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There is increasing recognition of the mental health burden of climate change and the effects on general well-being, even in those who have not (yet) experienced direct impacts. Climate anxiety, which is prominent among young people in particular, describes a state of heightened distress about the (future) effects of climate change. Despite evidence of a link between engagement in climate change issues and heightened climate anxiety, there is a dearth of knowledge on how this affects emerging professionals preparing for careers in the environmental sector. Furthermore, there is a paucity of literature regarding the extent to which young adults are coping with their thoughts and feelings about climate change, and the extent to which they consider climate change in making future plans. The aim of this study was to understand the occurrence and personal management of climate anxiety in UK university students through an online questionnaire. This study was the first to investigate the association between climate anxiety, coping strategies and future planning in university students. Environmental degree students (n = 249) reported greater levels of climate anxiety, more frequent employment of all three examined coping strategies and in particular considered climate change as a factor in their career plans, as compared to their non-environmental degree counterparts (n = 224). Problem-focused coping was the most commonly endorsed strategy, although the prior literature on coping suggests that this may not be sustainable for individually intractable problems. Highly climate-anxious students were more likely to consider climate change in all five decision-making domains, including family planning, long-term habitation, career, financial and travel decisions. This study has identified a need to communicate effective climate anxiety coping strategies to environmental practitioners, university students and educators. Additional research is required to validate the study findings and investigate what motivates students to incorporate climate change into future plans.

Awareness of the threats of climate change is engendering distress in increasingly documented ways, with young people particularly affected. Experiences such as climate distress and eco-anxiety have implications for the health and wellbeing of societies, economies, and for climate action, including mental health, agency to address the crisis, and future planning. While multi-country studies suggest that eco-anxiety and related experiences of distress may vary with context, the hypothesis that exposure to climate-related impacts increases eco-anxiety and associated psychological impacts is underexplored in youth at the individual level. Here we show that in a large sample of US youth (aged 16–24, n = 2834), self-reported direct experience of climate-related events significantly increased eco-anxiety, climate distress and the impact of climate change on future planning, but also psychological adaptation, meaning-focused coping and climate agency. As the climate crisis accelerates and exposure to climate-related hazards increases, these findings have important implications for the mental health of populations, life choices that have socioeconomic impact, and climate behaviours of the growing group of young people experiencing these threats.

In this mixed methods study, which complements an earlier publication (https://doi.org/10.1016/S2542-5196(22)00172-3), we delve deeper into the experience of ‘climate distress’ among UK residents aged 16-24 (N=539). We report on data collected from an online survey assessing general mental health, subjective wellbeing, and climate distress using existing psychometric scales. We also included novel questions assessing positive and negative life impacts of climate change, open-ended questions on aspirations and priorities for the future, and engagement in pro-environmental and climate actions. In addition to quantitative results, we analysed free-text responses to two open-ended questions about respondents' hopes for the future, and their experience with climate change and actions in response to it.

Conservation science practitioners seek to pre-empt irreversible impacts on species, ecosystems, and social-ecological systems, requiring efficient and timely action even when data and understanding are unavailable, incomplete, dated, or biased. These challenges are exacerbated by the scientific community's capacity to consistently distinguish between reliable and unreliable evidence, including the recognition of questionable research practices (QRPs, or ‘questionable practices’), which may threaten the credibility of research, including harming trust in well-designed and reliable scientific research. In this paper, we propose a ‘toolkit’ for open and pluralistic conservation science, highlighting common questionable practices and sources of bias and indicating where remedies for these problems may be found. The toolkit provides an accessible resource for anyone conducting, reviewing, or using conservation research, to identify sources of false claims or misleading evidence that arise unintentionally, or through misunderstandings or carelessness in the application of scientific methods and analyses. We aim to influence editorial and review practices and hopefully to remedy problems before they are published or deployed in policy or conservation practice.

The COVID-19 pandemic and climate change are both significant and pressing global challenges, posing threats to public health and wellbeing. Young people are particularly vulnerable to the distress both crises can cause, but understanding of the varied psychological responses to both issues is poor. We aimed to investigate these responses and their links with mental health conditions and feelings of agency.We conducted an online survey between Aug 5 and Oct 26, 2020, targeting a diverse sample of young people (aged 16-24 years, n=530) in the UK. The survey was distributed using a combination of a survey panel (panel sample) and direct approaches to youth groups and schools who shared the survey with young people in their networks (community sample). We collected data on respondents' psychological responses to both climate change and the COVID-19 pandemic, their sense of agency to respond to each crisis, and the range of impacts on their lives. We also collected demographics data and screened for mental health and wellbeing indicators. We used non-parametric tests for most statistical comparisons. For paired samples, we used Wilcoxon's signed-rank test, and used Mann-Whitney U-tests or Kruskal-Wallis tests for two or more independent samples. Summed scale scores were considered as interval-level data and analysed with Student's t tests and ANOVAs. Effect sizes are reported as Cohen's d and partial eta-squared (η·After excluding 18 suspected bots and 94 incomplete responses, 530 responses were retained for analysis. Of the 518 respondents who provided demographic data, 63% were female, 71·4% were White, and the mean family affluence score was 8·22 (SD 2·29). Most participants (n=343; 70%) did not report a history of diagnosis or treatment for a mental health disorder, but mental health scores indicated a common experience of (relatively mild) symptoms of anxiety, depression, and stress. Although UK youth reported more life disruption and concern for their future due to the COVID-19 pandemic, climate change was associated with significantly greater distress overall, particularly for individuals with low levels of generalised anxiety. The COVID-19 pandemic was more associated with feelings of anxiety, isolation, disconnection, and frustration; distress around loss and grief; and effects on quality of life. Climate change was more likely to evoke emotions such as interest and engagement, guilt, shame, anger, and disgust. The greater distress attributed to climate change overall was due, in particular, to higher levels of guilt, sense of personal responsibility, and greater distress triggered by upsetting media coverage. Agency to address climate change was associated with greater climate distress, but pandemic-related distress and agency were unrelated.The COVID-19 pandemic and climate change are affecting the wellbeing of UK young people in distinct ways, with implications for health service, policy, and research responses. There is a need for mental health practitioners, policy makers, and other societal actors to account for the complex relationship between climate agency, distress, and mental wellbeing in young people.Imperial College London.

Environmental decisions are often deferred to groups of experts, committees, or panels to develop climate policy, plan protected areas, or negotiate trade-offs for biodiversity conservation. There is, however, surprisingly little empirical research on the performance of group decision making related to the environment. We examined examples from a range of different disciplines, demonstrating the emergence of collective intelligence (CI) in the elicitation of quantitative estimates, crowdsourcing applications, and small-group problem solving. We explored the extent to which similar tools are used in environmental decision making. This revealed important gaps (e.g., a lack of integration of fundamental research in decision-making practice, absence of systematic evaluation frameworks) that obstruct mainstreaming of CI. By making judicious use of interdisciplinary learning opportunities, CI can be harnessed effectively to improve decision making in conservation and environmental management. To elicit reliable quantitative estimates an understanding of cognitive psychology and to optimize crowdsourcing artificial intelligence tools may need to be incorporated. The business literature offers insights into the importance of soft skills and diversity in team effectiveness. Environmental problems set a challenging and rich testing ground for collective-intelligence tools and frameworks. We argue this creates an opportunity for significant advancement in decision-making research and practice.Potencial No Explotado de la Inteligencia Colectiva en la Toma de Decisiones Ambientales y de Conservación Resumen Las decisiones ambientales comúnmente se difieren a grupos de expertos, comités, o paneles para desarrollar la política climática, planear las áreas protegidas o negociar compensaciones por la conservación de la biodiversidad. Aun así, sorprendentemente, existen pocas investigaciones empíricas sobre el desempeño de la toma grupal de decisiones en relación con el ambiente. Examinamos los ejemplos de una gama de disciplinas diferentes, demostrando el surgimiento de la inteligencia colectiva en la obtención de estimaciones cuantitativas, las aplicaciones de la colaboración masiva y la resolución de problemas en grupos pequeños. Exploramos el alcance que tienen las herramientas similares que se usan en la toma de decisiones ambientales. Esto último reveló vacíos importantes (p. ej.: la falta de integración de investigaciones fundamentales en la práctica de la toma de decisiones, la ausencia de marcos de trabajo de evaluación sistemática) que obstruyen la popularización de la inteligencia colectiva. Si hacemos un uso juicioso de las oportunidades de aprendizaje interdisciplinario, la inteligencia colectiva puede aprovecharse efectivamente para mejorar la toma de decisiones en el manejo ambiental y de conservación. La incorporación de un entendimiento de la psicología cognitiva y la optimización de las herramientas de IA para la colaboración masiva pueden ser necesarias para obtener estimados cuantitativos confiables. La literatura de los negocios ofrece conocimientos sobre la importancia de las habilidades blandas y la diversidad en la efectividad del equipo. Los problemas ambientales plantean un campo de pruebas rico y desafiante para las herramientas y los marcos de trabajo de inteligencia colectiva. Argumentamos que esto crea una oportunidad para el avance significativo en la investigación y la práctica de la toma de decisiones.在环境决策中, 通常由专家组、委员会或专门小组来制定气候政策、进行保护区规划或商讨生物多样性保护的利弊权衡。但令人惊讶的是, 很少有实证研究评估与环境相关的群体决策的成效。本研究利用不同学科的案例, 展示了在定量评估、众包应用和小群体问题解决等方面涌现的集体智慧。我们还分析了类似的工具在环境决策中的应用情况。研究结果揭示了一些阻碍集体智慧主流化的一些重要缺口, 如决策实践中缺乏基础研究的整合, 缺少系统的评价框架。而善用跨学科的学习机会, 则可以更有效地利用集体智慧来改善保护和环境管理方面的决策。为了获得可靠的定量评估, 可能需要结合对认知心理学的理解和对众包人工智能工具的优化。另外, 商业文献也有助于更好地了解软技能和多样的团队效能的重要性。环境问题为集体智慧的工具和框架提供了一个极具挑战又丰富多样的试验场, 这也为决策研究和实践取得重大进展创造了机会。【翻译: 胡怡思; 审校: 聂永刚】.

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences. The utility of processes to predict replicability is their capacity to test scientific claims without the costs of full replication. Experimental data supports the validity of this process, with a validation study producing a classification accuracy of 84% and an Area Under the Curve of 0.94, meeting or exceeding the accuracy of other techniques used to predict replicability. The repliCATS process provides other benefits. It is highly scalable, able to be deployed for both rapid assessment of small numbers of claims, and assessment of high volumes of claims over an extended period through an online elicitation platform, having been used to assess 3000 research claims over an 18 month period. It is available to be implemented in a range of ways and we describe one such implementation. An important advantage of the repliCATS process is that it collects qualitative data that has the potential to provide insight in understanding the limits of generalizability of scientific claims. The primary limitation of the repliCATS process is its reliance on human-derived predictions with consequent costs in terms of participant fatigue although careful design can minimise these costs. The repliCATS process has potential applications in alternative peer review and in the allocation of effort for replication studies.

Background: The COVID-19 pandemic and climate change are both significant and pressing global challenges, posing threats to public health and wellbeing. Young people represent a particularly vulnerable group to the distress both crises appear to engender, but we currently lack an understanding of the varied psychological responses to both issues, and their links with mental health conditions and feelings of agency. Methods: We conducted an online survey in August - October 2020 targeting a diverse sample of young people (16–24 years, N=530) in the United Kingdom. Findings: While UK youth reported more life disruption and concern for their future due to the COVID-19 pandemic, climate change was associated with significantly greater distress overall, particularly for individuals with low levels of generalised anxiety. COVID-19 was more associated with feelings of anxiety, isolation, disconnection, and frustration; distress around loss and grief; and effects on quality of life. Climate change was more likely to evoke interest and engagement, guilt, shame, anger, and disgust; and distress associated with guilt, feeling responsible and media coverage. Agency to address climate change was associated with greater climate distress, but COVID-related distress and agency were unrelated. Interpretation: COVID-19 and climate change are affecting the wellbeing of young people in distinct ways, with implications for health service, policy and research responses. There is a need for mental health practitioners and policy makers to account for the complex relationship between climate agency, distress and mental wellbeing in young people. Funding: Institute of Global Health Innovation, Imperial College London. Declaration of Interests: We declare no conflicts of interest. Ethics Approval Statement: The study was reviewed and received approval from the Imperial College London Science, Engineering, & Technology Research Ethics Committee (SETREC; approval number 20IC6060).

Introduction: Efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) targeting the temporo-parietal junction (TPJ) for the treatment of auditory verbal hallucinations (AVH) remains under debate. We assessed the influence of a 1 Hz rTMS treatment on neural networks involved in a cognitive mechanism proposed to subserve AVH.Methods: Patients with schizophrenia (N = 24) experiencing medication-resistant AVH completed a 10-day 1 Hz rTMS treatment. Participants were randomized to active stimulation of the left or bilateral TPJ, or sham stimulation. The effects of rTMS on neural networks were investigated with an inner speech task during fMRI. Changes within and between neural networks were analyzed using Independent Component Analysis.Results: rTMS of the left and bilateral TPJ areas resulted in a weaker network contribution of the left supramarginal gyro to the bilateral fronto-temporal network. Left-sided rTMS resulted in stronger network contributions of the right superior temporal gyrus to the auditory-sensorimotor network, right inferior gyrus to the left fronto-parietal network, and left middle frontal gyrus to the default mode network. Bilateral rTMS was associated with a predominant inhibitory effect on network contribution. Sham stimulation showed different patterns of change compared to active rTMS.Conclusion: rTMS of the left temporo-parietal region decreased the contribution of the left supramarginal gyros to the bilateral fronto-temporal network, which may reduce the likelihood of speech intrusions. On the other hand, left rTMS appeared to increase the contribution of functionally connected regions involved in perception, cognitive control and self-referential processing. These findings hint to potential neural mechanisms underlying rTMS for hallucinations but need corroboration in larger samples.

Aim Mega-diverse coral reef ecosystems are declining globally, necessitating conservation prioritizations to protect biodiversity and ecosystem services of sites with high functional integrity to promote persistence. In practice however, the design of marine-protected area (MPA) systems often relies on broad classifications of habitat class and size, making the tacit assumption that all reefs are of comparable condition. We explored the impact of this assumption through a novel, pragmatic approach for incorporating variability in coral cover in a large-scale regional spatial prioritization plan. Location The Coral Triangle. Methods We developed a spatially explicit predictive model of hard coral cover based on freely available macro-ecological data to generate a complete regional map of coral cover as a proxy for reef condition. We then incorporate this information in spatial conservation prioritization software Marxan to design an MPA system that meets specific conservation objectives. Results We discover prioritizations using area-based representation of reef habitat alone may overestimate the conservation benefit, defined as the amount of hard coral cover protected, by up to 64%. We find substantial differences in conservation priorities and an overall increase in habitat quality metrics when accounting for predicted coral cover. Main conclusions This study shows that including habitat condition in a large-scale marine spatial prioritization is feasible within time and resource constraints, and calls for increased implementation, and evaluation, of such ecologically relevant planning approaches to enhance potential conservation effectiveness.

In the wake of 9/11 and the assessment of Iraq's WMD, several inquiries placed the blame primarily on the Intelligence Community. Part of the reform that followed was a codification of analytic tradecraft standards into Intelligence Community Directive (ICD) 203 and the appointment of an analytic ombudsman in the newly created Office of the Director of National Intelligence charged with monitoring the quality of analytic products from across the intelligence community. In this paper we identify three assumptions behind ICD203: (1) tradecraft standards can be employed consistently; (2) tradecraft standards sufficiently capture the key elements of good reasoning; (3) good reasoning leads to more accurate judgments. We then report on two controlled experiments that uncover operational constraints in the reliable application of the ICD203 criteria for the assessment of intelligence products. Despite criticisms of the post-9/11 and post-Iraq reform, our results highlight that ICD203, properly applied, holds potential to improve precision and accountability of intelligence processes and products.

Spatial conservation prioritization is used globally to guide decision making with the aim of delivering the best conservation gain per unit investment. However, despite many publications on the topic, the extent to which this approach is used by decision makers has been unclear. To investigate the degree to which prioritization has been adopted by practitioners to guide conservation implementation, we conducted an online survey, collecting data on the approaches used to develop prioritizations and the reported extent of translation to on-the-ground action. Using a cluster analysis, we identified two categories of prioritizations, those developed to advance the field (42% of responses) and those intended for implementation (58% of responses). Respondents reported 74% of the prioritizations intended for implementation had translated to on-the-ground action. Additionally, we identified strong collaboration between academics and practitioners in prioritization development, suggesting a bridging of the theory-practice gap. We recommend continued collaboration and research into the effectiveness of prioritizations in delivering conservation impacts.

Growing evidence suggests that testosterone may play a role in the pathophysiology of schizophrenia given that testosterone has been linked to cognition and negative symptoms in schizophrenia. Here, we determine the extent to which serum testosterone levels are related to neural activity in affective processing circuitry in men with schizophrenia. Functional magnetic resonance imaging was used to measure blood-oxygen-level-dependent signal changes as 32 healthy controls and 26 people with schizophrenia performed a facial emotion identification task. Whole brain analyses were performed to determine regions of differential activity between groups during processing of angry versus non-threatening faces. A follow-up ROI analysis using a regression model in a subset of 16 healthy men and 16 men with schizophrenia was used to determine the extent to which serum testosterone levels were related to neural activity. Healthy controls displayed significantly greater activation than people with schizophrenia in the left inferior frontal gyrus (IFG). There was no significant difference in circulating testosterone levels between healthy men and men with schizophrenia. Regression analyses between activation in the IFG and circulating testosterone levels revealed a significant positive correlation in men with schizophrenia (r=.63, p=.01) and no significant relationship in healthy men. This study provides the first evidence that circulating serum testosterone levels are related to IFG activation during emotion face processing in men with schizophrenia but not in healthy men, which suggests that testosterone levels modulate neural processes relevant to facial emotion processing that may interfere with social functioning in men with schizophrenia.

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.

Schizophrenia is a severe mental disorder characterized by a diverse set of symptoms, including positive (hallucinations, delusions) and negative (lack of motivation, social withdrawal, blunted affect) symptoms and cognitive impairment. Cognitive deficits are recognized as forming part of the core psychopathology of schizophrenia, with impairments in learning, memory and attention being common (Weickert et al. 2000; Palmer et al. 2009). Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that potentiates synaptic strength and plasticity underlying learning and memory (Lu & Chow, 1999; Poo, 2001; Egan et al. 2003; Hariri et al. 2003; Lu, 2003; Dempster et al. 2005). A single nucleotide polymorphism in the human BDNF gene produces a valine to methionine substitution in the protein prodomain that influences intracellular trafficking, activity-dependent release of BDNF, learning and brain activity (Egan et al. 2003; Hariri et al. 2003). Lower levels of both brain and blood BDNF have also been implicated in the majority of studies of the pathophysiology of schizophrenia (Weickert et al. 2003; Xiu et al. 2009; Rizos et al. 2010; Green et al. 2011). Peripheral blood can provide an important reservoir of BDNF, reflecting BDNF secreted from the brain and BDNF that may be available to influence brain function (Schmidt & Duman, 2010). However, the extent to which circulating BDNF correlates with human brain activity during learning has not been demonstrated and the extent to which lower circulating BDNF may be indicative of the neural correlates of cognitive impairment in schizophrenia has not been shown. Low peripheral BDNF is reported in first-episode psychosis (Buckley et al. 2007) and is associated with cognitive impairment in chronically ill people with schizophrenia (Zhang et al. 2012b). Peripheral BDNF levels are also significantly decreased in people with mild cognitive impairment (Yu et al. 2008). Thus, peripheral BDNF levels may be useful as a biomarker in health and disease. However, to more fully interpret what any change in a potential biomarker may mean for brain function, a relationship between peripheral BDNF and brain activity should be established in the healthy and diseased states. One reason that general predictions about blood–brain relationships in schizophrenia are difficult to make is that studies of peripheral BDNF levels in schizophrenia have reported inconsistent results. Although the majority of studies report decreased circulating BDNF levels (Pirildar et al. 2004; Tan et al. 2005; Grillo et al. 2007; Rizos et al. 2008), some find increased levels (Gama et al. 2007; Reis et al. 2008), and one study reports no significant difference in plasma BDNF levels in people with schizophrenia compared to healthy controls (Lee & Kim, 2009). A recent meta-analysis supports an overall reduction in peripheral BDNF levels in schizophrenia (Green et al. 2011). However, the extent to which alterations in blood BDNF levels relate to abnormal learning-related brain activity in schizophrenia, as compared to healthy individuals, remains to be demonstrated. Healthy cortical neurons innervate and supply BDNF to several brain regions, including the striatum (Alexander et al. 1986; Altar & DiStefano, 1998). As striatal neurons are trophically dependent on BDNF supplied through anterograde transport from the frontal cortex (Hofer et al. 1990; Altar et al. 1997; Rauskolb et al. 2010; Dieni et al. 2012), higher levels of BDNF would be expected to relate to stronger frontal–striatal activity in a healthy brain, and a reduction of prefrontal cortical BDNF, as found in schizophrenia (Weickert et al. 2003; Hashimoto et al. 2005), would be expected to negatively impact striatal function in schizophrenia. There is abundant evidence from neuropsychological and neuroimaging studies demonstrating significant learning impairments and frontal–striatal dysfunction in schizophrenia (Pantelis et al. 1997; Meyer-Lindenberg et al. 2002; Murray et al. 2008; Howes et al. 2009; Weickert et al. 2010; Morris et al. 2012). Probabilistic association learning (requiring gradual learning of probabilistic-based cue–outcome associations) elicits frontal–parietal–striatal activity in healthy people (Poldrack et al. 1999; Fera et al. 2005) and is related to reduced activity in a neural network that includes the dorsolateral prefrontal cortex (DLPFC), parietal cortex and caudate nucleus in schizophrenia (Weickert et al. 2009). Probabilistic association learning is impaired in people with schizophrenia (Weickert et al. 2002; Foerde et al. 2008; Horan et al. 2008), the offspring of people with schizophrenia who are at high risk of developing schizophrenia (Wagshal et al. 2012, 2013) and in unaffected siblings of people with schizophrenia (Weickert et al. 2010; Wagshal et al. 2014), with deficits in overall performance and learning rate. In the present study, we sought to define the relationship between peripheral BDNF levels and the neural processes underlying probabilistic association learning in healthy people and people with schizophrenia. First, we confirmed the reduced brain activation in people with schizophrenia versus healthy controls during a probabilistic association learning test using functional magnetic resonance imaging (fMRI). Second, we tested the extent to which plasma BDNF levels are related to brain activity in healthy people during probabilistic association learning. Third, we determined whether a similar relationship was also present in schizophrenia. We predicted a positive relationship between plasma BDNF levels and brain activity in a neural network consisting of prefrontal–parietal cortices and striatum, which has previously been shown to be relevant for probabilistic association learning in healthy adults. Based on the majority of work showing dysregulation of either BDNF levels or prefrontal cortex activity along with an increase in the truncated BDNF receptor (Weickert et al. 2003; Hashimoto et al. 2005; Wong et al. 2010, 2013; Ray et al. 2014), which is thought to block trophic effects in schizophrenia, we further predicted an abnormal relationship between plasma BDNF levels and brain activity in schizophrenia.

Most transcranial Direct Current Stimulation (tDCS) trials of schizophrenia administer few sessions and do not assess transfer effects to other cognitive domains. In a randomized, double-blind, sham-controlled, parallel groups trial, we determined the extent to which 4-weeks of 2 mA tDCS at 20 min/day totalling 20 tDCS sessions administered during a spatial working memory test, with anodal right dorsolateral prefrontal cortex (DLPFC) and cathodal left tempo-parietal junction (TPJ) placement, as an adjunct to antipsychotics reduced auditory hallucinations and improved cognition in 12 outpatients with schizophrenia. Anodal tDCS significantly improved language-based working memory after 2 weeks and verbal fluency after 2 and 4 weeks. Thus, four weeks of tDCS appears to be safe and elicits transfer benefits to other prefrontal-dependent cognitive abilities in schizophrenia.

Auditory-verbal hallucinations (AVHs) are frequently associated with activation of the left superior temporal gyrus (including Wernicke’s area), left inferior frontal gyrus (including Broca’s area), and the right hemisphere homologs of both areas. It has been hypothesized that disconnectivity of both interhemispheric transfer and frontal and temporal areas may underlie hallucinations in schizophrenia. We investigated reduced information flow in this circuit for the first time using dynamic causal modeling, which allows for directional inference. A group of healthy subjects and 2 groups of schizophrenia patients—with and without AVH—performed a task requiring inner speech processing during functional brain scanning. We employed connectivity models between left hemispheric speech-processing areas and their right hemispheric homologs. Bayesian model averaging was used to estimate the connectivity strengths and evaluate group differences. Patients with AVH showed significantly reduced connectivity from Wernicke’s to Broca’s area (97% certainty) and a trend toward a reduction in connectivity from homologs of Broca’s and Wernicke’s areas to Broca’s area (93% and 94% certainty). The connectivity magnitude in patients without hallucinations was found to be intermediate. Our results point toward a reduced input from temporal to frontal language areas in schizophrenia patients with AVH, suggesting that Broca’s activity may be less constrained by perceptual information received from the temporal cortex. In addition, a lack of synchronization between Broca and its homolog may lead to the erroneous interpretation of emotional speech activity from the right hemisphere as coming from an external source.

While the majority of cognitive studies on auditory hallucinations (AHs) have been conducted in schizophrenia (SZ), an increasing number of researchers are turning their attention to different clinical and nonclinical populations, often using SZ findings as a model for research. Recent advances derived from SZ studies can therefore be utilized to make substantial progress on AH research in other groups. The objectives of this article were to (1) present an up-to-date review regarding the cognitive mechanisms of AHs in SZ, (2) review findings from cognitive research conducted in other clinical and nonclinical groups, and (3) integrate these recent findings into a cohesive framework. First, SZ studies show that the cognitive underpinnings of AHs include self-source-monitoring deficits and executive and inhibitory control dysfunctions as well as distortions in top-down mechanisms, perceptual and linguistic processes, and emotional factors. Second, consistent with SZ studies, findings in other population groups point to the role of top-down processing, abnormalities in executive inhibition, and negative emotions. Finally, we put forward an integrated model of AHs that incorporates the above findings. We suggest that AHs arise from an interaction between abnormal neural activation patterns that produce salient auditory signals and top-down mechanisms that include signal detection errors, executive and inhibition deficits, a tapestry of expectations and memories, and state characteristics that influence how these experiences are interpreted. Emotional factors play a particular prominent role at all levels of this hierarchy. Our model is distinctively powerful in explaining a range of phenomenological characteristics of AH across a spectrum of disorders.

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia.

Neuroimaging studies have shown both dorsolateral prefrontal (DLPFC) and inferior parietal cortex (iPARC) activation during probabilistic association learning. Whether these cortical brain regions are necessary for probabilistic association learning is presently unknown. Participants' ability to acquire probabilistic associations was assessed during disruptive 1 Hz repetitive transcranial magnetic stimulation (rTMS) of the left DLPFC, left iPARC, and sham using a crossover single-blind design. On subsequent sessions, performance improved relative to baseline except during DLPFC rTMS that disrupted the early acquisition beneficial effect of prior exposure. A second experiment examining rTMS effects on task-naive participants showed that neither DLPFC rTMS nor sham influenced naive acquisition of probabilistic associations. A third experiment examining consecutive administration of the probabilistic association learning test revealed early trial interference from previous exposure to different probability schedules. These experiments, showing disrupted acquisition of probabilistic associations by rTMS only during subsequent sessions with an intervening night's sleep, suggest that the DLPFC may facilitate early access to learned strategies or prior task-related memories via consolidation. Although neuroimaging studies implicate DLPFC and iPARC in probabilistic association learning, the present findings suggest that early acquisition of the probabilistic cue-outcome associations in task-naive participants is not dependent on either region.

Hallucinaties zijn een bijzonder menselijk fenomeen. Beschrijvingen van hallucinatieachtige fenomenen en ‘visioenen’ duiken regelmatig op in de literatuur, maar pas in de negentiende eeuw werden de eerste systematische wetenschappelijke studies gerapporteerd. De Franse psychiater Esquirol heeft hierin een zeer belangrijke rol gespeeld. Hij definieerde hallucinaties als ‘een sterke overtuiging van een sensorische ervaring, terwijl er geen extern object is dat het zintuig op de daarbij passende manier beinvloedt’. Vandaag accepteert de wetenschappelijke wereld dat hallucinaties ontstaan door het foutief toewijzen van intern gegenereerde informatie aan een externe bron. De precieze onderliggende cognitief-emotionele processen die aan de basis liggen van deze denkfout zijn echter tot op heden niet helemaal duidelijk.

BackgroundIt has recently been suggested that auditory hallucinations are the result of a criterion shift when deciding whether or not a meaningful signal has emerged. The approach proposes that a liberal criterion may result in increased false-positive identifications, without additional perceptual deficit. To test this hypothesis, we devised a speech discrimination task and used signal detection theory (SDT) to investigate the underlying cognitive mechanisms.MethodSchizophrenia patients with and without auditory hallucinations and a healthy control group completed a speech discrimination task. They had to decide whether a particular spoken word was identical to a previously presented speech stimulus, embedded in noise. SDT was used on the accuracy data to calculate a measure of perceptual sensitivity (Az) and a measure of response bias (β). Thresholds for the perception of simple tones were determined.ResultsCompared to healthy controls, perceptual thresholds were higher and perceptual sensitivity in the speech task was lower in both patient groups. However, hallucinating patients showed increased sensitivity to speech stimuli compared to non-hallucinating patients. In addition, we found some evidence of a positive response bias in hallucinating patients, indicating a tendency to readily accept that a certain stimulus had been presented.ConclusionsWithin the context of schizophrenia, patients with auditory hallucinations show enhanced sensitivity to speech stimuli, combined with a liberal criterion for deciding that a perceived event is an actual stimulus.

BACKGROUND: Repetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation. METHODS: In this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucinations Rating Scale (AHRS), and the Positive and Negative Affect Scale (PANAS). We included follow-up measures with the AHRS and PANAS at four weeks and three months. RESULTS: The interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups. CONCLUSION: We did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider investigating factors predicting individual response. TRIAL REGISTRATION: Dutch Trial Register NTR1813.

The authors regret an error in Fig. 2 of this manuscript. The figure shows the PANSS scores for the hallucination item (P3) for the rTMS groups, aggregating the left and the bilateral treatment group, compared to the placebo group. The X axis plots the time points at which measurements were available: before the start of the treatment and immediately following the 6-day treatment protocol. The Y axis shows the score on the P3 item. Bubble sizes represent the number of subjects with a particular score on the Y axis.

Summary Background Sex steroids such as oestrogen and testosterone are potent neurodevelopmental hormones that also play a role in neuromodulation and neuroprotection of the mature brain. Sex steroid hormones may also be involved in the pathophysiology of schizophrenia as reduced circulating sex steroid levels and changes in brain sex steroid receptors are found in people with schizophrenia compared to controls. In men with schizophrenia, recent studies have documented an inverse correlation between serum testosterone and negative symptoms. Our study sought to confirm whether men with schizophrenia had lower levels of testosterone relative to controls and to determine whether lower testosterone levels were related to higher symptom severity and impaired cognition. Method Circulating serum hormone levels (testosterone, oestrogen, and prolactin), cognitive function and symptoms were assessed in 29 chronically ill men with schizophrenia or schizoaffective disorder. Twenty healthy men were recruited as a comparison group. A series of regression analyses were performed to determine the extent to which circulating sex steroid hormone levels predict cognition and symptoms in men with schizophrenia. Results We did not find a significant difference in serum testosterone levels between groups. However, circulating testosterone levels significantly predicted performance on verbal memory, processing speed, and working memory in men with schizophrenia. With the exception of an effect of oestrogen on verbal memory, circulating sex steroid levels did not predict cognitive function in healthy men. Testosterone levels were not related to positive or negative symptom severity, but testosterone influenced excitement/hostility levels in our schizophrenia sample. Conclusions The results suggest that circulating sex steroids may modulate cognitive deficits associated with schizophrenia.

Estrogen has been implicated in the development and course of schizophrenia with most evidence suggesting a neuroprotective effect. Treatment with raloxifene, a selective estrogen receptor modulator, can reduce symptom severity, improve cognition and normalize brain activity during learning in schizophrenia. People with schizophrenia are especially impaired in the identification of negative facial emotions. The present study was designed to determine the extent to which adjunctive raloxifene treatment would alter abnormal neural activity during angry facial emotion recognition in schizophrenia. Twenty people with schizophrenia (12 men, 8 women) participated in a 13-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment (120 mg per day orally) and performed a facial emotion recognition task during functional magnetic resonance imaging after each treatment phase. Two-sample t-tests in regions of interest selected a priori were performed to assess activation differences between raloxifene and placebo conditions during the recognition of angry faces. Adjunctive raloxifene significantly increased activation in the right hippocampus and left inferior frontal gyrus compared with the placebo condition (family-wise error, P<0.05). There was no significant difference in performance accuracy or reaction time between active and placebo conditions. To the best of our knowledge, this study provides the first evidence suggesting that adjunctive raloxifene treatment changes neural activity in brain regions associated with facial emotion recognition in schizophrenia. These findings support the hypothesis that estrogen plays a modifying role in schizophrenia and shows that adjunctive raloxifene treatment may reverse abnormal neural activity during facial emotion recognition, which is relevant to impaired social functioning in men and women with schizophrenia.

Background: Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study as sessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mech an isms and emotion attribution processes in people with schizophrenia. Methods: Functional magnetic resonance imaging was per formed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence. Results: We en rolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal‐parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during re sponse inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex. Limitations: Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confound ing variables. Conclusion: Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life.

This chapter provides an overview of the literature on bottom-up and ­top-down processes that have been suggested as mechanisms in the generation and/or perpetuation of hallucinations, both in the context of disorders, and in otherwise healthy individuals. We start from the bottom-up, and first consider the case of abnormal perceptual input, as is the case when the sensory organs themselves are impaired, or in situations of sensory deprivation. We then move further down the perceptual pathway to consider the impact of attentional mechanisms on perception, and discuss these in the context models which integrate sensory and attentional deficits to explain to occurrence of hallucinations, such as the recent Perception and Attention Deficit model. Finally, we turn to theoretical frameworks that are implicitly or explicitly based on Bayesian inference theory of perception. Central to these models is the concept that top-down factors such as expectations and prior world-knowledge greatly influence our perception. We also consider experimental evidence for the hypothesis that hallucinations are caused by an imbalance between top-down influences and bottom-up processing.

Brain circuits involved in language processing have been suggested to be compromised in patients with schizophrenia. This does not only include regions subserving language production and perception, but also auditory processing and attention. We investigated resting state network connectivity of auditory, language and attention networks of patients with schizophrenia and hypothesized that patients would show reduced connectivity.Patients with schizophrenia (n=45) and healthy controls (n=30) underwent a resting state fMRI scan. Independent components analysis was used to identify networks of the auditory cortex, left inferior frontal language regions and the anterior cingulate region, associated with attention. The time courses of the components where correlated with each other, the correlations were transformed by a Fisher's Z transformation, and compared between groups. In patients with schizophrenia, we observed decreased connectivity between the auditory and language networks. Conversely, patients showed increased connectivity between the attention and language network compared to controls. There was no relationship with severity of symptoms such as auditory hallucinations.The decreased connectivity between auditory and language processing areas observed in schizophrenia patients is consistent with earlier research and may underlie language processing difficulties. Altered anterior cingulate connectivity in patients may be a correlate of habitual suppression of unintended speech, or of excessive attention to internally generated speech. This altered connectivity pattern appears to be present independent of symptom severity, and may be suggestive of a trait, rather than a state characteristic. (C) 2011 Elsevier B.V. All rights reserved.

Functional neuroimaging techniques such as PET and fMRI have been employed successfully over the past two decades to reveal brain areas involved in the mediation of hallucinations. Numerous studies converge on the involvement of bilateral secondary sensory areas. Auditory verbal hallucinations in patients diagnosed with schizophrenia (and in those with schizophrenia spectrum disorders) have been studied most extensively. These studies have shown a central role for speech-production and speech-perception areas not only in the left hemisphere but also their homotopes in the right hemisphere. The parahippocampal gyrus is also involved in such hallucinations, presumably even in their initiation. Other relevant areas are the anterior cingulate, the insula, cerebellum, and the thalamus. In conclusion, auditory verbal hallucinations would seem to depend primarily on distributed brain networks involved in perceptual attention and memory (which may well reflect top-down processing), in addition to various modality-specific sensory areas. Especially the role of monitoring systems and of the emotional connotations of hallucinations deserve further elucidation.

Schizophrenia is associated with heterogeneity in symptoms, cognition and treatment response. Probabilistic association learning, involving a gradual learning of cue–outcome associations, activates a frontal-striatal network in healthy adults. Studies of probabilistic association learning in schizophrenia have shown frontal-striatal dysfunction although considerable heterogeneity in performance has also been reported. Anodal transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex has been shown to improve probabilistic association learning in healthy adults. The aim of the current study was to determine the extent to which anodal tDCS to the left dorsolateral prefrontal cortex would reverse probabilistic association learning deficits in schizophrenia. Prior to tDCS, 20 people with schizophrenia performed an initial baseline assessment without stimulation. Anodal tDCS was administered continuously for 20 min at an intensity of 2.0 mA to the left dorsolateral prefrontal cortex in a single-blind, counterbalanced, sham-controlled, cross-over design while participants performed 150 trials of a probabilistic association learning test. Although anodal tDCS failed to improve probabilistic association learning based on the whole sample performance, greater variance in the active relative to the sham conditions suggested a subset of people may respond to treatment. Further correlation, regression and cluster analyses revealed differential effects of baseline performance on active tDCS and sham treatment and that there was a subset of people with schizophrenia who displayed improvement with tDCS suggesting that anodal tDCS to the dorsolateral prefrontal cortex may facilitate access to existing prefrontal cortex neural reserves in people with schizophrenia who show adequate capacity to learn at baseline.

Auditory-verbal hallucinations are a hallmark symptom of schizophrenia. In recent years, repetitive transcranial magnetic stimulation (rTMS) targeting speech perception areas has been advanced as a potential treatment of medication-resistant hallucinations. However, the underlying neural processes remain unclear.This study aimed to assess whether 1 Hz rTMS treatment would affect functional connectivity of the temporo-parietal junction (TPJ). Resting state fMRI scans were obtained from 18 patients with schizophrenia. Patients were assessed before and after a 6 day treatment with 1 Hz rTMS to the left TPJ, or placebo treatment with sham rTMS to the same location. We assessed functional connectivity between a priori defined regions-of-interest (ROIs) comprising the putative AVH network and the bilateral TPJ seed regions, targeted with rTMS.Symptom improvement following rTMS treatment was observed in the left rTMS group, whereas no change at occurred in the placebo group. Although no corresponding changes were observed in the functional connections previously found to be associated with AVH severity, an increase in connectivity between the left TPJ and the right insula was observed in group receiving rTMS to the left TPJ. The placebo group conversely showed a decrease in connectivity between the left TPJ and left anterior cingulate.We conclude that application of 1 Hz rTMS to the left TPJ region may affect functional connectivity of the targeted region. However, the relationship between these functional changes during the resting state and the rate of clinical improvement needs further clarification. (c) 2009 Elsevier Ltd. All rights reserved.