Altered Resting-State Functional Connectivity in Cortical Networks in Psychopathy

Psychopathy is a personality disorder characterized by callous antisocial behavior and criminal recidivism. Here we examine whether psychopathy is associated with alterations in functional connectivity in three large-scale cortical networks. Using fMRI in 142 adult male prison inmates, we computed resting-state functional connectivity using seeds from the default mode network, frontoparietal network, and cingulo-opercular network. To determine the specificity of our findings to these cortical networks, we also calculated functional connectivity using seeds from two comparison primary sensory networks: visual and auditory networks. Regression analyses related network connectivity to overall psychopathy scores and to subscores for the “factors” and “facets” of psychopathy: Factor 1, interpersonal/affective traits; Factor 2, lifestyle/antisocial traits; Facet 1, interpersonal; Facet 2, affective; Facet 3, lifestyle; Facet 4, antisocial. Overall psychopathy severity was associated with reduced functional connectivity between lateral parietal cortex and dorsal anterior cingulate cortex. The two factor scores exhibited contrasting relationships with functional connectivity: Factor 1 scores were associated with reduced functional connectivity in the three cortical networks, whereas Factor 2 scores were associated with heightened connectivity in the same networks. This dissociation was evident particularly in the functional connectivity between anterior insula and dorsal anterior cingulate cortex. The facet scores also demonstrated distinct patterns of connectivity. We found no associations between psychopathy scores and functional connectivity within visual or auditory networks. These findings provide novel evidence on the neural correlates of psychopathy and suggest that connectivity between cortical association hubs, such as the dorsal anterior cingulate cortex, may be a neurobiological marker of the disorder

Nondegenerate 3D complex Euclidean superintegrable systems and algebraic varieties

A classical (or quantum) second order superintegrable system is an integrable n-dimensional Hamiltonian system with potential that admits 2n-1 functionally independent second order constants of the motion polynomial in the momenta, the maximum possible. Such systems have remarkable properties: multi-integrability and multi-separability, an algebra of higher order symmetries whose representation theory yields spectral information about the Schroedinger operator, deep connections with special functions and with QES systems. Here we announce a complete classification of nondegenerate (i.e., 4-parameter) potentials for complex Euclidean 3-space. We characterize the possible superintegrable systems as points on an algebraic variety in 10 variables subject to six quadratic polynomial constraints. The Euclidean group acts on the variety such that two points determine the same superintegrable system if and only if they lie on the same leaf of the foliation. There are exactly 10 nondegenerate potentials.Comment: 35 page

Damage to the prefrontal cortex increases utilitarian moral judgements

The psychological and neurobiological processes underlying moral judgement have been the focus of many recent empirical studies1–11. Of central interest is whether emotions play a causal role in moral judgement, and, in parallel, how emotion-related areas of the brain contribute to moral judgement. Here we show that six patients with focal bilateral damage to the ventromedial prefrontal cortex (VMPC), a brain region necessary for the normal generation of emotions and, in particular, social emotions12–14, produce an abnor- mally ‘utilitarian’ pattern of judgements on moral dilemmas that pit compelling considerations of aggregate welfare against highly emotionally aversive behaviours (for example, having to sacrifice one person’s life to save a number of other lives)7,8. In contrast, the VMPC patients’ judgements were normal in other classes of moral dilemmas. These findings indicate that, for a selective set of moral dilemmas, the VMPC is critical for normal judgements of right and wrong. The findings support a necessary role for emotion in the generation of those judgements

Geometric discretization of the Koenigs nets

We introduce the Koenigs lattice, which is a new integrable reduction of the quadrilateral lattice (discrete conjugate net) and provides natural integrable discrete analogue of the Koenigs net. We construct the Darboux-type transformations of the Koenigs lattice and we show permutability of superpositions of such transformations, thus proving integrability of the Koenigs lattice. We also investigate the geometry of the discrete Koenigs transformation. In particular we characterize the Koenigs transformation in terms of an involution determined by a congruence conjugate to the lattice.Comment: 17 pages, 2 figures; some spelling and typing errors correcte

The effectiveness of cognitive bias modification in reducing substance use in detained juveniles: An RCT

Background and objective: Young offenders show high levels of substance use. Treatment programs within detention settings are less effective. Cognitive bias modification (CBM) is a promising supplement to substance use treatment. This study tests the effectiveness of CBM in young offenders to reduce cannabis and alcohol use, and delinquent recidivism. Method: A randomized controlled trial added CBM to treatment as usual (TAU), among 181 youth in juvenile detention centers. In a factorial design, participants were randomly assigned to either active- or sham-training for two varieties of CBM, targeting attentional-bias (AtB) and approach-bias (ApB) for their most used substance. Substance use was measured with the Alcohol and Cannabis Use Disorder Identification Tests. Delinquent recidivism was measured with the International Self-Report Delinquency (ISRD) survey. Results: At pretest, participants showed AtB but no ApB for both substances. For alcohol, a decrease was found in AtB in the active-training group. For cannabis, a decrease was found in AtB for both active- and sham-training groups. Regardless of condition, no effects were found on substance use or ISRD scores at follow-up. Limitations: The sample is judicial, not clinical, as is the setting. TAU and participant goals are not necessarily substance related. Conclusions: Young offenders show a significant attentional-bias towards substance cues. CBM changed attentional-biases but not substance use. Combining CBM with a motivational intervention is advised. Follow-up research should better integrate CBM with running treatment programs. New developments regarding CBM task design could be used that link training better to treatment

On two superintegrable nonlinear oscillators in N dimensions

We consider the classical superintegrable Hamiltonian system given by $H=T+U={p^2}/{2(1+\lambda q^2)}+{{\omega}^2 q^2}/{2(1+\lambda q^2)}$, where U is known to be the "intrinsic" oscillator potential on the Darboux spaces of nonconstant curvature determined by the kinetic energy term T and parametrized by {\lambda}. We show that H is Stackel equivalent to the free Euclidean motion, a fact that directly provides a curved Fradkin tensor of constants of motion for H. Furthermore, we analyze in terms of {\lambda} the three different underlying manifolds whose geodesic motion is provided by T. As a consequence, we find that H comprises three different nonlinear physical models that, by constructing their radial effective potentials, are shown to be two different nonlinear oscillators and an infinite barrier potential. The quantization of these two oscillators and its connection with spherical confinement models is briefly discussed.Comment: 11 pages; based on the contribution to the Manolo Gadella Fest-60 years-in-pucelandia, "Recent advances in time-asymmetric quantum mechanics, quantization and related topics" hold in Valladolid (Spain), 14-16th july 201

Path Integral Approach for Superintegrable Potentials on Spaces of Non-constant Curvature: II. Darboux Spaces DIII and DIV

This is the second paper on the path integral approach of superintegrable systems on Darboux spaces, spaces of non-constant curvature. We analyze in the spaces \DIII and \DIV five respectively four superintegrable potentials, which were first given by Kalnins et al. We are able to evaluate the path integral in most of the separating coordinate systems, leading to expressions for the Green functions, the discrete and continuous wave-functions, and the discrete energy-spectra. In some cases, however, the discrete spectrum cannot be stated explicitly, because it is determined by a higher order polynomial equation. We show that also the free motion in Darboux space of type III can contain bound states, provided the boundary conditions are appropriate. We state the energy spectrum and the wave-functions, respectively

Anticipation of guilt for everyday moral transgressions : the role of the anterior insula and the influence of interpersonal psychopathic traits

Psychopathy is a personality disorder characterised by atypical moral behaviour likely rooted in atypical affective/motivational processing, as opposed to an inability to judge the wrongness of an action. Guilt is a moral emotion believed to play a crucial role in adherence to moral and social norms, but the mechanisms by which guilt (or lack thereof) may influence behaviour in individuals with high levels of psychopathic traits are unclear. We measured neural responses during the anticipation of guilt about committing potential everyday moral transgressions, and tested the extent to which these varied with psychopathic traits. We found a significant interaction between the degree to which anticipated guilt was modulated in the anterior insula and interpersonal psychopathic traits: anterior insula modulation of anticipated guilt was weaker in individuals with higher levels of these traits. Data from a second sample confirmed that this pattern of findings was specific to the modulation of anticipated guilt and not related to the perceived wrongness of the transgression. These results suggest a central role for the anterior insula in coding the anticipation of guilt regarding potential moral transgressions and advance our understanding of the neurocognitive mechanisms that may underlie propensity to antisocial behaviour

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Identification of Protein Targets of Reactive Metabolites of Tienilic Acid in Human Hepatocytes

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx300103jTienilic acid (TA) is a uricosuric diuretic that was withdrawn from the market only months after its introduction because of reports of serious incidents of drug-induced liver injury including some fatalities. Its hepatotoxicity is considered to be primarily immunoallergic in nature. Like other thiophene compounds, TA undergoes biotransformation to a S-oxide metabolite which then reacts covalently with cellular proteins. To identify protein targets of TA metabolites, we incubated [14C]-TA with human hepatocytes, separated cellular proteins by 2D gel electrophoresis, and analyzed proteins in 36 radioactive spots by tryptic digestion followed by LC-MS/MS. Thirty one spots contained at least one identifiable protein. Sixteen spots contained only one of 14 non-redundant proteins which were thus considered to be targets of TA metabolites. Six of the 14 were also found in other radioactive spots that contained from 1 to 3 additional proteins. Eight of the 14 had not been reported to be targets for any reactive metabolite other than TA. The other 15 spots each contained from 2–4 identifiable proteins, many of which are known targets of other chemically reactive metabolites, but since adducted peptides were not observed, the identity of the adducted protein(s) in these spots is ambiguous. Interestingly, all the radioactive spots corresponded to proteins of low abundance, while many highly abundant proteins in the mixture showed no radioactivity. Furthermore, of approximately 16 previously reported protein targets of TA in rat liver (Methogo, R., Dansette, P. and Klarskov, K. (2007) Int. J. Mass Spectrom., 268, 284–295), only one (fumarylacetoacetase) is among the 14 targets identified in this work. One reason for this difference may be statistical, given that each study identified a small number of targets from among thousands present in hepatocytes. Another may be the species difference (i.e. rat vs. human), and still another may be the method of detection of adducted proteins (i.e. Western blot vs. C-14). Knowledge of human target proteins is very limited. Of more than 350 known protein targets of reactive metabolites, only 42 are known from human and only 21 of these are known to be targets for more than one chemical. Nevertheless, the demonstration that human target proteins can be identified using isolated hepatocytes in vitro should enable the question of species differences to be addressed more fully in the future