Missense Mutant Gain-of-Function Causes Inverted Formin 2 (INF2)-Related Focal Segmental Glomerulosclerosis (FSGS).

Inverted formin-2 (INF2) gene mutations are among the most common causes of genetic focal segmental glomerulosclerosis (FSGS) with or without Charcot-Marie-Tooth (CMT) disease. Recent studies suggest that INF2, through its effects on actin and microtubule arrangement, can regulate processes including vesicle trafficking, cell adhesion, mitochondrial calcium uptake, mitochondrial fission, and T-cell polarization. Despite roles for INF2 in multiple cellular processes, neither the human pathogenic R218Q INF2 point mutation nor the INF2 knock-out allele is sufficient to cause disease in mice. This discrepancy challenges our efforts to explain the disease mechanism, as the link between INF2-related processes, podocyte structure, disease inheritance pattern, and their clinical presentation remains enigmatic. Here, we compared the kidney responses to puromycin aminonucleoside (PAN) induced injury between R218Q INF2 point mutant knock-in and INF2 knock-out mouse models and show that R218Q INF2 mice are susceptible to developing proteinuria and FSGS. This contrasts with INF2 knock-out mice, which show only a minimal kidney phenotype. Co-localization and co-immunoprecipitation analysis of wild-type and mutant INF2 coupled with measurements of cellular actin content revealed that the R218Q INF2 point mutation confers a gain-of-function effect by altering the actin cytoskeleton, facilitated in part by alterations in INF2 localization. Differential analysis of RNA expression in PAN-stressed heterozygous R218Q INF2 point-mutant and heterozygous INF2 knock-out mouse glomeruli showed that the adhesion and mitochondria-related pathways were significantly enriched in the disease condition. Mouse podocytes with R218Q INF2, and an INF2-mutant human patient's kidney organoid-derived podocytes with an S186P INF2 mutation, recapitulate the defective adhesion and mitochondria phenotypes. These results link INF2-regulated cellular processes to the onset and progression of glomerular disease. Thus, our data demonstrate that gain-of-function mechanisms drive INF2-related FSGS and explain the autosomal dominant inheritance pattern of this disease.

Atypical pattern separation memory and its association with restricted interests and repetitive behaviors in autistic children.

LAY ABSTRACT: Memory challenges remain understudied in childhood autism. Our study investigates one specific aspect of memory function, known as pattern separation memory, in autistic children. Pattern separation memory refers to the critical ability to store unique memories of similar stimuli; however, its role in childhood autism remains largely uncharted. Our study first uncovered that the pattern separation memory was significantly reduced in autistic children, and then showed that reduced memory performance was linked to their symptoms of repetitive, restricted interest and behavior. We also identified distinct subgroups with profiles of reduced and increased generalization for pattern separation memory. More than 72% of autistic children showed a tendency to reduce memory generalization, focusing heavily on unique details of objects for memorization. This focus made it challenging for them to identify commonalities across similar entities. Interestingly, a smaller proportion of autistic children displayed an opposite pattern of increased generalization, marked by challenges in differentiating between similar yet distinct objects. Our findings advance the understanding of memory function in autism and have practical implications for devising personalized learning strategies that align with the unique memory patterns exhibited by autistic children. This study will be of broad interest to researchers in psychology, psychiatry, and brain development as well as teachers, parents, clinicians, and the wider public.

Adults systematically underestimate decimals and whole number exposure induces further magnitude-based underestimation.

Decimal numbers are generally assumed to be a straightforward extension of the base-ten system for whole numbers given their shared place value structure. However, in decimal notation, unlike whole numbers, the same magnitude can be expressed in multiple ways (e.g., 0.8, 0.80, 0.800, etc.). Here, we used a number line task with carefully selected stimuli to investigate how equivalent decimals (e.g., 0.8 and 0.80 on a 0-1 number line) and proportionally equivalent whole numbers (e.g., 80 on a 0-100 number line) are estimated. We find that young adults (n = 88, Mage = 20.22 years, SD = 1.65, 57 female) have a linear response pattern for both decimals and whole numbers, but those double-digit decimals (e.g., 0.08, 0.82, 0.80) are systematically underestimated relative to proportionally equivalent whole numbers (e.g., 8, 82, 80). Moreover, decimal string length worsens the underestimation, such that single-digit decimals (e.g., 0.8) are perceived as smaller than their equivalent double-digit decimals (e.g., 0.80). Finally, we find that exposing participants to whole number stimuli before decimal stimuli induces magnitude-based underestimation, that is, greater underestimation for larger decimals. Together, these results suggest a small but persistent underestimation bias for decimals less than one, and further that decimal magnitude estimation is fragile and subject to greater underestimation when exposed to whole numbers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Yeast lunapark regulates the formation of trans-Sey1p complexes for homotypic ER membrane fusion.

The endoplasmic reticulum (ER) consists of the nuclear envelope and a connected peripheral network of tubules and interspersed sheets. The structure of ER tubules is generated and maintained by various proteins, including reticulons, DP1/Yop1p, atlastins, and lunapark. Reticulons and DP1/Yop1p stabilize the high membrane curvature of ER tubules, and atlastins mediate homotypic membrane fusion between ER tubules; however, the exact role of lunapark remains poorly characterized. Here, using isolated yeast ER microsomes and reconstituted proteoliposomes, we directly examined the function of the yeast lunapark Lnp1p for yeast atlastin Sey1p-mediated ER fusion and found that Lnp1p inhibits Sey1p-driven membrane fusion. Furthermore, by using a newly developed assay for monitoring trans-Sey1p complex assembly, a prerequisite for ER fusion, we found that assembly of trans-Sey1p complexes was increased by the deletion of LNP1 and decreased by the overexpression of Lnp1p, indicating that Lnp1p inhibits Sey1p-mediated fusion by interfering with assembly of trans-Sey1p complexes.

Competing numerical magnitude codes in decimal comparison: Whole number and rational number distance both impact performance.

A critical difference between decimal and whole numbers is that among whole numbers the number of digits provides reliable information about the size of the number, e.g., double-digit numbers are larger than single-digit numbers. However, for decimals, fewer digits can sometimes denote a larger number (i.e., 0.8 > 0.27). Accordingly, children and adults perform worse when comparing such Inconsistent decimal pairs relative to Consistent pairs, where the larger number also has more digits (i.e., 0.87 > 0.2). Two explanations have been posited for this effect. The string length congruity account proposes that participants compare each position in the place value system, and they additionally compare the number of digits. The semantic interference account suggests that participants additionally activate the whole number referents of numbers - the numbers unadorned with decimal points (e.g., 8 < 27) - and compare these. The semantic interference account uniquely predicts that for Inconsistent problems with the same actual rational distance, those with larger whole number distances should be harder, e.g., 0.9 vs. 0.81 should be harder than 0.3 vs. 0.21 because 9 < < 81 whereas 3 < 21. Here we test this prediction in two experiments with college students (Study 1: n = 58 participants, Study 2: n = 78). Across both, we find a main effect of consistency, demonstrating string length effects, and also that whole number distance interferes with processing conflicting decimals, demonstrating semantic interference effects. Evidence for both effects supports the semantic interference account, highlighting that decimal comparison difficulties arise from multiple competing numerical codes. Finally, for accuracy we found no relationship between whole number distance sensitivity and math achievement, indicating that whole number magnitude interference affects participants similarly across the spectrum of math achievement.

Atypical cognitive training-induced learning and brain plasticity and their relation to insistence on sameness in children with autism.

Children with autism spectrum disorders (ASDs) often display atypical learning styles; however, little is known regarding learning-related brain plasticity and its relation to clinical phenotypic features. Here, we investigate cognitive learning and neural plasticity using functional brain imaging and a novel numerical problem-solving training protocol. Children with ASD showed comparable learning relative to typically developing children but were less likely to shift from rule-based to memory-based strategy. While learning gains in typically developing children were associated with greater plasticity of neural representations in the medial temporal lobe and intraparietal sulcus, learning in children with ASD was associated with more stable neural representations. Crucially, the relation between learning and plasticity of neural representations was moderated by insistence on sameness, a core phenotypic feature of ASD. Our study uncovers atypical cognitive and neural mechanisms underlying learning in children with ASD, and informs pedagogical strategies for nurturing cognitive abilities in childhood autism.

Better together: novel methods for measuring and modeling development of executive function diversity while accounting for unity.

Introduction: Executive functions (EFs) are linked to positive outcomes across the lifespan. Yet, methodological challenges have prevented precise understanding of the developmental trajectory of their organization. Methods: We introduce novel methods to address challenges for both measuring and modeling EFs using an accelerated longitudinal design with a large, diverse sample of students in middle childhood (N = 1,286; ages 8 to 14). We used eight adaptive assessments hypothesized to measure three EFs, working memory, context monitoring, and interference resolution. We deployed adaptive assessments to equate EF challenge across ages and a data-driven, network analytic approach to reveal the evolving diversity of EFs while simultaneously accounting for their unity. Results and discussion: Using this methodological paradigm shift brought new precision and clarity to the development of these EFs, showing these eight tasks are organized into three stable components by age 10, but refinement of composition of these components continues through at least age 14.

Advice from "pracademics" of how to apply ecological dynamics theory to practice design.

There has been an increase interest in knowing and enacting pedagogical approaches such as the Constraints-led Approach (CLA) and Nonlinear Pedagogy (NLP) which are underpinned by Ecological Dynamics in recent years among practitioners. While there seems to be a perceived uptake of such pedagogical approaches that encourages exploratory learning and the development of individualised movement solutions, there are still concerns on how these pedagogical approaches are enacted on the ground. In this paper, we the authors, as "pracademics", attempted to address some of the common concerns that we are aware of from our regular interactions with academics and practitioners. In brief, we highlighted some of the common challenges related to sense making concepts from Ecological Dynamics and building connections to practice. We stressed the need to invest time to think differently to create representative learning environment, rethink how assessment is to be done, finding a balance between theoretical jargon and practical application as well as intentionally situating coach development and support. We may not have all the answers, but we hope this paper could provide a useful starting point on how to apply Ecological Dynamics Theory to practice design.

Middle-schoolers' misconceptions in discretized nonsymbolic proportional reasoning explain fraction biases better than their continuous reasoning: Evidence from correlation and cluster analyses.

Early emerging nonsymbolic proportional skills have been posited as a foundational ability for later fraction learning. A positive relation between nonsymbolic and symbolic proportional reasoning has been reported, as well as successful nonsymbolic training and intervention programs enhancing fraction magnitude skills. However, little is known about the mechanisms underlying this relationship. Of particular interest are nonsymbolic representations, which can be in continuous formats that may emphasize proportional relations and in discretized formats that may prompt erroneous whole-number strategies and hamper access to fraction magnitudes. We assessed the proportional comparison skills of 159 middle-school students (mean age = 12.54 years, 43% females, 55% males, 2% other or prefer not to say) across three types of representations: (a) continuous, unsegmented bars, (b) discretized, segmented bars that allowed counting strategies, and (c) symbolic fractions. Using both correlational and cluster approaches, we also examined their relations to symbolic fraction comparison ability. Within each stimulus type, we varied proportional distance, and in the discretized and symbolic stimuli, we also manipulated whole-number congruency. We found that fraction distance across all formats modulated middle-schoolers' performance; however, whole-number information affected discretized and symbolic comparison performance. Further, continuous and discretized nonsymbolic performance was related to fraction comparison ability; however, discretized skills explained variance above and beyond the contributions of continuous skills. Finally, our cluster analyses revealed three nonsymbolic comparison profiles: students who chose the bars with the largest number of segments (whole-number bias), chance-level performers, and high performers. Crucially, students with a whole-number bias profile showed this bias in their fraction skills and failed to show any symbolic distance modulation. Together, our results indicate that the relation between nonsymbolic and symbolic proportional skills may be determined by the (mis)conceptions based on discretized representations, rather than understandings of proportional magnitudes, suggesting that interventions focusing on competence with discretized representations may show dividends for fraction understanding.

Testing the whole number interference hypothesis: Contributions of inhibitory control and whole number knowledge to fraction understanding.

The present study tests two predictions stemming from the hypothesis that a source of difficulty with rational numbers is interference from whole number magnitude knowledge. First, inhibitory control should be an independent predictor of fraction understanding, even after controlling for working memory. Second, if the source of interference is whole number knowledge, then it should hinder fraction understanding. These predictions were tested in a racially and socioeconomically diverse sample of U.S. children (N = 765; 337 female) in Grades 3 (ages 8-9), 5 (ages 10-11), and 7 (ages 12-13) who completed a battery of computerized tests. The fraction comparison task included problems with both shared components (e.g., 3/5 > 2/5) and distinct components (e.g., 2/3 > 5/9), and problems that were congruent (e.g., 5/6 > 3/4) and incongruent (e.g., 3/4 > 5/7) with whole number knowledge. Inhibitory control predicted fraction comparison performance over and above working memory across component and congruency types. Whole number knowledge did not hinder performance and instead positively predicted performance for fractions with shared components. These results highlight a role for inhibitory control in rational number understanding and suggest that its contribution may be distinct from inhibiting whole number magnitude knowledge. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Atypical cognitive training-induced learning and brain plasticity and their relation to insistence on sameness in children with autism.

Children with autism spectrum disorders (ASD) often display atypical learning styles, however little is known regarding learning-related brain plasticity and its relation to clinical phenotypic features. Here, we investigate cognitive learning and neural plasticity using functional brain imaging and a novel numerical problem-solving training protocol. Children with ASD showed comparable learning relative to typically developing children but were less likely to shift from rule-based to memory-based strategy. Critically, while learning gains in typically developing children were associated with greater plasticity of neural representations in the medial temporal lobe and intraparietal sulcus, learning in children with ASD was associated with more stable neural representations. Crucially, the relation between learning and plasticity of neural representations was moderated by insistence on sameness, a core phenotypic feature of ASD. Our study uncovers atypical cognitive and neural mechanisms underlying learning in children with ASD, and informs pedagogical strategies for nurturing cognitive abilities in childhood autism.

Human atlastins are sufficient to drive the fusion of liposomes with a physiological lipid composition.

The dynamin-like GTPase atlastin is believed to be the minimal machinery required for homotypic endoplasmic reticulum (ER) membrane fusion, mainly because Drosophila atlastin is sufficient to drive liposome fusion. However, it remains unclear whether mammalian atlastins, including the three human atlastins, are sufficient to induce liposome fusion, raising doubts about their major roles in mammalian cells. Here, we show that all human atlastins are sufficient to induce fusion when reconstituted into liposomes with a lipid composition mimicking that of the ER. Although the fusogenic activity of ATL1, which is predominantly expressed in neuronal cells, was weaker than that of ATL2 or ATL3, the addition of M1-spastin, a neuron-specific factor, markedly increased ATL1-mediated liposome fusion. Although we observed efficient fusion between ER microsomes isolated from cultured, non-neuronal cells that predominantly express ATL2-1, an autoinhibited isoform of ATL2, ATL2-1 failed to support liposome fusion by itself as reported previously, indicating that cellular factors enable ATL2-1 to mediate ER fusion in vivo.

Correspondence between cognitive and neural representations for phonology, orthography, and semantics in supramarginal compared to angular gyrus.

The angular and supramarginal gyri (AG and SMG) together constitute the inferior parietal lobule (IPL) and have been associated with cognitive functions that support reading. How those functions are distributed across the AG and SMG is a matter of debate, the resolution of which is hampered by inconsistencies across stereotactic atlases provided by the major brain image analysis software packages. Schematic results from automated meta-analyses suggest primarily semantic (word meaning) processing in the left AG, with more spatial overlap among phonological (auditory word form), orthographic (visual word form), and semantic processing in the left SMG. To systematically test for correspondence between patterns of neural activation and phonological, orthographic, and semantic representations, we re-analyze a functional magnetic resonance imaging data set of participants reading aloud 465 words. Using representational similarity analysis, we test the hypothesis that within cytoarchitecture-defined subregions of the IPL, phonological representations are primarily associated with the SMG, while semantic representations are primarily associated with the AG. To the extent that orthographic representations can be de-correlated from phonological representations, they will be associated with cortex peripheral to the IPL, such as the intraparietal sulcus. Results largely confirmed these hypotheses, with some nuanced exceptions, which we discuss in terms of neurally inspired computational cognitive models of reading that learn mappings among distributed representations for orthography, phonology, and semantics. De-correlating constituent representations making up complex cognitive processes, such as reading, by careful selection of stimuli, representational formats, and analysis techniques, are promising approaches for bringing additional clarity to brain structure-function relationships.

Consensus statement on Singapore integrated 24-hour activity guide for early childhood.

Introduction: Early childhood is a critical period for growth and development. Adopting healthy lifestyle behaviours during this period forms the foundation for future well-being and offers the best protection against non-communicable diseases. Singapore studies have shown that many young children are not achieving the recommendations on physical activity, sedentary behaviour and sleep. A workgroup was set up to develop recommendations for caregivers of infants, toddlers and preschoolers (aged <7 years) on how to integrate beneficial activities within a daily 24-hour period for optimal development and metabolic health. Method: The Grading of Recommendations Assessment, Development and Evaluation (GRADE)- ADOLOPMENT approach was employed for adoption, adaption or de novo development of recommendations. International and national guidelines were used as references, and an update of the literature reviews up to September 2021 was conducted through an electronic search of PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: Four consensus statements were developed for each age group: infants, toddlers and preschoolers. The statements focus on achieving good metabolic health through regular physical activity, limiting sedentary behaviour, achieving adequate sleep and positive eating habits. The 13th consensus statement recognises that integration of these activities within a 24-hour period can help obtain the best results. Conclusion: This set of recommendations guides and encourages caregivers of Singapore infants, toddlers and preschoolers to adopt beneficial lifestyle activities within each 24-hour period.

Exposure to violence is associated with decreased neural connectivity in emotion regulation and cognitive control, but not working memory, networks after accounting for socioeconomic status: a preliminary study.

Previous research has demonstrated behavioral and neural differences associated with experiencing adversity. However, adversity is unlikely to be a monolithic construct, and we expect that examining effects of more specific components such as exposure to violence in the home community will yield more concretely interpretable results. Here we account for effects of low socioeconomic status (SES) to examine the specific effects of exposure to violence on functional connectivity between brain areas known to be related to emotion regulation and working memory. Decreased resting state functional connectivity for individuals exposed to high compared to low levels of violence during childhood was predicted for two sets of areas: (1) bilateral amygdala with anterior medial regions involved in cognitive control of emotion, and (2) the right dorsolateral prefrontal cortex (dlPFC) with frontal and parietal regions implicated in working memory. Consistent with our predictions, increasing exposure to violence was related to decreased resting state functional connectivity between the right amygdala and anterior cingulate cortex, even after accounting for SES. Also after accounting for SES, exposure to violence was related to reductions in connectivity between the right dlPFC and frontal regions, but not with parietal regions typically associated with working memory. Overall, this pattern suggests increased exposure to violence in childhood is associated with reduced connectivity among key areas of the circuitry involved in emotion regulation and cognitive control, but not working memory. These results offer insight into the neural underpinnings of behavioral outcomes associated with exposure to violence, laying the foundation for ultimately designing interventions to address the effects of such exposure.

Automated exploitation of the big configuration space of large adsorbates on transition metals reveals chemistry feasibility.

Mechanistic understanding of large molecule conversion and the discovery of suitable heterogeneous catalysts have been lagging due to the combinatorial inventory of intermediates and the inability of humans to enumerate all structures. Here, we introduce an automated framework to predict stable configurations on transition metal surfaces and demonstrate its validity for adsorbates with up to 6 carbon and oxygen atoms on 11 metals, enabling the exploration of ~108 potential configurations. It combines a graph enumeration platform, force field, multi-fidelity DFT calculations, and first-principles trained machine learning. Clusters in the data reveal groups of catalysts stabilizing different structures and expose selective catalysts for showcase transformations, such as the ethylene epoxidation on Ag and Cu and the lack of C-C scission chemistry on Au. Deviations from the commonly assumed atom valency rule of small adsorbates are also manifested. This library can be leveraged to identify catalysts for converting large molecules computationally.

Neural differences in social and figurative language processing on the autism spectrum.

Individuals on the autism spectrum often have trouble with social and figurative language. As social language is often figurative, it can be challenging to disentangle the cognitive and neural sources of these difficulties. Neural systems for social cognition and language comprehension overlap in areas involved in retrieving linguistic meaning (semantics), such as the anterior temporal lobe (ATL), ventro-medial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), and posterior middle temporal gyrus (pMTG). Using adjective-noun phrases, we manipulated social/nonsocial and figurative/literal dimensions, which we expected to activate distinct but overlapping regions. We hypothesized that activation differences in the group with autism (AUT) would be greater for more social and figurative stimuli. During fMRI, participants in the AUT group (N = 19) and those in the non-autistic comparison (NAC) group (N = 22) made familiarity judgments to 192 phrases in a balanced 2 × 2 (social/nonsocial x figurative/literal) design. Social phrases activated the PCC in all participants, but only the NAC group activated the vmPFC. Figurative phrases were rated as more literal by the AUT group, with the figurative-literal phrase contrast showing no activation in the AUT group, but activating the PCC and right pMTG in the NAC group. The one significant group-level neural difference was for the social-figurative condition predicted to be most different between groups: greater activation for the AUT group in the right ATL. Differences in the right ATL and pMTG in the AUT group suggest altered engagement of right homologues of the canonical semantic network being recruited for processing combined social and figurative language.

Foundational Number Sense Training Gains Are Predicted by Hippocampal-Parietal Circuits.

The development of mathematical skills in early childhood relies on number sense, the foundational ability to discriminate among quantities. Number sense in early childhood is predictive of academic and professional success, and deficits in number sense are thought to underlie lifelong impairments in mathematical abilities. Despite its importance, the brain circuit mechanisms that support number sense learning remain poorly understood. Here, we designed a theoretically motivated training program to determine brain circuit mechanisms underlying foundational number sense learning in female and male elementary school-age children (7-10 years). Our 4 week integrative number sense training program gradually strengthened the understanding of the relations between symbolic (Arabic numerals) and nonsymbolic (sets of items) representations of quantity. We found that our number sense training program improved symbolic quantity discrimination ability in children across a wide range of math abilities including children with learning difficulties. Crucially, the strength of pretraining functional connectivity between the hippocampus and intraparietal sulcus, brain regions implicated in associative learning and quantity discrimination, respectively, predicted individual differences in number sense learning across typically developing children and children with learning difficulties. Reverse meta-analysis of interregional coactivations across 14,371 fMRI studies and 89 cognitive functions confirmed a reliable role for hippocampal-intraparietal sulcus circuits in learning. Our study identifies a canonical hippocampal-parietal circuit for learning that plays a foundational role in children's cognitive skill acquisition. Findings provide important insights into neurobiological circuit markers of individual differences in children's learning and delineate a robust target for effective cognitive interventions.SIGNIFICANCE STATEMENT Mathematical skill development relies on number sense, the ability to discriminate among quantities. Here, we develop a theoretically motivated training program and investigate brain circuits that predict number sense learning in children during a period important for acquisition of foundational cognitive skills. Our integrated number sense training program was effective in children across a wide a range of math abilities, including children with learning difficulties. We identify hippocampal-parietal circuits that predict individual differences in learning gains. Our study identifies a brain circuit critical for the acquisition of foundational cognitive skills, which will be useful for developing effective interventions to remediate learning disabilities.

Parietal and hippocampal hyper-connectivity is associated with low math achievement in adolescence - A preliminary study.

Mathematical cognition requires coordinated activity across multiple brain regions, leading to the emergence of resting-state functional connectivity as a method for studying the neural basis of differences in mathematical achievement. Hyper-connectivity of the intraparietal sulcus (IPS), a key locus of mathematical and numerical processing, has been associated with poor mathematical skills in childhood, whereas greater connectivity has been related to better performance in adulthood. No studies to date have considered its role in adolescence. Further, hippocampal connectivity can predict mathematical learning, yet no studies have considered its contributions to contemporaneous measures of math achievement. Here, we used seed-based resting-state fMRI analyses to examine IPS and hippocampal intrinsic functional connectivity relations to math achievement in a group of 31 adolescents (mean age = 16.42 years, range 15-17), whose math performance spanned the 1% to 99% percentile. After controlling for IQ, IPS connectivity was negatively related to math achievement, akin to findings in children. However, the specific temporo-occipital regions were more akin to the posterior loci implicated in adults. Hippocampal connectivity with frontal regions was also negatively correlated with concurrent math measures, which contrasts with results from learning studies. Finally, hyper-connectivity was not a global feature of low math performance, as math performance did not modulate connectivity of Heschl's gyrus, a control seed not involved in math cognition. Our results provide preliminary evidence that adolescence is a transitional stage in which patterns found in childhood and adulthood can be observed; most notably, hyper-connectivity continues to be related to low math ability into this period.

Linking inhibitory control to math achievement via comparison of conflicting decimal numbers.

The relationship between executive functions (EF) and academic achievement is well-established, but leveraging this insight to improve educational outcomes remains elusive. Here, we propose a framework for relating the role of specific EF on specific precursor skills that support later academic learning. Starting from the premise that executive functions contribute to general math skills both directly - supporting the execution of problem solving strategies - and indirectly - supporting the acquisition of precursor mathematical content, we hypothesize that the contribution of domain-general EF capacities to precursor skills that support later learning can help explain relations between EF and overall math skills. We test this hypothesis by examining whether the contribution of inhibitory control on general math knowledge can be explained by inhibition's contribution to processing rational number pairs that conflict with individual's prior whole number knowledge. In 97 college students (79 female, age = 20.58 years), we collected three measures of EF: working memory (backwards spatial span), inhibition (color-word Stroop) and cognitive flexibility (task switching), and timed and untimed standardized measures of math achievement. Our target precursor skill was a decimals comparison task where correct responses were inconsistent with prior whole number knowledge (e.g., 0.27 vs. 0.9). Participants performed worse on these trials relative to the consistent decimals pairs (e.g., 0.2 vs. 0.87). Individual differences in the Stroop task predicted performance on inconsistent decimal comparisons, which in turn predicted general math achievement. With respect to relating inhibitory control to math achievement, Stroop performance was an independent predictor of achievement after accounting for age, working memory and cognitive flexibility, but decimal performance mediated this relationship. Finally, we found inconsistent decimals performance mediated the relationship of inhibition with rational number performance, but not other advanced mathematical concepts. These results pinpoint the specific contribution of inhibitory control to rational number understanding, and more broadly are consistent with the hypothesis that acquisition of foundational mathematical content can explain the relationships between executive functions and academic outcomes, making them promising targets for intervention.