Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

A study with low statistical power has a reduced chance of detecting a true effect, but it is less well appreciated that low power also reduces the likelihood that a statistically significant result reflects a true effect. Here, we show that the average statistical power of studies in the neurosciences is very low. The consequences of this include overestimates of effect size and low reproducibility of results. There are also ethical dimensions to this problem, as unreliable research is inefficient and wasteful. Improving reproducibility in neuroscience is a key priority and requires attention to well-established but often ignored methodological principles.

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Power failure: why small sample size undermines the reliability of neuroscience

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Emotion and Adaptation

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

Abstract Background The association between major depressive disorder and motivation to invest cognitive effort for rewards is unclear. One reason might be that prior tasks of cognitive effort-based decision-making are limited by potential confounds such as physical effort and temporal delay discounting. Methods To address these interpretive challenges, we developed a new task – the Cognitive Effort Motivation Task – to assess one's willingness to exert cognitive effort for rewards. Cognitive effort was manipulated by varying the number of items (1, 2, 3, 4, 5) kept in spatial working memory. Twenty-six depressed patients and 44 healthy controls went through an extensive learning session where they experienced each possible effort level 10 times. They were then asked to make a series of choices between performing a fixed low-effort-low-reward or variable higher-effort-higher-reward option during the task. Results Both groups found the task more cognitively (but not physically) effortful when effort level increased, but they still achieved ⩾80% accuracy on each effort level during training and >95% overall accuracy during the actual task. Computational modelling revealed that a parabolic model best accounted for subjects' data, indicating that higher-effort levels had a greater impact on devaluing rewards than lower levels. These procedures also revealed that MDD patients discounted rewards more steeply by effort and were less willing to exert cognitive effort for rewards compared to healthy participants. Conclusions These findings provide empirical evidence to show, without confounds of other variables, that depressed patients have impaired cognitive effort motivation compared to the general population.

Cognitive effort-based decision-making in major depressive disorder

OBJECTIVE Evidence suggests that blunted reward responsiveness may account for poor clinical outcomes in both opioid use disorder (OUD) and chronic pain. Understanding how individuals with OUD and comorbid chronic pain (OUD+CP) respond to rewards is, therefore, of clinical interest because it may reveal a potential point of behavioral intervention. METHODS Patients with OUD (n = 28) and OUD+CP (n = 19) on opioid agonist treatment were compared on: 1) the Probabilistic Reward Task (an objective behavioral measure of reward response bias) and 2) ecological momentary assessment of affective responses to pleasurable events. RESULTS Both the OUD and the OUD+CP groups evidenced an increase in reward response bias in the Probabilistic Reward Task. The rate of change in response bias across blocks was statistically significant in the OUD group (B = 0.06, standard error [SE] = 0.02, t = 3.92, P < 0.001, 95% confidence interval [CI]: 0.03 to 0.09) but not in the OUD+CP group (B = 0.03, SE = 0.02, t = 1.90, P = 0.07, 95% CI: -0.002 to 0.07). However, groups did not significantly differ in the rate of change in response bias across blocks (B = 0.03, SE = 0.02, t = 1.21, P = 0.23, 95% CI: -0.02 to 0.07). Groups did not significantly differ on state measures of reward responsiveness (P's ≥0.50). CONCLUSIONS Overall, findings across objective and subjective measures were mixed, necessitating follow-up with a larger sample. The results suggest that although there is a reward response bias in patients with OUD+CP treated with opioid agonist treatment relative to patients with OUD without CP, it is modest and does not appear to translate into patients' responses to rewarding events as they unfold in daily life.

Reward Responsiveness in Patients with Opioid Use Disorder on Opioid Agonist Treatment: Role of Comorbid Chronic Pain.

INTRODUCTION Rates of light smoking have increased in recent years and are associated with adverse health outcomes. Reducing light smoking is a challenge because it is unclear why some but not others, progress to heavier smoking. Nicotine has profound effects on brain reward systems and individual differences in nicotine's reward-enhancing effects may drive variability in smoking trajectories. Therefore, we examined whether a genetic risk factor and personality traits known to moderate reward processing, also moderate the reward-enhancing effects of nicotine. METHODS Light smokers (n = 116) performed a Probabilistic Reward Task to assess reward responsiveness after receiving nicotine or placebo (order counterbalanced). Individuals were classified as nicotine dependence 'risk' allele carriers (rs16969968 A-allele carriers) or non-carriers (non-A-allele carriers), and self-reported negative affective traits were also measured. RESULTS Across the sample, reward responsiveness was greater following nicotine compared to placebo (p = 0.045). For Caucasian A-allele carriers but not non-A-allele carriers, nicotine enhanced reward responsiveness compared to placebo for those who received placebo first (p = 0.010). Furthermore, for A-allele carriers but not non-A-allele carriers who received nicotine first, the enhanced reward responsiveness in the nicotine condition carried over to the placebo condition (p < 0.001). Depressive traits also moderated the reward-enhancing effects of nicotine (p = 0.010) and were associated with blunted reward responsiveness following placebo but enhanced reward responsiveness following nicotine. CONCLUSION These findings suggest that individual differences in a genetic risk factor and depressive traits alter nicotine's effect on reward responsiveness in light smokers and may be important factors underpinning variability in smoking trajectories in this growing population. IMPLICATIONS Individuals carrying genetic risk factors associated with nicotine dependence(rs16969968 A-allele carriers) and those with higher levels of depressive personality traits, showmore pronounced increases in reward learning following acute nicotine exposure. These findingssuggest that genetic and personality factors may drive individual differences in smoking trajectoriesin young light smokers by altering the degree to which nicotine enhances reward processing. CLINICAL TRIAL REGISTRATION NCT02129387 (pre-registered hypothesis: www.clinicaltrials.gov).

Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers

Translational Perspectives on Anxiety Disorders and the Research Domain Criteria Construct of Potential Threat

the way to future human trials (Panksepp & Harro 2004). But what are the best animal models? With the amount of evolutionary diversification that exists, one must select model systems carefully (Panksepp et al. 1992; 2002), and D&M-S wisely prioritized primate data over rodent data. Dogs are also an excellent species (Panksepp et al. 1978). Certainly lab rats are not optimal for understanding separation-distress arising from severing specific social bonds. These excellent \" test-tube \" creatures thrive when housed alone in sterile environments , perhaps because their separation-distress systems are ves-tigial (Panksepp 2003). Selective opioid regulation of social distress is well documented in many species (Panksepp 1998), but is dubious in rats (Winslow & Insel 1991a). Perhaps because of this, they are excellent species for studying the affiliative energies of play and low-dose opioid facilitation of social interactions (Panksepp & Bishop 1981; Panksepp et al. 1985). As D&M-S recognize, the use of selected neurochemical systems to discuss processes as complex as affiliation needs to be advanced with the proviso that they only approximate the complexity of the underlying causal issues. If we try to extrapolate general neu-rochemical principles to excessively fine-circuit and synaptic levels , we may be encouraging a radical reductionism that is wrong (Bennett & Hacker 2003). Obviously, social attachments and affiliations are fully \" embodied \" within brain, body, and environment. Important fusion points between levels of analysis must not be construed as explanations. But, as this target article exemplifies, meaningful visions of the larger picture cannot deny nor should they shy away from investigations at finer layers of explanation. Continued attempts to stitch neuroscience details from animal studies into coherent, testable hypotheses at more molar, human levels are vital intellectual initiatives, as long as we recognize that the emergent neuropsychology of human beings lies at the root of our social dilemmas, not merely the biochemical mechanisms that underlie the electrical properties of subsets of neurons in limited brain regions. Ultimately, affiliation is an emergent property of being a mammal. Attachment does not simply exist in the brain, but in brains' interrelations with bodies and environments. Analysis of neuro-chemistries of brain/mind states that correlate in some way with affiliation is a most reasonable empirical way to proceed, especially if we carefully strip away erroneous philosophical assumptions , as well as potentially irrelevant fine details. If we do that well, translations between levels can be advanced at a …

Diego A. Pizzagalli

Papers

Cognitive effort-based decision-making in major depressive disorder

Reward Responsiveness in Patients with Opioid Use Disorder on Opioid Agonist Treatment: Role of Comorbid Chronic Pain.

Genetic and Depressive Traits Moderate the Reward-Enhancing Effects of Acute Nicotine in Young Light Smokers

Translational Perspectives on Anxiety Disorders and the Research Domain Criteria Construct of Potential Threat

Impaired hedonic capacity in major depressive disorder: Impact on affiliative behaviors