Improved estimation of general cognitive ability and its neural correlates with a large battery of cognitive tasks.

Elucidating the neural mechanisms of general cognitive ability (GCA) is an important mission of cognitive neuroscience. Recent large-sample cohort studies measured GCA through multiple cognitive tasks and explored its neural basis, but they did not investigate how task number, factor models, and neural data type affect the estimation of GCA and its neural correlates. To address these issues, we tested 1,605 Chinese young adults with 19 cognitive tasks and Raven's Advanced Progressive Matrices (RAPM) and collected resting state and n-back task fMRI data from a subsample of 683 individuals. Results showed that GCA could be reliably estimated by multiple tasks. Increasing task number enhances both reliability and validity of GCA estimates and reliably strengthens their correlations with brain data. The Spearman model and hierarchical bifactor model yield similar GCA estimates. The bifactor model has better model fit and stronger correlation with RAPM but explains less variance and shows weaker correlations with brain data than does the Spearman model. Notably, the n-back task-based functional connectivity patterns outperform resting-state fMRI in predicting GCA. These results suggest that GCA derived from a multitude of cognitive tasks serves as a valid measure of general intelligence and that its neural correlates could be better characterized by task fMRI than resting-state fMRI data.

Structural-functional brain network coupling predicts human cognitive ability.

Individual differences in general cognitive ability (GCA) have a biological basis within the structure and function of the human brain. Network neuroscience investigations revealed neural correlates of GCA in structural as well as in functional brain networks. However, whether the relationship between structural and functional networks, the structural-functional brain network coupling (SC-FC coupling), is related to individual differences in GCA remains an open question. We used data from 1030 adults of the Human Connectome Project, derived structural connectivity from diffusion weighted imaging, functional connectivity from resting-state fMRI, and assessed GCA as a latent g-factor from 12 cognitive tasks. Two similarity measures and six communication measures were used to model possible functional interactions arising from structural brain networks. SC-FC coupling was estimated as the degree to which these measures align with the actual functional connectivity, providing insights into different neural communication strategies. At the whole-brain level, higher GCA was associated with higher SC-FC coupling, but only when considering path transitivity as neural communication strategy. Taking region-specific variations in the SC-FC coupling strategy into account and differentiating between positive and negative associations with GCA, allows for prediction of individual cognitive ability scores in a cross-validated prediction framework (correlation between predicted and observed scores: r = 0.25, p < .001). The same model also predicts GCA scores in a completely independent sample (N = 567, r = 0.19, p < .001). Our results propose structural-functional brain network coupling as a neurobiological correlate of GCA and suggest brain region-specific coupling strategies as neural basis of efficient information processing predictive of cognitive ability.

Parental socioeconomic status weakly predicts specific cognitive and academic skills beyond general cognitive ability.

Parental socioeconomic status (SES) is a well-established predictor of children's neurocognitive development. Several theories propose that specific cognitive skills are particularly vulnerable. However, this can be challenging to test, because cognitive assessments are not pure measures of distinct neurocognitive processes, and scores across different tests are often highly correlated. Aside from one previous study by Tucker-Drob, little research has tested if associations between SES and cognition are explained by differences in general cognitive ability rather than specific cognitive skills. Using structural equation modelling (SEM), we tested if parental SES is associated with individual cognitive test scores after controlling for latent general cognitive ability. Data from three large-scale cohorts totalling over 16,360 participants from the UK and USA (ages 6-19) were used. Associations between SES and cognitive test scores are mainly (but not entirely) explained through general cognitive ability. Socioeconomic advantage was associated with particularly strong vocabulary performance, unexplained by general ability. When controlling for general cognitive ability, socioeconomic disadvantage was associated with better executive functions. Better characterizing relationships between cognition and adversity is a crucial first step toward designing interventions to narrow socioeconomic gaps. RESEARCH HIGHLIGHTS: Understanding environmental influences on cognitive development is a crucial goal for developmental science-parental socioeconomic status (SES) is one of the strongest predictors. Several theories have proposed that specific cognitive skills, such as language or certain executive functions, are particularly susceptible to socioeconomic adversity. Using structural equation modelling, we tested whether SES predicts specific cognitive and academic tests after controlling for latent general cognitive ability across three large-scale cohorts. SES moderately predicted latent general cognitive ability, but associations with specific cognitive skills were mainly small, with a few exceptions.

The relation between number line performance and mathematics outcomes: Two meta-analyses.

Understanding the magnitudes represented by numerals is a core component of early mathematical development and is often assessed by accuracy in situating numerals and fractions on a number line. Performance on these measures is consistently related to performance in other mathematics domains, but the strength of these relations may be overestimated because general cognitive ability has not been fully controlled in prior studies. The first of two meta-analyses (162 studies, 33,101 participants) confirmed a relation between performance on whole number (r = 0.33) and fractions number (r = 0.41) lines and overall mathematics performance. These relations were generally consistent across content domains (e.g., algebra and computation) and other moderators. The second (71 studies, 14,543 participants) used meta-analytic structural equation modeling to confirm these relations while controlling general cognitive ability (defined by IQ and working memory measures) and, in one analysis, general mathematics competence. The relation between number line performance and general mathematics competence remained significant but reduced (ß = 0.13). Controlling general cognitive ability, whole number line performance consistently predicted competence with fractions but not performance on numeracy or computations measures. The results suggest an understanding of the magnitudes represented by whole numbers might be particularly important for students' fractions learning. RESEARCH HIGHLIGHTS: Two meta-analyses examined the link between the number line and mathematics performance. The first revealed significant relations across domains (e.g., algebra and computation). The second controlled for general cognitive ability and resulted in reduced but still significant relations. The relation between number line and fractions performance was stronger than relations to other domains.

General cognitive ability in high school, attained education, occupational complexity, and dementia risk.

INTRODUCTION: We address the extent to which adolescent cognition predicts dementia risk in later life, mediated by educational attainment and occupational complexity. METHODS: Using data from Project Talent Aging Study (PTAS), we fitted two structural equation models to test whether adolescent cognition predicts cognitive impairment (CI) and Ascertain Dementia 8 (AD8) status simultaneously (NCognitive Assessment = 2477) and AD8 alone (NQuestionnaire = 6491) 60 years later, mediated by education and occupational complexity. Co-twin control analysis examined 82 discordant pairs for CI/AD8. RESULTS: Education partially mediated the effect of adolescent cognition on CI in the cognitive assessment aample and AD8 in the questionnaire sample (Ps < 0.001). Within twin pairs, differences in adolescent cognition were small, but intrapair differences in education predicted CI status. DISCUSSION: Adolescent cognition predicted dementia risk 60 years later, partially mediated through education. Educational attainment, but not occupational complexity, contributes to CI risk beyond its role as a mediator of adolescent cognition, further supported by the co-twin analyses. HIGHLIGHTS: Project Talent Aging Study follows enrollees from high school for nearly 60 years. General cognitive ability in high school predicts later-life cognitive impairment. Low education is a risk partially due to its association with cognitive ability.

Few temporally distributed brain connectivity states predict human cognitive abilities.

Human functional brain connectivity can be temporally decomposed into states of high and low cofluctuation, defined as coactivation of brain regions over time. Rare states of particularly high cofluctuation have been shown to reflect fundamentals of intrinsic functional network architecture and to be highly subject-specific. However, it is unclear whether such network-defining states also contribute to individual variations in cognitive abilities - which strongly rely on the interactions among distributed brain regions. By introducing CMEP, a new eigenvector-based prediction framework, we show that as few as 16 temporally separated time frames (< 1.5% of 10 min resting-state fMRI) can significantly predict individual differences in intelligence (N = 263, p < .001). Against previous expectations, individual's network-defining time frames of particularly high cofluctuation do not predict intelligence. Multiple functional brain networks contribute to the prediction, and all results replicate in an independent sample (N = 831). Our results suggest that although fundamentals of person-specific functional connectomes can be derived from few time frames of highest connectivity, temporally distributed information is necessary to extract information about cognitive abilities. This information is not restricted to specific connectivity states, like network-defining high-cofluctuation states, but rather reflected across the entire length of the brain connectivity time series.

Experience of Playing a Musical Instrument and Lifetime Change in General Cognitive Ability: Evidence From the Lothian Birth Cohort 1936.

We tested whether experience of playing a musical instrument was associated with lifetime change in cognitive ability. Participants were 366 older adults from the Lothian Birth Cohort 1936 who had completed general cognitive-ability assessments at ages 11 and 70 and reported their lifetime experience of playing a musical instrument at age 82. This sample included 117 participants with musical-instrument experience, mostly at a beginner or an intermediate level. There was a small, statistically significant positive association between experience of playing a musical instrument and change in general cognitive ability between ages 11 and 70; specifically, individuals with more musical-instrument experience were likely to show greater gains in general cognitive ability. This association was reduced but remained statistically significant following adjustment for covariates (childhood and adulthood socioeconomic status, years of education, and disease history). These findings suggest that playing a musical instrument is associated with a long-term cognitive advantage.

Genetic and environmental influences on executive functions and intelligence in middle childhood.

Executive functions (EFs) and intelligence (IQ) are phenotypically correlated. In twin studies, latent variables for EFs and IQ display moderate to high heritability estimates; however, they show variable genetic correlations in twin studies spanning childhood to middle age. We analyzed data from over 11,000 children (9- to 10-year-olds, including 749 twin pairs) in the Adolescent Brain Cognitive Development (ABCD) Study to examine the phenotypic and genetic relations between EFs and IQ in childhood. We identified two EF factors-Common EF and Updating-Specific-which were both related to IQ (rs = 0.64-0.81). Common EF and IQ were heritable (53%-67%), and their genetic correlation (rG = 0.86) was not significantly different than 1. These results suggest that EFs and IQ are phenotypically but not genetically separable in middle childhood, meaning that this phenotypic separability may be influenced by environmental factors.

Social Adversity Reduces Polygenic Score Expressivity for General Cognitive Ability, but Not Height.

It has been hypothesized that even 'perfect' polygenic scores (PGSs) composed of only causal variants may not be fully portable between different social groups owing to gene-by-environment interactions modifying the expression of relevant variants. The impacts of such interactions involving two forms of social adversity (low socioeconomic status [SES] and discrimination) are examined in relation to the expressivity of a PGS for educational attainment composed of putatively causal variants in a large, representatively sampled and genotyped cohort of US children. A relatively small-magnitude Scarr-Rowe effect is present (SES × PGSEDU predicting General Cognitive Ability [GCA]; sR = .02, 95% CI [.00, .04]), as is a distinct discrimination × PGSEDU interaction predicting GCA (sR = -.02, 95% CI [-.05, 00]). Both are independent of the confounding main effects of 10 ancestral principal components, PGSEDU, SES, discrimination and interactions among these factors. No sex differences were found. These interactions were examined in relation to phenotypic and genotypic data on height, a prospectively more socially neutral trait. They were absent in both cases. The discrimination × PGSEDU interaction is a co-moderator of the differences posited in modern versions of Spearman's hypothesis (along with shared environmentality), lending support to certain environmental explanations of those differences. Behavior-genetic analysis of self-reported discrimination indicates that it is nonsignificantly heritable (h2 = .027, 95% CI [-.05, .10]), meaning that it is not merely proxying some underlying source of heritable phenotypic variability. This suggests that experiences of discrimination might stem instead from the action of purely social forces.

Multivariate Lesion-Behavior Mapping of General Cognitive Ability and Its Psychometric Constituents.

General cognitive ability, or general intelligence (g), is central to cognitive science, yet the processes that constitute it remain unknown, in good part because most prior work has relied on correlational methods. Large-scale behavioral and neuroanatomical data from neurologic patients with focal brain lesions can be leveraged to advance our understanding of the key mechanisms of g, as this approach allows inference on the independence of cognitive processes along with elucidation of their respective neuroanatomical substrates. We analyzed behavioral and neuroanatomical data from 402 humans (212 males; 190 females) with chronic, focal brain lesions. Structural equation models (SEMs) demonstrated a psychometric isomorphism between g and working memory in our sample (which we refer to as g/Gwm), but not between g and other cognitive abilities. Multivariate lesion-behavior mapping analyses indicated that g and working memory localize most critically to a site of converging white matter tracts deep to the left temporo-parietal junction. Tractography analyses demonstrated that the regions in the lesion-behavior map of g/Gwm were primarily associated with the arcuate fasciculus. The anatomic findings were validated in an independent cohort of acute stroke patients (n = 101) using model-based predictions of cognitive deficits generated from the Iowa cohort lesion-behavior maps. The neuroanatomical localization of g/Gwm provided the strongest prediction of observed g in the new cohort (r = 0.42, p < 0.001), supporting the anatomic specificity of our findings. These results provide converging behavioral and anatomic evidence that working memory is a key mechanism contributing to domain-general cognition.SIGNIFICANCE STATEMENT General cognitive ability (g) is thought to play an important role in individual differences in adaptive behavior, yet its core processes remain unknown, in large part because of difficulties in making causal inferences from correlated data. Using data from patients with focal brain damage, we demonstrate that there is a strong psychometric correspondence between g and working memory - the ability to maintain and control mental information, and that the critical neuroanatomical substrates of g and working memory include the arcuate fasciculus. This work provides converging behavioral and neuroanatomical evidence that working memory is a key mechanism contributing to domain-general cognition.

Decreases in Brain Size and Encephalization in Anatomically Modern Humans.

Growth in human brain size and encephalization is well documented throughout much of prehistory and believed to be responsible for increasing cognitive faculties. Over the past 50,000 years, however, both body size and brain mass have decreased but little is known about the scaling relationship between the two. Here, changes to the human brain are examined using matched body remains to determine encephalization levels across an evolutionary timespan. The results find decreases to encephalization levels in modern humans as compared to earlier Holocene H. sapiens and Late Pleistocene anatomically modern Homo. When controlled for lean body mass, encephalization changes are isometric, suggesting that much of the declines in encephalization are driven by recent increases in obesity. A meta-review of genome-wide association studies finds some evidence for selective pressures acting on human cognitive ability, which may be an evolutionary consequence of the more than 5% loss in brain mass over the past 50,000 years.

The Contribution of Cognitive and Noncognitive Skills to Intergenerational Social Mobility.

We investigated intergenerational educational and occupational mobility in a sample of 2,594 adult offspring and 2,530 of their parents. Participants completed assessments of general cognitive ability and five noncognitive factors related to social achievement; 88% were also genotyped, allowing computation of educational-attainment polygenic scores. Most offspring were socially mobile. Offspring who scored at least 1 standard deviation higher than their parents on both cognitive and noncognitive measures rarely moved down and frequently moved up. Polygenic scores were also associated with social mobility. Inheritance of a favorable subset of parent alleles was associated with moving up, and inheritance of an unfavorable subset was associated with moving down. Parents' education did not moderate the association of offspring's skill with mobility, suggesting that low-skilled offspring from advantaged homes were not protected from downward mobility. These data suggest that cognitive and noncognitive skills as well as genetic factors contribute to the reordering of social standing that takes place across generations.

Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' by Lam et al.

Intelligence and educational attainment are strongly genetically correlated. This relationship can be exploited by Multi-Trait Analysis of GWAS (MTAG) to add power to Genome-wide Association Studies (GWAS) of intelligence. MTAG allows the user to meta-analyze GWASs of different phenotypes, based on their genetic correlations, to identify association's specific to the trait of choice. An MTAG analysis using GWAS data sets on intelligence and education was conducted by Lam et al. (2017). Lam et al. (2017) reported 70 loci that they described as 'trait specific' to intelligence. This article examines whether the analysis conducted by Lam et al. (2017) has resulted in genetic information about a phenotype that is more similar to education than intelligence.

Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

A Further Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' by Lam et al.

Lam et al. (2018) respond to a commentary of their paper entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' Lam et al. (2017). While Lam et al. (2018) have now provided the recommended quality control metrics for their paper, problems remain. Specifically, Lam et al. (2018) do not dispute that the results of their multi-trait analysis of genome-wide association study (MTAG) analysis has produced a phenotype with a genetic correlation of one with three measures of education, but do claim the associations found are specific to the trait of cognitive ability. In this brief paper, it is empirically demonstrated that the phenotype derived by Lam et al. (2017) is more genetically similar to education than cognitive ability. In addition, it is shown that of the genome-wide significant loci identified by Lam et al. (2017) are loci that are associated with education rather than with cognitive ability.

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies.

INTRODUCTION: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. METHODS: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. RESULTS: We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. DISCUSSION: Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia.

Genetic Polymorphism of GABRR2 Modulates Individuals' General Cognitive Ability in Healthy Chinese Han People.

Previous studies have indicated that the cognitive impairment or deficit is associated with GABAergic signaling in central nervous system. Inspired by the finding that receptor GABRR2 modulates concentration of GABA and phasic inhibitory GABAergic transmission in brain. This study investigated to what extent a genetic variant (c.1423C>T, rs282129) of GABRR2 gene modulates individuals' general cognitive ability in 987 Chinese Han people. Results showed a significant influence of GABRR2 gene polymorphism on individuals' Raven's Standard Progressive Matrices (RSPM) performance (F = 3.58, P = .028 by ANOVA and χ 2 = 9.35, P = .009 by K-W test, respectively), even if non-genetic factors were partialed out (gender, major, types of birthplace, and socioeconomic index) (B = -.67, SE = .26, t = 2.63, P = .009). The finding provided a strong evidence, to our knowledge, for the view that genetic variant of GABRR2 gene may contribute to the difference of individuals' general cognitive ability, independently.

The high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

Because educational achievement at the end of compulsory schooling represents a major tipping point in life, understanding its causes and correlates is important for individual children, their families, and society. Here we identify the general ingredients of educational achievement using a multivariate design that goes beyond intelligence to consider a wide range of predictors, such as self-efficacy, personality, and behavior problems, to assess their independent and joint contributions to educational achievement. We use a genetically sensitive design to address the question of why educational achievement is so highly heritable. We focus on the results of a United Kingdom-wide examination, the General Certificate of Secondary Education (GCSE), which is administered at the end of compulsory education at age 16. GCSE scores were obtained for 13,306 twins at age 16, whom we also assessed contemporaneously on 83 scales that were condensed to nine broad psychological domains, including intelligence, self-efficacy, personality, well-being, and behavior problems. The mean of GCSE core subjects (English, mathematics, science) is more heritable (62%) than the nine predictor domains (35-58%). Each of the domains correlates significantly with GCSE results, and these correlations are largely mediated genetically. The main finding is that, although intelligence accounts for more of the heritability of GCSE than any other single domain, the other domains collectively account for about as much GCSE heritability as intelligence. Together with intelligence, these domains account for 75% of the heritability of GCSE. We conclude that the high heritability of educational achievement reflects many genetically influenced traits, not just intelligence.

Is bigger always better? The importance of cortical configuration with respect to cognitive ability.

General cognitive ability (GCA) has substantial explanatory power for behavioral and health outcomes, but its cortical substrate is still not fully established. GCA is highly polygenic and research to date strongly suggests that its cortical substrate is highly polyregional. We show in map-based and region-of-interest-based analyses of adult twins that a complex cortical configuration underlies GCA. Having relatively greater surface area in evolutionary and developmentally high-expanded prefrontal, lateral temporal, and inferior parietal regions is positively correlated with GCA, whereas relatively greater surface area in low-expanded occipital, medial temporal, and motor cortices is negatively correlated with GCA. Essentially the opposite pattern holds for relative cortical thickness. The phenotypic positive-to-negative gradients in our cortical-GCA association maps were largely driven by a similar pattern of genetic associations. The patterns are consistent with regional cortical stretching whereby relatively greater surface area is related to relatively thinner cortex in high-expanded regions. Thus, the typical "bigger is better" view does not adequately capture cortical-GCA associations. Rather, cognitive ability is influenced by complex configurations of cortical development patterns that are strongly influenced by genetic factors. Optimal cognitive ability appears to be driven both by the absolute size and the polyregional configuration of the entire cortex rather than by small, circumscribed regions.

Long-term cognitive and school outcomes of late-preterm and early-term births: a systematic review.

BACKGROUND: Children born before full term (39-41 weeks' gestation) are at increased risk of adverse cognitive outcomes. Risk quantification is important as late-preterm (LPT; 34-36 weeks) and early-term (ET; 37-38 weeks) births are common. METHOD: This review analyses the effect of LPT and ET births on long-term cognitive and educational outcomes. The primary outcome was general cognitive ability. Secondary outcomes included verbal/non-verbal intelligence quotient, subject-specific school performance and special educational needs. The search strategy included Medline and Embase from January 1975 to June 2013. Eligible studies investigated specified outcomes and included suitable gestational age participants assessed at 2 years and older. Outcome measures and socio-demographic descriptors were extracted, and data meta-analysed where possible. RESULTS: Eight studies compared ET birth with full-term birth. Fourteen studies compared LPT birth with either term birth (>37 weeks, n = 12 studies) or full-term birth (39-41 weeks, n = 2 studies). Substantial between-study heterogeneity existed. LPT and ET children underperformed in most outcomes compared with their term/full-term counterparts, respectively. For example, LPT children had an increased risk of lower general cognitive ability (adjusted risk ratio 1.38 [95% confidence interval 1.06-1.79]), and full-term children performed 5% of a standard deviation higher (z-score 0.05 [0.02, 0.08]) than ET children. Poorer outcomes persist into adulthood; term cohorts performed 5% of a standard deviation higher than LPT cohorts (z-score 0.05 [0.04, 0.07]), and full-term cohorts performed 3% of a standard deviation higher than ET cohorts (z-score 0.03 [0.02, 0.04]). CONCLUSION: This review critically examines the knowledge around long-term cognitive outcomes of LPT and ET births, demonstrating multiple, small, adverse differences between LPT/ET and term/full-term births.