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.

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.

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.

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.