to determine if post closure uses involving grazing were safe for the animals. The heaviest and widest spread soil contamination was due to Ni. Concentrations at all sites exceeded the 95th percentile value for rural soils, in one case by a factor of 30. Cu and Pb contamination was identified at some sites, but no evidence of Al or Zn contamination was found. Oral bioaccessibility testing showed that the availability of Ni in soil was exceedingly low, whilst that of Cu and Pb was high. Concentrations in plant shoots differed significantly amongst the sites, but interspecific differences in shoot concentration were only significant in the case of Cu. The results indicated that exposure levels to grazers would be at or below tolerable levels, indicating that it is generally safe to graze historic landfill. However, animals could be exposed to higher levels of PTMs than would be expected from rural locations, and grazing under conditions where soil consumption may be high could result in levels of exposure to Al, Ni and Pb exceeding tolerable levels. © Springer International Publishing 2014

Quantifying the impact of shape uncertainty on predicted arrhythmias

Background.: Personalised computer models are increasingly used to diagnose cardiac arrhythmias and tailor treatment. Patient-specific models of the left atrium are often derived from pre-procedural imaging of anatomy and fibrosis. These images contain noise that can affect simulation predictions. There are few computationally tractable methods for propagating uncertainties from images to clinical predictions. Method.: We describe the left atrium anatomy using our Bayesian shape model that captures anatomical uncertainty in medical images and has been validated on 63 independent clinical images. This algorithm describes the left atrium anatomy using N modes=15 principal components, capturing 95% of the shape variance and calculated from 70 clinical cardiac magnetic resonance (CMR) images. Latent variables encode shape uncertainty: we evaluate their posterior distribution for each new anatomy. We assume a normally distributed prior. We use the unscented transform to sample from the posterior shape distribution. For each sample, we assign the local material properties of the tissue using the projection of late gadolinium enhancement CMR (LGE-CMR) onto the anatomy to estimate local fibrosis. To test which activation patterns an atrium can sustain, we perform an arrhythmia simulation for each sample. We consider 34 possible outcomes (31 macro-re-entries, functional re-entry, atrial fibrillation, and non-sustained arrhythmia). For each sample, we determine the outcome by comparing pre- and post-ablation activation patterns following a cross-field stimulus. Results.: We create patient-specific atrial electrophysiology models of ten patients. We validate the mean and standard deviation maps from the unscented transform with the same statistics obtained with 12,000 Monte Carlo (ground truth) samples. We found discrepancies &lt;3% and &lt;2% for the mean and standard deviation for fibrosis burden and activation time, respectively. For each patient case, we then compare the predicted outcome from a model built on the clinical data (deterministic approach) with the probability distribution obtained from the simulated samples. We found that the deterministic approach did not predict the most likely outcome in 80% of the cases. Finally, we estimate the influence of each source of uncertainty independently. Fixing the anatomy to the posterior mean and maintaining uncertainty in fibrosis reduced the prediction of self-terminating arrhythmias from ≃14% to ≃7%. Keeping the fibrosis fixed to the sample mean while retaining uncertainty in shape decreased the prediction of substrate-driven arrhythmias from ≃33% to ≃18% and increased the prediction of macro-re-entries from ≃54% to ≃68%. Conclusions.: We presented a novel method for propagating shape uncertainty in atrial models through to uncertainty in numerical simulations. The algorithm takes advantage of the unscented transform to compute the output distribution of the outcomes. We validated the unscented transform as a viable sampling strategy to deal with anatomy uncertainty. We then showed that the prediction computed with a deterministic model does not always coincide with the most likely outcome. Finally, we found that shape uncertainty affects the predictions of macro-re-entries, while fibrosis uncertainty affects the predictions of functional re-entries.</p

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Resolving early mesoderm diversification through single-cell expression profiling.

In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak. Subsequently, cells migrate, either surrounding the prospective ectoderm contributing to the embryo proper, or into the extra-embryonic region to form the yolk sac, umbilical cord and placenta. Fate mapping has shown that mature tissues such as blood and heart originate from specific regions of the pre-gastrula epiblast, but the plasticity of cells within the embryo and the function of key cell-type-specific transcription factors remain unclear. Here we analyse 1,205 cells from the epiblast and nascent Flk1(+) mesoderm of gastrulating mouse embryos using single-cell RNA sequencing, representing the first transcriptome-wide in vivo view of early mesoderm formation during mammalian gastrulation. Additionally, using knockout mice, we study the function of Tal1, a key haematopoietic transcription factor, and demonstrate, contrary to previous studies performed using retrospective assays, that Tal1 knockout does not immediately bias precursor cells towards a cardiac fate.We thank M. de Bruijn, A. Martinez-Arias, J. Nichols and C. Mulas for discussion, the Cambridge Institute for Medical Research Flow Cytometry facility for their expertise in single-cell index sorting, and S. Lorenz from the Sanger Single Cell Genomics Core for supervising purification of Tal1−/− sequencing libraries. ChIP-seq reads were processed by R. Hannah. Research in the authors’ laboratories is supported by the Medical Research Council, Cancer Research UK, the Biotechnology and Biological Sciences Research Council, Bloodwise, the Leukemia and Lymphoma Society, and the Sanger-EBI Single Cell Centre, and by core support grants from the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute and by core funding from Cancer Research UK and the European Molecular Biology Laboratory. Y.T. was supported by a fellowship from the Japan Society for the Promotion of Science. W.J. is a Wellcome Trust Clinical Research Fellow. A.S. is supported by the Sanger-EBI Single Cell Centre. This work was funded as part of Wellcome Trust Strategic Award 105031/D/14/Z ‘Tracing early mammalian lineage decisions by single-cell genomics’ awarded to W. Reik, S. Teichmann, J. Nichols, B. Simons, T. Voet, S. Srinivas, L. Vallier, B. Göttgens and J. Marioni.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1863