Reserve, resilience and maintenance of episodic memory and other cognitive functions in aging.

We tested if cognitive and brain reserve and maintenance explain individual differences in episodic memory and other cognitive domains from late middle to early older adulthood. We used The Vietnam Era Twin Study of Aging data (n=1604 men) with episodic memory measured at mean ages of 56, 62 and 68 years, and magnetic resonance imaging data for a subsample of participants (n=321). Cognitive reserve -young adult general cognitive ability at a mean age of 20 years and, to a lesser degree, educational attainment- was positively related to episodic memory performance at each assessment, but not to memory change. We found no evidence for the associations of brain reserve or brain maintenance on memory change. Results were highly similar when looking at processing speed, executive function and verbal fluency. In conclusion, higher young adult cognitive reserve was related to better episodic memory in midlife and older adulthood, but it did not confer better cognitive maintenance with respect to memory. This supports the importance of early cognitive development in dementia prevention.

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.

The brain entropy dynamics in resting state.

As a novel measure for irregularity and complexity of the spontaneous fluctuations of brain activities, brain entropy (BEN) has attracted much attention in resting-state functional magnetic resonance imaging (rs-fMRI) studies during the last decade. Previous studies have shown its associations with cognitive and mental functions. While most previous research assumes BEN is approximately stationary during scan sessions, the brain, even at its resting state, is a highly dynamic system. Such dynamics could be characterized by a series of reoccurring whole-brain patterns related to cognitive and mental processes. The present study aims to explore the time-varying feature of BEN and its potential links with general cognitive ability. We adopted a sliding window approach to derive the dynamical brain entropy (dBEN) of the whole-brain functional networks from the HCP (Human Connectome Project) rs-fMRI dataset that includes 812 young healthy adults. The dBEN was further clustered into 4 reoccurring BEN states by the k-means clustering method. The fraction window (FW) and mean dwell time (MDT) of one BEN state, characterized by the extremely low overall BEN, were found to be negatively correlated with general cognitive abilities (i.e., cognitive flexibility, inhibitory control, and processing speed). Another BEN state, characterized by intermediate overall BEN and low within-state BEN located in DMN, ECN, and part of SAN, its FW, and MDT were positively correlated with the above cognitive abilities. The results of our study advance our understanding of the underlying mechanism of BEN dynamics and provide a potential framework for future investigations in clinical populations.

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.

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.

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.

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.

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.

Examining Voting Capacity in Older Adults with and without Cognitive Decline.

BACKGROUND: Nowadays, controversy exists regarding the stage of cognitive decline and/or dementia where voting capacity is diminished. AIM: To evaluate whether general cognitive status in advancing age predicts voting capacity in its specific aspects. METHODS: The study sample comprised 391 people: 88 cognitively healthy older adults (CH), 150 people with Mild Cognitive Impairment (MCI), and 153 people with Alzheimer's disease dementia (ADD). The assessment included CAT-V for the voting capacity and Mini Mental State Examination (MMSE) for general cognitive ability. ANOVAs and ROC curves were the tools of statistical analysis towards (a) indicating under which MMSE rate participants are incapable of voting and (b) whether the CAT-V total score can discriminate people with dementia (PwADD) from people without dementia (PwtD). RESULTS: Out of the six CAT-V questions, one question was associated with a low MMSE cutoff score (19.50), having excellent sensitivity (92.5%) and specificity (77.20%), whilst the other five questions presented a higher MMSE cutoff score, with a good sensitivity (78.4% to 87.6%) and specificity (75.3% to 81.7%), indicating that voting difficulties are associated with cognitive status. Secondarily, the total CAT-V score discriminates PwADD from PwtD of 51-65 years (sensitivity 93.2%/specificity 100%-excellent), PwADD from PwtD of 66-75 years (sensitivity 73.3%/specificity 97.1%-good), PwADD from PwtD of 76-85 years (sensitivity 92.2%/specificity 64.7%-good), whilst for 86-95 years, a cutoff of 9.5 resulted in perfect sensitivity and specificity (100%). CONCLUSION: According to MMSE, PwADD have no full voting competence, whilst PwtD seem to have intact voting capacity. The calculated cut-off scores indicate that only people who score more than 28 points on the MMSE have voting capacity.

The relationship between subconstructs of empathy and general cognitive ability in the context of policing.

Purpose: Empathy has been widely theorized as an important ability in professions such as policing, in which to perform well individuals require multiple and interacting abilities, not least when resolving conflict situations. Even so, there are few studies investigating how subconstructs of empathy relate to other constructs such as general cognitive ability. The purpose of this paper is to establish, after evaluating psychometric properties, relationships among measures of empathy and cognitive ability in a sample of Swedish police students (n = 157). Design/methodology/approach: Multiple latent variable models of how the different measures work to predict tasks that can be seen as proxies for the ability to understand another person's situation and intentions are evaluated to determine the most robust relationship(s) within the data. Findings: We find support for the psychometric properties reported in previous studies with the used instruments. We also find support for perspective-taking, a cognitive empathy subconstruct predicting the ability to recognize emotions, and also the affective part of empathy, predicting general cognitive ability. These findings are discussed at length in the paper. Originality/value: This research adds more knowledge to the issue of how general cognitive ability relates to cognitive empathy and other subconstructs of empathy or Theory of Mind.

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.

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.

A shortened version of Raven's standard progressive matrices for children and adolescents.

Numerous developmental studies assess general cognitive ability, not as the primary variable of interest, but rather as a background variable. Raven's Progressive Matrices is an easy to administer non-verbal test that is widely used to measure general cognitive ability. However, the relatively long administration time (up to 45 min) is still a drawback for developmental studies as it often leaves little time to assess the primary variable of interest. Therefore, we used a machine learning approach - regularized regression in combination with cross-validation - to develop a short 15-item version. We did so for two age groups, namely 9 to 12 years and 13 to 16 years. The short versions predicted the scores on the standard full 60-item versions to a very high degree r = 0.89 (9-12 years) and r = 0.93 (13-16 years). We, therefore, recommend using the short version to measure general cognitive ability as a background variable in developmental studies.

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.

Paradoxical cognitive trajectories in men from earlier to later adulthood.

Because longitudinal studies of aging typically lack cognitive data from earlier ages, it is unclear how general cognitive ability (GCA) changes throughout the life course. In 1173 Vietnam Era Twin Study of Aging (VETSA) participants, we assessed young adult GCA at average age 20 and current GCA at 3 VETSA assessments beginning at average age 56. The same GCA index was used throughout. Higher young adult GCA and better GCA maintenance were associated with stronger specific cognitive abilities from age 51 to 73. Given equivalent GCA at age 56, individuals who had higher age 20 GCA outperformed those whose GCA remained stable in terms of memory, executive function, and working memory abilities from age 51 to 73. Thus, paradoxically, despite poorer maintenance of GCA, high young adult GCA still conferred benefits. Advanced predicted brain age and the combination of elevated vascular burden and APOE-ε4 status were associated with poorer maintenance of GCA. These findings highlight the importance of distinguishing between peak and current GCA for greater understanding of cognitive aging.

Preliminary evidence for the Matrix Matching Test as a valid and reliable measure of general cognitive ability / Evidencia preliminar para el uso del Matrix Matching Test como una medida válida y confiable de habilidad cognitiva general en adolescentes

Abstract Introduction: In research, a simple measure of general cognitive ability is often required. One method is the Matrix Matching Test, a brief, free-to-use, language-free assessment of general cognitive ability or intelligence in adults, which taps both fluid and crystalized processes. We investigated its reliability and validity with adolescent participants. Method: The Matrix Matching Test was administered to 111 participants, aged 12 to 17 (46% female). Subsamples also completed two standard measures of cognitive ability: Vocabulary (crystalized) and Matrix Reasoning (fluid) tests from the Wechsler Intelligence Scale for Children IV (WISC-IV). Results: The Matrix Matching Test was found to have acceptable internal consistency and good retest reliability. Criterion validity was indicated by its ability to distinguish between psychosocially deprived participants living in foster care (n = 40) and controls, and by its positive correlation with grade point average. There were large positive correlations between the Matrix Matching Test and the standard measures of Vocabulary, and Matrix Reasoning, suggesting convergent validity. Conclusions: Our preliminary evidence suggests that The Matrix Matching Test is a reliable and valid measure of general cognitive ability for ages 12 to 17.

Resumen Introducción: En ámbitos de investigación, el uso de una herramienta de medición general de habilidad cognitiva es comúnmente requerido. Una de estas herramientas es el Matrix Matching Test, una evaluación de habilidad cognitiva o inteligencia para adultos que es corta, de uso gratuito y no tiene impedimentos de lenguaje. Esta herramienta evalúa los procesos fluidos, así como los procesos cristalizados de la inteligencia adulta. Investigamos la confiabilidad y la validez de esta herramienta con participantes adolescentes. Método: Se administró la herramienta Matrix Matching Test a 111 participantes de edades entre 12 y 17 años (46 % mujeres). Los subgrupos además completaron dos medidas de habilidad cognitiva del más alto estándar obtenidos de la Escala de inteligencia de Wechsler para Niños IV (WISC-IV): Vocabulario (cristalizada) y Matrices (fluida). Resultados: Se encontró que el Matrix Matching Test tiene una consistencia interna aceptable y buena confiabilidad retest. Se indicó el criterio de validez por su capacidad para distinguir entre participantes habitantes en hogares sustitutos (n = 40) y participantes del grupo control. Asimismo, existe una correlación positiva con el GPA. Además, se encontró correlaciones positivas fuertes entre el Matrix Matching Test y las mediciones de más alto estándar de Vocabulario y Matrices, lo que sugiere una validez convergente. Conclusiones: Nuestra evidencia preliminar sugiere que el Matrix Matching Test es una medida confiable y válida para las habilidades cognitivas generales en edades de 12 a 17 años.

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.

Lifestyle and the aging brain: interactive effects of modifiable lifestyle behaviors and cognitive ability in men from midlife to old age.

We examined the influence of lifestyle on brain aging after nearly 30 years, and tested the hypothesis that young adult general cognitive ability (GCA) would moderate these effects. In the community-dwelling Vietnam Era Twin Study of Aging (VETSA), 431 largely non-Hispanic white men completed a test of GCA at mean age 20. We created a modifiable lifestyle behavior composite from data collected at mean age 40. During VETSA, MRI-based measures at mean age 68 included predicted brain age difference (PBAD), Alzheimer's disease (AD) brain signature, and abnormal white matter scores. There were significant main effects of young adult GCA and lifestyle on PBAD and the AD signature (ps ≤ 0.012), and a GCA-by-lifestyle interaction on both (ps ≤ 0.006). Regardless of GCA level, having more favorable lifestyle behaviors predicted less advanced brain age and less AD-like brain aging. Unfavorable lifestyles predicted advanced brain aging in those with lower age 20 GCA, but did not affect brain aging in those with higher age 20 GCA. Targeting early lifestyle modification may promote dementia risk reduction, especially among lower reserve individuals.

Rare Copy Number Variants Are Associated With Poorer Cognition in Schizophrenia.

BACKGROUND: Cognitive impairment in schizophrenia is a major contributor to poor outcomes, yet its causes are poorly understood. Some rare copy number variants (CNVs) are associated with schizophrenia risk and affect cognition in healthy populations, but their contribution to cognitive impairment in schizophrenia has not been investigated. We examined the effect of 12 schizophrenia CNVs on cognition in those with schizophrenia. METHODS: General cognitive ability was measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia composite z score in 875 patients with schizophrenia and in a replication sample of 519 patients with schizophrenia using Wechsler Adult Intelligence Scale Full Scale IQ. Using linear regression, we tested for association between cognition and schizophrenia CNV status, covarying for age and sex. In addition, we tested whether CNVs hitting genes in schizophrenia-enriched gene sets (loss-of-function intolerant and synaptic gene sets) were associated with cognitive impairment. RESULTS: A total of 23 schizophrenia CNV carriers were identified. Schizophrenia CNV carriers had lower general cognitive ability than nonschizophrenia CNV carriers in discovery (ß = -0.66, 95% confidence interval [CI] = -1.31 to -0.01) and replication samples (ß = -0.91, 95% CI = -1.71 to -0.11) and after meta-analysis (ß = -0.76, 95% CI = -1.26 to -0.25, p = .003). CNVs hitting loss-of-function intolerant genes were associated with lower cognition (ß = -0.15, 95% CI = -0.29 to -0.001, p = .048). CONCLUSIONS: In those with schizophrenia, cognitive ability in schizophrenia CNV carriers is 0.5-1.0 standard deviations below non-CNV carriers, which may have implications for clinical assessment and management. We also demonstrate that rare CNVs hitting genes intolerant to loss-of-function variation lead to more severe cognitive impairment, above and beyond the effect of known schizophrenia CNVs.

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.