The monetary incentive delay task breaks down reward processing into discrete stages for fMRI analysis. Here we look at anticipation of monetary gain and loss contrasted with neutral anticipation. We meta-analysed data from 15 original whole-brain group maps (n = 346) and report extensive areas of relative activation and deactivation throughout the whole brain. For both anticipation of gain and loss we report robust activation of the striatum, activation of key nodes of the putative salience network, including anterior cingulate and anterior insula, and more complex patterns of activation and deactivation in the central executive and default networks. On between-group comparison, we found significantly greater relative deactivation in the left inferior frontal gyrus associated with incentive valence. This meta-analysis provides a robust whole-brain map of a reward anticipation network in the healthy human brain.Electronic supplementary materialThe online version of this article (10.1007/s11065-018-9385-5) contains supplementary material, which is available to authorized users.

isrctn.org Identifier: ISRCTN46322781.

Solutions of 0.2% and 2% chlorhexidine, 0.2% and 2% sodium hypochlorite (NaOCl) and normal saline were tested for their efficacy in disinfecting dentinal tubules following root canal irrigation in vitro. Freshly extracted bovine incisor roots were prepared as cylindrical shapes, 4 mm high and 5 mm wide with a lumen 2.1 mm wide. After mechanical removal of the cementum and elimination of the smear layer on the dentine surface with EDTA and NaOCl, the root sections were autoclaved and the dentinal tubules infected with E. faecalis (NCTC 775) by incubating in yeast extract glucose broth for 1 week. The root canals were irrigated with 20 ml of an irrigant solution using a syringe. Each irrigant was used in six specimens. Dentine was removed from the canal wall by sterile burs of increasing diameter to give samples 100, 100-300 and 300-500 microns deep. The dentine samples were then cultured to determine the presence and quantity of remaining micro-organisms. The results indicated that chlorhexidine and NaOCl were equally effective antibacterial agents at similar concentrations against the test microorganism. They significantly reduced the bacterial counts in the first 100 microns of dentinal tubules, however up to 50% of dentine samples remained infected following use of both agents.

ObjectivesTo review the systemic impact of smoking on bone healing as evidenced within the orthopaedic literature.MethodsA protocol was established and studies were sourced from five electronic databases. Screening, data abstraction and quality assessment was conducted by two review authors. Prospective and retrospective clinical studies were included. The primary outcome measures were based on clinical and/or radiological indicators of bone healing. This review specifically focused on non-spinal orthopaedic studies.ResultsNine tibia studies and eight other orthopaedic studies were considered for systematic review. Of these 17 studies, 13 concluded that smoking negatively influenced bone healing.ConclusionsSmoking has a negative effect on bone healing, in terms of delayed union, nonunion and more complications.

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Objective To investigate whether cannabis use is associated with increased risk of relapse, as indexed by number of hospital admissions, and whether antipsychotic treatment failure, as indexed by number of unique antipsychotics prescribed, may mediate this effect in a large data set of patients with first episode psychosis (FEP). Design Observational study with exploratory mediation analysis. Setting Anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust. Participants 2026 people presenting to early intervention services with FEP. Exposure Cannabis use at presentation, identified using natural language processing. Main outcome measures admission to psychiatric hospital and clozapine prescription up to 5 years following presentation. Mediator Number of unique antipsychotics prescribed. Results Cannabis use was present in 46.3% of the sample at first presentation and was particularly common in patients who were 16–25, male and single. It was associated with increased frequency of hospital admission (incidence rate ratio 1.50, 95% CI 1.25 to 1.80), increased likelihood of compulsory admission (OR 1.55, 1.16 to 2.08) and greater number of days spent in hospital (β coefficient 35.1 days, 12.1 to 58.1). The number of unique antipsychotics prescribed, mediated increased frequency of hospital admission (natural indirect effect 1.09, 95% CI 1.01 to 1.18; total effect 1.50, 1.21 to 1.87), increased likelihood of compulsory admission (natural indirect effect (NIE) 1.27, 1.03 to 1.58; total effect (TE) 1.76, 0.81 to 3.84) and greater number of days spent in hospital (NIE 17.9, 2.4 to 33.4; TE 34.8, 11.6 to 58.1). Conclusions Cannabis use in patients with FEP was associated with an increased likelihood of hospital admission. This was linked to the prescription of several different antipsychotic drugs, indicating clinical judgement of antipsychotic treatment failure. Together, this suggests that cannabis use might be associated with worse clinical outcomes in psychosis by contributing towards failure of antipsychotic treatment.

Background Recent evidence suggests that cannabidiol (CBD), a non-intoxicating ingredient present in cannabis extract, has an antipsychotic effect in people with established psychosis. However, the effect of CBD on the neurocognitive mechanisms underlying psychosis is unknown. Methods Patients with established psychosis on standard antipsychotic treatment were studied on separate days at least one week apart, to investigate the effects of a single dose of orally administered CBD (600 mg) compared to a matched placebo (PLB), using a double-blind, randomized, PLB-controlled, repeated-measures, within-subject cross-over design. Three hours after taking the study drug participants were scanned using a block design functional magnetic resonance imaging (fMRI) paradigm, while performing a verbal paired associate learning task. Fifteen psychosis patients completed both study days, 13 completed both scanning sessions. Nineteen healthy controls (HC) were also scanned using the same fMRI paradigm under identical conditions, but without any drug administration. Effects of CBD on brain activation measured using the blood oxygen level-dependent hemodynamic response fMRI signal were studied in the mediotemporal, prefrontal, and striatal regions of interest. Results Compared to HC, psychosis patients under PLB had altered prefrontal activation during verbal encoding, as well as altered mediotemporal and prefrontal activation and greater mediotemporal-striatal functional connectivity during verbal recall. CBD attenuated dysfunction in these regions such that activation under its influence was intermediate between the PLB condition and HC. CBD also attenuated hippocampal-striatal functional connectivity and caused trend-level symptom reduction in psychosis patients. Conclusions This suggests that normalization of mediotemporal and prefrontal dysfunction and mediotemporal-striatal functional connectivity may underlie the antipsychotic effects of CBD.

Accumulating evidence points towards the antipsychotic potential of cannabidiol. However, the neurocognitive mechanisms underlying the antipsychotic effect of cannabidiol remain unclear. We investigated this in a double-blind, placebo-controlled, parallel-arm study. We investigated 33 antipsychotic-naïve subjects at clinical high risk for psychosis (CHR) randomised to 600 mg oral cannabidiol or placebo and compared them with 19 healthy controls. We used the monetary incentive delay task while participants underwent fMRI to study reward processing, known to be abnormal in psychosis. Reward and loss anticipation phases were combined to examine a motivational salience condition and compared with neutral condition. We observed abnormal activation in the left insula/parietal operculum in CHR participants given placebo compared to healthy controls associated with premature action initiation. Insular activation correlated with both positive psychotic symptoms and salience perception, as indexed by difference in reaction time between salient and neutral stimuli conditions. CBD attenuated the increased activation in the left insula/parietal operculum and was associated with overall slowing of reaction time, suggesting a possible mechanism for its putative antipsychotic effect by normalising motivational salience and moderating motor response.