Recalled through this day but forgotten next week?-retrieval activity predicts durability of partly consolidated memories.

Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales remains unclear. Here, we aimed to identify brain activity associated with retrieval of partly consolidated episodic memories that continued to be remembered in the future. Forty-nine younger (20 to 38 years; 25 females) and 43 older adults (60 to 80 years, 25 females) were scanned with functional magnetic resonance imaging during associative memory retrieval 12 h post-encoding. Twelve hours is sufficient to allow short-term synaptic consolidation as well as early post-encoding replay to initiate memory consolidation. Successful memory trials were classified into durable and transient source memories based on responses from a memory test ~6 d post-encoding. Results demonstrated that successful retrieval of future durable vs. transient memories was supported by increased activity in a medial prefrontal and ventral parietal area. Individual differences in activation as well as the subjective vividness of memories during encoding were positively related to individual differences in memory performance after 6 d. The results point to a unique and novel aspect of brain activity supporting long-term memory, in that activity during retrieval of memories even after 12 h of consolidation contains information about potential for long-term durability.

Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer's disease (DEBBIE-AD): a prospective observational multicohort study protocol.

INTRODUCTION: Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer's disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). METHODS AND ANALYSIS: DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies. ETHICS AND DISSEMINATION: Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Hippocampal-cortical functional connectivity during memory encoding and retrieval.

Memory encoding and retrieval are critical sub-processes of episodic memory. While the hippocampus is involved in both, less is known about its connectivity with the neocortex during memory processing in humans. This is partially due to variations in demands in common memory tasks, which inevitably recruit cognitive processes other than episodic memory. Conjunctive analysis of data from different tasks with the same core elements of encoding and retrieval can reduce the intrusion of patterns related to subsidiary perceptual and cognitive processing. Leveraging data from two large-scale functional resonance imaging studies with different episodic memory tasks (514 and 237 participants), we identified hippocampal-cortical networks active during memory tasks. Whole-brain functional connectivity maps were similar during resting state, encoding, and retrieval. Anterior and posterior hippocampus had distinct connectivity profiles, which were also stable across resting state and memory tasks. When contrasting encoding and retrieval connectivity, conjunctive encoding-related connectivity was sparse. During retrieval hippocampal connectivity was increased with areas known to be active during recollection, including medial prefrontal, inferior parietal, and parahippocampal cortices. This indicates that the stable functional connectivity of the hippocampus along its longitudinal axis is superposed by increased functional connectivity with the recollection network during retrieval, while auxiliary encoding connectivity likely reflects contextual factors.

Tracing the development and lifespan change of population-level structural asymmetry in the cerebral cortex.

Cortical asymmetry is a ubiquitous feature of brain organization that is subtly altered in some neurodevelopmental disorders, yet we lack knowledge of how its development proceeds across life in health. Achieving consensus on the precise cortical asymmetries in humans is necessary to uncover the developmental timing of asymmetry and the extent to which it arises through genetic and later influences in childhood. Here, we delineate population-level asymmetry in cortical thickness and surface area vertex-wise in seven datasets and chart asymmetry trajectories longitudinally across life (4-89 years; observations = 3937; 70% longitudinal). We find replicable asymmetry interrelationships, heritability maps, and test asymmetry associations in large-scale data. Cortical asymmetry was robust across datasets. Whereas areal asymmetry is predominantly stable across life, thickness asymmetry grows in childhood and peaks in early adulthood. Areal asymmetry is low-moderately heritable (max h2SNP ~19%) and correlates phenotypically and genetically in specific regions, indicating coordinated development of asymmetries partly through genes. In contrast, thickness asymmetry is globally interrelated across the cortex in a pattern suggesting highly left-lateralized individuals tend towards left-lateralization also in population-level right-asymmetric regions (and vice versa), and exhibits low or absent heritability. We find less areal asymmetry in the most consistently lateralized region in humans associates with subtly lower cognitive ability, and confirm small handedness and sex effects. Results suggest areal asymmetry is developmentally stable and arises early in life through genetic but mainly subject-specific stochastic effects, whereas childhood developmental growth shapes thickness asymmetry and may lead to directional variability of global thickness lateralization in the population.

Visual processing deficits in patients with schizophrenia spectrum and bipolar disorders and associations with psychotic symptoms, and intellectual abilities.

Objective: Low-level sensory disruption is hypothesized as a precursor to clinical and cognitive symptoms in severe mental disorders. We compared visual discrimination performance in patients with schizophrenia spectrum disorder or bipolar disorder with healthy controls, and investigated associations with clinical symptoms and IQ. Methods: Patients with schizophrenia spectrum disorder (n = 32), bipolar disorder (n = 55) and healthy controls (n = 152) completed a computerized visual discrimination task. Participants responded whether the latter of two consecutive grids had higher or lower spatial frequency, and discrimination thresholds were estimated using an adaptive maximum likelihood procedure. Case-control differences in threshold were assessed using linear regression, F-test and post-hoc pair-wise comparisons. Linear models were used to test for associations between visual discrimination threshold and psychotic symptoms derived from the PANSS and IQ assessed using the Matrix Reasoning and Vocabulary subtests from the Wechsler Abbreviated Scale of Intelligence (WASI). Results: Robust regression revealed a significant main effect of diagnosis on discrimination threshold (robust F = 6.76, p = .001). Post-hoc comparisons revealed that patients with a schizophrenia spectrum disorder (mean = 14%, SD = 0.08) had higher thresholds compared to healthy controls (mean = 10.8%, SD = 0.07, ß = 0.35, t = 3.4, p = .002), as did patients with bipolar disorder (12.23%, SD = 0.07, ß = 0.21, t = 2.42, p = .04). There was no significant difference between bipolar disorder and schizophrenia (ß = -0.14, t = -1.2, p = .45). Linear models revealed negative associations between IQ and threshold across all participants when controlling for diagnostic group (ß = -0.3, t = -3.43, p = .0007). This association was found within healthy controls (t = -3.72, p = .0003) and patients with bipolar disorder (t = -2.53, p = .015), and no significant group by IQ interaction on threshold (F = 0.044, p = .97). There were no significant associations between PANSS domain scores and discrimination threshold. Conclusion: Patients with schizophrenia spectrum or bipolar disorders exhibited higher visual discrimination thresholds than healthy controls, supporting early visual deficits among patients with severe mental illness. Discrimination threshold was negatively associated with IQ among healthy controls and bipolar disorder patients. These findings elucidate perception-related disease mechanisms in severe mental illness, which warrants replication in independent samples.

Sustained upregulation of widespread hippocampal-neocortical coupling following memory encoding.

Systems consolidation of new experiences into lasting episodic memories involves hippocampal-neocortical interactions. Evidence of this process is already observed during early post-encoding rest periods, both as increased hippocampal coupling with task-relevant perceptual regions and reactivation of stimulus-specific patterns following intensive encoding tasks. We investigate the spatial and temporal characteristics of these hippocampally anchored post-encoding neocortical modulations. Eighty-nine adults participated in an experiment consisting of interleaved memory task- and resting-state periods. We observed increased post-encoding functional connectivity between hippocampus and individually localized neocortical regions responsive to stimuli encountered during memory encoding. Post-encoding modulations were manifested as a nearly system-wide upregulation in hippocampal coupling with all major functional networks. The configuration of these extensive modulations resembled hippocampal-neocortical interaction patterns estimated from active encoding operations, suggesting hippocampal post-encoding involvement exceeds perceptual aspects. Reinstatement of encoding patterns was not observed in resting-state scans collected 12 h later, nor when using other candidate seed regions. The similarity in hippocampal functional coupling between online memory encoding and offline post-encoding rest suggests reactivation in humans involves a spectrum of cognitive processes engaged during the experience of an event. There were no age effects, suggesting that upregulation of hippocampal-neocortical connectivity represents a general phenomenon seen across the adult lifespan.

Whole-brain connectivity during encoding: age-related differences and associations with cognitive and brain structural decline.

There is a limited understanding of age differences in functional connectivity during memory encoding. In the present study, a sample of cognitively healthy adult participants (n = 488, 18-81 years), a subsample of whom had longitudinal cognitive and brain structural data spanning on average 8 years back, underwent functional magnetic resonance imaging while performing an associative memory encoding task. We investigated (1) age-related differences in whole-brain connectivity during memory encoding; (2) whether encoding connectivity patterns overlapped with the activity signatures of specific cognitive processes, and (3) whether connectivity associated with memory encoding related to longitudinal brain structural and cognitive changes. Age was associated with lower intranetwork connectivity among cortical networks and higher internetwork connectivity between networks supporting higher level cognitive functions and unimodal and attentional areas during encoding. Task-connectivity between mediotemporal and posterior parietal regions-which overlapped with areas involved in mental imagery-was related to better memory performance only in older age. The connectivity patterns supporting memory performance in older age reflected preservation of thickness of the medial temporal cortex. The results are more in accordance with a maintenance rather than a compensation account.

Reduced Hippocampal-Striatal Interactions during Formation of Durable Episodic Memories in Aging.

Encoding of durable episodic memories requires cross-talk between the hippocampus and multiple brain regions. Changes in these hippocampal interactions could contribute to age-related declines in the ability to form memories that can be retrieved after extended time intervals. Here we tested whether hippocampal-neocortical- and subcortical functional connectivity (FC) observed during encoding of durable episodic memories differed between younger and older adults. About 48 younger (20-38 years; 25 females) and 43 older (60-80 years; 25 females) adults were scanned with fMRI while performing an associative memory encoding task. Source memory was tested ~20 min and ~6 days postencoding. Associations recalled after 20 min but later forgotten were classified as transient, whereas memories retained after long delays were classified as durable. Results demonstrated that older adults showed a reduced ability to form durable memories and reduced hippocampal-caudate FC during encoding of durable memories. There was also a positive relationship between hippocampal-caudate FC and higher memory performance among the older adults. No reliable age group differences in durable memory-encoding activity or hippocampal-neocortical connectivity were observed. These results support the classic theory of striatal alterations as one cause of cognitive decline in aging and highlight that age-related changes in episodic memory extend beyond hippocampal-neocortical connections.

The Functional Foundations of Episodic Memory Remain Stable Throughout the Lifespan.

It has been suggested that specific forms of cognition in older age rely largely on late-life specific mechanisms. Here instead, we tested using task-fMRI (n = 540, age 6-82 years) whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural, and evolutionary influences. We clustered regions of the cerebral cortex according to the shape of the lifespan trajectory of memory activity in each region so that regions showing the same pattern were clustered together. The results revealed that lifespan trajectories of memory encoding function showed a continuity through life but no evidence of age-specific mechanisms such as compensatory patterns. Encoding activity was related to general cognitive abilities and variations of grey matter as captured by a multi-modal independent component analysis, variables reflecting core aspects of cognitive and structural change throughout the lifespan. Furthermore, memory encoding activity aligned to fundamental aspects of brain organization, such as large-scale connectivity and evolutionary cortical expansion gradients. Altogether, we provide novel support for a perspective on memory aging in which maintenance and decay of episodic memory in older age needs to be understood from a comprehensive life-long perspective rather than as a late-life phenomenon only.

Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression.

Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker ß-amyloid (Aß). Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, which has also been implicated in brain Aß accumulation. Here, we tested whether the relationship between cortical Aß accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, Aß correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-Aß relationship followed closely the Aß accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and Aß accumulation may involve Homer1 activity in the cortical regions, where harbor Aß deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.

Anterior and posterior hippocampus macro- and microstructure across the lifespan in relation to memory-A longitudinal study.

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.

Age-Related Differences in Functional Asymmetry During Memory Retrieval Revisited: No Evidence for Contralateral Overactivation or Compensation.

Brain asymmetry is inherent to cognitive processing and seems to reflect processing efficiency. Lower frontal asymmetry is often observed in older adults during memory retrieval, yet it is unclear whether lower asymmetry implies an age-related increase in contralateral recruitment, whether less asymmetry reflects compensation, is limited to frontal regions, or predicts neurocognitive stability or decline. We assessed age-related differences in asymmetry across the entire cerebral cortex, using functional magnetic resonance imaging data from 89 young and 76 older adults during successful retrieval, and surface-based methods allowing direct homotopic comparison of activity between cortical hemispheres . An extensive left-asymmetric network facilitated retrieval in both young and older adults, whereas diverse frontal and parietal regions exhibited lower asymmetry in older adults. However, lower asymmetry was not associated with age-related increases in contralateral recruitment but primarily reflected either less deactivation in contralateral regions reliably signaling retrieval failure in the young or lower recruitment of the dominant hemisphere-suggesting that functional deficits may drive lower asymmetry in older brains, not compensatory activity. Lower asymmetry predicted neither current memory performance nor the extent of memory change across the preceding ~ 8 years in older adults. Together, these findings are inconsistent with a compensation account for lower asymmetry during retrieval and aging.

Volumetric and microstructural regional changes of the hippocampus underlying development of recall performance after extended retention intervals.

Performance on recall tests improves through childhood and adolescence, in part due to structural maturation of the medial temporal cortex. Although partly different processes support successful recall over shorter vs. longer intervals, recall is usually tested after less than an hour. The aim of the present study was to test whether there are unique developmental changes in recall performance using extended retention intervals, and whether these are related to structural maturation of sub-regions of the hippocampus. 650 children and adolescents from 4.1 to 24.8 years were assessed in total 962 times (mean interval ≈ 1.8 years). The California Verbal Learning Test (CVLT) and the Rey Complex Figure Test (CFT) were used. Recall was tested 30 min and ≈ 10 days after encoding. We found unique developmental effects on recall in the extended retention interval condition independently of 30 min recall performance. For CVLT, major improvements happened between 10 and 15 years. For CFT, improvement was linear and was accounted for by visuo-constructive abilities. The relationships did not show anterior-posterior hippocampal axis differences. In conclusion, performance on recall tests using extended retention intervals shows unique development, likely due to changes in encoding depth or efficacy, or improvements of long-term consolidation processes.

Elaboration Benefits Source Memory Encoding Through Centrality Change.

Variations in levels of processing affect memory encoding and subsequent retrieval performance, but it is unknown how processing depth affects communication patterns within the network of interconnected brain regions involved in episodic memory encoding. In 113 healthy adults scanned with functional MRI, we used graph theory to calculate centrality indices representing the brain regions' relative importance in the memory network. We tested how communication patterns in 42 brain regions involved in episodic memory encoding changed as a function of processing depth, and how these changes were related to episodic memory ability. Centrality changes in right middle frontal gyrus, right inferior parietal lobule and left superior frontal gyrus were positively related to semantic elaboration during encoding. In the same regions, centrality during successful episodic memory encoding was related to performance on the episodic memory task, indicating that these centrality changes reflect processes that support memory encoding through deep elaborative processing. Similar analyses were performed for congruent trials, i.e. events that fit into existing knowledge structures, but no relationship between centrality changes and congruity were found. The results demonstrate that while elaboration and congruity have similar beneficial effects on source memory performance, the cortical signatures of these processes are probably not identical.

Development and Decline of the Hippocampal Long-Axis Specialization and Differentiation During Encoding and Retrieval of Episodic 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.

Maintained Frontal Activity Underlies High Memory Function Over 8 Years in Aging.

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.

Unilateral neglect post stroke: Eye movement frequencies indicate directional hypokinesia while fixation distributions suggest compensational mechanism.

INTRODUCTION: Eye movements and spatial attention are closely related, and eye-tracking can provide valuable information in research on visual attention. We investigated the pathology of overt attention in right hemisphere (RH) stroke patients differing in their severity of neglect symptoms by using eye-tracking during a dynamic attention task. METHODS: Eye movements were recorded in 26 RH stroke patients (13 with and 13 without unilateral spatial neglect, and a matched group of 26 healthy controls during a Multiple Object Tracking task. We assessed the frequency and spatial distributions of fixations, as well as frequencies of eye movements to the left and to the right side of visual space so as to investigate individuals' efficiency of visual processing, distribution of attentional processing resources, and oculomotoric orienting mechanisms. RESULTS: Both patient groups showed increased fixation frequencies compared to controls. A spatial bias was found in neglect patients' fixation distribution, depending on neglect severity (indexed by scores on the Behavioral Inattention Test). Patients with more severe neglect had more fixations within the right field, while patients with less severe neglect had more fixations within their left field. Eye movement frequencies were dependent on direction in the neglect patient group, as they made more eye movements toward the right than toward the left. CONCLUSION: The patient groups' higher fixation rates suggest that patients are generally less efficient in visual processing. The spatial bias in fixation distribution, dependent on neglect severity, suggested that patients with less severe neglect were able to use compensational mechanisms in their contralesional space. The observed relation between eye movement rates and directions observed in neglect patients provides a measure of the degree of difficulty these patients may encounter during dynamic situations in daily life and supports the idea that directional oculomotor hypokinesia may be a relevant component in this syndrome.

Continuity and Discontinuity in Human Cortical Development and Change From Embryonic Stages to Old Age.

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.

High-Expanding Regions in Primate Cortical Brain Evolution Support Supramodal Cognitive Flexibility.

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.

The Lifespan Trajectory of the Encoding-Retrieval Flip: A Multimodal Examination of Medial Parietal Cortex Contributions to Episodic Memory.

The formation of episodic memories is associated with deactivation during encoding and activation during retrieval in the posteromedial cortex (PMC). We hypothesized that the encoding/retrieval (E/R) flip is a critical component of episodic memory across the lifespan because structural and metabolic changes in the PMC coincide with the fine tuning of the episodic memory system in development and the reductions of memory performance in aging. The aims of the present study were, first, to describe lifespan trajectories of PMC encoding and retrieval activity in 270 human participants (167 females) from 6 to 80 years of age. Our second goal was to construct a model for episodic memory development in which contributions from brain activity, cortical thickness (CT), and structural connectivity are accounted for. We found that modulation of neural activity in response to memory encoding and retrieval demands was not fully developed until adolescence and decreased from adulthood through old age. The magnitude of the E/R flip was related to source memory and 55% of the age-related variance in source memory performance during childhood and adolescence could be accounted for by the E/R flip, CT, and mean diffusivity together. However, only CT and the E/R flip provided unique contributions with which to explain memory performance. The results suggest that neural dynamics in the PMC is related to the development of episodic memory during childhood and adolescence. The similar trajectories of the E/R flip and episodic memory emergence and decline through development and aging further suggests that a lifelong relationship exists.SIGNIFICANCE STATEMENT Modulation of neural activity in the posteromedial cortex (PMC) in response to memory encoding/retrieval (E/R) demands (E/R flip) does not reach its peak until adolescence and decreases from adulthood through old age. The magnitude of the E/R flip is related to source memory and 55% of the age-related variance in source memory performance during childhood and adolescence can be accounted for by the E/R flip and brain structure together. The results suggest that neural dynamics in the PMC is related to the development of episodic memory function during childhood and adolescence and the similar trajectories of the E/R flip and episodic memory performance through development and aging suggests that a lifelong relationship exists.