Growth Histories in Bimetric Massive Gravity

We perform cosmological perturbation theory in Hassan-Rosen bimetric gravity for general homogeneous and isotropic backgrounds. In the de Sitter approximation, we obtain decoupled sets of massless and massive scalar gravitational fluctuations. Matter perturbations then evolve like in Einstein gravity. We perturb the future de Sitter regime by the ratio of matter to dark energy, producing quasi-de Sitter space. In this more general setting the massive and massless fluctuations mix. We argue that in the quasi-de Sitter regime, the growth of structure in bimetric gravity differs from that of Einstein gravity.Comment: 28 pages + appendix, 11 figure

The relative balance of goal-directed and habitual behaviours in obsessive-compulsive disorder

Our decisions are based on parallel and competing systems of goal-directed and habitual learning, systems which can be impaired in pathological behaviours. Here we focus on the influence of motivation and compare reward and loss outcomes in subjects with obsessive-compulsive disorder (OCD) on model-based goal-directed and model-free habitual behaviours using the two-step task. We further investigate the relationship with acquisition learning using a one-step probabilistic learning task. Forty-eight OCD subjects and 96 healthy volunteers were tested on a reward and 30 OCD subjects and 53 healthy volunteers on the loss version of the two-step task. Thirty-six OCD subjects and 72 healthy volunteers were also tested on a one-step reversal task. OCD subjects compared with healthy volunteers were less goal oriented (model-based) and more habitual (model-free) to reward outcomes with a shift towards greater model-based and lower habitual choices to loss outcomes. OCD subjects also had enhanced acquisition learning to loss outcomes on the one-step task, which correlated with goal-directed learning in the two-step task. OCD subjects had greater stay behaviours or perseveration in the one-step task irrespective of outcome. Compulsion severity was correlated with habitual learning in the reward condition. Obsession severity was correlated with greater switching after loss outcomes. In healthy volunteers, we further show that greater reward magnitudes are associated with a shift towards greater goal-directed learning further emphasizing the role of outcome salience. Our results highlight an important influence of motivation on learning processes in OCD and suggest that distinct clinical strategies based on valence may be warranted.The study was funded through a Wellcome Trust Intermediate Clinical Fellowship for VV (093705/Z/10/Z).This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.16

Disorders of compulsivity: a common bias towards learning habits.

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.This study was funded by the WT fellowship grant for VV (093705/Z/ 10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. YW is supported by the Fyssen Fondation and MRC Studentships. PD is supported by the Gatsby Charitable Foundation. JEG has received grants from the National Institute of Drug Abuse and the National Center for Responsible Gaming. TWR and BJS are supported on a WT Programme Grant (089589/Z/09/Z). The BCNI is supported by a WT and MRC grant.This is the final published version. It's also available from Molecular Psychiatry at http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201444a.html

Sensing peptide–oligonucleotide interactions by a two-color fluorescence label: application to the HIV-1 nucleocapsid protein

We present a new methodology for site-specific sensing of peptide–oligonucleotide (ODN) interactions using a solvatochromic fluorescent label based on 3-hydroxychromone (3HC). This label was covalently attached to the N-terminus of a peptide corresponding to the zinc finger domain of the HIV-1 nucleocapsid protein (NC). On interaction with target ODNs, the labeled peptide shows strong changes in the ratio of its two emission bands, indicating an enhanced screening of the 3HC fluorophore from the bulk water by the ODN bases. Remarkably, this two-color response depends on the ODN sequence and correlates with the 3D structure of the corresponding complexes, suggesting that the 3HC label monitors the peptide–ODN interactions site-specifically. By measuring the two-color ratio, we were also able to determine the peptide–ODN-binding parameters and distinguish multiple binding sites in ODNs, which is rather difficult using other fluorescence methods. Moreover, this method was found to be more sensitive than the commonly used steady-state fluorescence anisotropy, especially in the case of small ODNs. The described methodology could become a new universal tool for investigating peptide–ODN interactions

Internet administration of the Dimensional Obsessive-Compulsive Scale: A psychometric evaluation

The Dimensional Obsessive-Compulsive Scale (DOCS) was designed to address the current limitations of existing obsessive-compulsive (OC) symptom measures and is a self-report questionnaire that assesses the severity of the four most empirically supported OC symptom dimensions. The aim of this study was to examine the psychometric properties of a Swedish version of the DOCS when administered via the Internet. Internal consistency, factor structure, and convergent and discriminant validity were examined in a sample consisting of 101 patients diagnosed with obsessive-compulsive disorder. The DOCS sensitivity to treatment effects were examined in a sample consisting of 48 patients treated with Internet-delivered cognitive behavioral therapy were the main intervention was exposure with response prevention. Results showed that the internal consistency was high. The DOCS also showed adequate convergent and discriminant validity, as well as fair sensitivity to treatment effects. The factor analysis supported the DOCS four-factor solution. In summary, the results from the present study give initial support that the DOCS can be administered via the Internet with adequate psychometric properties. © 2012 Elsevier Ltd