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Charting human brain maturation between childhood and adulthood is a fundamental prerequisite for understanding the rapid biological and psychological changes during human development. Two barriers have precluded the quantification of maturational trajectories: demands on data and demands on estimation. Using high-temporal resolution neuroimaging data of up to 12-waves in the HUBU cohort (N = 90, aged 7-21 years) we investigate changes in apparent cortical thickness across childhood and adolescence. Fitting a four-parameter logistic nonlinear random effects mixed model, we quantified the characteristic, s-shaped, trajectory of cortical thinning in adolescence. This approach yields biologically meaningful parameters, including the midpoint of cortical thinning (MCT), which corresponds to the age at which the cortex shows most rapid thinning - in our sample occurring, on average, at 14 years of age. These results show that, given suitable data and models, cortical maturation can be quantified with precision for each individual and brain region.

SummaryAccurate identification of brain function is necessary to understand neurocognitive ageing, and thereby promote health and well-being. Many studies of neurocognitive aging have investigated brain function with the blood-oxygen level-dependent (BOLD) signal measured by functional magnetic resonance imaging. However, the BOLD signal is a composite of neural and vascular signals, which are differentially affected by aging. It is therefore essential to distinguish the age effects on vascularversusneural function. The BOLD signal variability at rest (known as resting state fluctuation amplitude, RSFA), is a safe, scalable and robust means to calibrate vascular responsivity, as an alternative to breath-holding and hypercapnia. However, the use of RSFA for normalization of BOLD imaging assumes that age differences in RSFA reflecting only vascular factors, rather than age-related differences in neural function (activity) or neuronal loss (atrophy). Previous studies indicate that two vascular factors, cardiovascular health and cerebrovascular function, are insufficient when used alone to fully explain age-related differences in RSFA. It remains possible that their joint consideration is required to fully capture age differences in RSFA. We tested the hypothesis that RSFA no longer varies with age after adjusting for a combination of cardiovascular and cerebrovascular measures. We also tested the hypothesis that RSFA variation with age is not associated with atrophy. We used data from the population-based, lifespan Cam-CAN cohort. After controlling for cardiovascular and cerebrovascular estimates alone, the residual variance in RSFA across individuals was significantly associated with age. However, when controlling for both cardiovascular and cerebrovascular estimates, the variance in RSFA was no longer associated with age. Grey matter volumes did not explain age-differences in RSFA, after controlling for cardiovascular health. The results were consistent between voxel-level analysis and independent component analysis. Our findings indicate that cardiovascular and cerebrovascular signals are together sufficient predictors of age differences in RSFA. We suggest that RSFA can be used to separate vascular from neuronal factors, to characterise neurocognitive aging. We discuss the implications and make recommendations for the use of RSFA in the research of aging.

Much evidence suggests that the angular gyrus (AnG) is involved in episodic memory, but its precise role is yet to be determined. We examined two possible accounts, within the same experimental paradigm: the CoBRA account (Shimamura, 2011), which suggests that the AnG acts as a convergence zone that binds multimodal episodic features; and the Subjectivity account (Yazar et al., 2012), which implicates AnG involvement in subjective mnemonic experience (such as vividness or confidence). fMRI was employed during both encoding and retrieval of paired-associates. During study, female and male human participants memorised picture-pairs of common objects (in the unimodal task) or of an object-picture and an environmental sound (in the crossmodal task). At test, they performed a cued-recall task, and further indicated the vividness of their memory. During retrieval, BOLD activation in the AnG was greatest for vividly remembered associates, consistent with the Subjectivity account. During encoding, the same effect of vividness was found, but this was further modulated by task: Greater activations were associated with subsequent recall in the crossmodal than the unimodal task. Thus, encoding data suggests an additional role to the AnG in cross-modal integration, consistent with its role at retrieval proposed by CoBRA. These results resolve some of the puzzles in the literature and indicate that the AnG can play different roles during encoding and retrieval, determined by the cognitive demands posed by different mnemonic tasks.Significance StatementWe offer new insights into the multiplicity of processes that are associated with angular gyrus (AnG) activation during encoding and retrieval of newly formed memories. We used fMRI while human participants learned and subsequently recalled pairs of objects presented to the same sensory modality or to different modalities. We were able to show that the AnG is involved when vivid memories are created and retrieved, as well as when encoded information is integrated across different sensory modalities. These findings provide novel evidence for the contribution of the AnG to our subjective experience of remembering, alongside its role in integrative processes that promote subsequent memory.

Cardiovascular health declines with age, increasing the risk of hypertension and elevated heart rate in middle- and old age. Here, we used multivariate techniques to investigate the associations between cardiovascular health (diastolic blood pressure, systolic blood pressure and heart rate) and white matter macrostructure (lesion volume and number), and microstructure (as measured by Diffusion Weighted Imaging) in the cross-sectional, population-based Cam-CAN cohort (N = 667, aged 18 to 88). We found that cardiovascular health and age made approximately similar contributions to white matter health and explained up to 56% of variance. Lower diastolic blood pressure, higher systolic blood pressure and higher heart rate were each strongly, and independently, associated with white matter abnormalities on all indices. Body mass and exercise were associated with white matter health, both directly and indirectly via cardiovascular health. These results highlight the importance of cardiovascular risk factors for white matter health across the adult lifespan and suggest that systolic blood pressure, diastolic blood pressure and heart rate affect white matter via separate mechanisms.