Long-term impact of digital media on brain development in children.

Digital media (DM) takes an increasingly large part of children's time, yet the long-term effect on brain development remains unclear. We investigated how individual effects of DM use (i.e., using social media, playing video games, or watching television/videos) on the development of the cortex (i.e., global cortical surface area), striatum, and cerebellum in children over 4 years, accounting for both socioeconomic status and genetic predisposition. We used a prospective, multicentre, longitudinal cohort of children from the Adolescent Brain and Cognitive Development Study, aged 9.9 years when entering the study, and who were followed for 4 years. Annually, children reported their DM usage through the Youth Screen Time Survey and underwent brain magnetic resonance imaging scans every 2 years. Quadratic-mixed effect modelling was used to investigate the relationship between individual DM usage and brain development. We found that individual DM usage did not alter the development of cortex or striatum volumes. However, high social media usage was associated with a statistically significant change in the developmental trajectory of cerebellum volumes, and the accumulated effect of high-vs-low social media users on cerebellum volumes over 4 years was only ß = - 0.03, which was considered insignificant. Nevertheless, the developmental trend for heavy social media users was accelerated at later time points. This calls for further studies and longer follow-ups on the impact of social media on brain development.

Remote neurocognitive interventions for attention-deficit/hyperactivity disorder - Opportunities and challenges.

Improving neurocognitive functions through remote interventions has been a promising approach to developing new treatments for attention-deficit/hyperactivity disorder (AD/HD). Remote neurocognitive interventions may address the shortcomings of the current prevailing pharmacological therapies for AD/HD, e.g., side effects and access barriers. Here we review the current options for remote neurocognitive interventions to reduce AD/HD symptoms, including cognitive training, EEG neurofeedback training, transcranial electrical stimulation, and external cranial nerve stimulation. We begin with an overview of the neurocognitive deficits in AD/HD to identify the targets for developing interventions. The role of neuroplasticity in each intervention is then highlighted due to its essential role in facilitating neuropsychological adaptations. Following this, each intervention type is discussed in terms of the critical details of the intervention protocols, the role of neuroplasticity, and the available evidence. Finally, we offer suggestions for future directions in terms of optimizing the existing intervention protocols and developing novel protocols.

A multi-faceted role of dual-state dopamine signaling in working memory, attentional control, and intelligence.

Genetic evidence strongly suggests that individual differences in intelligence will not be reducible to a single dominant cause. However, some of those variations/changes may be traced to tractable, cohesive mechanisms. One such mechanism may be the balance of dopamine D1 (D1R) and D2 (D2R) receptors, which regulate intrinsic currents and synaptic transmission in frontal cortical regions. Here, we review evidence from human, animal, and computational studies that suggest that this balance (in density, activity state, and/or availability) is critical to the implementation of executive functions such as attention and working memory, both of which are principal contributors to variations in intelligence. D1 receptors dominate neural responding during stable periods of short-term memory maintenance (requiring attentional focus), while D2 receptors play a more specific role during periods of instability such as changing environmental or memory states (requiring attentional disengagement). Here we bridge these observations with known properties of human intelligence. Starting from theories of intelligence that place executive functions (e.g., working memory and attentional control) at its center, we propose that dual-state dopamine signaling might be a causal contributor to at least some of the variation in intelligence across individuals and its change by experiences/training. Although it is unlikely that such a mechanism can account for more than a modest portion of the total variance in intelligence, our proposal is consistent with an array of available evidence and has a high degree of explanatory value. We suggest future directions and specific empirical tests that can further elucidate these relationships.

Schooling substantially improves intelligence, but neither lessens nor widens the impacts of socioeconomics and genetics.

Schooling, socioeconomic status (SES), and genetics all impact intelligence. However, it is unclear to what extent their contributions are unique and if they interact. Here we used a multi-trait polygenic score for cognition (cogPGS) with a quasi-experimental regression discontinuity design to isolate how months of schooling relate to intelligence in 6567 children (aged 9-11). We found large, independent effects of schooling (ß ~ 0.15), cogPGS (ß ~ 0.10), and SES (ß ~ 0.20) on working memory, crystallized (cIQ), and fluid intelligence (fIQ). Notably, two years of schooling had a larger effect on intelligence than the lifetime consequences, since birth, of SES or cogPGS-based inequalities. However, schooling showed no interaction with cogPGS or SES for the three intelligence domains tested. While schooling had strong main effects on intelligence, it did not lessen, nor widen the impact of these preexisting SES or genetic factors.

The impact of digital media on children's intelligence while controlling for genetic differences in cognition and socioeconomic background.

Digital media defines modern childhood, but its cognitive effects are unclear and hotly debated. We believe that studies with genetic data could clarify causal claims and correct for the typically unaccounted role of genetic predispositions. Here, we estimated the impact of different types of screen time (watching, socializing, or gaming) on children's intelligence while controlling for the confounding effects of genetic differences in cognition and socioeconomic status. We analyzed 9855 children from the USA who were part of the ABCD dataset with measures of intelligence at baseline (ages 9-10) and after two years. At baseline, time watching (r = - 0.12) and socializing (r = - 0.10) were negatively correlated with intelligence, while gaming did not correlate. After two years, gaming positively impacted intelligence (standardized ß = + 0.17), but socializing had no effect. This is consistent with cognitive benefits documented in experimental studies on video gaming. Unexpectedly, watching videos also benefited intelligence (standardized ß = + 0.12), contrary to prior research on the effect of watching TV. Although, in a posthoc analysis, this was not significant if parental education (instead of SES) was controlled for. Broadly, our results are in line with research on the malleability of cognitive abilities from environmental factors, such as cognitive training and the Flynn effect.

Change by challenge: A common genetic basis behind childhood cognitive development and cognitive training.

The interplay of genetic and environmental factors behind cognitive development has preoccupied multiple fields of science and sparked heated debates over the decades. Here we tested the hypothesis that developmental genes rely heavily on cognitive challenges-as opposed to natural maturation. Starting with a polygenic score (cogPGS) that previously explained variation in cognitive performance in adults, we estimated its effect in 344 children and adolescents (mean age of 12 years old, ranging from 6 to 25) who showed changes in working memory (WM) in two distinct samples: (1) a developmental sample showing significant WM gains after 2 years of typical, age-related development, and (2) a training sample showing significant, experimentally-induced WM gains after 25 days of an intense WM training. We found that the same genetic factor, cogPGS, significantly explained the amount of WM gain in both samples. And there was no interaction of cogPGS with sample, suggesting that those genetic factors are neutral to whether the WM gains came from development or training. These results represent evidence that cognitive challenges are a central piece in the gene-environment interplay during cognitive development. We believe our study sheds new light on previous findings of interindividual differences in education (rich-get-richer and compensation effects), brain plasticity in children, and the heritability increase of intelligence across the lifespan.

Déjà vu All Over Again: A Unitary Biological Mechanism for Intelligence Is (Probably) Untenable.

Nearly a century ago, Spearman proposed that "specific factors can be regarded as the 'nuts and bolts' of cognitive performance…, while the general factor is the mental energy available to power the specific engines". Geary (2018; 2019) takes Spearman's analogy of "mental energy" quite literally and doubles-down on the notion by proposing that a unitary energy source, the mitochondria, explains variations in both cognitive function and health-related outcomes. This idea is reminiscent of many earlier attempts to describe a low-level biological determinant of general intelligence. While Geary does an admirable job developing an innovative theory with specific and testable predictions, this new theory suffers many of the shortcomings of previous attempts at similar goals. We argue that Geary's theory is generally implausible, and does not map well onto known psychological and genetic properties of intelligence or its relationship to health and fitness. While Geary's theory serves as an elegant model of "what could be", it is less successful as a description of "what is".

Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment.

Genetic factors and socioeconomic status (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.

Inter-Individual Differences in Striatal Connectivity Is Related to Executive Function Through Fronto-Parietal Connectivity.

The striatum has long been associated with cognitive functions, but the mechanisms behind this are still unclear. Here we tested a new hypothesis that the striatum contributes to executive function (EF) by strengthening cortico-cortical connections. Striatal connectivity was evaluated by measuring the resting-state functional connectivity between ventral and dorsal striatum in 570 individuals, aged 3-20 years. Using structural equation modeling, we found that inter-individual differences in striatal connectivity had an indirect effect (via fronto-parietal functional connectivity) and a direct effect on a compound EF measure of working memory, inhibition, and set-shifting/flexibility. The effect of fronto-parietal connectivity on cognition did not depend on age: the influence was as strong in older as younger children. In contrast, striatal connectivity was closely related to changes in cognitive ability during childhood development, suggesting a specific role of the striatum in cognitive plasticity. These results support a new principle for striatal functioning, according to which striatum promotes cognitive development by strengthening of cortico-cortical connectivity.

The impact of environmental interventions among mouse siblings on the heritability and malleability of general cognitive ability.

General cognitive ability can be highly heritable in some species, but at the same time, is very malleable. This apparent paradox could potentially be explained by gene-environment interactions and correlations that remain hidden due to experimental limitations on human research and blind spots in animal research. Here, we shed light on this issue by combining the design of a sibling study with an environmental intervention administered to laboratory mice. The analysis included 58 litters of four full-sibling genetically heterogeneous CD-1 male mice, for a total of 232 mice. We separated the mice into two subsets of siblings: a control group (maintained in standard laboratory conditions) and an environmental-enrichment group (which had access to continuous physical exercise and daily exposure to novel environments). We found that general cognitive ability in mice has substantial heritability (24% for all mice) and is also malleable. The mice that experienced the enriched environment had a mean intelligence score that was 0.44 standard deviations higher than their siblings in the control group (equivalent to gains of 6.6 IQ points in humans). We also found that the estimate of heritability changed between groups (55% in the control group compared with non-significant 15% in the enrichment group), analogous to findings in humans across socio-economic status. Unexpectedly, no evidence of gene-environment interaction was detected, and so the change in heritability might be best explained by higher environmental variance in the enrichment group. Our findings, as well as the 'sibling intervention procedure' for mice, may be valuable to future research on the heritability, mechanisms and evolution of cognition.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.

Dopamine D1 receptor density in the mPFC responds to cognitive demands and receptor turnover contributes to general cognitive ability in mice.

In both humans and mice, performance on tests of intelligence or general cognitive ability (GCA) is related to dopamine D1 receptor-mediated activity in the prelimbic cortex, and levels of DRD1 mRNA predict the GCA of mice. Here we assessed the turnover rate of D1 receptors as well as the expression level of the D1 chaperone protein (DRiP78) in the medial PPC (mPFC) of mice to determine whether rate of receptor turnover was associated with variations in the GCA of genetically heterogeneous mice. Following assessment of GCA (aggregate performance on four diverse learning tests) mice were administered an irreversible dopamine receptor antagonist (EEDQ), after which the density of new D1 receptors were quantified. GCA was positively correlated with both the rate of D1 receptor recovery and levels of DRiP78. Additionally, the density of D1 receptors was observed to increase within 60 min (or less) in response to intense demands on working memory, suggesting that a pool of immature receptors was available to accommodate high cognitive loads. These results provide evidence that innate general cognitive abilities are related to D1 receptor turnover rates in the prefrontal cortex, and that an intracellular pool of immature D1 receptors are available to accommodate cognitive demands.

The paradox of intelligence: Heritability and malleability coexist in hidden gene-environment interplay.

Intelligence can have an extremely high heritability, but also be malleable; a paradox that has been the source of continuous controversy. Here we attempt to clarify the issue, and advance a frequently overlooked solution to the paradox: Intelligence is a trait with unusual properties that create a large reservoir of hidden gene-environment (GE) networks, allowing for the contribution of high genetic and environmental influences on individual differences in IQ. GE interplay is difficult to specify with current methods, and is underestimated in standard metrics of heritability (thus inflating estimates of "genetic" effects). We describe empirical evidence for GE interplay in intelligence, with malleability existing on top of heritability. The evidence covers cognitive gains consequent to adoption/immigration, changes in IQ's heritability across life span and socioeconomic status, gains in IQ over time consequent to societal development (the Flynn effect), the slowdown of age-related cognitive decline, and the gains in intelligence from early education. The GE solution has novel implications for enduring problems, including our inability to identify intelligence-related genes (also known as IQ's "missing heritability"), and the loss of initial benefits from early intervention programs (such as "Head Start"). The GE solution can be a powerful guide to future research, and may also aid policies to overcome barriers to the development of intelligence, particularly in impoverished and underprivileged populations. (PsycINFO Database Record

A broader phenotype of persistence emerges from individual differences in response to extinction.

The typical practice of averaging group performance during extinction gives the impression that responding declines gradually and homogeneously. However, previous studies of extinction in human infants have shown that some individuals persist in responding, whereas others abruptly cease responding. As predicted by theories of control, the infants who quickly resign typically display signs of sadness and despair when the expected reward is omitted. Using genetically diverse mice, here we observed a similar pattern of individual differences and the associated phenotypes. After learning to approach a food reward, upon extinction, some animals rapidly abandoned approach to the goal box, whereas other animals persisted in entering and searching the goal box. Interestingly, the persistent mice were slower to "give up" when confined to an inescapable pool of water (a test asserted to be indicative of susceptibility to depression) and exhibited a more extensive pattern of search for omitted rewards. Thus, extinction reveals a continuum in persistence, in which low values might reflect a susceptibility to the negative effects of stress and might predispose individuals to depression.

Individual differences: Case studies of rodent and primate intelligence.

Early in the 20th century, individual differences were a central focus of psychologists. By the end of that century, studies of individual differences had become far less common, and attention to these differences played little role in the development of contemporary theory. To illustrate the important role of individual differences, here we consider variations in intelligence as a compelling example. General intelligence (g) has now been demonstrated in at least 2 distinct genera: primates (including humans, chimpanzees, bonobos, and tamarins) and rodents (mice and rats). The expression of general intelligence varies widely across individuals within a species; these variations have tremendous functional consequence, and are attributable to interactions of genes and environment. Here we provide evidence for these assertions, describe the processes that contribute to variations in general intelligence, as well as the methods that underlie the analysis of individual differences. We conclude by describing why consideration of individual differences is critical to our understanding of learning, cognition, and behavior, and illustrate how attention to individual differences can contribute to more effective administration of therapeutic strategies for psychological disorders. (PsycINFO Database Record

A link between thrifty phenotype and maternal care across two generations of intercrossed mice.

Maternal effects are causal influences from mother to offspring beyond genetic information, and have lifelong consequences for multiple traits. Previously, we reported that mice whose mothers did not nurse properly had low birth weight followed by rapid fat accumulation and disturbed development of some organs. That pattern resembles metabolic syndromes known collectively as the thrifty phenotype, which is believed to be an adaptation to a stressful environment which prepares offspring for reduced nutrient supply. The potential link between maternal care, stress reactivity, and the thrifty phenotype, however, has been poorly explored in the human and animal literature: only a couple of studies even mention (much less, test) these concepts under a cohesive framework. Here, we explored this link using mice of the parental inbred strains SM/J and LG/J-who differ dramatically in their maternal care-and the intercrossed generations F1 and F2. We measured individual differences in 15 phenotypes and used structural equation modeling to test our hypotheses. We found a remarkable relationship between thrifty phenotype and lower quality of maternal behaviors, including nest building, pup retrieval, grooming/licking, and nursing. To our knowledge, this is the first study to show, in any mammal, a clear connection between the natural variation in thrifty phenotype and maternal care. Both traits in the mother also had a substantial effect on survival rate in the F3 offspring. To our surprise, however, stress reactivity seemed to play no role in our models. Furthermore, the strain of maternal grandmother, but not of paternal grandmother, affected the variation of maternal care in F2 mice, and this effect was mediated by thrifty phenotype in F2. Since F1 animals were all genetically identical, this finding suggests that maternal effects pass down both maternal care and thrifty phenotype in these mice across generations via epigenetic transmission.

Evolution, brain size, and variations in intelligence.

Across taxonomic subfamilies, variations in intelligence (G) are sometimes related to brain size. However, within species, brain size plays a smaller role in explaining variations in general intelligence (g), and the cause-and-effect relationship may be opposite to what appears intuitive. Instead, individual differences in intelligence may reflect variations in domain-general processes that are only superficially related to brain size.

The tendency for social submission predicts superior cognitive performance in previously isolated male mice.

The imposition of subordination may negatively impact cognitive performance in common social settings (e.g., the classroom), and likewise, laboratory studies of animals indicate that the stress associated with social defeat can impair cognitive performance. It is less clear whether an animal's predisposition for social subordination (i.e., a tendency that is expressed prior to experience with social defeat) is related to its cognitive abilities (e.g., "general" intelligence). Using genetically diverse CD-1 male mice, here we determined that in the absence of adult experience with social hierarchies or social defeat, the predisposition for social subordination was associated with superior general cognitive ability (aggregate performance across a battery of five learning tasks). The tendency for social subordination was not dependent on the mice' body weight, but both general cognitive ability and the tendency for social subordination were directly related to high stress reactivity (i.e., free corticosterone elevations induced by mild stress). This pattern of results suggests that submissive behavior and sensitivity to stress may be associated with superior cognitive potential, and this can reflect a native predisposition that precedes exposure to social pressures. More broadly, these results raise the possibility that socially subordinate animals evolved compensatory strategies to facilitate their survival, and that absent the imposition of subordination, normally submissive individuals may be better prepared for cognitive/academic achievement.

Heterozygous L1-deficient mice express an autism-like phenotype.

The L1CAM (L1) gene encodes a cell adhesion molecule that contributes to several important processes in the developing and adult nervous system, including neuronal migration, survival, and plasticity. In humans and mice, mutations in the X chromosome-linked gene L1 cause severe neurological defects in males. L1 heterozygous female mice with one functional copy of the L1 gene show complex morphological features that are different from L1 fully-deficient and wild-type littermate mice. However, almost no information is available on the behavior of L1 heterozygous mice and humans. Here, we investigated the behavior of heterozygous female mice in which the L1 gene is constitutively inactivated. These mice were compared to wild-type littermate females. Animals were assessed in five categories of behavioral tests: five tests for anxiety/stress/exploration, four tests for motor abilities, two tests for spatial learning, three tests for social behavior, and three tests for repetitive behavior. We found that L1 heterozygous mice express an autism-like phenotype, comprised of reduced social behaviors and excessive self-grooming (a repetitive behavior also typical in animal models of autism). L1 heterozygous mice also exhibited an increase in sensitivity to light, assessed by a reluctance to enter the lighted areas of novel environments. However, levels of anxiety, stress, motor abilities, and spatial learning in L1 heterozygous mice were similar to those of wild-type mice. These observations raise the possibility that using molecules known to trigger L1 functions may become valuable in the treatment of autism in humans.

The external-internal loop of interference: two types of attention and their influence on the learning abilities of mice.

Attention is a component of the working memory system, and is responsible for protecting task-relevant information from interference. Cognitive performance (particularly outside of the laboratory) is often plagued by interference, and the source of this interference, either external or internal, might influence the expression of individual differences in attentional ability. By definition, external attention (also described as "selective attention") protects working memory against sensorial distractors of all kinds, while internal attention (also called "inhibition") protects working memory against emotional impulses, irrelevant information from memory, and automatically-generated responses. At present, it is unclear if these two types of attention are expressed independently in non-human animals, and how they might differentially impact performance on other cognitive processes, such as learning. By using a diverse battery of four attention tests (with varying levels of internal and external sources of interference), here we aimed both to explore this issue, and to obtain a robust and general (less task-specific) measure of attention in mice. Exploratory factor analyses revealed two factors (external and internal attention) that in total, accounted for 73% of the variance in attentional performance. Confirmatory factor analyses found an excellent fit with the data of the model of attention that assumed an external and internal distinction (with a resulting correlation of 0.43). In contrast, a model of attention that assumed one source of variance (i.e., "general attention") exhibited a poor fit with the data. Regarding the relationship between attention and learning, higher resistance against external sources of interference promoted better new learning, but tended to impair performance when cognitive flexibility was required, such as during the reversal of a previously instantiated response. The present results suggest that there can be (at least) two types of attention that contribute to the common variance in attentional performance in mice, and that external and internal attentions might have opposing influences on the rate at which animals learn.