Rapid Processing of Both Reward Probability and Reward Uncertainty in the Human Anterior Cingulate Cortex

Reward probability and uncertainty are two fundamental parameters of decision making. Whereas reward probability indicates the prospect of winning, reward uncertainty, measured as the variance of probability, indicates the degree of risk. Several lines of evidence have suggested that the anterior cingulate cortex (ACC) plays an important role in reward processing. What is lacking is a quantitative analysis of the encoding of reward probability and uncertainty in the human ACC. In this study, we addressed this issue by analyzing the feedback-related negativity (FRN), an event-related potential (ERP) component that reflects the ACC activity, in a simple gambling task in which reward probability and uncertainty were parametrically manipulated through predicting cues. Results showed that at the outcome evaluation phase, while both win and loss-related FRN amplitudes increased as the probability of win or loss decreased, only the win-related FRN was modulated by reward uncertainty. This study demonstrates the rapid encoding of reward probability and uncertainty in the human ACC and offers new insights into the functions of the ACC

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

Craniodental Morphology and Systematics of a New Family of Hystricognathous Rodents (Gaudeamuridae) from the Late Eocene and Early Oligocene of Egypt

BACKGROUND: Gaudeamus is an enigmatic hystricognathous rodent that was, until recently, known solely from fragmentary material from early Oligocene sites in Egypt, Oman, and Libya. Gaudeamus' molars are similar to those of the extant cane rat Thryonomys, and multiple authorities have aligned Gaudeamus with Thryonomys to the exclusion of other living and extinct African hystricognaths; recent phylogenetic analyses have, however, also suggested affinities with South American caviomorphs or Old World porcupines (Hystricidae). METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the oldest known remains of Gaudeamus, including largely complete but crushed crania and complete upper and lower dentitions. Unlike younger Gaudeamus species, the primitive species described here have relatively complex occlusal patterns, and retain a number of plesiomorphic features. Unconstrained parsimony analysis nests Gaudeamus and Hystrix within the South American caviomorph radiation, implying what we consider to be an implausible back-dispersal across the Atlantic Ocean to account for Gaudeamus' presence in the late Eocene of Africa. An analysis that was constrained to recover the biogeographically more plausible hypothesis of caviomorph monophyly does not place Gaudeamus as a stem caviomorph, but rather as a sister taxon of hystricids. CONCLUSIONS/SIGNIFICANCE: We place Gaudeamus species in a new family, Gaudeamuridae, and consider it likely that the group originated, diversified, and then went extinct over a geologically brief period of time during the latest Eocene and early Oligocene in Afro-Arabia. Gaudeamurids are the only known crown hystricognaths from Afro-Arabia that are likely to be aligned with non-phiomorph members of that clade, and as such provide additional support for an Afro-Arabian origin of advanced stem and basal crown members of Hystricognathi

The 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers

RATIONALE: Brain 5-HT2C receptors form part of a neural network that controls eating behaviour. 5-HT2C receptor agonists decrease food intake by activating proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, but recent research in rodents has suggested that 5-HT2C receptor agonists may also act via dopaminergic circuitry to reduce the rewarding value of food and other reinforcers. No mechanistic studies on the effects of 5-HT2C agonists on food intake in humans have been conducted to date. OBJECTIVES: The present study examined the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) on food consumption, eating microstructure and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to food pictures in healthy female volunteers. METHODS: In a double-blind, placebo-controlled, crossover design, participants were randomized immediately after screening to receive oral mCPP (30mg) in a single morning dose, or placebo, in a counterbalanced order. Test foods were served from a Universal Eating Monitor (UEM) that measured eating rate and fMRI BOLD signals to the sight of food and non-food images were recorded. RESULTS: mCPP decreased rated appetite and intake of a palatable snack eaten in the absence of hunger but had no significant effect on the consumption of a pasta lunch (although pasta eating rate was reduced). mCPP also decreased BOLD fMRI responses to the sight of food pictures in areas of reward-associated circuitry. A post hoc analysis identified individual variability in the response to mCPP (exploratory responder-non-responder analysis). Some participants did not reduce their cookie intake after treatment with mCPP and this lack of response was associated with enhanced ratings of cookie pleasantness and enhanced baseline BOLD responses to food images in key reward and appetite circuitry. CONCLUSIONS: These results suggest that 5-HT2C receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT2C receptor agonists is warranted

The impact of perfectionism and anxiety traits on action monitoring in major depressive disorder

Perfectionism and anxiety features are involved in the clinical presentation and neurobiology of major depressive disorder (MDD). In MDD, cognitive control mechanisms such as action monitoring can adequately be investigated applying electrophysiological registrations of the error-related negativity (ERN) and error positivity (Pe). It is also known that traits of perfectionism and anxiety influence ERN amplitudes in healthy subjects. The current study explores the impact of perfectionism and anxiety traits on action monitoring in MDD. A total of 39 MDD patients performed a flankers task during an event-related potential (ERP) session and completed the multidimensional perfectionism scale (MPS) with its concern over mistakes (CM) and doubt about actions (DA) subscales and the trait form of the State Trait Anxiety Inventory. Multiple regression analyses with stepwise backward elimination revealed MPS-DA to be a significant predictor (R2:0.22) for the ERN outcomes, and overall MPS (R2:0.13) and MPS-CM scores (R2:0.18) to have significant predictive value for the Pe amplitudes. Anxiety traits did not have a predictive capacity for the ERPs. MPS-DA clearly affected the ERN, and overall MPS and MPS-CM influenced the Pe, whereas no predictive capacity was found for anxiety traits. The manifest impact of perfectionism on patients’ error-related ERPs may contribute to our understanding of the action-monitoring process and the functional significance of the Pe in MDD. The divergent findings for perfectionism and anxiety features also indicate that the wide range of various affective personality styles might exert a different effect on action monitoring in MDD, awaiting further investigation

Lifespan development of stimulus-response conflict cost: similarities and differences between maturation and senescence

Age gradient of the mechanism of stimulus-response conflict cost was investigated in a population-based representative sample of 291 individuals, covering the age range from 6 to 89 years. Stimulus-response conflict cost, indicated by the amount of additional processing time required when there is a conflict between stimulus and response options, follows a U-shaped function across the lifespan. Lifespan age gradient of conflict cost parallels closely those of processing fluctuation and fluid intelligence. Individuals at both ends of the lifespan displayed a greater amount of processing fluctuation and at the same time a larger amount of conflict cost and a lower level of fluid intelligence. After controlling for chronological age and baseline processing speed, conflict cost continues to correlate significantly with fluid intelligence in adulthood and old age and with processing fluctuation in old age. The relation between processing fluctuation and conflict cost in old age lends further support for the neuromodulation of neuronal noise theory of cognitive aging as well as for theories of dopaminergic modulation of conflict monitoring

A Systematically Improved High Quality Genome and Transcriptome of the Human Blood Fluke Schistosoma mansoni

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior

The effects of rTMS on impulsivity in normal adults: a systematic review and meta-analysis

Background: Impulsivity is a multi-dimensional construct that is regarded as a symptom of many psychiatric disorders. Harm resulting from impulsive behaviour can be substantial for the individuals concerned, people around them and the society they live in. Therefore, the importance of developing therapeutic interventions to target impulsivity is paramount. Aims and methods: We conducted a systematic review and meta-analysis of the literature from AMED, Embase, Medline, and PsycINFO databases on the use of repetitive transcranial magnetic stimulation (rTMS) in healthy adults to modulate different subdomains (motor, temporal and reflection) of impulsivity. Results: The results indicated that rTMS has distinct effects on different impulsivity subdomains. It has a significant, albeit small, effect on modulating motor impulsivity (g = 0.30, 95% CI, 0.17 to 0.43, p < .001) and a moderate effect on temporal impulsivity (g = 0.59, 95% CI, 0.32 to 0.86, p < .001). Subgroup analyses (e.g., excitatory vs. inhibitory rTMS, conventional rTMS vs. theta burst stimulation, analyses by stimulation sites, and type of outcome measure used) identified key parameters associated with the effects of rTMS on motor and temporal impulsivity. Age, sex, stimulation intensity and the number of pulses were not significant moderators for effects of rTMS on motor impulsivity. Due to lack of sufficient data to inform a meta-analysis, it has not been possible to assess the effects of rTMS on reflection impulsivity. Conclusions: The present findings provide preliminary evidence that rTMS can be used to modulate motor and temporal impulsivity in healthy individuals. Further studies are required to extend the use of rTMS to modulate impulsivity in those at most risk of engaging in harmful behaviour as a result of impulsivity, such as patients with offending histories and those with a history of self-harming behaviour