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.

We continuously encounter and process novel events in the surrounding world, but only some episodes will leave detailed memory traces that can be recollected after weeks and months. Here, our aim was to monitor brain activity during encoding of events that eventually transforms into long-term stable memories. Previous functional magnetic resonance imaging (fMRI) studies have shown that the degree of activation of different brain regions during encoding is predictive of later recollection success. However, most of these studies tested participants' memories the same day as encoding occurred, whereas several lines of research suggest that extended post-encoding processing is of crucial importance for long-term consolidation. Using fMRI, we tested whether the same encoding mechanisms are predictive of recollection success after hours as after a retention interval of several weeks. Seventy-eight participants were scanned during an associative encoding task and given a source memory test the same day or after ϳ6 weeks. We found a strong link between regional activity levels during encoding and recollection success over short time intervals. However, results further showed that durable source memories, i.e., events recollected after several weeks, were not simply the events associated with the highest activity levels at encoding. Rather, strong levels of connectivity between the right hippocampus and perceptual areas, as well as with parts of the self-referential default-mode network, seemed instrumental in establishing durable source memories. Thus, we argue that an initial intensity-based encoding is necessary for short-term encoding of events, whereas additional processes involving hippocampal-cortical communication aid transformation into stable long-term memories.

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.

At a large scale, the human brain is organized into modules of interconnected regions, some of which play opposing roles in supporting cognition. In particular, the Default-Mode Network (DMN) has been linked to operations on internal representations, while task-positive networks are recruited during interactions with the external world. Here, we test the hypothesis that the generation of durable long-term memories depends on optimal recruitment of such antagonistic large-scale networks. As long-term memory consolidation is a process ongoing for days and weeks after an experience, we propose that individuals characterized by strong decoupling of the DMN and task-positive networks at rest operate in a mode beneficial for the long-term stabilization of episodic memories. To capture network connectivity unaffected by transient task demands and representative of brain behavior outside an experimental setting, 87 participants were scanned during rest before performing an associative encoding task. To link individual resting-state functional connectivity patterns to time-dependent memory consolidation processes, participants were given an unannounced memory test, either after a brief interval or after a retention period of ~6 weeks. We found that participants with a resting state characterized by high synchronicity in a DMN-centered network system and low synchronicity between task-positive networks showed superior recollection weeks after encoding. These relationships were not observed for information probed only hours after encoding. Furthermore, the two network systems were found to be anticorrelated. Our results suggest that this memory-relevant antagonism between DMN and task-positive networks is maintained through complex regulatory interactions between the systems.

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