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 Adolescents frequently engage in high-risk behaviours (HRB) following childhood sexual abuse (CSA). Aberrant reward processes are implicated in HRB, and their underlying fronto-striatal networks are vulnerable to neurodevelopmental changes during adversity representing a promising candidate for understanding links between CSA and HRB. We examined whether fronto-striatal responses during reward anticipation and feedback (i) are altered in depressed adolescents with CSA compared to depressed, non-abused peers and (ii) moderate the relationship between CSA and HRB irrespective of depression. Forty-eight female adolescents {14 with CSA and depression [CSA +  major depressive disorder (MDD)]; 17 with MDD but no CSA (MDD); 17 healthy, non-abused controls} completed a monetary reward task during functional magnetic resonance imaging. No differences in fronto-striatal response to reward emerged between CSA + MDD and MDD. Critically, high left nucleus accumbens activation during reward anticipation was associated with greater HRB in CSA + MDD compared to MDD and controls. Low left putamen activation during reward feedback was associated with the absence of HRB in CSA + MDD compared to MDD. Striatal reward responses appear to play a key role in HRB for adolescents with CSA irrespective of depression, providing initial support for a CSA ecophenotype. Such information is pivotal to identify at-risk youth and prevent HRB in adolescents after CSA.

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Emerging ecophenotype: reward anticipation is linked to high-risk behaviours after sexual abuse

https://doi.org/10.1016/j.nsa.2022.100472

COVID-19 consequences on motivational functioning: an ecological investigation of the role of momentary gustative-olfactory sensitivity and tonic heart rate variability

Stress and Reward: A Multimodal Assessment of Resilience after Childhood Sexual Abuse

Although a number of patients with anorexia nervosa— especially adolescents with relatively recent onset of the disorder—experiencemarked improvement andevenremission after treatment, toomanypatientsdonot. Anorexia nervosa is characterized by low weight due to persistent efforts to restrict energy intake, often through the consumption of lowfat, low-calorie foods (1). There is no U.S. Food and Drug Administration–approved medication for anorexia nervosa, and no medication has demonstrated substantial efficacy for both weight regain and the psychological symptoms of anorexia nervosa. Although it is more difficult to assess the absolute efficacy of nonpharmacological treatments for anorexia nervosa (e.g., nutritional rehabilitation in more intensive settings and/or psychotherapies), recent high-quality clinical trials comparing treatments make it clear that the majority of patients, especially adults, do notmeet criteria for remission or recovery after treatment (2). Given the need for more efficacious interventions, repeated calls have been made to develop treatments targeting anorexia nervosa–specific mechanisms (3), which would require an improved understanding of those mechanisms. In this issue of the Journal, Kaye and colleagues advance this important inquiry by probing mechanisms related to the response to gustatory stimuli in varying metabolic states (4). In healthy individuals, metabolic state modulates the reward salience of food in an adaptive fashion: fasting potentiates its subjective (reward) value, whereas satiation attenuates it. Kaye et al. used functional MRI to investigate whether this adaptive pattern is altered in women with remitted anorexia nervosa. Specifically, the authors examined how fed and fasted conditions affect blood-oxygen-level-dependent (BOLD) activation and functional connectivity in response to two tastants in women with remitted anorexia nervosa compared to women without a history of the disorder. Contrary to the expectation that the two tastants (a sucrose solution and ionic water) would exhibit different neural responses across conditions and groups, the pattern of results was similar for the two tastants. For both tastants together, two clusters within prespecified tasteand reward-related brain regions showed group differences in the pattern of activation across the fed and fasted conditions. In comparison women, the fasted condition was associated with a greater tastant-related increase in BOLD signal in two ventral caudal putamen clusters, consistent with adaptive potentiation of food reward when metabolic needs are more pressing. In women with remitted anorexia nervosa, the pattern was reversed, with the fed condition associated with the greater increase in BOLD signal in these two clusters. This opposing pattern of activation was also observed for tastant-related connectivity in one of the ventral caudal putamen clusters: in comparison women, this cluster had more positive correlations with seed regions in the right dorsal mid insula and the right ventral caudal putamen in the fasted condition versus the fed condition, whereas in womenwith remitted anorexia nervosa, these correlations were more positive in the fed condition. When looking at each condition separately, group differences were found for the fasted but not the fed condition: in the fasted condition,womenwith remitted anorexia nervosa were generally characterized by lower activation andlesspositivefunctional connectivity in response to tastants in the striatal regions. Interestingly, despite the groups’ opposing neural patterns across metabolic conditions, they reportedhighly similar subjective experiences of hunger and tastant pleasantness across the two conditions. In summary, despite similar ratings of hunger and tastant pleasantness in women with remitted anorexia nervosa, findings within the prespecified tasteand reward-related regions suggest smaller increases in tastant-related activation, and reduced tastant-related positive functional connectivity, in the fasted state for women with remitted anorexia nervosa. The authors suggest that the “reduced recruitment of the striatal aspects of this circuitry in response to tastants when hungry” may result in impaired “translation of taste reward value to motivated eating behavior,” representing a potential neural explanation for the persistent dietary restriction observed in anorexia nervosa. [This study] addresses many of the challenges involved in advancing our understanding of the mechanisms underlying persistent dietary restriction in anorexia nervosa.

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Neural Insensitivity to the Effects of Hunger: A Potential Mechanism Underlying Persistent Dietary Restriction in Anorexia Nervosa?

Objective Studies in estrogen deficiency states such as primary ovarian insufficiency and Turner syndrome suggest that estrogen status may be an important modulator of mood and emotions. In this study we compared depressive and anxiety symptoms between adolescent and young adult female oligo-amenorrheic athletes (AA) and eumenorrheic females (EM), and explored structural, and functional changes in related brain areas during reward processing, a behavioral construct that is altered in depression and anxiety. Methods We included (i) 24 AA participating in ≥4 hours/week of aerobic exercise or running ≥20 miles/week for ≥6 months in the preceding year, with lack of menstrual cycles for ≥3 months within at least 6 preceding months of oligo-amenorrhea, OR in premenarchal girls, absence of menses at >15 years), and (ii) 27 EM aged 14-25 years. Participants completed the Beck Depression Inventory-II (BDI-II), State and Trait Anxiety Inventory (STAI), and Mood and Anxiety Symptoms Questionnaire (MASQ). Structural MRI and brain activation during a functional MRI (fMRI) task that probes reward and punishment processing was examined in a subset of 10 AA and 23 EM. Results Median (IQR) age and BMI of AA and EM groups were 20.6 (19.0-22.6) vs. 20.6 (19.2-23.7) years, p=0.6 and v 20.3 (18.8-21.5) vs. 21.9 (19.6-23.5) kg/m2, p=0.005, respectively. While groups did not differ for BDI-II scores, AA had higher anhedonic depression MASQ scores (p=0.04), and STAI (p=0.03) scores vs. EM. In the fMRI subset, AA had higher caudate volumes vs. EM [F(1, 29)=9.930, p=0.004]. Lower activation observed in the right caudate during reward anticipation in AA compared with EM (p=0.036) suggests blunted reward processing in the striatum in estrogen deficient states. Conclusion Athletes with amenorrhea had higher depressive and anxiety symptomatology compared to eumenorrheic young women. Exploratory analyses demonstrated increased caudate volumes and decreased caudate activation during reward processing in athletes with amenorrhea suggesting that estrogen may play a role in reward processing.

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Diego A. Pizzagalli

Papers

Emerging ecophenotype: reward anticipation is linked to high-risk behaviours after sexual abuse

COVID-19 consequences on motivational functioning: an ecological investigation of the role of momentary gustative-olfactory sensitivity and tonic heart rate variability

Stress and Reward: A Multimodal Assessment of Resilience after Childhood Sexual Abuse

Neural Insensitivity to the Effects of Hunger: A Potential Mechanism Underlying Persistent Dietary Restriction in Anorexia Nervosa?

Depressive and anxiety symptoms, and neural correlates of reward and punishment anticipation in female athletes with amenorrhea