Sala Giovanni

Abstract Objectives Cognitive and physical functions are both associated with disability and death. Recent studies have addressed the relationship between cognitive declines and physical declines; however, whether various facets of cognition are diversely associated with specific physical functions is yet to be ascertained. The present work examines the longitudinal associations between fluid and crystallized cognitive functions (Gf and Gc) and physical functions. Methods The sample consisted of 863 community-dwelling older adults (baseline age 60-79 years) from the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA). The participants were tested on a set of Gf and Gc tests and physical tests (grip strength and gait speed). We ran a series of Multivariate Latent Growth Curve (MLGC) models. Specifically, we tested the relationship between cognitive and physical functions in terms of baseline performance (intercept) and rate of change (slope). Results The slope-slope correlations between Gf and physical function were large (grip strength r = 0.64 and gait speed r = 0.68, ps < 0.001). By contrast, the slope correlations between Gc and physical functions were weak (rs ≤ 0.31) and barely or marginally significant (ps ≤ 0.06). Discussion The results show that distinct domains of cognitive functions have different associations with physical functions. Namely, the aging-associated declines in the tested physical functions are robustly correlated with the declines in Gf, but are only weakly correlated with the declines in Gc. Therefore, Gc measures may be poor proxies for the patient’s frailty and should be considered with caution in clinical assessment.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2,294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer’s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

Education has been claimed to reduce aging-associated declines in cognitive function. Given its societal relevance, considerable resources have been devoted to this research. However, because of the difficulty of detecting modest rates of change, findings have been mixed. These discrepancies may stem from methodological shortcomings such as short time spans, few waves, and small samples. The present study overcame these limitations ( N = 1,892, nine waves over a period of 20 years). We tested the effect of education level on baseline performance (intercept) and the rate of change (slope) in crystallized and fluid cognitive abilities ( gc and gf, respectively) in a sample of Japanese adults. Albeit positively related to both intercepts, education had no impact on either the gc or the gf slope. Furthermore, neither intercept exhibited any appreciable correlation with either slope. These results thus suggest that education has no substantial role (direct or mediated) in aging-related changes in cognition.

<title>Abstract</title>We used a multi-method approach to investigate how children avoid (or retreat from) argument structure overgeneralisation errors (e.g., *<italic>You giggled me</italic>). Experiment 1 investigated how semantic and statistical constraints (preemption and entrenchment) influence children’s and adults’ judgments of the grammatical acceptability of 120 verbs in transitive and intransitive sentences. Experiment 2 used syntactic priming to elicit overgeneralisation errors from children (aged 5–6) to investigate whether the same constraints operate in production. For judgments, the data showed effects of preemption, entrenchment, and semantics for all ages. For production, only an effect of preemption was observed, and only for transitivisation errors with intransitive-only verbs (e.g., <italic>*The man laughed the girl</italic>). We conclude that preemption, entrenchment, and semantic effects are real, but are obscured by particular features of the present production task.

<p>This study investigates how Japanese-speaking children learn interactional dependencies in conversations to use un, a token typically used as a positive response for yes-no questions, backchannel and acknowledgement. We predict that children learn the probability of different types of cues in the immediately preceding turns to respond with un appropriately. To this end, we built generalised linear models on the longitudinal conversation data from seven children aged between 1 and 5 years, and their caregivers. Our model revealed those children not only increased the general probability of un to reach the adults’ rate, but also learned to attend relevant cues in the preceding turns to respond with un. Children increasingly produce un when their interlocutors ask a yes-no question or signal the continuation of their own speech. Our results illustrate how children learn the probabilistic dependency between adjacent turns, and become able to participate in conversational interactions.</p>

<p>How do children learn to use discourse markers in conversational interactions? This study focused on a Japanese discourse marker un, typically used as a positive response for yes-no questions and as a backchannel, and tested our prediction that children first learn to use un to respond to questions and then use it as backchannels after interlocutors signal the continuation of their discourse. To this end, we built generalised linear models on the longitudinal conversation data from seven children aged between 1 and 5 years and their caregivers. Our model revealed that children not only increase the general probability of un to reach adults’ rates, but also learn to use un in response to yes-no questions as we predicted. Children also tend to produce un as a backchannel after the interlocutor’s final modal particle ne, which is typically used to set a common ground. Our results show that children gradually learn different interactional contexts for the use of un from local probabilistic coherence between turns in conversations.</p>

<title>Abstract</title>The human vesicular monoamine transporter 1 (<italic>VMAT1</italic>) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmission, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse <italic>Vmat1</italic> via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological and molecular levels. Behavioral tests revealed reduced anxiety-related traits of <italic>Vmat1</italic>^Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified amygdala-specific changes in the expression of genes involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors.

A recent meta-analysis (Stanmore et al. Neurosci. Biobehav. Rev. 78:34-43, 2017) claimed that exergames exert medium-size positive effects on people's overall cognitive function. The present article critically tests this claim. We argue that the meta-analysis reported inflated effect sizes mainly for three reasons: (a) some effect sizes were miscalculated; (b) there was an excessive amount of true heterogeneity; and (c) no publication-bias-corrected estimates were provided. We have thus recalculated the effect sizes and reanalyzed the data using a more robust approach and more sophisticated techniques. Compared to Stanmore's et al., our models show that: (a) the overall effect sizes are substantially smaller; (b) the amount of true heterogeneity, when any, is much lower; and (c) the publication-bias analyses suggest that the actual effect of exergames on overall cognitive function is slim to null. Therefore, the cognitive benefits of exergames are far from being established.

<title>Abstract</title>Altered brain energy metabolism associated with increase in lactate levels and the resultant decrease in pH have been increasingly implicated in multiple neuropsychiatric disorders, such as schizophrenia, bipolar disorder, autism spectrum disorder and neurodegenerative disorders. Although it is controversial, change of pH/ lactate level as a primary feature of these diseases, rather than a result of confounding factors such as medication and agonal state, has been evidenced. Animal models that can be studied without such confounding factors inherent to humans are a suitable alternative to understand the controversy. However, the knowledge in animal models regarding brain pH and lactate and their relation to behavioral outcomes is limited in the context of neuropsychiatric disease conditions. In this study, we investigated the common occurrence of changes in the pH and lactate levels in the brain in animal models by analyzing 65 animal models related to neuropsychiatric and neurodegenerative diseases with 1,239 animals. Additionally, we evaluated the behavioral phenotypes relative to the chemical changes in the brain. Among the models, 27 and 24 had significant changes in brain pH and lactate levels, respectively, including Shank2 KO mice, Clock mutant mice, serotonin transporter KO mice, mice with a paternal duplication of human chromosome 15q11-13, Fmr1 KO mice, BTBR mice, APP-J20 Tg mice, social defeat stress-exposed mice, corticosterone-treated mice, and streptozotocin-induced diabetic mice. Meta-analysis of the data revealed a highly significant negative correlation between brain pH and lactate levels, suggestive of increased lactate levels causing decreased brain pH. Statistical learning algorithm based on the comprehensive data has revealed that the increased brain lactate levels can be predominantly predicted by the indices for the percentage of correct response in working memory test, with a significant simple, negative correlation. Our results suggest that brain energy metabolism is commonly altered in many animal models of neuropsychiatric and neurodegenerative diseases, which may be associated with working memory performance. We consider our study to be an essential step suggesting that the brain endophenotypes serve as a basis for the transdiagnostic characterization of the biologically heterogeneous and debilitating cognitive illnesses. Based on these results, we are openly accepting collaborations to extend these findings and to test the hypotheses generated in this study using more animal models. We welcome any mice/rat models of diseases with or without any behavioral phenotypes.

Abstract. The Montreal Cognitive Assessment (MoCA) is a test assessing global cognition in older adults which is often used by researchers and clinicians worldwide, although some of its psychometric properties have yet to be established. We focus on three fundamental aspects: the factorial structure of the MoCA, its general factor saturation, and the measurement invariance of the test. We administered the MoCA to a large sample of Japanese older adults clustered in three cohorts (69–71-year-olds, 79–81-year-olds, and 89–91-year-olds; N = 2,408). Our results show that the test has an overall stable hierarchical factorial structure with a general factor at its apex and satisfactory general-factor saturation. We also found measurement invariance across participants of different ages, educational levels, economic status, and sex. This comprehensive investigation thus supports the idea that the MoCA is a valid tool to assess global cognition in older adults of different socioeconomic status and age ranges.

<p>The Home Cage Social Interaction (HCSI) test is a standard tool for assessing locomotor activity and social behaviour in numerous mouse models of psychiatric disorders. Data obtained from this test are commonly analysed with linear modelling. However, linear modelling is unfit for HCSI data because the relation between HCSI response variables and time is cyclic rather than linear. Moreover, the response variables are commonly assumed to follow a Gaussian (normal) distribution, which is pretty much never the case with HCSI data. In brief, the statistical model currently applied to HCSI data is substantially incorrect.We thus propose to employ nonlinear modelling techniques such as General Additive Modelling (GAM) for HCSI data. GAM utilizes smoothing functions that allow for nonlinear relationships between the response variable and the covariates. Moreover, GAM enables the researcher to employ smoothing functions designed for analysing cyclic data. Finally, GAM also implements non-Gaussian exponential family distributions to meet the model’s statistical assumptions. We compare linear modelling and GAM on 27 HCSI statistically independent experiments involving wild-type and mutant mice over seven days. In all the cases, the GAM models outperform the linear models in both explained deviance and inference reliability. Most notably, the linear models tend towards Type I error with regard to the group effect and Type II error with respect to the time-by-group interaction. We thus recommend researchers to adopt the present statistical model to analyse HCSI data.</p>

<p>Green et al. (2019) provide methodological recommendations for improving research on the effects of behavioural interventions aimed at cognitive enhancement. After addressing some points made by Green et al. with which we (partially) disagree, we discuss additional recommendations for making progress in cognitive training research, focusing on the use of computer modelling and the analysis of detailed data to understand participants’ knowledge and strategies. We then discuss the importance of using meta-analyses to understand the effects of cognitive training and show that meta-analyses have resolved the apparent lack of consensus in the field. Finally, taking a broader perspective, we conclude that the available empirical evidence on cognitive training and other fields of research suggests that the likelihood of finding reliable and robust far-transfer effects is low. Thus, research efforts should be redirected to near transfer or to other methods for improving cognition.</p>

Music training has repeatedly been claimed to positively impact children's cognitive skills and academic achievement (literacy and mathematics). This claim relies on the assumption that engaging in intellectually demanding activities fosters particular domain-general cognitive skills, or even general intelligence. The present meta-analytic review (N = 6,984, k = 254, m = 54) shows that this belief is incorrect. Once the quality of study design is controlled for, the overall effect of music training programs is null ([Formula: see text] ≈ 0) and highly consistent across studies (τ2 ≈ 0). Results of Bayesian analyses employing distributional assumptions (informative priors) derived from previous research in cognitive training corroborate these conclusions. Small statistically significant overall effects are obtained only in those studies implementing no random allocation of participants and employing non-active controls ([Formula: see text] ≈ 0.200, p < .001). Interestingly, music training is ineffective regardless of the type of outcome measure (e.g., verbal, non-verbal, speed-related, etc.), participants' age, and duration of training. Furthermore, we note that, beyond meta-analysis of experimental studies, a considerable amount of cross-sectional evidence indicates that engagement in music has no impact on people's non-music cognitive skills or academic achievement. We conclude that researchers' optimism about the benefits of music training is empirically unjustified and stems from misinterpretation of the empirical data and, possibly, confirmation bias.

Abstract Background Evidence suggests non-specific benefits of the tuberculosis vaccine bacillus Calmette-Guérin (BCG) against non-related infections. Recent studies propose such protection may extend to the novel COVID-19 as well. This is a contested hypothesis. Methods Our ecological study confronts this hypothesis. We examine the effects of BCG vaccination on countries’ COVID-19 (a) cases and deaths (per million) and (b) exponential growth factors over specific periods of the pandemic. Since the BCG vaccine was derived from Mycobacterium bovis, a bacterium causing tuberculosis in cattle, having suffered from tuberculosis also may exert a non-specific protection against the COVID-19 as well. Along with BCG vaccination, we test the effect of the prevalence of tuberculosis. We employ multiple regression and principal component analysis (PCA) to control for potentially confounding variables (n= 16). Results BCG vaccination policy and incidence of tuberculosis is associated with a reduction in both COVID-19 cases and deaths, and the effects of these two variables are additive (≈ 5% to 15% of total unique variance explained). The study of exponential growth factors in the initial stages of the pandemic further shows that BCG vaccination exerts a significant effect (up to 35% of unique variance explained). Conclusions Overall, these findings corroborate the hypothesis that BCG vaccination and exposure to tuberculosis may induce a non-specific protection against the novel SARS-CoV-2 infection, even after accounting for a large number of confounding influences. However, given the potential public-health benefits, our results indicate that the hypothesis deserves further attention and should not be hastily dismissed.

It has been proposed that playing chess enables children to improve their ability in mathematics. These claims have been recently evaluated in a meta-analysis (Sala & Gobet, 2016, Educational Research Review, 18, 46-57), which indicated a significant effect in favor of the groups playing chess. However, the meta-analysis also showed that most of the reviewed studies used a poor experimental design (in particular, they lacked an active control group). We ran two experiments that used a three-group design including both an active and a passive control group, with a focus on mathematical ability. In the first experiment (N = 233), a group of third and fourth graders was taught chess for 25 hours and tested on mathematical problem-solving tasks. Participants also filled in a questionnaire assessing their meta-cognitive ability for mathematics problems. The group playing chess was compared to an active control group (playing checkers) and a passive control group. The three groups showed no statistically significant difference in mathematical problem-solving or metacognitive abilities in the posttest. The second experiment (N = 52) broadly used the same design, but the Oriental game of Go replaced checkers in the active control group. While the chess-treated group and the passive control group slightly outperformed the active control group with mathematical problem solving, the differences were not statistically significant. No differences were found with respect to metacognitive ability. These results suggest that the effects (if any) of chess instruction, when rigorously tested, are modest and that such interventions should not replace the traditional curriculum in mathematics.

Chess masters and expert musicians appear to be, on average, more intelligent than the general population. Some researchers have thus claimed that playing chess or learning music enhances children's cognitive abilities and academic attainment. We here present two meta-analyses assessing the effect of chess and music instruction on children's cognitive and academic skills. A third meta-analysis evaluated the effects of working memory traininga cognitive skill correlated with music and chess expertiseon the same variables. The results show small to moderate effects. However, the effect sizes are inversely related to the quality of the experimental design (e.g., presence of active control groups). This pattern of results casts serious doubts on the effectiveness of chess, music, and working memory training. We discuss the theoretical and practical implications of these findings; extend the debate to other types of training such as spatial training, brain training, and video games; and conclude that far transfer of learning rarely occurs.

The relationship between handedness and mathematical ability is still highly controversial. While some researchers have claimed that left-handers are gifted in mathematics and strong right-handers perform the worst in mathematical tasks, others have more recently proposed that mixed-handers are the most disadvantaged group. However, the studies in the field differ with regard to the ages and the gender of the participants, and the type of mathematical ability assessed. To disentangle these discrepancies, we conducted five studies in several Italian schools (total participants: N = 2,314), involving students of different ages (six to seventeen) and a range of mathematical tasks (e.g., arithmetic and reasoning). The results show that (a) linear and quadratic functions are insufficient for capturing the link between handedness and mathematical ability; (b) the percentage of variance in mathematics scores explained by handedness was larger than in previous studies (between 3 and 10% vs. 1%), and (c) the effect of handedness on mathematical ability depended on age, type of mathematical tasks, and gender. In accordance with previous research, handedness does represent a correlate of achievement in mathematics, but the shape of this relationship is more complicated than has been argued so far.

The putative effectiveness of working memory (WM) training at enhancing cognitive and academic skills is still ardently debated. Several researchers have claimed that WM training fosters not only skills such as visuospatial WM and short-term memory (STM), but also abilities outside the domain of WM, such as fluid intelligence and mathematics. Other researchers, while acknowledging the positive effect of WM training on WM-related cognitive skills, are much more pessimistic about the ability of WM training to improve other cognitive and academic skills. In other words, the idea that far-transfer-that is, the generalization of a set of skills across two domains only loosely related to each other-may take place in WM training is still controversial. In this meta-analysis, the authors focused on the effects of WM training on cognitive and academic skills (e.g., fluid intelligence, attention/inhibition, mathematics, and literacy) in typically developing (TD) children (aged 3 to 16). Whereas WM training exerted a significant effect on cognitive skills related to WM training ((g) over bar = 0.46), little evidence was found regarding far-transfer effects ((g) over bar = 0.12). Moreover, the size of the effects was inversely related to the quality of the design (i.e., random allocation to the groups and presence of an active control group). Results suggest that WM training is ineffective at enhancing TD children's cognitive or academic skills and that, when positive effects are observed, they are modest at best. Thus, in line with other types of training, far-transfer rarely occurs and its effects are minimal.

Music training has been recently claimed to enhance children and young adolescents ' cognitive and academic skills. However, substantive research on transfer of skills suggests that far-transfer - i.e., the transfer of skills between two areas only loosely related to each other - occurs rarely. In this meta-analysis, we examined the available experimental evidence regarding the impact of music training on children and young adolescents ' cognitive and academic skills. The results of the random-effects models showed (a) a small overall effect size ((d) over bar = 0.16); (b) slightly greater effect sizes with regard to intelligence ((d) over bar= 0.35) and memory-related outcomes ((d) over bar = 0.34); and (c) an inverse relation between the size of the effects and the methodological quality of the study design. These results suggest that music training does not reliably enhance children and young adolescents ' cognitive or academic skills, and that previous positive findings were probably due to confounding variables. (C) 2016 The Authors. Published by Elsevier Ltd.

Why are some people more skilled in complex domains than other people? Here, we conducted a meta-analysis to evaluate the relationship between cognitive ability and skill in chess. Chess skill correlated positively and significantly with fluid reasoning (Gf) ((r) over bar = 024), comprehension-knowledge (Gc) ((r) over bar = 0.22), short-term memory (Gsm) ((r) over bar = 0.25), and processing speed (Gs) ((r) over bar = 0.24); the meta-analytic average of the correlations was ((r) over bar = 024). Moreover, the correlation between Gf and chess skill was moderated by age ((r) over bar = 032 for youth samples vs. (r) over bar = 0.11 for adult samples), and skill level ((r) over bar = 032 for unranked samples vs. (r) over bar = 0.14 for ranked samples). Interestingly, chess skill correlated more strongly with numerical ability ((r) over bar = 035) than with verbal ability ((r) over bar = 0.19) or visuospatial ability ((r) over bar = 0.13). The results suggest that cognitive ability contributes meaningfully to individual differences in chess skill, particularly in young chess players and/or at lower levels of skill. (C) 2016 Elsevier Inc. All rights reserved.

In recent years, pupils' poor achievement in mathematics has been a concern in many Western countries. Chess instruction has been proposed as one way to remedy this state of affairs, as well as improving other academic topics such as reading and general cognitive abilities such as intelligence. The aim of this paper is to quantitatively evaluate the available empirical evidence that skills acquired during chess instruction in schools positively transfer to mathematics, reading and general cognitive skills. The selection criteria were satisfied by 24 studies (40 effect sizes), with 2788 young people in the chess condition and 2433 in the control groups. The results show (a) a moderate overall effect size (g = 0.338); (b) a tendency for a stronger effect on mathematical (g = 0.382) than reading skill (g = 0.248), and (c) a significant and positive effect of duration of treatment (Q(1) = 3.89, b = 0.0038, p &lt; .05). However, no study used an "ideal design" including pre- and post-test, full random allocation of participants to conditions and, most importantly, both a do-nothing control group and an active control group - a problem common in education research. Directions for further research are discussed. (C) 2016 The Authors. Published by Elsevier Ltd.

Recently, chess in school activities has attracted the attention of policy makers, teachers and researchers. Chess has been claimed to be an effective tool to enhance children's mathematical skills. In this study, 931 primary school pupils were recruited and then assigned to two treatment groups attending chess lessons, or to a control group, and were tested on their mathematical problem-solving abilities. The two treatment groups differed from each other on the teaching method adopted: The trainers of one group taught the pupils heuristics to solve chess problems, whereas the trainers of the other treatment group did not teach any chess-specific problem-solving heuristic. Results showed that the former group outperformed the other two groups. These results foster the hypothesis that a specific type of chess training does improve children's mathematical skills, and uphold the idea that teaching general heuristics can be an effective way to promote transfer of learning.