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npj Science of Learning

○ Springer Science and Business Media LLC

Preprints posted in the last 30 days, ranked by how well they match npj Science of Learning's content profile, based on 19 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

1
Computer mouse weight is associated with one-week motor skill improvement in a large naturalistic video game cohort

Listman, J. B.; Mackey, W. E.

2026-10-08 neuroscience 10.64898/2026.10.06.757150 medRxiv
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Computer mouse weight has been proposed to influence human motor performance, but existing evidence comes largely from small, short-duration controlled studies, leaving its relationship to performance during naturalistic gameplay unresolved. We analyzed one-week skill improvement in Aimlabs, a popular first-person shooter aim-training and assessment platform, among 9,067 players whose telemetry recorded a mouse-model change (switchers) during self-directed game use, using a 21-day baseline and 7-day follow-up; 4,991 players with a single mouse model (non-switchers) observed over matched pseudo-anchor intervals provided a secondary contextual comparison. Post-switch mouse weight was represented by eight bands spanning 35-124 g. The primary multivariable generalized additive regression model accounted for baseline skill, pre- and post-switch practice intensity, and pre- and post-switch mouse sensitivity, and allowed the association between weight band and improvement to vary with baseline skill, post-switch practice, and post-switch sensitivity. For each weight band, predicted mean one-week improvement was standardized to the observed distribution of these covariates among switchers and reported in percentile-rank points. Statistical significance was evaluated using 1,000 permutations in which observed mouse weights were randomly reassigned among switchers without replacement and the model was refitted to generate empirical null distributions for the weight-related test statistics. Predicted improvement differed significantly across the eight weight bands (p = 0.001). Pairwise comparisons identified significant differences between bands (p < 0.05), but no single band was associated with significantly greater predicted improvement than all seven others. In this large naturalistic cohort, predicted improvement was highest for players with 35-44 g mice, followed by 45-54 and 55-64 g, and several pairwise comparisons showed significantly greater improvement in lighter than in heavier weight bands. Across the examined baseline-skill profiles, the lowest predicted improvements occurred in either the 85-99 or 115-124 g band. Predicted improvement differed across weight bands at the 25th-percentile and median baseline-skill values (p = 0.002 and p = 0.003) but not at the 75th percentile (p = 0.153). However, the weight-band x baseline-skill interaction was not significant (p = 0.181), indicating that the analysis did not establish that weight-related differences varied by skill level.

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Motivational incentives improve working memory performance by enhancing memory-based representations rather than altering response strategies

Nair, V.; Agnel, O.; Mizrak, E.; Manohar, S. G.

2026-10-08 neuroscience 10.64898/2026.10.02.755939 medRxiv
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Motivational incentives are known to improve working memory (WM) when items differ in value, but whether they enhance performance when all items are equally valued, and if so, by what mechanism, remains unclear. Improvements could reflect enhanced memory-based representations or speed-accuracy trade-offs, whereby incentives promote slower, more cautious responding without improving memory itself. Here, we tested these alternatives across two experiments using an auditory WM task in which incentives varied across trials, but all items on a trial were equally incentivised. In Experiment 1,we allowed participants to resubmit their responses if desired. Reward-related improvements in WM performance were selectively observed when memory load was high, and only at serial positions associated with greater interference. These improvements were also dissociated from systematic response slowing and resubmission behaviour. This indicated that the benefits of incentives were unlikely to be attributable to response caution. Critically, in Experiment 2, motivational benefits persisted under strict response deadlines, where speed cannot be traded for accuracy. Computational modelling showed that reward selectively improved the precision of memory-based responses without reducing guessing. Together, these findings indicate that motivational incentives improve WM by enhancing the quality of memory-based representations, rather than by strategic slowing or altering response strategies.

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Successor representation supports structural learning of syllable sequences

Liu, J.; Wang, Y.; Feng, J.; Zhao, H.; He, Q.; Yang, X.; Liang, B.

2026-10-06 neuroscience 10.64898/2026.10.03.756368 medRxiv
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Humans efficiently learn the temporal structure of speech, yet the underlying cognitive mechanisms remain unclear. Recent research in visuospatial sequential memory has proposed the successor representation (SR), important in reinforcement learning, which encodes multi-step transitional relationships. To test whether SR also supports the structural learning of rapidly changing speech syllable sequences, we adapted a pyramid-structured sequential learning paradigm using syllable streams presented at a natural speech rate (~ 4 Hz). Participants exhibited robust structural learning, evidenced by asymmetric memory performance modulated by adjacent transitional probabilities. Notably, the SR model captured recognition performance for non-adjacent syllable pairs. Moreover, SR-based learning effects generalized across all syllable sequences, regardless of adjacency. Furthermore, the effectiveness of SR learning was associated with cognitive flexibility and working memory capacity. Together, these findings suggest that humans rely on effortful SR-like mechanisms for the structural learning of syllable sequences, highlighting a modality-general computational principle for sequential learning across various temporal modulation scales.

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Establishing parallel and scalar measures of executive and semantic demand: an online norming study of matched, cross-domain judgement tasks

Bozianu, G.; Woolgar, A.; Lambon Ralph, M.; Halai, A.

2026-09-29 neuroscience 10.64898/2026.09.24.753760 medRxiv
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Task demand has a long-standing history in experimental psychology, with numerous investigations of the capacity of different systems and processes under varying cognitive load. Whilst demand is a broadly used term in the literature, it is limited by a lack of cross-domain operationalisation, and thus can be a confound in many inter-domain investigations. To address this, we generated and validated two large-scale, open-source, widely applicable stimuli sets that: (i) can probe a wide, continuous range of objective behaviourally-measured processing demand, and (ii) can be directly matched across two highly contrastive cognitive domains (semantic and visuospatial processing). We normed these tasks in a large, online cohort of healthy adults, enabling future studies to utilise and benefit from reliable baseline measures of demand. Using a matching algorithm that takes into account both speed and accuracy, we then closely paired each semantic judgement trial with a trial of comparable difficulty from the corresponding visuospatial task to produce a cross domain matched set of over 400 items. Finally, we analysed the psycholinguistic and perceptual properties of these stimuli to explore some of the underlying factors driving demand.

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Why Is Spontaneous Blink Timing Informative? An Adaptive Scheduling Perspective

Arnau, S.; Plachti, A.; Alyan, E.; Wascher, E.; Schneider, D.

2026-09-28 neuroscience 10.64898/2026.09.21.753188 medRxiv
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Spontaneous eye blinks have long been linked to cognitive processing, yet how task demands shape blink timing and its relationship to behavioral performance remains unclear. We examined spontaneous blink behavior in 576 adults performing two variants of the Continuous Performance Task (CPT). Blink occurrence and timing were most strongly modulated by the experimental condition in the more demanding CPT-AX task, whereas their association with response time was stronger in the CPT-X task, where more consistent blink timing predicted faster responses. This dissociation suggests that task structure changes not only blink behavior but also the behavioral relevance of blink timing. These findings are consistent with an adaptive scheduling account of spontaneous blinking and provide a conceptual framework for understanding when and why blink timing contains chronometric information about ongoing cognition.

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The role of personality traits in COVID-19 vaccination: A socio-cultural and gender-stratified analysis in Japan

Takamatsu, M.; Tokiya, M.; Hara, M.

2026-10-07 epidemiology 10.64898/2026.10.04.26363389 medRxiv
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Background: COVID-19 vaccination uptake is influenced by various sociodemographic and psychological factors. Previous studies have suggested that the relationship between personality traits and vaccination is context-dependent. However, this association has not been investigated in Japan, a unique sociocultural context characterized by historically low vaccine confidence but exceptionally high COVID-19 vaccine uptake. We examined the association between the Big Five personality traits and completion of the primary COVID-19 vaccination series, exploring potential gender-personality interactions. Methods: A web-based, cross-sectional survey was conducted among 7,210 Japanese adults (aged 20-85 years) in December 2021. Personality was assessed using the Japanese version of the Ten-Item Personality Inventory. Multivariable Poisson generalized estimating equations were used to calculate adjusted prevalence ratios (PRs) and assess gender-personality interactions. Results: Higher extraversion and lower openness were significantly associated with vaccination completion across genders. A significant gender-agreeableness interaction was observed: agreeableness (PR = 1.016, 95% CI: 1.008-1.024) was positively associated with vaccination completion among men but not women. A similar, though only marginally significant, interaction pattern was observed for neuroticism (PR = 1.011, 95% CI: 1.004-1.019 among men). Conclusions: Personality traits act as modest but meaningful, gender-specific psychological modifiers of vaccination behavior in Japan. Public health campaigns should transition from traditional "one-size-fits-all" messages to personality-tailored and gender-responsive communication strategies to optimize vaccine uptake and bolster psychological resilience in future pandemics.

7
Associations Between Neural Responses to Social Fairness and Financial Exploitation Vulnerability Vary With Age and Emotional Intelligence

Stanley, J. M.; Sazhin, D.; Helion, C.; Giovannetti, T.; Fareri, D.; Smith, D. V.

2026-10-08 neuroscience 10.64898/2026.09.30.755119 medRxiv
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Financial exploitation often arises in social contexts in which individuals must evaluate fairness, trust, and interpersonal information during financial decisions. We examined whether neural responses to fairness in social versus nonsocial contexts relate to financial exploitation vulnerability and whether these relationships vary with age, emotional intelligence, and affect. A total of 310 adults spanning ages 21-89 completed an fMRI Ultimatum Game in which they accepted or rejected offers from human and computer partners, along with measures of financial exploitation vulnerability, emotional intelligence, and affect. Participants were strongly sensitive to offer fairness, and individual differences in behavioral sensitivity to partner type were associated with social-relative anterior insula responses to unfairness. Greater baseline negative affect was associated with stronger anterior insula differentiation between social and nonsocial fairness. Financial exploitation vulnerability was associated with prefrontal responses to social-relative fairness in ways that depended on individual characteristics: age moderated its association with dorsomedial prefrontal cortex activation, whereas emotional intelligence moderated its association with dorsolateral prefrontal cortex activation. Whole-brain connectivity analyses further showed that age moderated associations between emotional intelligence and executive control network connectivity with posterior cingulate and right temporoparietal regions. These findings suggest that vulnerability to financial exploitation is reflected in how social context is integrated with affective and individual characteristics across adulthood.

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Life-course patterns of heavy menstrual bleeding and menstrual pain across multiple population-based cohorts

Kundu, S.; Sawyer, G.; Magnus, M. C.; Howe, L. D.; Fraser, A.; Hickey, M.; O'Mahen, H.; Tyrrell, J.; Maybin, J. A.; Critchley, H.; Barrington, D. J.; Sharp, G. C.

2026-10-09 epidemiology 10.64898/2026.10.07.26364868 medRxiv
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Background: Heavy menstrual bleeding (HMB) and menstrual pain (MP) are among the most common menstrual cycle related symptoms with substantial impacts on quality of life. Despite this, population-level evidence on their prevalence across the life course is scarce. Methods: We conducted descriptive analyses of six longitudinal population-based cohorts from the United Kingdom, United States, Norway, and Australia. We estimated cumulative prevalence (across all available timepoints) and age-specific point prevalence of HMB and MP. Cumulative prevalence estimates were stratified by sociodemographic factors, where data permitted. We also examined HMB and MP incidence in adolescent cohorts with repeated measurements. Findings: HMB and MP are commonly reported, with cumulative prevalence across all the cohorts and timepoints (i.e., ever reported) ranging from 36% to 89% for HMB and 46% to 72% for MP. In adolescence, MP (point-prevalence: 33% to 47%) is more commonly reported than HMB (16% to 24%), whereas in later ages (45 years and above), HMB (47% to 70%) is more prevalent than MP (24% to 40%). We found no consistent evidence that symptoms were more likely to co-occur than occur independently; patterns varied across life stages and cohorts. Symptoms were more common in those from lower socioeconomic backgrounds and minoritised ethnic groups. Incidence of both HMP and MP peaked in the years immediately following menarche. Interpretation: Most women experience heavy and/or painful periods at some point. MP is more common in adolescence and HMB in later reproductive life. Generating robust life-course evidence on menstrual symptom patterns is essential to inform clinical guidelines, reduce diagnostic delays, and address inequalities in menstrual health.

9
Goals Drive Adaptive Analysis of Linguistic Features During Reading

Alex, P.; Schwarz, J.; Tatler, B. W.; Konopka, A.; Klimovich-Gray, A.

2026-09-26 neuroscience 10.64898/2026.09.25.754337 medRxiv
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Reading behaviour is sensitive to contextual demands. For example, when reading to study or answer questions, readers strategically allocate more attention to goal-relevant sections, read slower, and regress more frequently to extract specific information based on task demands. This suggests that readers flexibly adapt their strategies according to goals and situational constraints. However, the neurocognitive mechanisms supporting this flexibility remain unclear. To test this, we combined eye-tracking with EEG during naturalistic reading and examined how short-term reading goals modulated the neural tracking of hierarchical linguistic features at the orthographic (orthographic neighbourhood size), lexical (word frequency), and contextual-semantic (Surprisal) levels. Forty native English speakers read narratives in three goal conditions: Baseline (no goal), Proofreading (detect spelling errors), and Comprehension (attend to content). Fixation-aligned word-level EEG activity was modelled using multivariate temporal response function to estimate the strength of feature-specific neural tracking. Orthographic tracking was significantly enhanced during Proofreading relative to Baseline, and predicted better Proofreading accuracy. Conversely, stronger frequency tracking predicted better Comprehension accuracy. Contextual-semantic tracking was not modulated by task goal. These findings suggest that reading goals selectively bias neural processing towards linguistic features (sublexical vs. lexical) that support successful task performance, providing evidence for short-term functional plasticity in linguistic processing and supporting a flexible predictive processing account of goal-directed reading.

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Domain-specific and domain-general signatures of dyscalculia in computational models of behavior and parietal cortex

Renkert, M. F.; de Hollander, G.; Biegel, C.; Valk, S.; Kucian, K.; Ruff, C. C.

2026-10-11 neuroscience 10.64898/2026.10.08.757623 medRxiv
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Developmental dyscalculia is a learning disorder characterized by marked difficulties in numerical cognition, yet its cognitive and neural underpinnings remain debated. Competing accounts attribute dyscalculia either to domain-specific imprecise representations of number or to domain-general deficits in the maintenance and integration of numerical information. Here, we test both accounts in 33 adolescents and young adults with dyscalculia and 33 age- and gender-matched controls (15-23 years) who performed a sequential numerosity comparison task during fMRI. Joint computational modeling of choices and response times allowed us to dissociate perceptual and memory noise from decision variables governing the speed-accuracy tradeoff, while complementary neuroimaging analyses characterized neural number representations and their network embedding. Specifically, we quantified the precision of parietal numerosity tuning with numerical population receptive field (nPRF) modeling and derived individualized functional network maps of the same region using community detection algorithms applied to connectivity patterns. Dyscalculic participants showed greater perceptual and memory noise but also a more cautious response criterion, trading speed for accuracy to compensate for representational imprecision. Neurally, the numerosity model explained less variance in parietal cortex, suggesting less precise numerical representations, and individualized network maps assigned less of this cortex to the dorsal attention network and more to a visual network. Rather than supporting a dichotomy between the two accounts, our findings suggest that dyscalculia reflects both less precise numerical representations in parietal cortex and an altered allocation of this cortex to distributed functional systems.

11
Caudate dopamine predicts cognitive effort decisions both in the lab and daily life

Crawford, J. L.; Brough, R. E.; Eisenstein, S. A.; Peelle, J. E.; Braver, T. S.

2026-09-29 neuroscience 10.64898/2026.09.26.754663 medRxiv
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Making choices about whether and when to engage cognitive effort is a common feature of human everyday experience with important consequences for academic, career, and health outcomes. Yet, despite its importance, little is understood about the neurochemical mechanisms that underlie individual differences in the willingness to engage in cognitively effortful activities. To examine this question, we employed a multi-modal neuroimaging approach in which participants performed the Cognitive Effort Discounting paradigm (Cog-ED) while simultaneous PET-fMRI was acquired. We assessed both individual differences in dopamine-D2 receptor availability and brain activity during decision-making. In addition, the same participants performed a parametric working memory task (N-Back) and reported the cognitive effort associated with their daily life activities through a seven-day Ecological Momentary Assessment (EMA) protocol. The findings suggest a central role for caudate dopamine-D2 receptors in modulating cognitive effort-related motivation. People with higher caudate dopamine-D2 receptor availability had better working memory function, heightened sensitivity to effort costs, and greater modulation of brain activity during effort valuation. These laboratory findings also translated directly to daily life: higher levels of caudate dopamine-D2 receptors were associated with greater engagement in cognitively effortful activities. Together, the results suggest that how individuals determine the motivational value of cognitively effortful activities strongly depends on the dopamine system.

12
Comparing serial and parallel language input: Shared neural representations with distinct encoding strengths

Krogh, S. M.; Pylkkänen, L.

2026-09-24 neuroscience 10.64898/2026.09.23.753812 medRxiv
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Language can be experienced in highly serial form, as in speech, or in fully parallel form, as in text, yet how our brains adapt to differences in seriality is not understood. Here, we held modality constant (visual) and examined whether processing mechanisms underlying grammaticality detection are similar under Rapid Serial Visual Presentation (RSVP) and Rapid Parallel Visual Presentation (RPVP). To identify shared neural representations of grammaticality, we trained a classifier on magnetoencephalography (MEG) responses to grammatical and ungrammatical three-word phrases in one presentation mode and tested its generalization to the other. Behaviorally, accuracy was higher and reaction times faster for grammatical vs. ungrammatical phrases across presentation modes. Neurally, cross-presentation decoding revealed shared representations of grammaticality at word 2 across train-test directions--albeit with different latencies and durations--and an early shared representation at word 3 when trained on RPVP. We take the bidirectional representations at word 2 to capture distinct but presentation-invariant combinatorial processes and the asymmetry at word 3 as reflecting stronger global structure encoding in RPVP.

13
Change-point oddball elicits pupil-linked signatures of Bayesian belief updating

Kopel, L.; Hoomans, J. M.; van Gastel, E.; Tijhuis, J. V.; van de Graaf, M.; Shafik, M.; Matthijsse, S.; Murphy, P. R.; van Gaal, S.; Suzuki, M.; de Gee, J. W.

2026-10-01 neuroscience 10.64898/2026.09.25.754382 medRxiv
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The auditory oddball protocol is widely used to study neural responses to unexpected events. In conventional designs, however, stimulus statistics are stationary: deviants do not indicate environmental change and therefore should not drive learning. Here, we introduce change-point oddball, a passive, no-report protocol in which the standard-oddball mapping reverses at unpredictable change points, requiring inference over latent environmental states. We measured pupil-linked arousal in three human cohorts. Pupil responses were larger for state-specific oddballs than standards, decayed across newly established standards after state changes, and scaled with model-derived change-point probability. A many-standards control experiment implicated a prediction-based rather than repetition-based mechanism. Finally, within participants, stronger pupil encoding of change-point probability during the passive task was associated with greater change-point-sensitive belief updating in a separate active navigation task. Thus, passive change-point oddball preserves core signatures of adaptive belief updating, enabling cross-species and clinical investigations.

14
Brain Mechanisms of Lexicality in Bilingual Emotion Processing

Xiao, C.; Liu, J.; Zhang, Y.; Lyu, W.; Desai, R. H.; Feilong, M.

2026-09-22 neuroscience 10.64898/2026.09.21.753217 medRxiv
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Understanding how native speakers and second language (L2) learners process language differently is fundamental to theories of language acquisition, comprehension, and use. A central debate in this literature concerns the inconsistent findings in emotional prosody processing between native speakers and L2 learners, partly attributable to stimulus lexicality: some studies use real words, whereas others use pseudowords. To resolve this discrepancy, we measured fMRI responses in 15 native speakers and 15 L2 learners while they listened to Mandarin real-word and pseudoword stimuli. Both groups engaged in overlapping auditory, cognitive, and affective regions, including the auditory cortex, inferior frontal cortex, superior temporal cortex, and the temporoparietal junction. However, the two groups showed distinct responses depending on lexicality: native speakers showed stronger recruitment of temporal regions for pseudowords, whereas L2 learners showed greater frontoparietal activation for real words. These patterns were consistent across positive and negative prosody conditions. Furthermore, among L2 learners, higher proficiency was associated with greater frontal activation for real words, but not pseudowords. Together, these findings demonstrate that the differences between native speakers and L2 learners depend critically on stimulus lexicality, highlighting the role of lexicality in bilingual emotion processing.

15
Consensus Formation History Shapes Collective Updating

Sun, C.; Zhou, R.; Zhang, D.; Wang, J.; Meng, Y.; Tang, R.

2026-09-29 neuroscience 10.64898/2026.09.23.753723 medRxiv
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Consensus is rarely a one-off achievement. In a changing world, groups must repeatedly update judgments they have already agreed upon, making consensus updating a common feature of real-world collective decisions. However, previous research on collective decision-making has focused mainly on how groups reach a single consensus, leaving the updating of established consensus largely unexamined. This raises two unanswered questions: does consensus updating involve biases analogous to sunk cost, and are such biases related to the cost of the previous consensus? Building a Fake Consensus paradigm, we manipulated consensus-formation cost and examined how dyads updated a subjectively established consensus after new information arrived. An independent individual experiment provided information-matched updating baselines, allowing us to determine whether dyads updated less or more than individuals responding to the same evidence. Contrary to sunk-cost predictions, low-cost consensus led dyads to update less than the individual baseline, whereas medium- and high-cost consensus led them to update more. The pathway through perceived consensus sharedness was significant, and the association between sharedness and updating was stronger at higher left temporoparietal junction inter-brain synchrony. These findings indicate that the history of consensus formation shapes subsequent updating by altering the psychological meaning of shared endorsement, while interpersonal alignment determines how this shared experience translates into coordinated behavior. To our knowledge, this is the first experimentally controlled study of consensus updating in teams to isolate formation history from actual disagreement, providing a new paradigm for studying how collective judgments change after agreement.

16
Episodic memory adaptively expands retrieval through typicality-guided transformation while concrete details remain accessible

Delmarco, M.; Gonzalez-Garcia, C.; Linde-Domingo, J.

2026-09-29 neuroscience 10.64898/2026.09.24.754119 medRxiv
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Memory faces a fundamental challenge. It has to become flexible enough to be accessed by novel cues without losing the specific information that defines each individual episode. Whether memory transformation solves this problem by sacrificing details or by adaptively expanding retrieval while preserving them is unclear. We tested this by manipulating the match between a memory and its retrieval cue. Participants retrieved object associations after 6, 24 and 48 hours using either the original encoded image or novel exemplars that were more typical or more distinctive of the same object category. Retrieval initially benefited from the originally encoded image, but this advantage was reduced across delay. By 48 hours, a never-seen, more typical exemplar triggered retrieval as effectively as the original one, while the same convergence was not evident for less-typical exemplars. Crucially, such cue expansion was not accompanied by a loss of perceptual specificity. Participants retained access to the originally encoded exemplar across delays, while errors increasingly favoured more typical alternatives. At the item level, stronger episodic memories predicted better access to perceptual detail, but did not predict the tendency of errors for category-like information, which instead increased with delay. This dissociation suggests that memory generalisation and the continued accessibility of visual detail reflect partly separable transformations rather than opposite ends of a single continuum.

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Variability of Head Motion Reveals Development of Spatial Attention

Woestmann, M.; Kunke, D.; Wetzel, N.

2026-09-25 animal behavior and cognition 10.64898/2026.09.23.753739 medRxiv
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Selective attention, the ability to focus on relevant information while ignoring task-irrelevant information, is crucial for learning. Selective attention has largely been studied in motionless individuals. However, body movements are intrinsic to cognition and particularly frequent in children. To test whether movements explain successful attention control throughout childhood, we tracked head rotations while younger children (6-8 years, n = 25), older children (9-10 years, n = 20) and adults (18-30 years; n = 21) identified a spatial target sound under distraction. Distractor reports decreased with age, confirming a developmental increase in attention control. Importantly, a dissociation of two distinct types of movement emerged: Task-dependent head rotation to lateral targets was similar across age groups. Contrary, task-independent movements before and early during a trial decreased with age and predicted attention accuracy. Thus, movements unrelated to the attention goal do not reflect noise but signify attentional control across development.

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Dual ecological-cultural pathways of sociocultural environment and resting state functional connectivity among Hispanic adolescents in the ABCD Study

Laird, A. R.; Hampson, C. L.; Lembo, M.; Bottenhorn, K. L.; Sukumaran, K.; Cardenas-Iniguez, C.; Thompson, E.; Adise, S.; Sanchez, M.; Gonzalez, R.; Herting, M. M.; Meca, A.

2026-10-08 neuroscience 10.64898/2026.09.25.754508 medRxiv
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Hispanic Americans face persistent health disparities rooted in complex sociocultural and bioecodevelopmental dynamics. Identifying early neurodevelopmental trajectories that confer risk or resilience during adolescence is critical for developing targeted health equity interventions. Grounded in the NIMHD Research Framework and bioecodevelopmental theory, data from 12- to 14-year-old Hispanic adolescents in the Adolescent Brain Cognitive Development (ABCD) Study were analyzed (n=236). Partial least squares correlation (PLSC) was used to evaluate multivariate associations between sociocultural measures, spanning individual, family, and community levels, and resting-state functional connectivity (rsFC) networks. Post hoc linear mixed-effects models examined how derived sociocultural-rsFC patterns predicted measures of physical and mental health, linking bioecodevelopmental patterns to adolescent well-being. PLSC revealed dual community- and family-level neural pathways of biological embedding, diverging from traditional nested bioecodevelopmental assumptions. The community pathway linked child opportunity and neighborhood disadvantage to connectivity across Cingulo-Opercular, Default, Dorsal Attention, Visual Networks. This community-rsFC profile was associated with lower respiratory functioning, reflecting an allostatic load marker of environmental stress. The family pathway linked caregiver ethnic identity and heritage acculturation to Default, Ventral Attention, Sensorimotor-Mouth, and Visual Networks connectivity, suggesting that the family system shapes neural systems underlying social attunement and identity formation. Structural community factors and familial culture impose distinct neurobiological demands on the adolescent connectome among Hispanic youth. Findings highlight respiratory health as a biological marker of environmental adversity and underscore the necessity of structural and culturally sustaining interventions to promote health equity among Hispanic youth.

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White matter cognition mapping in pediatric cancer survivors: a two-cohort NODDI-Bingham study

Nandi, S.; McKenna, F.; Henry, S.; Nayak, S.; Duong, T.

2026-10-01 neuroscience 10.64898/2026.09.25.754456 medRxiv
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Childhood cancer survivors (CS) treated with chemotherapy frequently experience long-term cognitive impairments, commonly referred to as CRCI. Whether these deficits reflect disrupted white matter microstructure, altered relationships between microstructure and cognition, or both remains unclear. Here, we applied the NODDI-Bingham model, which quantifies neurite density (NDI), isotropic free water (ISO), and orientation dispersion along primary (ODIp), secondary (ODIs), and total (ODIt) fiber axes, to characterize biophysically specific white matter microstructure in CS and examine its relationship to cognition. Twenty-one pediatric cancer survivors and 21 age-matched healthy controls (HC) underwent multi-shell diffusion MRI. Voxel-wise NODDI-Bingham analyses were performed within JHU atlas regions. Group differences were tested by ANCOVA, and associations between microstructure and cognition were examined with the NIH Toolbox Crystallized, Fluid, and Early Childhood composites using group-specific regressions. Confirmatory analyses were performed in an age-matched subsample of the HCP (n = 679). Notably, CS showed reduced NDI in the corona radiata, cerebral peduncles, and corpus callosum, with elevated ODIt and ODIp in the middle cerebellar peduncle, pathways that subserve processing speed and interhemispheric integration, cognitive domains among the most vulnerable in CRCI. Group-specific regressions revealed qualitatively different relationships between microstructure and cognition: HC exhibited mixed positive and negative relationships across four of five metrics (138 clusters spanning approximately 305,000 voxels; peak Cohen's d up to 3.00), whereas CS showed a predominantly uniformly negative pattern (67 clusters across 57,000 voxels), with no positive clusters for ISO, ODIt, ODIp, or ODIs, thus highlighting that reduced dispersion and extracellular free water are linked to better cognitive performance in CS. HCP analyses reproduced the HC pattern across all five metrics at proportionally smaller effect sizes, ruling out sample-size effects. NODDI-Bingham identifies two aspects of chemotherapy-related white matter pathology that standard diffusion metrics cannot resolve. First, pediatric cancer survivors show selective elevation of ODIp and ODIt in the cerebellar peduncles and reduced NDI in the corona radiata and corpus callosum, localizing group-level injury to specific fanning and neurite density signatures. Second, whereas in healthy controls white matter shows mixed positive and negative relationships between microstructure and cognition, survivors retain only negative relationships for ODIp and ODIt and a diminished mixed pattern for NDI, such that in the chemotherapy-exposed brain, only reduced neurite density and increased primary-axis fanning relate to cognitive impairment. These findings implicate a biophysically specific restructuring of the relationships between white matter and cognition as a candidate mechanism for CRCI and support NODDI-Bingham as a targeted biomarker panel for monitoring and intervention trials.

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Frontoparietal effective connectivity supports working memory in early childhood

Guedj, C.; Bollinger, L.; Marie, D.; Laera, G.; Ceresetti, R.; Comparini, A.; Richiardi, J.; Kliegel, M.; James, C. E.

2026-09-25 neuroscience 10.64898/2026.09.23.753700 medRxiv
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Working memory (WM), a core executive function that supports learning and reasoning, undergoes rapid development during early childhood years. Neural activation patterns underlying WM have been extensively studied in both adults and children, revealing increasing involvement of the frontoparietal network (FPN) with age and coordinated interactions with the default mode network (DMN). However, relatively little is known about how these network interactions develop in children, particularly within the visuospatial domain. The present study investigated the influence of age and task performance on effective connectivity within the FPN and its interactions with DMN hubs during a visuospatial WM task in early childhood. Functional MRI data were collected during a visual n-back task with two WM load levels (0-back and 2-back) in 120 typically developing children aged 5-8 years. Dynamic Causal Modeling (DCM) with parametric empirical Bayes was used to estimate effective connectivity among eight regions of interest spanning the FPN and DMN. Behaviorally, age-related gains were steepest under high-load for accuracy, and under low-load for reaction time, suggesting WM capacity is a demand-sensitive marker of development at this age. At the network level, high-load robustly engaged the FPN, whereas low-load was associated with relatively greater engagement of DMN and episodic memory-related regions. Baseline effective connectivity was dominated by parietal-to-frontal drive and strong self-inhibition in the anterior cingulate cortex. Age-related effects on this architecture were sparse, involving asymmetric interhemispheric frontal coupling and reduced parieto-cingulate coupling, whereas accuracy-related effects were larger in magnitude, particularly at self-connections. More accurate children showed greater excitability in frontal and parietal FPN nodes alongside increased self-inhibition in the precuneus, a DMN hub, consistent with a neural efficiency account in which better performance reflects more selective, rather than more global, network engagement. Task load further shaped connectivity in distinct ways: low-load elicited widespread inter-regional modulation, whereas high-load predominantly modulated self-connections, with age and accuracy effects on this modulation dissociating by load. These findings suggest that, in primary school children, current task performance was associated with more pronounced differences in frontoparietal effective connectivity than was age, and that WM-related network engagement becomes increasingly selective and load-dependent across this developmental window.