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Tobacco smoking is associated with deleterious health outcomes. Most smokers want to quit smoking, yet relapse rates are high. Understanding neural differences associated with tobacco use may help generate novel treatment options. Several animal studies have recently highlighted the central role of the thalamus in substance use disorders, but this research focus has been understudied in human smokers. Here, we investigated associations between structural and functional magnetic resonance imaging measures of the thalamus and its subnuclei to distinct smoking characteristics. We acquired anatomical scans of 32 smokers as well as functional resting‐state scans before and after a cue‐reactivity task. Thalamic functional connectivity was associated with craving and dependence severity, whereas the volume of the thalamus was associated with dependence severity only. Craving, which fluctuates rapidly, was best characterized by differences in brain function, whereas the rather persistent syndrome of dependence severity was associated with both brain structural differences and function. Our study supports the notion that functional versus structural measures tend to be associated with behavioural measures that evolve at faster versus slower temporal scales, respectively. It confirms the importance of the thalamus to understand mechanisms of addiction and highlights it as a potential target for brain‐based interventions to support smoking cessation, such as brain stimulation and neurofeedback.

Craving is a core symptom of cocaine use disorder and a major factor for relapse risk. To date, there is no pharmacological therapy to treat this disease or at least to alleviate cocaine craving as a core symptom. In animal models, impaired prefrontal-striatal signalling leading to altered glutamate release in the nucleus accumbens appear to be the prerequisite for cocaine-seeking. Thus, those network and metabolic changes may constitute the underlying mechanisms for cocaine craving and provide a potential treatment target. In humans, there is recent evidence for corresponding glutamatergic alterations in the nucleus accumbens, however, the underlying network disturbances that lead to this glutamate imbalance remain unknown. In this state-dependent randomized, placebo-controlled, double-blinded, cross-over multimodal study, resting state functional magnetic resonance imaging in combination with small-voxel proton magnetic resonance spectroscopy (voxel size: 9.4 × 18.8 × 8.4 mm3) was applied to assess network-level and associated neurometabolic changes during a non-craving and a craving state, induced by a custom-made cocaine-cue film, in 18 individuals with cocaine use disorder and 23 healthy individuals. Additionally, we assessed the potential impact of a short-term challenge of N-acetylcysteine, known to normalize disturbed glutamate homeostasis and to thereby reduce cocaine-seeking in animal models of addiction, compared to a placebo. We found increased functional connectivity between the nucleus accumbens and the dorsolateral prefrontal cortex during the cue-induced craving state. However, those changes were not linked to alterations in accumbal glutamate levels. Whereas we additionally found increased functional connectivity between the nucleus accumbens and a midline part of the thalamus during the cue-induced craving state. Furthermore, obsessive thinking about cocaine and the actual intensity of cocaine use were predictive of cue-induced functional connectiv

The brain and its health are essential for our (physical mental, social, and spiritual) wellbeing, for being able to realize our potential as individuals, and also for a fair, well-functioning, and productive society. However, today the world is facing a healthcare crisis related to the very high (and increasing) burden of brain disorders. As a response to this crisis, the “Swiss Brain Health Plan” (SBHP) was conceptualized in the context of other initiatives launched to value, promote, and protect brain health over the entire life course. In the first section of this position paper, the following fundamental considerations of the SBHP are discussed: (1) the high (and increasing) burden of brain disorders in terms of prevalence (>50% of the population suffers from a brain disorder), disability, mortality, and costs; (2) the prevention of brain disorders; (3) the operational definition of brain health; (4) determinants of brain health; (5) international initiatives to promote brain (including mental) health including the World Health Organization (WHO) intersectorial global action plan on epilepsy and other neurological disorders (NDs) (IGAP) and the WHO comprehensive mental health action plan. In the second section of the paper, the five strategic objectives of the SBHP, which has the vision of promoting brain health for all across the entire life course, are presented: (1) to raise awareness; (2) strengthen cross-disciplinary and interprofessional training/educational programs for healthcare professionals; (3) foster research on brain health determinants and individualized prevention of brain disorders; (4) prioritize a holistic (non-disease-specific), integrated, person-centered public health approach to promote brain health and prevent brain disorders through collaborations across scientific, health care, commercial, societal and governmental stakeholders and insurance providers; (5) support, empower, and engage patients, caregivers, and patient organizations, an

Tobacco smoking is one of the leading causes of preventable death and disease worldwide. Most smokers want to quit, but relapse rates are high. To improve current smoking cessation treatments, a better understanding of the underlying mechanisms of nicotine dependence and related craving behaviour is needed. Studies on cue-driven cigarette craving have been a particularly useful tool for investigating the neural mechanisms of drug craving. Here, functional neuroimaging studies in humans have identified a core network of craving-related brain responses to smoking cues that comprises of amygdala, anterior cingulate cortex, orbitofrontal cortex, posterior cingulate cortex and ventral striatum. However, most functional Magnetic Resonance Imaging (fMRI) cue-reactivity studies do not adjust their stimuli for emotional valence, a factor assumed to confound craving-related brain responses to smoking cues. Here, we investigated the influence of emotional valence on key addiction brain areas by disentangling craving- and valence-related brain responses with parametric modulators in 32 smokers. For one of the suggested key regions for addiction, the amygdala, we observed significantly stronger brain responses to the valence aspect of the presented images than to the craving aspect. Our results emphasize the need for carefully selecting stimulus material for cue-reactivity paradigms, in particular with respect to emotional valence. Further, they can help designing future research on teasing apart the diverse psychological dimensions that comprise nicotine dependence and, therefore, can lead to a more precise mapping of craving-associated brain areas, an important step towards more tailored smoking cessation treatments. Keywords: craving; cue-reactivity; functional Magnetic Resonance Imaging; neuroimaging; nicotine use disorder; smoking.

Background and aimsAlcohol Use Disorder (AUD) is characterized by a reduction in goal-directed behavior, with alcohol use taking precedence over other areas of life. These features in AUD resemble negative symptoms in schizophrenia, especially the reduction in motivation and pleasure (MAP). Given the clinical similarities of negative symptoms across diagnostic categories, it comes as a surprise that there are few investigations on negative symptoms in alcohol and other substance use disorders. To our knowledge, our study is the first to assess negative symptoms in AUD based on a two-factorial approach, and to investigate the interrelation of these dimensions with the severity of AUD, and alcohol craving.Materials and methodsWe examined a sample of 42 patients with AUD at the Psychiatric University Hospital in Zurich. Participants provided self-report and interview-based measures of the severity of AUD, negative symptoms, and alcohol craving. Finally, we used data from the electronic health records of the patients.ResultsPatients with AUD show negative symptoms to a similar extent as patients with schizophrenia or bipolar disorder. We found a positive correlation between the extent of impairment within the MAP factor and overall severity of AUD. Furthermore, MAP negative symptoms were correlated with alcohol craving. In a linear regression, negative symptoms predicted alcohol craving whereas depression did not.SummaryNegative symptoms as conceptualized for schizophrenia are prevalent in patients with AUD and associated with the severity of AUD. More specifically, severity of AUD correlates with diminished motivation and pleasure, highlighting the importance of disturbances in motivational functions in AUD. This is further supported by the correlation between negative symptoms and craving, a hallmark of AUD. Taken together, our findings suggest that negative symptoms might be a highly relevant but hitherto often neglected therapeutic target in AUD.

The dopaminergic midbrain is associated with reinforcement learning, motivation and decision-making – functions often disturbed in neuropsychiatric disorders. Previous research has shown that dopaminergic midbrain activity can be endogenously modulated via neurofeedback. However, the robustness of endogenous modulation, a requirement for clinical translation, is unclear. Here, we examine whether the activation of particular brain regions associates with successful regulation transfer when feedback is no longer available. Moreover, to elucidate mechanisms underlying effective self-regulation, we study the relation of successful transfer with learning (temporal difference coding) outside the midbrain during neurofeedback training and with individual reward sensitivity in a monetary incentive delay (MID) task. Fifty-nine participants underwent neurofeedback training either in standard (Study 1 N = 15, Study 2 N = 28) or control feedback group (Study 1, N = 16). We find that successful self-regulation is associated with prefrontal reward sensitivity in the MID task (N = 25), with a decreasing relation between prefrontal activity and midbrain learning signals during neurofeedback training and with increased activity within cognitive control areas during transfer. The association between midbrain self-regulation and prefrontal temporal difference and reward sensitivity suggests that reinforcement learning contributes to successful self-regulation. Our findings provide insights in the control of midbrain activity and may facilitate individually tailoring neurofeedback training.

Tobacco smoking is associated with deleterious health outcomes. Most smokers want to quit smoking, yet relapse rates are high. Understanding neural differences associated with tobacco use may help generate novel treatment options. Several animal studies have recently highlighted the central role of the thalamus in substance use disorders, but this research focus has been understudied in human smokers. Here, we investigated associations between structural and functional magnetic resonance imaging measures of the thalamus and its subnuclei to distinct smoking characteristics. We acquired anatomical scans of 32 smokers as well as functional resting-state scans before and after a cue-reactivity task. Thalamic functional connectivity was associated with craving and dependence severity, whereas the volume of the thalamus was associated with dependence severity only. Craving, which fluctuates rapidly, was best characterized by differences in brain function, whereas the rather persistent syndrome of dependence severity was associated with both brain structural differences and function. Our study supports the notion that functional versus structural measures tend to be associated with behavioral measures that evolve at faster versus slower temporal scales, respectively. It confirms the importance of the thalamus to understand mechanisms of addiction and highlights it as a potential target for brain-based interventions to support smoking cessation, such as brain stimulation and neurofeedback.

Due to high infections rates and a high death toll of the COVID-19 pandemic, it is important to have daily updated forecasted estimates for the next weeks in order to allocate the scare resources as good as possible. We propose a pragmatic model to forecast the COVID-19 epidemic by applying a mixture normal distribution to open accessible WHO data. We specified a simple joint model on data from 20 countries with number of confirmed COVID-19 infections and number of COVID-19 deaths. We found that the duration of an epidemic wave (99% of total size) was usually between 45 – 48 days. Using data up to April 6, 2020, we found in six of 20 counties two waves, spaced between 21 and 47 days. In China and Korea the first wave was bigger, and in Denmark, Iran, Japan, and Sweden the second wave was stronger. Lag time between time trends in confirmed infections and time trends in deaths varied between 3.1 and 9.5 days. We obtained a good fit between observed and modelled data in almost all countries. In about halve of the countries the highest peak of the COVID-19 epidemic had been reached until April 6, 2020. Among the 20 countries, it is predicted that the USA will reach the highest numbers of confirmed infections (653 683 – 802 205) and number of deaths (36 591 – 53 286). Taken together, for many countries reasonable and up-to-date forecasting seems to be feasible. This method therefore bears a high potential for assisting decision makers to adjust the measures aiming at reducing the spread of the virus appropriately.

Substance use disorders (SUD) represent a significant public health issue with a high need for novel and efficacious treatment options. In light of this high unmet need, recent results reporting beneficial outcomes of psychedelic-assisted therapy in SUD are particularly relevant. However, several questions remain with regard to this treatment approach. The clinical mechanisms of action of psychedelic substances in the treatment of SUD are not well understood. Closing this knowledge gap is critical to inform and optimize the psychotherapeutic embedding of the acute substance administration. In this chapter, we discuss potential mechanisms that have implications on psychotherapeutic approaches including induced neuroplasticity, alterations in brain network connectivity, reward and emotion processing, social connectedness, insight, and mystical experiences. Furthermore, we outline considerations and approaches that leverage these mechanisms in order to optimize the therapeutic embedding by maximizing synergy between substance effects and psychotherapy. Understanding the mechanisms of action, developing psychotherapeutic approaches accordingly, and evaluating their synergistic efficacy in scientific studies will be critical to advance the framework of psychedelic-assisted therapy for addiction, create evidence-based approaches, and achieve the best treatment outcome for patients with SUD.