Hippocampus and striatum show distinct contributions to longitudinal changes in value-based learning in middle childhood.

The hippocampal-dependent memory system and striatal-dependent memory system modulate reinforcement learning depending on feedback timing in adults, but their contributions during development remain unclear. In a 2-year longitudinal study, 6-to-7-year-old children performed a reinforcement learning task in which they received feedback immediately or with a short delay following their response. Children's learning was found to be sensitive to feedback timing modulations in their reaction time and inverse temperature parameter, which quantifies value-guided decision-making. They showed longitudinal improvements towards more optimal value-based learning, and their hippocampal volume showed protracted maturation. Better delayed model-derived learning covaried with larger hippocampal volume longitudinally, in line with the adult literature. In contrast, a larger striatal volume in children was associated with both better immediate and delayed model-derived learning longitudinally. These findings show, for the first time, an early hippocampal contribution to the dynamic development of reinforcement learning in middle childhood, with neurally less differentiated and more cooperative memory systems than in adults.

Deficits in memory metacognitive efficiency in late adulthood are related to distinct brain profile.

The tendency of falsely remembering events that did not happen in the past increases with age. This is particularly evident in cases in which features presented at study are re-presented at test in a recombined constellation (termed rearranged pairs). Interestingly, older adults also express high confidence in such false memories, a tendency that may indicate reduced metacognitive efficiency. Within an existing cohort study, we aimed at investigating age-related differences in memory metacognitive efficiency (as measured by meta d' ratio) in a sample of 1522 older adults and 397 young adults. The analysis showed an age-related deficit in metacognition which was more pronounced for rearranged pairs than for new pairs. We then explored associations between cortical thickness and memory metacognitive efficiency for rearranged pairs in a subsample of 231 older adults. By using partial least square analysis, we found that a multivariate profile composed by ventromedial prefrontal cortex, insula, and parahippocampal cortex was uniquely associated with between-person differences in memory metacognitive efficiency. These results suggest that the impairment in memory metacognitive efficiency for false alarms is a distinct age-related deficit, above and beyond a general age-related decline in memory discrimination, and that it is associated with brain regions involved in metacognitive processes.

Short- and long-delay consolidation of memory accessibility and precision across childhood and young adulthood.

Childhood is a period when memory consolidation and knowledge base undergo rapid changes. The present study examined short-delay (overnight) and long-delay (after a 2-week period) consolidation of new information either congruent or incongruent with prior knowledge in typically developing 6- to 8-year-old children (n = 32), 9- to 11-year-old children (n = 33), and 18- to 30-year-old young adults (YA; n = 39). Both memory accessibility (cued recall of objects) and precision (precision of object placement) of initially well-learned object-scene pairs were measured. Our results showed that overnight, memory accessibility declined similarly in all age groups; memory precision improved more in younger children (YC) compared to older children (OC) and even declined in YA. After a 2-week period, both memory accessibility and precision became worse. Specifically, while age groups showed similar decline in memory accessibility, precision decline was less in YC than in OC and YA. The accessibility and precision of congruent and incongruent information changed similarly with consolidation in all age groups. Taken together, our results showed that, for initially well-learned information, YC have robust memory consolidation, despite their overall lower mnemonic performance compared to OC and YA, which is potentially crucial for stable and precise knowledge accumulation early on in development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mnemonic But Not Contextual Feedback Signals Defy Dedifferentiation in the Aging Early Visual Cortex.

Perception is an intricate interplay between feedforward visual input and internally generated feedback signals that comprise concurrent contextual and time-distant mnemonic (episodic and semantic) information. Yet, an unresolved question is how the composition of feedback signals changes across the lifespan and to what extent feedback signals undergo age-related dedifferentiation, that is, a decline in neural specificity. Previous research on this topic has focused on feedforward perceptual representation and episodic memory reinstatement, suggesting reduced fidelity of neural representations at the item and category levels. In this fMRI study, we combined an occlusion paradigm that filters feedforward input to the visual cortex and multivariate analysis techniques to investigate the information content in cortical feedback, focusing on age-related differences in its composition. We further asked to what extent differentiation in feedback signals (in the occluded region) is correlated to differentiation in feedforward signals. Comparing younger (18-30 years) and older female and male adults (65-75 years), we found that contextual but not mnemonic feedback was prone to age-related dedifferentiation. Semantic feedback signals were even better differentiated in older adults, highlighting the growing importance of generalized knowledge across ages. We also found that differentiation in feedforward signals was correlated with differentiation in episodic but not semantic feedback signals. Our results provide evidence for age-related adjustments in the composition of feedback signals and underscore the importance of examining dedifferentiation in aging for both feedforward and feedback processing.

Prediction error and memory across the lifespan.

The influence of Prediction Errors (PEs) on episodic memory has generated growing empirical and theoretical interest. This review explores how the relationship between PE and memory may evolve throughout lifespan. Drawing upon the predictive processing framework and the Predictive, Interactive Multiple Memory System (PIMMS) model in particular, the paper highlights the hierarchical organization of memory systems and the interaction between top-down predictions and bottom-up sensory input, proposing that PEs promote synaptic change and improve encoding and consolidation processes. We discuss the neuroscientific mechanisms underlying PE-driven memory enhancement, focusing on the involvement of the hippocampus, the entorhinal cortex-hippocampus pathway, and the noradrenergic sympathetic system. Recognizing the divergent trajectories of episodic and semantic memory across the lifespan is crucial when examining the effects of PEs on memory. This review underscores the heterogeneity of memory processes and neurocognitive mechanisms underlying PE-driven memory enhancement across age. Future research is suggested to directly compare neural networks involved in learning from PEs across different age groups and to contribute to a deeper understanding of PE-driven learning across age.

The effect of prediction error on episodic memory encoding is modulated by the outcome of the predictions.

Expectations can lead to prediction errors of varying degrees depending on the extent to which the information encountered in the environment conforms with prior knowledge. While there is strong evidence on the computationally specific effects of such prediction errors on learning, relatively less evidence is available regarding their effects on episodic memory. Here, we had participants work on a task in which they learned context/object-category associations of different strengths based on the outcomes of their predictions. We then used a reinforcement learning model to derive subject-specific trial-to-trial estimates of prediction error at encoding and link it to subsequent recognition memory. Results showed that model-derived prediction errors at encoding influenced subsequent memory as a function of the outcome of participants' predictions (correct vs. incorrect). When participants correctly predicted the object category, stronger prediction errors (as a consequence of weak expectations) led to enhanced memory. In contrast, when participants incorrectly predicted the object category, stronger prediction errors (as a consequence of strong expectations) led to impaired memory. These results highlight the important moderating role of choice outcome that may be related to interactions between the hippocampal and striatal dopaminergic systems.

Not what u expect: Effects of prediction errors on item memory.

The characterization of the relationship between predictions and one-shot episodic encoding poses an important challenge for memory research. On the one hand, events that are compatible with our previous knowledge are thought to be remembered better than incompatible ones. On the other hand, unexpected situations, by virtue of their novelty, are known to cause enhanced learning. Several theoretical accounts try to solve this apparent paradox by conceptualizing prediction error (PE) as a continuum ranging from low PE (for expectation-matching events) to high PE (for expectation-mismatching ones). Under such a framework, the relationship between PE and memory encoding would be described by a U-shape function with higher memory performance for extreme levels of PE and lower memory for middle levels of PE. In this study, we tested the framework by using a gradual manipulation of the strength of association between scenes and objects to render different levels of PE and then tested for item memory of the (mis)matching events. In two experiments, in contrast to what was anticipated, recognition memory for object identity followed an inverted U-shape as a function of PE, with higher performance for intermediate levels of PE. Furthermore, in two additional experiments, we showed the relevance of explicit predictions at encoding to reveal such an inverted U pattern, thus providing the boundary conditions of the effect. We discussed our findings in light of existing literature relating PE and episodic memory, pointing out the potential roles of uncertainty in the environment, and the importance of the cognitive operations underlying encoding tasks. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The first year in formal schooling improves working memory and academic abilities.

Neurocognition and academic abilities during the period of 4 and 7 years of age are impacted by both the transition from kindergarten to primary school and age-related developmental processes. Here, we used a school cut-off design to tease apart the impact of formal schooling from age, on working memory (WM) function, vocabulary, and numeracy scores. We compared two groups of children with similar age, across two years: first-graders (FG), who were enrolled into primary school the year that they became eligible and kindergarteners (KG), who were deferred school entry until the following year. All children completed a change detection task while brain activation was recorded using portable functional near-infrared spectroscopy, a vocabulary assessment, and a numeracy screener. Our results revealed that FG children showed greater improvement in WM performance and greater engagement of a left-lateralized fronto-parietal network compared to KG children. Further, they also showed higher gains in vocabulary and non-symbolic numeracy scores. This improvement in vocabulary and non-symbolic numeracy scores following a year in primary school was predicted by WM function. Our findings contribute to a growing body of literature examining neurocognitive and academic benefits conferred to children following exposure to formal schooling.

Concurrent contextual and time-distant mnemonic information co-exist as feedback in the human visual cortex.

Efficient processing of the visual environment necessitates the integration of incoming sensory evidence with concurrent contextual inputs and mnemonic content from our past experiences. To examine how this integration takes place in the brain, we isolated different types of feedback signals from the neural patterns of non-stimulated areas of the early visual cortex in humans (i.e., V1 and V2). Using multivariate pattern analysis, we showed that both contextual and time-distant information, coexist in V1 and V2 as feedback signals. In addition, we found that the extent to which mnemonic information is reinstated in V1 and V2 depends on whether the information is retrieved episodically or semantically. Critically, this reinstatement was independent on the retrieval route in the object-selective cortex. These results demonstrate that our early visual processing contains not just direct and indirect information from the visual surrounding, but also memory-based predictions.

Distinct multivariate structural brain profiles are related to variations in short- and long-delay memory consolidation across children and young adults.

From early to middle childhood, brain regions that underlie memory consolidation undergo profound maturational changes. However, there is little empirical investigation that directly relates age-related differences in brain structural measures to memory consolidation processes. The present study examined memory consolidation of intentionally studied object-location associations after one night of sleep (short delay) and after two weeks (long delay) in normally developing 5-to-7-year-old children (n = 50) and young adults (n = 39). Behavioural differences in memory retention rate were related to structural brain measures. Our results showed that children, in comparison to young adults, retained correctly learnt object-location associations less robustly over short and long delay. Moreover, using partial least squares correlation method, a unique multivariate profile comprised of specific neocortical (prefrontal, parietal, and occipital), cerebellar, and hippocampal head and subfield structures in the body was found to be associated with variation in short-delay memory retention. A different multivariate profile comprised of a reduced set of brain structures, mainly consisting of neocortical (prefrontal, parietal, and occipital), hippocampal head, and selective hippocampal subfield structures (CA1-2 and subiculum) was associated with variation in long-delay memory retention. Taken together, the results suggest that multivariate structural pattern of unique sets of brain regions are related to variations in short- and long-delay memory consolidation across children and young adults.

Spontaneous discovery of novel task solutions in children.

Children often perform worse than adults on tasks that require focused attention. While this is commonly regarded as a sign of incomplete cognitive development, a broader attentional focus could also endow children with the ability to find novel solutions to a given task. To test this idea, we investigated children's ability to discover and use novel aspects of the environment that allowed them to improve their decision-making strategy. Participants were given a simple choice task in which the possibility of strategy improvement was neither mentioned by instructions nor encouraged by explicit error feedback. Among 47 children (8-10 years of age) who were instructed to perform the choice task across two experiments, 27.5% showed a full strategy change. This closely matched the proportion of adults who had the same insight (28.2% of n = 39). The amount of erroneous choices, working memory capacity and inhibitory control, in contrast, indicated substantial disadvantages of children in task execution and cognitive control. A task difficulty manipulation did not affect the results. The stark contrast between age-differences in different aspects of cognitive performance might offer a unique opportunity for educators in fostering learning in children.

Longitudinal developmental trajectories do not follow cross-sectional age associations in hippocampal subfield and memory development.

Cross-sectional findings suggest that volumes of specific hippocampal subfields increase in middle childhood and early adolescence. In contrast, a small number of available longitudinal studies reported decreased volumes in most subfields over this age range. Further, it remains unknown whether structural changes in development are associated with corresponding gains in children's memory. Here we report cross-sectional age differences in children's hippocampal subfield volumes together with longitudinal developmental trajectories and their relationships with memory performance. In two waves, 109 participants aged 6-10 years (wave 1: MAge=7.25, wave 2: MAge=9.27) underwent high-resolution magnetic resonance imaging to assess hippocampal subfield volumes (imaging data available at both waves for 65 participants) and completed tasks assessing hippocampus dependent memory processes. We found that cross-sectional age-associations and longitudinal developmental trends in hippocampal subfield volumes were discrepant, both by subfields and in direction. Further, volumetric changes were largely unrelated to changes in memory, with the exception that increase in subiculum volume was associated with gains in spatial memory. Longitudinal and cross-sectional patterns of brain-cognition couplings were also discrepant. We discuss potential sources of these discrepancies. This study underscores that children's structural brain development and its relationship to cognition cannot be inferred from cross-sectional age comparisons.

Disentangling age and schooling effects on inhibitory control development: An fNIRS investigation.

Children show marked improvements in executive functioning (EF) between 4 and 7 years of age. In many societies, this time period coincides with the start of formal school education, in which children are required to follow rules in a structured environment, drawing heavily on EF processes such as inhibitory control. This study aimed to investigate the longitudinal development of two aspects of inhibitory control, namely response inhibition and response monitoring and their neural correlates. Specifically, we examined how their longitudinal development may differ by schooling experience, and their potential significance in predicting academic outcomes. Longitudinal data were collected in two groups of children at their homes. At T1, all children were roughly 4.5 years of age and neither group had attended formal schooling. One year later at T2, one group (P1, n = 40) had completed one full year of schooling while the other group (KG, n = 40) had stayed in kindergarten. Behavioural and brain activation data (measured with functional near-infrared spectroscopy, fNIRS) in response to a Go/No-Go task and measures of academic achievement were collected. We found that P1 children, compared to KG children, showed a greater change over time in activation related to response monitoring in the bilateral frontal cortex. The change in left frontal activation difference showed a small positive association with math performance. Overall, the school environment is important in shaping the development of the brain functions underlying the monitoring of one own's performance.

Neural Correlates of Successful Memory Encoding in Kindergarten and Early Elementary School Children: Longitudinal Trends and Effects of Schooling.

From age 5 to 7, there are remarkable improvements in children's cognitive abilities ("5-7 shift"). In many countries, including Germany, formal schooling begins in this age range. It is, thus, unclear to what extent exposure to formal schooling contributes to the "5-7 shift." In this longitudinal study, we investigated if schooling acts as a catalyst of maturation. We tested 5-year-old children who were born close to the official cutoff date for school entry and who were still attending a play-oriented kindergarten. One year later, the children were tested again. Some of the children had experienced their first year of schooling whereas the others had remained in kindergarten. Using 2 functional magnetic resonance imaging tasks that assessed episodic memory formation (i.e., subsequent memory effect), we found that children relied strongly on the medial temporal lobe (MTL) at both time points but not on the prefrontal cortex (PFC). In contrast, older children and adults typically show subsequent memory effects in both MTL and PFC. Both children groups improved in their memory performance, but there were no longitudinal changes nor group differences in neural activation. We conclude that successful memory formation in this age group relies more heavily on the MTL than in older age groups.

Home assessment of visual working memory in pre-schoolers reveals associations between behaviour, brain activation and parent reports of life stress.

Visual working memory (VWM) is reliably predictive of fluid intelligence and academic achievements. The objective of the current study was to investigate individual differences in pre-schoolers' VWM processing by examining the association between behaviour, brain function and parent-reported measures related to the child's environment. We used a portable functional near-infrared spectroscopy system to record from the frontal and parietal cortices of 4.5-year-old children (N = 74) as they completed a colour change-detection VWM task in their homes. Parents were asked to fill in questionnaires on temperament, academic aspirations, home environment and life stress. Children were median-split into a low-performing (LP) and a high-performing (HP) group based on the number of items they could successfully remember during the task. LPs increasingly activated channels in the left frontal and bilateral parietal cortices with increasing load, whereas HPs showed no difference in activation. Our findings suggest that LPs recruited more neural resources than HPs when their VWM capacity was challenged. We employed mediation analyses to examine the association between the difference in activation between the highest and lowest loads and variables from the questionnaires. The difference in activation between loads in the left parietal cortex partially mediated the association between parent-reported stressful life events and VWM performance. Critically, our findings show that the association between VWM capacity, left parietal activation and indicators of life stress is important to understand the nature of individual differences in VWM in pre-school children.

Effects of stress on 6- and 7-year-old children's emotional memory differs by gender.

Understanding effects of emotional valence and stress on children's memory is important for educational and legal contexts. This study disentangled the effects of emotional content of to-be-remembered information (i.e., items differing in emotional valence and arousal), stress exposure, and associated cortisol secretion on children's memory. We also examined whether girls' memory is more affected by stress induction. A total of 143 6- and 7-year-old children were randomly allocated to the Trier Social Stress Test for Children (n = 103) or a control condition (n = 40). At 25 min after stressor onset, children incidentally encoded 75 objects varying in emotional valence (crossed with arousal) together with neutral scene backgrounds. We found that response bias corrected memory was worse for low-arousing negative items than for neutral and positive items, with the latter two categories not being different from each other. Whereas boys' memory was largely unaffected by stress, girls in the stress condition showed worse memory for negative items, especially the low-arousing ones, than girls in the control condition. Girls, compared with boys, reported higher subjective stress increases following stress exposure and had higher cortisol stress responses. Whereas a higher cortisol stress response was associated with better emotional memory in girls in the stress condition, boys' memory was not associated with their cortisol secretion. Taken together, our study suggests that 6- and 7-year-old children, more so girls, show memory suppression for negative information. Girls' memory for negative information, compared with that of boys, is also more strongly modulated by stress experience and the associated cortisol response.

Clinical Phenotype of LRRK2 R1441C in 2 Chinese Sisters.

Pathogenic and risk variants in the LRRK2 gene are among the main genetic contributors to Parkinson's disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to the LRRK2 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative LRRK2 mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation in LRRK2 (which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n = 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall "real world" PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.

Hair cortisol concentrations are associated with hippocampal subregional volumes in children.

The human hippocampus, a brain structure crucial for memory across the lifespan, is highly sensitive to adverse life events. Stress exposures during childhood have been linked to altered hippocampal structure and memory performance in adulthood. Animal studies suggest that these differences are in part driven by aberrant glucocorticoid secretion during development, with strongest effects on the CA3 region and the dentate gyrus (CA3-DG) of the hippocampus, alongside associated memory impairments. However, only few pediatric studies have examined glucocorticoid associations with hippocampal subfield volumes and their functional relevance. In 84 children (age range: 6-7 years), we assessed whether volumes of hippocampal subregions were related to cumulative glucocorticoid levels (hair cortisol), parenting stress, and performance on memory tasks known to engage the hippocampus. We found that higher hair cortisol levels were specifically related to lower CA3-DG volume. Parenting stress did not significantly correlate with hair cortisol, and there was no evidence to suggest that individual differences in hippocampal subregional volumes manifest in memory performance. Our results suggest that the CA3-DG may be the hippocampal region most closely associated with hair cortisol levels in childhood. Establishing causal pathways underlying this association and its relation to environmental stress and memory development necessitates longitudinal studies.

Oscillatory Mechanisms of Successful Memory Formation in Younger and Older Adults Are Related to Structural Integrity.

We studied oscillatory mechanisms of memory formation in 48 younger and 51 older adults in an intentional associative memory task with cued recall. While older adults showed lower memory performance than young adults, we found subsequent memory effects (SME) in alpha/beta and theta frequency bands in both age groups. Using logistic mixed effects models, we investigated whether interindividual differences in structural integrity of key memory regions could account for interindividual differences in the strength of the SME. Structural integrity of inferior frontal gyrus (IFG) and hippocampus was reduced in older adults. SME in the alpha/beta band were modulated by the cortical thickness of IFG, in line with its hypothesized role for deep semantic elaboration. Importantly, this structure-function relationship did not differ by age group. However, older adults were more frequently represented among the participants with low cortical thickness and consequently weaker SME in the alpha band. Thus, our results suggest that differences in the structural integrity of the IFG contribute not only to interindividual, but also to age differences in memory formation.

I know that I know nothing: Cortical thickness and functional connectivity underlying meta-ignorance ability in pre-schoolers.

Metacognition plays a pivotal role in human development. The ability to realize that we do not know something, or meta-ignorance, emerges after approximately five years of age. We sought for the brain systems that underlie the developmental emergence of this ability in a preschool sample. Twenty-four children aged between five and six years answered questions under three conditions. In the critical partial knowledge condition, an experimenter first showed two toys to a child, then announced that she would place one of them in a box, out of sight from the child. The experimenter then asked the child whether she knew which toy was in the box. Children who gave consistently correct answers to this question (n = 9) showed greater cortical thickness in a cluster within left medial orbitofrontal cortex than children who did not (n = 15). Further, seed-based functional connectivity analyses of the brain during resting state revealed that this region is functionally connected to the medial orbitofrontal gyrus, posterior cingulate gyrus and precuneus, and mid- and inferior temporal gyri. This finding suggests that the default mode network, critically through its prefrontal regions, supports introspective processing. It leads to the emergence of metacognitive monitoring allowing children to explicitly report their own ignorance.