Household socioeconomic status relates to specific hippocampal subfield volumes across development.

The hippocampus is composed of cytoarchitecturally distinct subfields that support specific memory functions. Variations in total hippocampal volume across development have been linked to socioeconomic status (SES), a proxy for access to material resources, medical care, and quality education. High childhood household SES is associated with greater cognitive abilities in adulthood. Currently, it is not known whether household SES differentially impacts specific hippocampal subfield volumes. We assessed susceptibility of subfields to variations in household SES across development in a sample of 167 typically developing 5- to 25-year-old. Bilateral cornu ammonis (CA) 1-2, combined CA3-dentate gyrus (DG), and subiculum (Sub) volumes were measured by highly reliable manual segmentation of high-resolution T2-weighted images and adjusted for intracranial volume. A summary component score of SES measures (paternal education, maternal education, and income-to-needs ratio) was used to examine variability in volumes across ages. We did not identify age-related differences in any of the regional volumes, nor did age modify SES-related effects. Controlling for age, larger volumes of CA3-DG and CA1-2 were associated with lower SES, while Sub volume was not. Overall, these findings support the specific impact of SES on CA3-DG and CA1-2 and highlight the importance of considering environmental influences on hippocampal subfield development.

Age-related differences in hippocampal subfield volumes across the human lifespan: A meta-analysis.

The human hippocampus (Hc) is critical for memory function across the lifespan. It is comprised of cytoarchitectonically distinct subfields: dentate gyrus (DG), cornu ammonis sectors (CA) 1-4, and subiculum, each of which may be differentially susceptible to neurodevelopmental and neurodegenerative mechanisms. Identifying age-related differences in Hc subfield volumes can provide insights into neural mechanisms of memory function across the lifespan. Limited evidence suggests that DG and CA3 volumes differ across development while other regions remain relatively stable, and studies of adulthood implicate a downward trend in all subfield volumes with prominent age effects on CA1. Due to differences in methods and limited sampling for any single study, the magnitude of age effects on Hc subfield volumes and their probable lifespan trajectories remain unclear. Here, we conducted a meta-analysis on cross-sectional studies (n = 48,278 participants, ages = 4-94 years) to examine the association between age and Hc subfield volumes in development (n = 11 studies), adulthood (n = 30 studies), and a combined lifespan sample (n = 41 studies) while adjusting estimates for sample sizes. In development, age was positively associated with DG and CA3-4 volumes, whereas in adulthood a negative association was observed with all subfield volumes. Notably, the observed age effects were not different across subfield volumes within each age group. All subfield volumes showed a nonlinear age pattern across the lifespan with DG and CA3-4 volumes showing a more distinct age trajectory as compared to the other subfields. Lastly, among all the study-level variables, only female percentage of the study sample moderated the age effect on CA1 volume: a higher female-to-male ratio in the study sample was linked to the greater negative association between age and CA1 volume. These results document that Hc subfield volumes differ as a function of age offering broader implications for constructing theoretical models of lifespan memory development.

Meta-Analysis of Hippocampal Volume and Episodic Memory in Preterm and Term Born Individuals.

Preterm birth (< 37 weeks gestation) has been associated with memory deficits, which has prompted investigation of possible alterations in hippocampal volume in this population. However, existing literature reports varying effects of premature birth on hippocampal volume. Specifically, it is unclear whether smaller hippocampal volume in preterm-born individuals is merely reflective of smaller total brain volume. Further, it is not clear if hippocampal volume is associated with episodic memory functioning in preterm-born individuals. Meta-analysis was used to investigate the effects of premature birth on hippocampal volume and episodic memory from early development to young adulthood (birth to 26). PubMed, PsychINFO, and Web of Science were searched for English peer-reviewed articles that included hippocampal volume of preterm and term-born individuals. Thirty articles met the inclusion criteria. Separate meta-analyses were used to evaluate standardized mean differences between preterm and term-born individuals in uncorrected and corrected hippocampal volume, as well as verbal and visual episodic memory. Both uncorrected and corrected hippocampal volume were smaller in preterm-born compared to term-born individuals. Although preterm-born individuals had lower episodic memory performance than term-born individuals, the limited number of studies only permitted a qualitative review of the association between episodic memory performance and hippocampal volume. Tested moderators included mean age, pre/post-surfactant era, birth weight, gestational age, demarcation method, magnet strength, and slice thickness. With this meta-analysis, we provide novel evidence of the effects of premature birth on hippocampal volume.

Microstructure of Human Corpus Callosum across the Lifespan: Regional Variations in Axon Caliber, Density, and Myelin Content.

The myeloarchitecture of the corpus callosum (CC) is characterized as a mosaic of distinct differences in fiber density of small- and large-diameter axons along the anterior-posterior axis; however, regional and age differences across the lifespan are not fully understood. Using multiecho T2 magnetic resonance imaging combined with multi-T2 fitting, the myelin water fraction (MWF) and geometric-mean of the intra-/extracellular water T2 (geomT2IEW) in 395 individuals (7-85 years; 41% males) were examined. The approach was validated where regional patterns along the CC closely resembled the histology; MWF matched mean axon diameter and geomT2IEW mirrored the density of large-caliber axons. Across the lifespan, MWF exhibited a quadratic association with age in all 10 CC regions with evidence of a positive linear MWF-age relationship among younger participants and minimal age differences in the remainder of the lifespan. Regarding geomT2IEW, a significant linear age × region interaction reflected positive linear age dependence mostly prominent in the regions with the highest density of small-caliber fibers-genu and splenium. In all, these two indicators characterize distinct attributes that are consistent with histology, which is a first. In addition, these results conform to rapid developmental progression of CC myelination leveling in middle age as well as age-related degradation of axon sheaths in older adults.

Test-retest reliability of hippocampal subfield volumes in a developmental sample: Implications for longitudinal developmental studies.

The hippocampus (Hc) is composed of cytoarchitectonically distinct subfields: dentate gyrus (DG), cornu ammonis sectors 1-3 (CA1-3), and subiculum. Limited evidence suggests differential maturation rates across the Hc subfields. While longitudinal studies are essential in demonstrating differential development of Hc subfields, a prerequisite for interpreting meaningful longitudinal effects is establishing test-retest consistency of Hc subfield volumes measured in vivo over time. Here, we examined test-retest consistency of Hc subfield volumes measured from structural MR images in two independent developmental samples. Sample One (n = 28, ages 7-20 years, M = 12.64, SD = 3.35) and Sample Two (n = 28, ages 7-17 years, M = 11.72, SD = 2.88) underwent MRI twice with a 1-month and a 2-year delay, respectively. High-resolution PD-TSE-T2 -weighted MR images (0.4 × 0.4 × 2 mm3 ) were collected and manually traced using a longitudinal manual demarcation protocol. In both samples, we found excellent consistency of Hc subfield volumes between the two visits, assessed by two-way mixed intraclass correlation (ICC (3) single measures ≥ 0.87), and no difference between children and adolescents. The results further indicated that discrepancies between repeated measures were not related to Hc subfield volumes, or visit number. In addition to high consistency, with the applied longitudinal protocol, we detected significant variability in Hc subfield volume changes over the 2-year delay, implying high sensitivity of the method in detecting individual differences. Establishing unbiased, high longitudinal consistency of Hc subfield volume measurements optimizes statistical power of a hypothesis test and reduces standard error of the estimate, together improving external validity of the measures in constructing theoretical models of memory development.

Age-associated increase in mnemonic strategy use is linked to prefrontal cortex development.

Memory functioning undergoes dynamic changes between childhood and adulthood. Spontaneous use of elaborative strategies, which can enhance the recall of information, expands with age and contributes to age-associated improvement in memory functioning. Findings from lesion and neuroimaging studies suggest that the ability to use elaborative strategies is dependent upon intact functioning of the prefrontal cortex (PFC), particularly the dorsolateral PFC region. Because the PFC undergoes protracted maturation, we examined whether age difference in the structure of the PFC is correlated with age-associated increase in strategy use. Here, we investigated the relationship between PFC volume and spontaneous strategy use in a sample of 120 participants aged 5-25 years. We assessed semantic clustering during recall with a standardized word-list recall task (California Verbal Learning Task children's version, CVLT-C) and computed PFC regional volumes from participants' structural brain images. We observed an age-associated increase in the use of semantic clustering and an age-associated decrease in volumes of the PFC. Further, we found that smaller PFC volume was linked to increased use of semantic clustering. Importantly, the volume of the right dorsolateral PFC partially explained the relation between age and the use of semantic clustering. These findings suggest that PFC maturation supports the development of strategy use and lends further support for the notion that brain-behavior relations change across development.

KIBRA single nucleotide polymorphism is associated with hippocampal subfield volumes and cognition across development.

The hippocampus (Hc) consists of cytoarchitectonically and functionally distinct subfields: dentate gyrus (DG), cornu ammonis (CA1-3), and subiculum. In adults, a single nucleotide polymorphism (rs17070145, C→ T) in KIBRA, a gene encoding the eponymous (KIdney-BRAin) protein, is associated with variability in Hc subfield volumes and episodic memory. T-allele carriers have larger DG and CA volumes and better episodic memory compared to C-homozygotes. Little is known, however, about KIBRA's role in the development of the brain and cognition. In a sample of children, adolescents, and young adults (N = 176, ages 5- 25 years), we replicated the adult association between KIBRA T-allele and larger DG and CA volumes but observed no relationship between KIBRA rs17070145 polymorphism and episodic memory. We noted, however, that a general cognitive performance index (IQ) differed across the allelic groups, with the lowest scores among T-homozygotes and the highest among C-homozygotes. Thus, in this developmental sample, KIBRA appears to have opposing effects on regional brain volume and cognition. These influences of KIBRA SNP may stem from associations between developmental reduction in brain volume and gains in cognitive performance-a hypothesis to be tested in longitudinal studies.

Reliability of subsequent memory effects in children and adults: The good, the bad, and the hopeful.

Functional MRI (fMRI) is a key tool for investigating neural underpinnings of cognitive development. Yet, in recent years, the reliability of fMRI effects has come into question and with it, the feasibility of using task-based fMRI to identify developmental changes related to cognition. Here, we investigated the reliability of task-based fMRI activations with a widely used subsequent memory paradigm using two developmental samples: a cross-sectional sample (n = 85, age 8-25 years) and a test-retest sample (n = 24, one-month follow up, age 8-20 years). In the large cross-sectional sample, we found good to excellent group-level reliability when assessing activation patterns related to the encoding task and subsequent memory effects. In the test-retest sample, while group-level reliability was excellent, the consistency of activation patterns within individuals was low, particularly for subsequent memory effects. We observed consistent activation patterns in frontal, parietal, and occipital cortices, but comparatively lower test-retest reliability in subcortical regions and the hippocampus. Together, these findings highlight the limitations of interpreting task-based fMRI effects and the importance of incorporating reliability analyses in developmental studies. Leveraging larger and densely collected longitudinal data may help contribute to increased reproducibility and the accumulation of knowledge in developmental sciences.

Differential Functional Connectivity in Anterior and Posterior Hippocampus Supporting the Development of Memory Formation.

Neuroimaging evidence suggests that the development of the hippocampus, a brain structure critical for memory function, contributes to the improvements of episodic memory between middle childhood to adulthood. However, investigations on age differences in hippocampal activation and functional connectivity and their contributions to the development of memory have yielded mixed results. Given the known structural and functional heterogeneity along the long axis of the hippocampus, we investigated age differences in the activation and functional connectivity in hippocampal subregions with a cross-sectional sample of 96 participants ages 8-25 years. We found that anterior and posterior hippocampus supported memory formation, and there was overall stability in memory-related hippocampal activation with age. Without taking account of memory outcome, direct contrast between subregions showed higher functional connectivity of anterior, compared to the posterior hippocampus, with regions in the inferior frontal and lateral temporal lobes, and higher functional connectivity of posterior, compared to the anterior hippocampus, with regions in the medial and superior frontal, inferior parietal, and occipital lobes. A direct contrast between the memory-related connectivity patterns of anterior and posterior hippocampus identified a region in the medial frontal cortex, with which anterior and posterior hippocampus was differentially functionally connected. Finally, we identified age differences in memory-related differential hippocampal functional connectivity with several frontal and visual/sensory cortices, underscoring the importance of examining age differences in the patterns of hippocampal connectivity. Moreover, the specific patterns of differential anterior and posterior functional connectivity indicate an increase in the functional specialization along the long axis of the hippocampus and a dynamic shift in hippocampal connectivity patterns that supports memory development.