There is evidence for a hippocampal long axis anterior–posterior (AP) differentiation in memory processing, which may have implications for the changes in episodic memory performance seen across development and aging. The hippocampus shows substantial structural changes with age, but the lifespan trajectories of hippocampal sub‐regions along the AP axis are not established. The aim of the present study was to test whether the micro‐ and macro‐structural age‐trajectories of the anterior (aHC) and posterior (pHC) hippocampus are different. In a single‐center longitudinal study, 1,790 cognitively healthy participants, 4.1–93.4 years of age, underwent a total of 3,367 MRI examinations and 3,033 memory tests sessions over 1–6 time points, spanning an interval up to 11.1 years. T1‐weighted scans were used to estimate the volume of aHC and pHC (macrostructure), and diffusion tensor imaging to measure mean diffusion (MD, microstructure) within each region. We found that the macro‐ and microstructural lifespan‐trajectories of aHC and pHC were clearly distinguishable, with partly common and partly unique variance shared with age. aHC showed a protracted period of microstructural development, while pHC microstructural development as indexed by MD was more or less completed in early childhood. In contrast, pHC showed larger unique aging‐related changes. An aHC–pHC difference was also observed for volume, with pHC changing relatively more with higher age. All regions showed age‐dependent relationships with episodic memory. aHC micro‐ and macrostructure was significantly related to verbal memory independently of age, but the relationships were still strongest among the older participants. We suggest that memory processes supported by each sub‐region improve or decline in concert with volumetric and microstructural changes in the same age‐period. Future research should disentangle the lifespan relationship between changes in these structural properties and different memory processes, encoding versus retrieval in particular, as well as other cognitive functions depending on the hippocampal long‐axis specialization.

Human brain structure topography is thought to be related in part to functional specialization. However, the extent of such relationships is unclear. Here, using a data-driven, multimodal approach for studying brain structure across the lifespan (N ϭ 484, n ϭ 260 females), we demonstrate that numerous structural networks, covering the entire brain, follow a functionally meaningful architecture. These gray matter networks (GMNs) emerge from the covariation of gray matter volume and cortical area at the population level. We further reveal fine-grained anatomical signatures of functional connectivity. For example, within the cerebellum, a structural separation emerges between lobules that are functionally connected to distinct, mainly sensorimotor, cognitive and limbic regions of the cerebral cortex and subcortex. Structural modes of variation also replicate the fine-grained functional architecture seen in eight well defined visual areas in both task and resting-state fMRI. Furthermore, our study shows a structural distinction corresponding to the established segregation between anterior and posterior default-mode networks (DMNs). These fine-grained GMNs further cluster together to form functionally meaningful larger-scale organization. In particular, we identify a structural architecture bringing together the functional posterior DMN and its anticorrelated counterpart. In summary, our results demonstrate that the relationship between structural and functional connectivity is fine-grained, widespread across the entire brain, and driven by covariation in cortical area, i.e. likely differences in shape, depth, or number of foldings. These results suggest that neurotrophic events occur during development to dictate that the size and folding pattern of distant, functionally connected brain regions should vary together across subjects.Questions about the relationship between structure and function in the human brain have engaged neuroscientists for centuries in a debate that continues to this day. Here, by investigating intersubject variation in brain structure across a large number of individuals, we reveal modes of structural variation that map onto fine-grained functional organization across the entire brain, and specifically in the cerebellum, visual areas, and default-mode network. This functionally meaningful structural architecture emerges from the covariation of gray matter volume and cortical folding. These results suggest that the neurotrophic events at play during development, and possibly evolution, which dictate that the size and folding pattern of distant brain regions should vary together across subjects, might also play a role in functional cortical specialization.

Change in hippocampal function is a major factor in life span development and decline of episodic memory. Evidence indicates a long-axis specialization where anterior hippocampus is more engaged during encoding than during retrieval, and posterior more engaged during retrieval than during encoding. We tested the life span trajectory of hippocampal long-axis episodic memory-related activity and functional connectivity (FC) in 496 participants (6.8–80.8 years) encoding and retrieving associative memories. We found evidence for a long-axis encoding–retrieval specialization that declined linearly during development and aging, eventually vanishing in the older adults. This was mainly driven by age effects on retrieval, which was associated with gradually lower activity from childhood to adulthood, followed by positive age relationships until 70 years. This pattern of age effects characterized task engagement regardless of memory success or failure. Especially for retrieval, children engaged posterior hippocampus more than anterior, while anterior was relatively more activated already in teenagers. Significant intrahippocampal connectivity was found during task, which declined with age. The results suggest that hippocampal long-axis differentiation and communication during episodic memory tasks develop rapidly during childhood, are different in older compared with younger adults, and that the age effects are related to task engagement, not the successful retrieval of episodic memories specifically.

Aging is characterized by substantial average decline in memory performance. Yet contradictory explanations have been given for how the brains of high-performing older adults work: either by engagement of compensatory processes such as recruitment of additional networks or by maintaining young adults' patterns of activity. Distinguishing these components requires large experimental samples and longitudinal follow-up. Here, we investigate which features are key to high memory in aging, directly testing these hypotheses by studying a large sample of adult participants (n > 300) with fMRI during an episodic memory experiment where item-context relationships were implicitly encoded. The analyses revealed that low levels of activity in frontal networks-known to be involved in memory encoding-were associated with low memory performance in the older adults only. Importantly, older participants with low memory performance and low frontal activity exhibited a strong longitudinal memory decline in an independent verbal episodic memory task spanning 8 years back (n = 52). These participants were also characterized by lower hippocampal volumes and steeper rates of cortical atrophy. Altogether, maintenance of frontal brain function during encoding seems to be a primary characteristic of preservation of memory function in aging, likely reflecting intact ability to integrate information.

The human cerebral cortex is highly regionalized, and this feature emerges from morphometric gradients in the cerebral vesicles during embryonic development. We tested if this principle of regionalization could be traced from the embryonic development to the human life span. Data-driven fuzzy clustering was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) (n = 301, 4–12 years). The principal divide for the developmental SA clusters extended from the inferior–posterior to the superior–anterior cortex, corresponding to the major embryonic morphometric anterior–posterior (AP) gradient. Embryonic factors showing a clear AP gradient were identified, and we found significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT clusters showed distinguishable life span trajectories in a larger longitudinal dataset (4–88 years, 1633 observations), and the SA and CT clusters showed differential relationships to cognitive functions. This means that regions that developed together in childhood also changed together throughout life, demonstrating continuity in regionalization of cortical changes. The AP divide in SA development also characterized genetic patterning obtained in an adult twin sample. In conclusion, the development of cortical regionalization is a continuous process from the embryonic stage throughout life.

Primate cortical evolution has been characterized by massive and disproportionate expansion of a set of specific regions in the neocortex. The associated increase in neocortical neurons comes with a high metabolic cost, thus the functions served by these regions must have conferred significant evolutionary advantage. In the present series of analyses, we show that evolutionary high-expanding cortex – as estimated from patterns of surface growth from several primate species – shares functional connections with different brain networks in a context-dependent manner. Specifically, we demonstrate that high-expanding cortex is characterized by high internetwork functional connectivity; is recruited flexibly over many different cognitive tasks; and changes its functional coupling pattern between rest and a multimodal task-state. The capacity of high-expanding cortex to connect flexibly with various specialized brain networks depending on particular cognitive requirements suggests that its selective growth and sustainment in evolution may have been linked to an involvement in supramodal cognition. In accordance with an evolutionary-developmental view, we find that this observed ability of high-expanding regions – to flexibly modulate functional connections as a function of cognitive state – emerges gradually through childhood, with a prolonged developmental trajectory plateauing in young adulthood.

Socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. Here we show that relationships between SES, brain volumes and general cognitive ability differ significantly across European and US cohorts (4-97 years, N ≈ 500,000; 54,000 with brain imaging). Education was positively related to intracranial (ICV) and total brain gray matter (GM) volume. Income was related to ICV, but not GM. Relationships varied significantly across samples, and SES was more strongly related to brain and cognition in US than European cohorts. Differences in neuroanatomical volumes explained part of the SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. Rather, a relationship may be established early in life. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.

BACKGROUND AND PURPOSE: Although methylphenidate is frequently used to treat children with attention-deficit/hyperactivity disorder, it is currently unknown how methylphenidate affects brain development. In a randomized controlled trial, we investigated whether the cortical effects of methylphenidate are modulated by age.