Bayesian varying-effects vector autoregressive models for inference of brain connectivity networks and covariate effects in pediatric traumatic brain injury.

In this article, we develop an analytical approach for estimating brain connectivity networks that accounts for subject heterogeneity. More specifically, we consider a novel extension of a multi-subject Bayesian vector autoregressive model that estimates group-specific directed brain connectivity networks and accounts for the effects of covariates on the network edges. We adopt a flexible approach, allowing for (possibly) nonlinear effects of the covariates on edge strength via a novel Bayesian nonparametric prior that employs a weighted mixture of Gaussian processes. For posterior inference, we achieve computational scalability by implementing a variational Bayes scheme. Our approach enables simultaneous estimation of group-specific networks and selection of relevant covariate effects. We show improved performance over competing two-stage approaches on simulated data. We apply our method on resting-state functional magnetic resonance imaging data from children with a history of traumatic brain injury (TBI) and healthy controls to estimate the effects of age and sex on the group-level connectivities. Our results highlight differences in the distribution of parent nodes. They also suggest alteration in the relation of age, with peak edge strength in children with TBI, and differences in effective connectivity strength between males and females.

Parenting Influences on Frontal Lobe Gray Matter and Preterm Toddlers' Problem-Solving Skills.

Children born preterm often face challenges with self-regulation during toddlerhood. This study examined the relationship between prematurity, supportive parent behaviors, frontal lobe gray matter volume (GMV), and emotion regulation (ER) among toddlers during a parent-assisted, increasingly complex problem-solving task, validated for this age range. Data were collected from preterm toddlers (n = 57) ages 15-30 months corrected for prematurity and their primary caregivers. MRI data were collected during toddlers' natural sleep. The sample contained three gestational groups: 22-27 weeks (extremely preterm; EPT), 28-33 weeks (very preterm; VPT), and 34-36 weeks (late preterm; LPT). Older toddlers became more compliant as the Tool Task increased in difficulty, but this pattern varied by gestational group. Engagement was highest for LPT toddlers, for older toddlers, and for the easiest task condition. Parents did not differentiate their support depending on task difficulty or their child's age or gestational group. Older children had greater frontal lobe GMV, and for EPT toddlers only, more parent support was related to larger right frontal lobe GMV. We found that parent support had the greatest impact on high birth risk (≤27 gestational weeks) toddler brain development, thus early parent interventions may normalize preterm child neurodevelopment and have lasting impacts.

Virtual Teaching Together: engaging parents and young children in STEM activities.

Introduction: Early informal learning experiences are essential for sparking long-term interest in science, technology, engineering, and math (STEM). In a prior study, we found more promising parent involvement outcomes when families of young children were provided with STEM family education events along with home STEM activity kits compared to providing workshops alone. This study was a conceptual replication using the same program-Teaching Together STEM-to deliver educational workshops plus home activity kits; however, we varied the delivery method by using virtual "funshops" to evaluate if parents perceived this modality as feasible and useful. Methods: Museum informal science educators introduced four units via virtual video chat sessions linked to 12 hands-on STEM activities that were mailed to families randomly assigned to the treatment group. Half of the families were assigned to a waitlist control group that received a portion of the virtual program after the posttest. Participants included 60 families with children aged 3 to 5 years from diverse linguistic and socioeconomic backgrounds. Results: Our results indicate no significant group differences in the primary outcome of parents' involvement in informal STEM but a small, positive effect size (ES = 0.18) that was similar in magnitude to the prior, in-person study. Although parents mostly perceived the remote delivery as convenient and the materials as engaging for their child, there were no significant program impacts on children's general science interests (ES = -0.19). Discussion: Despite the convenience, parents reported time was a barrier to doing STEM activities at home. Parents with lower education levels were less likely to attend, suggesting virtual approaches are not sufficient for ensuring broad access to family engagement programs for populations underrepresented in STEM.

Effective connectivity between resting-state networks in depression.

RATIONALE: Although depression has been widely researched, findings characterizing how brain regions influence each other remains scarce, yet this is critical for research on antidepressant treatments and individual responses to particular treatments. OBJECTIVES: To identify pre-treatment resting state effective connectivity (rsEC) patterns in patients with major depressive disorder (MDD) and explore their relationship with treatment response. METHODS: Thirty-four drug-free MDD patients had an MRI scan and were subsequently treated for 6 weeks with an SSRI escitalopram 10 mg daily; the response was defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score. RESULTS: rsEC networks in default mode, central executive, and salience networks were identified for patients with depression. Exploratory analyses indicated higher connectivity strength related to baseline depression severity and response to treatment. CONCLUSIONS: Preliminary analyses revealed widespread dysfunction of rsEC in depression. Functional rsEC may be useful as a predictive tool for antidepressant treatment response. A primary limitation of the current study was the small size; however, the group was carefully chosen, well-characterized, and included only medication-free patients. Further research in large samples of placebo-controlled studies would be required to confirm the results.

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.

Effective connectivity in the default mode network after paediatric traumatic brain injury.

Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi-subject vector autoregressive modelling (BVAR-connect), which used white matter integrity as priors to evaluate effective connectivity-the time-dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions-within the default mode network (DMN). In a prospective longitudinal study, children ages 8-15 years with mild to severe TBI underwent diffusion tensor imaging and resting state fMRI 7 weeks after injury; post-concussion and anxiety symptoms were assessed 7 months after injury. The goals of this study were to (1) characterize differences in positive effective connectivity of resting-state DMN circuitry between healthy controls and children with TBI, (2) determine if severity of TBI was associated with differences in DMN connectivity and (3) evaluate whether patterns of DMN effective connectivity predicted persistent post-concussion symptoms and anxiety. Healthy controls had unique positive connectivity that mostly emerged from the inferior temporal lobes. In contrast, children with TBI had unique effective connectivity among orbitofrontal and parietal regions. These positive orbitofrontal-parietal DMN effective connectivity patterns also differed by TBI severity and were associated with persisting behavioural outcomes. Effective connectivity may be a sensitive neuroimaging marker of TBI severity as well as a predictor of chronic post-concussion symptoms and anxiety.

BVAR-Connect: A Variational Bayes Approach to Multi-Subject Vector Autoregressive Models for Inference on Brain Connectivity Networks.

In this paper we propose BVAR-connect, a variational inference approach to a Bayesian multi-subject vector autoregressive (VAR) model for inference on effective brain connectivity based on resting-state functional MRI data. The modeling framework uses a Bayesian variable selection approach that flexibly integrates multi-modal data, in particular structural diffusion tensor imaging (DTI) data, into the prior construction. The variational inference approach we develop allows scalability of the methods and results in the ability to estimate subject- and group-level brain connectivity networks over whole-brain parcellations of the data. We provide a brief description of a user-friendly MATLAB GUI released for public use. We assess performance on simulated data, where we show that the proposed inference method can achieve comparable accuracy to the sampling-based Markov Chain Monte Carlo approach but at a much lower computational cost. We also address the case of subject groups with imbalanced sample sizes. Finally, we illustrate the methods on resting-state functional MRI and structural DTI data on children with a history of traumatic injury.

Frontostriatal White Matter Integrity Relations with "Cool" and "Hot" Self-Regulation after Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) produces microstructural damage to white matter pathways connecting neural structures in pre-frontal and striatal regions involved in self-regulation (SR). Dorsal and ventral frontostriatal pathways have been linked to cognitive ("cool") and emotional ("hot") SR, respectively. We evaluated the relation of frontostriatal pathway fractional anisotropy (FA) 2 months post-TBI on cool and hot SR assessed 7 months post-TBI. Participants were 8-15 years of age, including children with uncomplicated mild TBI (mTBI; n = 24), more severe TBI (complicated-mild, moderate, severe [cms]TBI; n = 60), and typically developing (TD) children (n = 55). Diffusion tensor tractography was used to map frontostriatal pathways. Cool SR included focused and sustained attention performance, and parent-reported attention, whereas hot SR included risk-taking performance and parent-reported emotional control. Multivariate general linear models showed that children with cmsTBI had greater parent-reported cool and hot SR difficulties and lower dorsal and ventral FA than TD children. Focused attention, risk taking, and emotional control correlated with FA of specific dorsal and ventral pathways; however, only the effect of TBI on focused attention was mediated by integrity of dorsal pathways. Results suggest that frontostriatal FA may serve as a biomarker of risk for SR difficulties or to assess response to interventions targeting SR in pediatric TBI and in broader neurodevelopmental populations.

Post-Traumatic Stress Symptoms after Pediatric Injury: Relation to Pre-Frontal Limbic Circuitry.

Pre-frontal limbic circuitry is vulnerable to effects of stress and injury. We examined microstructure of pre-frontal limbic circuitry after traumatic brain injury (TBI) or extracranial injury (EI) and its relation to post-traumatic stress symptoms (PTSS). Participants aged 8 to 15 years who sustained mild to severe TBI (n = 53) or EI (n = 26) in motor vehicle incidents were compared with healthy children (n = 38) in a prospective longitudinal study. At the seven-week follow-up, diffusion tensor imaging was obtained in all groups; injured children completed PTSS ratings using a validated scale. Using probabilistic diffusion tensor tractography, pathways were seeded from bilateral amygdalae and hippocampi to estimate the trajectory of white matter connecting them to each other and to targeted pre-frontal cortical (PFC) regions. Microstructure was estimated using fractional anisotropy (FA) in white matter and mean diffusivity (MD) in gray matter. Pre-frontal limbic microstructure was similar across groups, except for reduced FA in the right hippocampus to orbital PFC pathway in the injured versus healthy group. We examined microstructure of components of pre-frontal limbic circuitry with concurrently obtained PTSS cluster scores in the injured children. Neither microstructure nor PTSS scores differed significantly in the TBI and EI groups. Across PTSS factors, specific symptom clusters were related positively to higher FA and MD. Higher hyperarousal, avoidance, and re-experiencing symptoms were associated with higher FA in amygdala to pre-frontal and hippocampus to amygdala pathways. Higher hippocampal MD had a central role in hyperarousal and emotional numbing symptoms. Age moderated the relation of white and gray matter microstructure with hyperarousal scores. Our findings are consistent with models of traumatic stress that implicate disrupted top-down PFC and hippocampal moderation of overreactive subcortical threat arousal systems. Alterations in limbic pre-frontal circuitry and PTSS place children with either brain or body injuries at elevated risk for both current and future psychological health problems.

Graph theory analysis of DTI tractography in children with traumatic injury.

OBJECTIVE: To evaluate brai structural connectivity in children with traumatic injury (TI) following a motor vehicle accident using graph theory analysis of DTI tractography data. METHODS: DTI scans were acquired on a 3 T Philips scanner from children aged 8-15 years approximately 2 months post-injury. The TI group consisted of children with traumatic brain injury (TBI; n = 44) or extracranial injury (EI; n = 23). Healthy control children (n = 36) were included as an age-matched comparison group. A graph theory approach was applied to DTI tractography data to investigate injury-related differences in connectivity network characteristics. Group differences in structural connectivity evidenced by graph metrics including efficiency, strength, and modularity were assessed using the multi-threshold permutation correction (MTPC) and network-based statistic (NBS) methods. RESULTS: At the global network level, global efficiency and mean network strength were lower, and modularity was higher, in the TBI than in the control group. Similarly, strength was lower and modularity higher when comparing the EI to the control group. At the vertex level, nodal efficiency, vertex strength, and average shortest path length were different between all pairwise comparisons of the three groups. Both nodal efficiency and vertex strength were higher in the control than in the EI group, which in turn were higher than in the TBI group. The opposite between-group relationships were seen with path length. These between-group differences were distributed throughout the brain, in both hemispheres. NBS analysis resulted in a cluster of 22 regions and 21 edges with significantly lower connectivity in the TBI group compared to controls. This cluster predominantly involves the frontal lobe and subcortical gray matter structures in both hemispheres. CONCLUSIONS: Graph theory analysis of DTI tractography showed diffuse differences in structural brain network connectivity in children 2 months post-TI. Network differences were consistent with lower network integration and higher segregation in the injured groups compared to healthy controls. Findings suggest that inclusion of trauma-exposed comparison groups in studies of TBI outcome is warranted to better characterize the indirect effect of stress on brain networks.

Nurturing the preterm infant brain: leveraging neuroplasticity to improve neurobehavioral outcomes.

An intrinsic feature of the developing brain is high susceptibility to environmental influence-known as plasticity. Research indicates cascading disruption to neurological development following preterm (PT) birth; yet, the interactive effects of PT birth and plasticity remain unclear. It is possible that, with regard to neuropsychological outcomes in the PT population, plasticity is a double-edged sword. On one side, high plasticity of rapidly developing neural tissue makes the PT brain more vulnerable to injury resulting from events, including inflammation, hypoxia, and ischemia. On the other side, plasticity may be a mechanism through which positive experience can normalize neurological development for PT children. Much of the available literature on PT neurological development is clinically weighted and focused on diagnostic utility for predicting long-term outcomes. Although diagnostic utility is valuable, research establishing neuroprotective factors is equally beneficial. This review will: (1) detail specific mechanisms through which plasticity is adaptive or maladaptive depending on the experience; (2) integrate research from neuroimaging, intervention, and clinical science fields in a summary of findings suggesting inherent plasticity of the PT brain as a mechanism to improve child outcomes; and (3) summarize how responsive caregiving experiences situate parents as agents of change in normalizing PT infant brain development.

Children's head motion during fMRI tasks is heritable and stable over time.

Head motion during fMRI scans negatively impacts data quality, and as post-acquisition techniques for addressing motion become increasingly stringent, data retention decreases. Studies conducted with adult participants suggest that movement acts as a relatively stable, heritable phenotype that serves as a marker for other genetically influenced phenotypes. Whether these patterns extend downward to childhood has critical implications for the interpretation and generalizability of fMRI data acquired from children. We examined factors affecting scanner motion in two samples: a population-based twin sample of 73 participants (ages 7-12 years) and a case-control sample of 32 non-struggling and 78 struggling readers (ages 8-11 years), 30 of whom were scanned multiple times. Age, but not ADHD symptoms, was significantly related to scanner movement. Movement also varied as a function of task type, run length, and session length. Twin pair concordance for head motion was high for monozygotic twins and moderate for dizygotic twins. Cross-session test-retest reliability was high. Together, these findings suggest that children's head motion is a genetically influenced trait that has the potential to systematically affect individual differences in BOLD changes within and across groups. We discuss recommendations for future work and best practices for pediatric neuroimaging.

Memory and the hippocampal formation following pediatric traumatic brain injury.

Introduction: Previous research indicates disruption of learning and memory in children who have experienced traumatic brain injury (TBI). Objective: This research evaluates the impact of pediatric TBI on volumetric differences along the long axis of the hippocampus, a region of the brain that is critical for explicit memory. Methods: Structural brain data and behavioral measures were collected 6 weeks following TBI or extracranial injury (EI), in children aged 8-15 years and from a group of age matched typically developing controls (TDC). Total hippocampal volume and hippocampal subregion volumes corresponding to hippocampal head, body, and tail were compared across groups and were examined in relation to verbal and visual memory. Results: Group differences were evident such that hippocampal body volume was found to be smaller for TBI and EI groups compared to the TDC group. Analysis restricted to the TBI group indicated that hippocampal head volume was associated with severity of injury. The relation between severity of injury and hippocampal head volume is particularly important considering results from our investigation of hippocampal volume-to-memory performance relations indicating positive correlations between hippocampal head volume and performance on memory measures for both the TBI group and the TDC group. Significant negative correlations between hippocampal body volume and memory were evident for the TBI group but not EI or TDC groups. Correlations between memory performance and hippocampal tail volume were not significant for the TBI or TDC groups, although for the EI group, a positive correlation was found between hippocampal tail volume and memory. Conclusion: Together these results underscore an important relation between hippocampal structure and memory function during the subacute stage of recovery from pediatric TBI.

Longitudinal diffusion tensor imaging after pediatric traumatic brain injury: Impact of age at injury and time since injury on pathway integrity.

Following pediatric traumatic brain injury (TBI), longitudinal diffusion tensor imaging may characterize alterations in initial recovery and subsequent trajectory of white matter development. Our primary aim examined effects of age at injury and time since injury on pathway microstructure in children ages 6-15 scanned 3 and 24 months after TBI. Microstructural values generated using tract-based spatial statistics extracted from core association, limbic, and projection pathways were analyzed using general linear mixed models. Relative to children with orthopedic injury, the TBI group had lower fractional anisotropy (FA) bilaterally in all seven pathways. In left-hemisphere association pathways, school-aged children with TBI had the lowest initial pathway integrity and showed the greatest increase in FA over time suggesting continued development despite incomplete recovery. Adolescents showed limited change in FA and radial diffusivity and had the greatest residual deficit suggesting relatively arrested development. Radial diffusivity was persistently elevated in the TBI group, implicating dysmyelination as a core contributor to chronic post-traumatic neurodegenerative changes. The secondary aim compared FA values over time in the total sample, including participants contributing either one or two scans to the analysis, to the longitudinal cases contributing two scans. For each pathway, FA values and effect sizes were very similar and indicated extremely small differences in measurement of change over time in the total and longitudinal samples. Statistical approaches incorporating missing data may reliably estimate the effects of TBI and provide increased power to identify whether pathways show neurodegeneration, arrested development, or continued growth following pediatric TBI. Hum Brain Mapp 37:3929-3945, 2016. © 2016 Wiley Periodicals, Inc.

Retrieval flexibility and reinstatement in the developing hippocampus.

Episodic memory improves during childhood and this improvement has been associated with age differences in hippocampal function, but previous research has not manipulated the possible underlying mechanisms. We tested the hypothesis that age-related differences in hippocampal activation may reflect changes in retrieval flexibility. We expected these activation differences to be observed most prominently in the anterior hippocampus. Functional magnetic resonance imaging (fMRI) data were collected from children ages 8 and 10, and adults (N = 63) during an associative recognition task that required participants to recognize pairs of pictures which either appeared in the same location as during encoding (Same location), or in a flipped location, such that each picture switched their location with the other member of the pair (Flipped location). Recognition of same-location pairs placed lower demands on flexible retrieval compared to recognition of flipped-location pairs. Behaviorally, 8-year-olds exhibited the strongest correct recognition gains for same-location compared to flipped-location pairs, and females unexpectedly outperformed males across all ages. When we examined correct recognition, adults recruited the hippocampal head more strongly for flipped- versus same-location pairs compared to both groups of children; in contrast both adults and 10-year-olds recruited the hippocampal tail more strongly for flipped- versus same-location pairs compared to 8-year-olds. This pattern was stronger in the left hippocampus and for females. Moreover hippocampal discrimination between recognized and forgotten items in the same-location condition was stronger in 8-year-olds compared to adults, and was stronger in the flipped-location condition in adults compared to 8-year-olds; this pattern was stronger in the left hippocampus. Individual differences in this discrimination contrast for flipped-location trials in the head and body predicted performance on an index of creative thinking. Overall, these results lend new support to the idea that hippocampal development may reflect change in retrieval flexibility with implications for additional forms of flexible cognition.

Structural development of the hippocampus and episodic memory: developmental differences along the anterior/posterior axis.

The hippocampus is critically involved in episodic memory, yet relatively little is known about how the development of this structure contributes to the development of episodic memory during middle to late childhood. Previous research has inconsistently reported associations between hippocampal volume and episodic memory performance during this period. We argue that this inconsistency may be due to assessing the hippocampus as a whole, and propose to examine associations separately for subregions along the longitudinal axis of the hippocampus. In the present study, we examined age-related differences in volumes of the hippocampal head, body, and tail, and collected episodic memory measures in children ages 8-11 years and young adults (N = 62). We found that adults had a smaller right hippocampal head, larger hippocampal body bilaterally, and smaller right hippocampal tail compared with children. In adults, but not in children, better episodic memory performance was associated with smaller right hippocampal head and larger hippocampal body. In children, but not in adults, better episodic memory was associated with larger left hippocampal tail. Overall, the results suggest that protracted development of hippocampal subregions contribute to age-related differences in episodic memory.

Development of memory for spatial context: hippocampal and cortical contributions.

The goal of the present study was to examine age-related differences in hippocampal and cortical contribution to episodic retrieval of spatial context in 3 age groups. Children ages 8-9 and 10-11 years old, and adults ages 18-25 (N=48) encoded black and white line drawings appearing either on the right side or the left side of a screen. Functional magnetic resonance imaging (fMRI) data were acquired while participants attempted to recall where each studied drawing had originally appeared. Correct recall of spatial source indicated successful episodic retrieval of spatial context. Activity in head and body of the hippocampus was associated with episodic retrieval in adults, but not in children. In children, individual differences in hippocampal activation for recognition predicted rates of correct spatial recall. Developmental differences were also found in regions in posterior parietal cortex, anterior prefrontal cortex, and insula. Overall, these results support the view that the development of episodic memory is supported by functional changes in the hippocampus as well as cortical regions.

Developmental differences in hippocampal and cortical contributions to episodic retrieval.

Episodic memory, or the ability to form and retrieve conscious memories about specific past events, improves during childhood. Previous adult neuroimaging results indicate a central role of the hippocampus in episodic retrieval, but it is not clear whether the contribution of the hippocampus changes during development. Traditionally, developmental improvements in episodic retrieval have been thought to depend on strategic processes mediated by the prefrontal cortex (PFC), a region that is considered to have a protracted course of development relative to the hippocampus. The primary goal of the present study was to test the hypothesis that the development of episodic retrieval is also associated with changes in hippocampal function. Children ages 8- to 11-years-old and adults ages 18-25 (N = 41) encoded black and white line drawings surrounded by either a green or red border. Functional magnetic resonance imaging (fMRI) data were acquired while participants attempted to recall which colour was originally paired with each drawing. Correct recall of item-colour pairings indicated successful episodic retrieval. Activity in the anterior hippocampus, but not in the posterior hippocampus, was associated with episodic retrieval in adults, whereas activity in the posterior, but not in the anterior hippocampus, was associated with episodic retrieval in children. Developmental differences were also found in regions in anterior lateral PFC and posterior parietal cortex. Overall, these results support the view that the development of episodic memory is supported by functional changes in the hippocampus as well as in other critical cortical regions.

Developmental differences in medial temporal lobe function during memory encoding.

The ability to recollect details about past events improves during childhood. Most researchers favor the view that this improvement depends largely on the development of the prefrontal cortex, which is thought to have a protracted course of development relative to the medial temporal lobes (MTL). The primary goal of the present study was to test the hypothesis that the development of detail recollection is also associated with changes in MTL function. We collected functional magnetic resonance imaging data during an incidental encoding task in 80 participants, divided equally across four age groups: 8-year-olds, 10- to 11-year-olds, 14-year-olds, and young adults. Developmental differences in MTL activation profiles were observed. Fourteen-year-olds and adults engaged regions of the hippocampus and posterior parahippocampal gyrus selectively for subsequent detail recollection, whereas 8- and 10- to 11-year-olds did not. In 8-year-olds, these regions were recruited indiscriminately for detail recollection and item recognition; in 10- to 11-year-olds, activation in these regions did not consistently predict subsequent memory. These results suggest there are changes in the functional organization of the MTL, such that the hippocampus and posterior parahippocampal gyrus become increasingly specialized for recollection; these changes may be in part responsible for long-term memory improvements during childhood.

Diabetic ketoacidosis and memory dysfunction in children with type 1 diabetes.

OBJECTIVE: We tested the hypothesis that diabetic ketoacidosis (DKA) results in memory deficits typical of hypoxic/ischemic injury because recent studies suggest that cerebral metabolic changes similar to those observed in hypoxic/ischemic cerebral injury are observed in children with DKA, even without symptoms suggesting cerebral injury. STUDY DESIGN: Thirty-three children with type 1 diabetes mellitus (T1DM) and a history of DKA and 29 children with T1DM without a history of DKA were enrolled from an academic hospital pediatric endocrinology clinic. These groups were comparable on demographic and disease-related variables. These groups' ability to recall events in association with specific details, the memory function most directly affected by mild hypoxia/ischemia, was compared on 2 tasks (ie, event-color associations and event-spatial position associations). RESULTS: In multivariate analyses controlling for other critical variables, children with DKA history had significantly lower rates of accurate memory on both tasks (mean, 0.34 +/- 0.13 on the color task and 0.57 +/- 0.15 on the spatial task) than did children without DKA history (mean, 0.44 +/- 0.11 and 0.65 +/- 0.18, P < .01). CONCLUSIONS: DKA disrupts memory function, underscoring the importance of DKA prevention when T1DM is known and prompt diagnosis of children with new onset of T1DM.