Probing the content of affective semantic memory following caregiving-related early adversity.

Cognitive science has demonstrated that we construct knowledge about the world by abstracting patterns from routinely encountered experiences and storing them as semantic memories. This preregistered study tested the hypothesis that caregiving-related early adversities (crEAs) shape affective semantic memories to reflect the content of those adverse interpersonal-affective experiences. We also tested the hypothesis that because affective semantic memories may continue to evolve in response to later-occurring positive experiences, child-perceived attachment security will inform their content. The sample comprised 160 children (ages 6-12 at Visit 1; 87F/73 M), 66% of whom experienced crEAs (n = 105). At Visit 1, crEA exposure prior to study enrollment was operationalized as parental-reports endorsing a history of crEAs (abuse/neglect, permanent/significant parent-child separation); while child-reports assessed concurrent attachment security. A false memory task was administered online ∼2.5 years later (Visit 2) to probe the content of affective semantic memories-specifically attachment schemas. Results showed that crEA exposure (vs. no exposure) was associated with a higher likelihood of falsely endorsing insecure (vs. secure) schema scenes. Attachment security moderated the association between crEA exposure and insecure schema-based false recognition. Findings suggest that interpersonal-affective semantic schemas include representations of parent-child interactions that may capture the quality of one's own attachment experiences and that these representations shape how children remember attachment-relevant narrative events. Findings are also consistent with the hypothesis that these affective semantic memories can be modified by later experiences. Moving forward, the approach taken in this study provides a means of operationalizing Bowlby's notion of internal working models within a cognitive neuroscience framework. RESEARCH HIGHLIGHTS: Affective semantic memories representing insecure schema knowledge (child needs + needs-not-met) may be more salient, elaborated, and persistent among youths exposed to early caregiving adversity. All youths, irrespective of early caregiving adversity exposure, may possess affective semantic memories that represent knowledge of secure schemas (child needs + needs-met). Establishing secure relationships with parents following early-occurring caregiving adversity may attenuate the expression of insecure semantic memories, suggesting potential malleability. Affective semantic memories include schema representations of parent-child interactions that may capture the quality of one's own attachment experiences and shape how youths remember attachment-relevant events.

Seeking versus receiving help: How children integrate suggestions in memory decisions.

The current research examined how seeking versus receiving help affected children's memory and confidence decisions. Baseline performance, when no help was available, was compared to performance when help could be sought (Experiment 1: N = 83, 41 females) or was provided (Experiment 2: N = 84, 44 females) in a sample of predominately White 5-, 7-, and 9-year-olds from Northern California. Data collection occurred from 2018 to 2019. In Experiment 1, 5-year-olds agreed most often with sought-help, whereas 9-year-olds were the only age group reporting lower confidence for sought-help relative to baseline trials. In Experiment 2, agreement and confidence after provided help were similar across age groups. Different developmental patterns when help was sought versus provided underscore the importance of active help-seeking for memory decision-making.

Attention to novelty interferes with toddlers' emerging memory decision-making.

Memory decision-making in 26- to 32-month-olds was investigated using visual-paired comparison paradigms, requiring toddlers to select familiar stimuli (Active condition) or view familiar and novel stimuli (Passive condition). In Experiment 1 (N = 108, 54.6% female, 62% White; replication N = 98), toddlers with higher accuracy in the Active condition showed reduced novelty preference in that condition, but not in the Passive condition (d = -.11). In Experiment 2 (N = 78; 52.6% female; 70.5% White), a brief 5% increase in target size boosted gaze transitions across conditions (d = .50) and accuracy in the Active condition (d = .53). Overall, evidence suggests that better attentional distribution can support decision-making. Research was conducted between 2014 and 2020 in Northern California.

Multisensory processing impacts memory for objects and their sources.

Multisensory object processing improves recognition memory for individual objects, but its impact on memory for neighboring visual objects and scene context remains largely unknown. It is therefore unclear how multisensory processing impacts episodic memory for information outside of the object itself. We conducted three experiments to test the prediction that the presence of audiovisual objects at encoding would improve memory for nearby visual objects, and improve memory for the environmental context in which they occurred. In Experiments 1a and 1b, participants viewed audiovisual-visual object pairs or visual-visual object pairs with a control sound during encoding and were subsequently tested on their memory for each object individually. In Experiment 2, objects were paired with semantically congruent or meaningless control sounds and appeared within four different scene environments. Memory for the environment was tested. Results from Experiments 1a and 1b showed that encoding a congruent audiovisual object did not significantly benefit memory for neighboring visual objects, but Experiment 2 showed that encoding a congruent audiovisual object did improve memory for the environments in which those objects were encoded. These findings suggest that multisensory processing can influence memory beyond the objects themselves and that it has a unique role in episodic memory formation. This is particularly important for understanding how memories and associations are formed in real-world situations, in which objects and their surroundings are often multimodal.

Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis.

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes. METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we described associations between dehydration severity and DKA outcomes. RESULTS: Mean dehydration was 5.7% (SD 3.6%). Mild (0 to <5%), moderate (5 to <10%), and severe (≥10%) dehydration were observed in 47% (N=379), 42% (N=343), and 11% (N=89) of episodes, respectively. In multivariable analyses, more severe dehydration was associated with new onset of diabetes, higher blood urea nitrogen, lower pH, higher anion gap, and diastolic hypertension. However, there was substantial overlap in these variables between dehydration groups. The mean length of hospital stay was longer for patients with moderate and severe dehydration, both in new onset and established diabetes. CONCLUSION: Most children with DKA have mild-to-moderate dehydration. Although biochemical measures were more closely associated with the severity of dehydration than clinical assessments, neither were sufficiently predictive to inform rehydration practice.

Contextual features in the developing hippocampus: A representational similarity analysis.

Functional divisions of labor in support of memory have been reported along the anterior-posterior axis of the hippocampus. However, little is known about how the developing hippocampus represents associative memories along this axis. The present research employed representational similarity analysis to ask whether developmental differences exist in the extent to which the anterior versus the posterior hippocampus represent features of the context and associative memories. Functional magnetic resonance imaging data were collected during the retrieval phase of an associative recognition task from 8-year-olds, 10-year-olds, and adults (N = 58). Participants were asked to retrieve pairs of items, which were presented either in the same location as during encoding or in a flipped location. In the anterior hippocampus and only for adults, pattern similarity between the two studied pair conditions was greater than pattern similarity between studied pairs presented in the same location and novel pairs. In contrast, this difference was not significant in the posterior hippocampus. Older, but not younger, children showed a similar, albeit attenuated, similarity pattern to that of adults, but measures of patterns similarity predicted associative recognition across ages. In addition, exploratory analyses showed that similarity patterns in the adult posterior, but not anterior, hippocampus tracked the order of the runs. Overall, the results suggest functional and developmental dissociations in processing different contextual features, with the anterior hippocampus responding to salient and rapid-changing features and the posterior hippocampus responding to slower-changing features of the context.

Clinical Characteristics of Children with Cerebral Injury preceding Treatment of Diabetic Ketoacidosis.

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

The development of uncertainty monitoring during kindergarten: Change and longitudinal relations with executive function and vocabulary in children from low-income backgrounds.

Children's ability to monitor subjective feelings of uncertainty (i.e., engage in uncertainty monitoring) is a central metacognitive skill. In the current study, we examined the development of uncertainty monitoring as well as its relations with vocabulary and executive function development in children (N = 137, 52% female) from predominately White and Latinx/Hispanic backgrounds when they were 4-6 years old and enrolled in a Head Start preschool and kindergarten between 2018 and 2019. We found that children's uncertainty monitoring improved during the kindergarten year. Children's executive function and vocabulary in preschool and vocabulary growth from preschool to kindergarten predicted uncertainty monitoring at the end of kindergarten, which sheds new light on potential mechanisms supporting children's metacognitive development.

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. METHODS: We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis. RESULTS: A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups. CONCLUSIONS: Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).

Developmental Differences in Subjective Recollection and Its Role in Decision Making.

We examined how subjective assessments of recollection guide decision making. Subjective recollection was dissociated from accuracy during a forced-choice recognition task. Distracters were either similar to targets (match condition) or to other studied, but untested items (nonmatch condition). We assessed 223 participants (112 males) across three experiments (137 White, 37 Asian-American, 7 African-American, 4 American-Indian, 32 mixed race, 6 undisclosed). In Experiment 1, 6- to 10-year-olds and adults (N = 119) were less accurate (d = 0.70), but more likely to claim subjective recollection and make memory selections in anticipation of a reward in the nonmatch condition (ds = 0.64-0.70). This pattern was eliminated in 6- to 7-year-olds when we limited the number of selections (Experiment 2, N = 52), but was replicated when we required the selections to be counted (Experiment 3, N = 52), underscoring the effects of decision complexity on children's self-reflections.

Memory-related hippocampal activation in the sleeping toddler.

Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but methodological challenges have hindered assessments of this possibility in humans. Here, we delivered a previously learned song and a novel song to 2-year-old toddlers during natural nocturnal sleep and, using functional magnetic resonance imaging, found that hippocampal activation was stronger for the learned song compared with the novel song. This was true regardless of whether the song was presented intact or backwards. Toddlers who remembered where and in the presence of which toy character they heard the song exhibited stronger hippocampal activation for the song. The results establish that hippocampal activation in toddlers reflects past experiences, persists despite some alteration of the stimulus, and is associated with behavior. This research sheds light on early hippocampal and memory functioning and offers an approach to interrogate the neural substrates of early memory.

Hypertension during Diabetic Ketoacidosis in Children.

OBJECTIVES: To characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension. STUDY DESIGN: This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension. RESULTS: Among 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower pCO2), and stage 2 or 3 acute kidney injury. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment. CONCLUSIONS: Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower pCO2, and lower Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.

Connecting the Dots Between Past and Future: Constraints in Episodic Future Thinking in Early Childhood.

Preschoolers have limited capacity to use past experiences to prepare for the future. Two experiments sought to further understand these limitations. Experiment 1 (N = 42) showed that 3- to 4-year olds' difficulty performing anticipated future actions was constrained by their memory for relevant past actions, especially those including temporal information. Experiment 2 (N = 94) sought to determine whether preschoolers fail to see that past experiences can inform future-oriented actions. When the connection between the past and future was experimentally heightened, future thinking accuracy improved, but only if preschoolers remembered past experiences. The results indicate that past recall is a prerequisite for future thinking but failure to bridge past and future further accounts for observed limitations in future thinking in early childhood.

Changes in ventromedial prefrontal and insular cortex support the development of metamemory from childhood into adolescence.

Metamemory monitoring, or the ability to introspect on the accuracy of one's memories, improves considerably during childhood, but the underlying neural changes and implications for intellectual development are largely unknown. The present study examined whether cortical changes in key brain areas hypothesized to support metacognition contribute to the development of metamemory monitoring from late childhood into early adolescence. Metamemory monitoring was assessed among 7- to 12-y-old children (n = 145) and adults (n = 31). Children returned for up to two additional assessments at 8 to 14 y of age (n = 120) and at 9 to 15 y of age (n = 107) (n = 347 longitudinal scans). Results showed that metamemory monitoring continues to improve from childhood into adolescence. More pronounced cortical thinning in the anterior insula and a greater increase in the thickness of the ventromedial prefrontal cortex over the three assessment points predicted these improvements. Thus, performance benefits are linked to the unique patterns of regional cortical change during development. Metamemory monitoring at the first time point predicted intelligence at the third time point and vice versa, suggesting parallel development of these abilities and their reciprocal influence. Together, these results provide insights into the neuroanatomical correlates supporting the development of the capacity to self-reflect, and highlight the role of this capacity for general intellectual development.

Associative binding in early childhood: Evidence from a preferential looking paradigm.

Relational memory processes are responsible for forming representations that bind together the co-occurring elements of an experience. These processes provide a foundation of episodic memory, the capacity to remember specific events about one's past. In the present research, we used a visual comparison paradigm to determine whether toddlers can form memories for the relation between co-occurring items. In Experiment 1, 66 2-year-olds viewed pairs of cartoon faces (AB; CD) and did not show a significant novelty preference for the violated associations (i.e., did not look longer at AD rearranged pair than old AB pair when exposed to AD-AB). However, toddlers looked longest at the individual face (i.e., D) violating a studied pair, which appeared to be supported by visual preference for centrally located stimuli. In Experiment 2, 46 2-year-olds participated in a similar procedure, but faces violating the pair during test were located to the periphery (e.g., AB-AC). Under these conditions, toddlers looked longer at recombined pair AC. Overall, our results show that toddlers show some ability to make item-item associations but may need to overcome preferential looking biases to demonstrate this capacity. Furthermore, looking behaviors beyond overall novelty preference may be informative even when overall novelty preference is not found.

Neural specificity of scene representations is related to memory performance in childhood.

Successful memory encoding is supported by medial temporal, retrosplenial, and occipital regions, which show developmental differences in recruitment from childhood to adulthood. However, little is known about the extent to which neural specificity in these brain regions, or the distinctiveness with which sensory information is represented, continues to develop during middle childhood and how it contributes to memory performance. The present study used multivariate pattern analysis to examine the distinctiveness of different scene representations in 169 children and 31 adults, and its relation to memory performance. Most children provided data over up to three measurement occasions between 8 and 15 years (267 total scans), allowing us to examine changes in memory and neural specificity over time. Memory performance was lower in children than in adults, and increased in children over time. Different scenes presented during memory encoding could be reliably decoded from parahippocampal, lateral occipital, and retrosplenial regions in children and adults. Neural specificity in children was similar to adults, and did not change reliably over time. Among children, higher neural specificity in scene-processing regions was associated with better memory concurrently. These results suggest that the distinctiveness with which incoming information is represented is important for memory performance in childhood, but other processes operating on these representations support developmental improvements in memory performance over time.

The Importance of Knowing When You Don't Remember: Neural Signaling of Retrieval Failure Predicts Memory Improvement Over Time.

Just as the ability to remember prior events is critical for guiding our decision-making, so too is the ability to recognize the limitations of our memory. Indeed, we hypothesize that neural signaling of retrieval failure promotes more accurate memory judgments over time. To test this hypothesis, we collected longitudinal functional magnetic resonance imaging data from 8 to 9 years olds, 10 to 12 years olds, and adults, with two time points spaced approximately 1.4 years apart (198 scan sessions in total). Participants performed an episodic memory retrieval task in which they could either select a response or report uncertainty about the target memory detail. Children who engaged anterior insula more strongly during inaccurate or uncertain responses exhibited greater longitudinal increases in anterior prefrontal cortex activation for decisions to report uncertainty; both of these neural variables predicted improvements in episodic memory. Together, the results suggest that the brain processes supporting effective cognitive control and decision-making continue to develop in middle childhood and play an important role for memory development.

Development of Episodic Prospection: Factors Underlying Improvements in Middle and Late Childhood.

Episodic prospection is the mental simulation of a personal future event in rich contextual detail. This study examined age-related differences in episodic prospection in 5- to 11-year-olds and adults (N = 157), as well as factors that may contribute to developmental improvements. Participants' narratives of past, future, and make-believe events were coded for episodic content, and self-concept coherence (i.e., how coherently an individual sees himself or herself) and narrative ability were tested as predictors of episodic prospection. Although all ages provided less episodic content for future event narratives, age-related improvements were observed across childhood, suggesting future event generation is particularly difficult for children. Self-concept coherence and narrative ability each independently predicted the episodic content of 5- and 7-year-olds' future event narratives.

Here is a hint! How children integrate reliable recommendations in their memory decisions.

Children's own memory is not the only reliable source of information about past events. Others may possess relevant knowledge, and children must learn to appropriately consider it in combination with their own memories. In the current study, we investigated 5-, 7-, and 9-year-olds' (N = 72) ability to incorporate probabilistically reliable (70% accurate) hints into their memory decisions. Results revealed that children across ages were appropriately sensitive to these cues without following them blindly and indiscriminately. Furthermore, individual differences in metamemory monitoring predicted overall accuracy improvements after receiving cues in 9-year-olds but not in 5- and 7-year-olds, revealing a developmental role of metamemory for discerning when cues are most informative or needed. Although 5-year-olds increased overall confidence in their memory after receiving invalid cues, they still preserved the capacity to monitor their memory in the face of inaccurate information. Overall, children were sensitive to reliable recommendations, but developing metacognitive mechanisms predicted judicious benefits from cues.

Frontoparietal Structural Connectivity in Childhood Predicts Development of Functional Connectivity and Reasoning Ability: A Large-Scale Longitudinal Investigation.

Prior research points to a positive concurrent relationship between reasoning ability and both frontoparietal structural connectivity (SC) as measured by diffusion tensor imaging (Tamnes et al., 2010) and frontoparietal functional connectivity (FC) as measured by fMRI (Cocchi et al., 2014). Further, recent research demonstrates a link between reasoning ability and FC of two brain regions in particular: rostrolateral prefrontal cortex (RLPFC) and the inferior parietal lobe (IPL) (Wendelken et al., 2016). Here, we sought to investigate the concurrent and dynamic, lead-lag relationships among frontoparietal SC, FC, and reasoning ability in humans. To this end, we combined three longitudinal developmental datasets with behavioral and neuroimaging data from 523 male and female participants between 6 and 22 years of age. Cross-sectionally, reasoning ability was most strongly related to FC between RLPFC and IPL in adolescents and adults, but to frontoparietal SC in children. Longitudinal analysis revealed that RLPFC-IPL SC, but not FC, was a positive predictor of future changes in reasoning ability. Moreover, we found that RLPFC-IPL SC at one time point positively predicted future changes in RLPFC-IPL FC, whereas, in contrast, FC did not predict future changes in SC. Our results demonstrate the importance of strong white matter connectivity between RLPFC and IPL during middle childhood for the subsequent development of both robust FC and good reasoning ability.SIGNIFICANCE STATEMENT The human capacity for reasoning develops substantially during childhood and has a profound impact on achievement in school and in cognitively challenging careers. Reasoning ability depends on communication between lateral prefrontal and parietal cortices. Therefore, to understand how this capacity develops, we examined the dynamic relationships over time among white matter tracts connecting frontoparietal cortices (i.e., structural connectivity, SC), coordinated frontoparietal activation (functional connectivity, FC), and reasoning ability in a large longitudinal sample of subjects 6-22 years of age. We found that greater frontoparietal SC in childhood predicts future increases in both FC and reasoning ability, demonstrating the importance of white matter development during childhood for subsequent brain and cognitive functioning.