Biology subjects

Sneve, M. H.

Publications and source records attributed to Sneve, M. H..

18 recordsLinked to original sources

bioRxiv2025

Phase-Specific Hippocampal and Cortical Medial Temporal Lobe Involvement in Allocentric Working Memory

The hippocampus and cortices of the medial temporal lobe (MTL) are increasingly implicated in working memory, particularly for tasks requiring complex, high-resolution relational binding, but their precise contributions--particularly during delay maintenance--remain debated. Using functional magnetic resonance imaging (fMRI), we investigated the involvement of hippocampal and cortical MTL in a demanding allocentric working memory task requiring high-resolution, relational binding. During fMRI, 128 healthy human adults (92 females) aged 20-83 (mean 39) years performed a task in which object-location bindings had to be learned, maintained, and manipulated across an 8 second delay. The design included a passive viewing condition to control for perceptual and attentional demands and a staircase procedure to balance task difficulty across participants. Across the full sample, anterior and mid hippocampal subregions and cortical MTL areas were engaged during encoding. In the delay phase, we observed a non-uniform pattern, with hippocampal and entorhinal deactivation alongside perirhinal and parahippocampal activation. During test, activation occurred in posterior hippocampus and several cortical MTL regions. Contrary to predictions, hippocampal and cortical MTL activation did not vary with performance among younger adults. Instead, differences emerged in a left temporoparietal cluster, potentially reflecting verbal encoding strategies. Older adults, relative to younger adults with the most comparable performance levels, showed lower anterior hippocampal activation and smaller correct-passive viewing differences in perirhinal and parahippocampal cortices. Taken together, these findings demonstrate distinct phase-specific hippocampal and cortical MTL involvement across the temporal unfolding of allocentric working memory, with evidence of hippocampal engagement even during the delay, yet the absence of MTL-performance associations among younger adults suggests this involvement, while robust, may play a more auxiliary role.

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bioRxiv2025

Differential expression of spatiotemporal sleep spindle clusters in ageing

ObjectivesSleep spindles are potential biomarkers for memory decline in aging. However, significant within-person variability in spindle attributes complicates their utility in predicting cognitive deterioration. This study aimed to uncover distinct spindle types and their relevance to memory decline using data-driven clustering. MethodsPolysomnography was collected from younger (n = 43, ages 20-45 years) and older cognitively healthy adults (n = 34, ages 60-81 years). Spindles were clustered into four groups using multiple features and spatiotemporal context, irrespective of participant age. ResultsResulting clusters were hierarchically defined by the sleep stage, slow oscillation concurrence, and hemisphere. Stage N3 spindles (15%; predominantly coinciding with slow oscillations) formed a distinct group, followed by N2 spindles coinciding with slow oscillations (27%). Remaining N2 spindles were categorized into unilateral (41%) and bilateral clusters (17%). In older adults, there was a reduced proportion of N2 bilateral spindles and an increased proportion of N2 spindles concurrent with slow oscillations. Reduced proportion of N2 bilateral spindles was associated with better composite memory performance in younger adults, whereas higher spindle power, regardless of cluster belonging, was associated with reduced memory benefit from sleep compared with wakefulness. ConclusionsOur results indicate differing expression of spatiotemporal spindle clusters in older age, as well as intertwined dynamics between spindle propagation, SO concurrence, and frequency shifts in ageing. In addition, spindle heterogeneity aligned with global sleep stage dynamics. These results emphasize the interconnectedness of spindle activity with overall sleep patterns, underscoring the importance of spatiotemporal context within and across sleep stages. Statement of significanceThis study used data-driven clustering to explore sleep spindles as potential markers for age-related memory decline. We identified spindle clusters determined by sleep stage, slow oscillation concurrence, and hemisphere propagation. Notably, older adults showed altered expression of these clusters, indicating age-specific dynamics. Further research should focus on distinguishing spindle deterioration from broader sleep changes in older age. Such insights could pave the way for early detection and intervention strategies in cognitive decline, highlighting sleeps crucial role in maintaining cognitive health and resilience in aging populations. These findings hold promise for developing targeted approaches to enhance mental wellness and quality of life in older adults.

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bioRxiv2025

How and when can environmental influences change cerebral cortex? An experimental training study of twins with birth weight differences

How environmental variation shapes the human cerebral cortex remains incompletely understood. We compared cortical brainprints based in 210 twins (71 MZ and 34 DZ pairs, age 16-78 years) to distinguish prenatal, adult naturalistic and experimentally induced environmental variation from genetic contributions. Genetic effects were reflected in higher brainprint similarity within monozygotic (MZ) than dizygotic (DZ) pairs. Early environmental contributions were evident in lower brainprint similarity in MZ twin pairs with larger birthweight discordances, driven by area across the cortical ribbon. Later within-pair environmental differences in adult weight and lifestyle had minimal influence. Still, a 10-week virtual-reality navigation intervention revealed training-induced changes in the gray-white interface, with curvature and area changes supported by microstructural reconfigurations. In support of gene-environment interactions, relative brainprint similarity increased in MZ but diverged in DZ pairs following training. The results demonstrate that in adulthood, early life environmental difference persistently contributes to make the cortical architecture of genetically identical twins deviate. Environmental influence in adulthood in the form of training can still affect similarity of twin brainprints at the grey-white-matter boundary. These findings show that distinct environmental influences at prenatal and adult stage are differentially expressed across cortical features within a genetically informed framework.

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bioRxiv2024

Network Segregation During Episodic Memory Shows Age-Invariant Relations with Memory Performance From 7 to 82 Years

Lower episodic memory capability, as seen in development and aging compared with younger adulthood, may partly depend on lower brain network segregation. Here, our objective was twofold: (1) test this hypothesis using within- and between-network functional connectivity (FC) during episodic memory encoding and retrieval, in two independent samples (n=734, age 7-82 years). (2) Assess associations with age and the ability to predict memory comparing task-general FC and memory-modulated FC. In a multiverse-inspired approach, we performed tests across multiple analytic choices. Results showed that relationships differed based on these analytic choices, were often weak, and mainly present in the cohort with the most data. Significant relationships indicated that (i) memory-modulated FC predicted memory performance and associated with memory in an age-invariant manner. (ii) In line with the so- called neural dedifferentiation view, task-general FC showed lower segregation with higher age in adults which was associated with worse memory performance. In development, although there were only weak signs of a neural differentiation, that is, gradually higher segregation with higher age, we observed similar lower segregation-worse memory relationships. This age-invariant relationships between FC and episodic memory suggest that network segregation is pivotal for memory across the healthy lifespan. Declarations of interestnone. HighlightsO_LIWithin- and between network functional connectivity predict memory performance. C_LIO_LIMultiverse-inspired analyses showed varying results depending on analytic choices. C_LIO_LIMemory associations particularly in the cohort with most data were age-invariant across the lifespan. C_LIO_LIDedifferentiation might be better characterized as degrees of differentiation. C_LI

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bioRxiv2024

Reliability of structural brain change in cognitively healthy adult samples.

In neuroimaging research, tracking individuals over time is key to understanding the interplay between brain changes and genetic, environmental, or cognitive factors across the lifespan. Yet, the extent to which we can estimate the individual trajectories of brain change over time with precision remains uncertain. In this study, we estimated the reliability of structural brain change in cognitively healthy adults from multiple samples and assessed the influence of follow-up time and number of observations. Estimates of cross-sectional measurement error and brain change variance were obtained using the longitudinal FreeSurfer processing stream. Our findings showed, on average, modest longitudinal reliability with two years of follow-up. Increasing the follow-up time was associated with a substantial increase in longitudinal reliability while the impact of increasing the number of observations was comparatively minor. On average, 2-year follow-up studies require {approx}2.7 and {approx}4.0 times more individuals than designs with follow-ups of 4 and 6 years to achieve comparable statistical power. Subcortical volume exhibited higher longitudinal reliability compared to cortical area, thickness, and volume. The reliability estimates were comparable to those estimated from empirical data. The reliability estimates were affected by both the cohorts age where younger adults had lower reliability of change, and the preprocessing pipeline where the FreeSurfers longitudinal stream was notably superior than the cross-sectional. Suboptimal reliability inflated sample size requirements and compromised the ability to distinguish individual trajectories of brain aging. This study underscores the importance of long-term follow-ups and the need to consider reliability in longitudinal neuroimaging research.

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bioRxiv2024

What underlies exceptional memory function in older age? No evidence for aging-specific relationships to hippocampal atrophy and retrieval activity

Some older adults show superior memory performance compared to same-age peers, even performing on par with young participants. These are often referred to as SuperAgers. It is not known whether their superior memory function is caused by special features of their brains in aging, or whether superior memory has the same brain foundation throughout adult life. To address this, we measured hippocampal volume and atrophy, microstructural integrity by diffusion tensor imaging, and activity during an episodic memory encoding and retrieval task, in 277 cognitively healthy adults (age 20.1-81.5 years at baseline, mean 49.2 years). For quantification of hippocampal atrophy, all participants had repeated MRIs, from two to seven examinations, covering a mean of 9.3 years between first and last scan (2.5-17.3 years). 15.7% of the participants above 60 years had episodic memory scores above the mean of the young and middle-aged participants and were classified as SuperAgers. We found that superior memory in older adults was associated with higher retrieval activity in the anterior hippocampus and less hippocampal atrophy. However, there were no significant age-interactions, suggesting that the relationships reflected stable correlates of superior memory function. Although SuperAgers had superior memory compared to their same-age peers, they still performed worse than the best-performing young participants. Further, age-memory performance curves across the full age-range were similar for participants with superior memory performance compared to those with normal and low performance. These trajectories were based on cross-sectional data, but do not indicate preserved memory among the superior functioning older adults. In conclusion, the current results confirm that aspects of hippocampal structure and function are related to superior memory across age, without evidence to suggest that SuperAgers have special features compared to their younger counterparts.

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bioRxiv2022

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, its connectivity with the neocortex during memory processing in humans has been elusive. 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 core hippocampal-cortical networks active during memory processing. Anterior and posterior hippocampus had distinct connectivity profiles, which were stable across resting state and memory tasks. Whereas no encoding-specific connectome emerged across tasks, 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 encoding connectivity likely reflects contextual factors.

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bioRxiv2022

Sustained upregulation of widespread hippocampal-neocortical coupling following memory encoding

Systems consolidation of new experiences into lasting episodic memories involves interactions between hippocampus and the neocortex. Evidence of this process is seen already during early awake post-encoding rest periods. Functional MRI (fMRI) studies have demonstrated increased hippocampal coupling with task-relevant perceptual regions and reactivation of stimulus-specific encoding patterns following intensive encoding tasks. Here 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. As expected, we observed increased post-encoding functional connectivity between hippocampus and individually localized neocortical regions responsive to stimulus categories encountered during memory encoding. Post-encoding modulations were however not restricted to stimulus-selective cortex, but manifested as a nearly system-wide upregulation in hippocampal coupling with all major functional networks. The spatial configuration of these extensive modulations resembled hippocampal-neocortical interaction patterns estimated from active encoding operations, suggesting hippocampal post-encoding involvement by far exceeds reactivation of perceptual aspects. This reinstatement of encoding patterns during immediate post-encoding rest was not observed in resting-state scans collected 12 hours later, nor in control analyses estimating post-encoding neocortical modulations in functional connectivity using other candidate seed regions. The broad similarity in hippocampal functional coupling between online memory encoding and offline post-encoding rest suggests reactivation in humans may involve a spectrum of cognitive processes engaged during experience of an event. Significance statementStabilization of newly acquired information into lasting memories occurs through systems consolidation - a process which gradually spreads the locus of memory traces from hippocampus to more distributed neocortical representations. One of the earliest signs of consolidation is the upregulation of hippocampal-neocortical interactions during periods of awake rest following an active encoding task. We here show that these modulations involve much larger parts of the brain than previously reported in humans. Comparing changes in hippocampal coupling during post-encoding rest with those observed under active encoding, we find evidence for encoding-like hippocampal reinstatement throughout cortex during task-free periods. This suggests early systems consolidation of an experience involves reactivating not only core sensory details but multiple additional aspects of the encoding event.

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bioRxiv2021

Population-level asymmetry of the cerebral cortex: reproducibility, lifespan changes, heritability, and individual differences

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 genetic and later influences that shape them, such as age. Here, we delineate population-level asymmetry in cortical thickness and surface area vertex-wise in 7 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 correlates phenotypically and genetically in specific regions, and is low-moderately heritable (max h2SNP [~]19%). 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 in early 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.

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bioRxiv2021

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), a subsample of whom had longitudinal cognitive and brain structural data spanning 8 years back, underwent fMRI while performing an associative memory encoding task. We investigated 1) age changes in whole-brain connectivity during memory encoding; whether 2) encoding connectivity patterns overlap with the activity signatures of specific cognitive processes and whether 3) connectivity changes associated with memory encoding related to longitudinal brain structural and cognitive changes. Age was associated with decreased intranetwork connectivity and increased connectivity 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. These investigations collectively indicate that functional patterns of connectivity should be interpreted in accordance with a maintenance rather than a compensation account.

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bioRxiv2020

The functional foundations of episodic memory remain stable throughout the lifespan

It is suggested that the functional mechanisms behind specific forms of cognition, particularly episodic memory, may be dynamic over the lifespan and that cognitive preservation or decay in older age thus relies on age-specific mechanisms such as compensatory processes. Here instead, we tested whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural and evolutionary influences. We identified the generic lifespan patterns of memory encoding function across the brain (n = 540; age range = 6 - 82 years). The lifespan trajectories of brain activity were organized in a topologically meaningful manner and aligned to fundamental aspects of brain organization, such as large-scale connectivity hierarchies and evolutionary cortical expansion gradients. None of the normative trajectories of encoding function was solely determined by late-life patterns of activity, but rather showed continuities across development and adulthood. Inter-individual differences in activity in age-sensitive regions were predicted by general cognitive abilities and variation in grey matter structure, which are core variables of cognitive and structural change throughout the lifespan. Altogether, the results provide evidence for the lifelong continuity of the functional foundations of episodic memory which are bounded by both brain architecture and core mechanisms of cognitive and structural change over life. 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. Significance statementIt is suggested that cognitive function in older age largely relies on late-life specific mechanisms such as compensatory processes. In contrast, here we tested whether and to what degree brain activity during episodic memory encoding adheres to fundamental principles of life-long brain organization and continuity. The results revealed that generic lifespan trajectories of memory encoding function were not specific to late-life. Instead, the age-trajectories showed a continuity through life, were related to fundamental features of brain structure and cognition and to functional and evolutionary hierarchies. We argue that rather than focusing on older-age specific mechanisms, a framework that takes lifespan mechanisms of cognition and brain anatomy into account is necessary to understand episodic memory vulnerability in older age.

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bioRxiv2019

Volumetric and microstructural regional changes of the hippocampus underlying development of extended delay long-term memory

Episodic memory function improves through childhood and adolescence, in part due to structural maturation of the medial temporal cortex. Although partly different processes support long-term memory over shorter vs. longer intervals, memory is usually assessed after less than an hour. The aim of the present study was to test whether there are unique developmental changes in extended memory, 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 {approx} 1.8 years). Memory was assessed by the California Verbal Learning Test (CVLT) and the Rey Complex Figure Test (CFT). In addition to 30 min recall, an extended delay recall condition was administered {approx} 10 days after encoding. We found unique developmental effects on extended delay memory independently of 30 min recall performance. For visuo-constructive memory, this could be accounted for by visuo-constructive ability levels. Performance was modestly related to anterior and posterior hippocampal volume and mean diffusion. The relationships did not show an anterior-posterior hippocampal axis difference. In conclusion, extended delay memory shows unique development, likely due to changes in encoding depth or efficacy, or improvements of long-term consolidation processes.\n\nHighlightsO_LIUnique developmental effects on episodic memories over days rather than minutes\nC_LIO_LIDevelopment of visuoconstructive recall explainable by visuoconstructive abilitity\nC_LIO_LIDevelopment of verbal recall cannot be explained by verbal ability\nC_LIO_LIModest relationships between memory and hippocampal structural features\nC_LI

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bioRxiv2019

Lifespan trajectories and relationships to memory of the macro- and microstructure of the anterior and posterior hippocampus - a longitudinal multi-modal imaging 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 typically seen across development and aging. The hippocampal formation 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, 1790 cognitively healthy participants, 4.1-93.4 years of age, underwent a total of 3367 MRI examinations and 3033 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, and diffusion tensor imaging to measure mean diffusion (MD) 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. A similar aHC - pHC difference was observed for volume, although not as evident as for microstructure. All sub-regions showed age-dependent relationships to episodic memory function. For aHC micro- and macrostructure, the relationships to verbal memory performance varied significantly with age, being stronger among the older participants. Future research should disentangle the relationship between these structural properties and different memory processes - encoding vs. retrieval in particular - across the lifespan.

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bioRxiv2018

Age-differences in functional asymmetry during memory retrieval revisited: no evidence for contralateral over-activation 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-differences in asymmetry across the entire cerebral cortex, using fMRI data from 89 young and 76 older adults during successful retrieval, and surface-based methods that allowed direct homotopic comparison of activity between 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 signalling 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 neither predicted 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.

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bioRxiv2018

Longitudinal increase in sleep problems is related to amyloid deposition in cortical regions with high HOMER1 gene expression

Older adults who report more sleep problems tend to have elevated levels of the Alzheimers disease (AD) biomarker {beta}-amyloid (A{beta}), but the mechanisms responsible for this relationship are largely unknown. Molecular markers of sleep problems are now emerging from rodent research, yielding opportunities to generate hypotheses about the causes of the sleep-A{beta} relationship. A major molecular marker of sleep deprivation is Homer1a, a neural protein coded by the HOMER1 gene, involved in control of sleep homeostasis and also implied in A{beta} accumulation. Here, in a sample of 109 cognitively healthy middle-aged and older adults, we tested whether the relationship between cortical A{beta} accumulation and self-reported sleep quality, as well as changes in sleep quality over three years, was stronger in cortical regions with high HOMER1 mRNA expression levels. A{beta} correlated with poorer sleep quality cross-sectionally and longitudinally. This relationship was stronger in the younger (50-67 years) than the older (68-81 years) participants. Effects were mainly found in regions with high expression of HOMER1, suggesting a possible molecular pathway between sleep problems and A{beta} accumulation. The anatomical distribution of the sleep-A{beta} relationships followed closely the A{beta} accumulation pattern in 69 patients with mild cognitive impairment (MCI) or AD. Thus, the results indicate that the relationship between sleep problems and A{beta}-accumulation may involve Homer1 activity in the cortical regions that harbor A{beta} in AD. Analysis of cortical gene expression patterns represent a promising avenue to unveil molecular mechanisms behind the relationship between sleep problems and AD risk.

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bioRxiv2018

The hotspots 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. Here, across a series of experiments, we show that the evolutionary high-expanding hotspots - as estimated from patterns of evolutionary expansion from several primate species - share functional connections with different brain networks in a context-dependent manner. This capacity of the hotspots to connect flexibly with various specialized brain networks depending on particular cognitive requirements suggests that their selective growth and sustainment in evolution has been linked to their involvement in supramodal cognition. In accordance with an evolutionary-developmental view, we find that this ability to flexibly modulate functional connections as a function of cognitive state emerges gradually through childhood, with a prolonged developmental trajectory plateauing in young adulthood.

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bioRxiv2018

Continuity and discontinuity in human cortical development and change from embryonic stages to old age

The human cerebral cortex is highly regionalized. We aimed to test whether principles of regionalization could be traced from embryonic development throughout the human lifespan. A data-driven fuzzy-clustering approach was used to identify regions of coordinated longitudinal development of cortical surface area (SA) and thickness (CT) over 1.5 years (n = 301, 4-12 years). First, the SA clusters were compared to patterns from embryonic cortical development. The earliest sign of cortical regionalization is the emergence of morphometric gradients in the cerebral vesicles, with a major gradient running along the anterior-posterior (AP) axis. We found that the principal divide for the developmental SA clusters extended from the inferior-posterior to the superior-anterior cortex, corresponding to the embryonic morphometric AP gradient. Second, embryonic factors showing a clear AP gradient were identified, and tests revealed significant differences in gene expression of these factors between the anterior and posterior clusters. Further, each identified developmental SA and CT cluster showed distinguishable lifespan trajectories in a larger longitudinal dataset (4-88 years, 1633 observations). This means that regions that developed together 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, but otherwise regionalized CT development adhered more to the genetic boundaries. Finally, SA and CT clusters showed differential relationships to cognitive functions. In sum, the results suggest that development of cortical regionalization is a continuous process from the embryonic stage throughout human life.\n\nSignificance statement (120 words)The protomap and the radial unit theories of brain development have shown that graded expression patterns of several factors are responsible for shaping the ultimately highly partitioned and specialized neocortical landscape. The present study shows that the major anterior-posterior gradient of embryonic development can be detected in the regional cortical expansion profiles of children. The study further demonstrates that brain regions that develop together during childhood also tend to change together throughout the lifespan. This suggests that regional cortical development is a continuous process through the entire life, and that early-life factors have life-long impacts on this process.

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bioRxiv2018

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 lifespan development and decline of episodic memory. Evidence indicates a long-axis specialization where anterior hippocampus is more engaged during encoding and posterior during retrieval. We tested the lifespan trajectory of hippocampal long-axis episodic memory-related activity and functional connectivity (FC). 496 participants (6.8-80.8 years) were scanned with functional MRI while encoding and retrieving associative memories. We found clear evidence for a long-axis encoding-retrieval specialization. These long-axis effects declined linearly during development and aging, eventually vanishing in the older adults. This was mainly driven by age effects on retrieval. Retrieval was associated with gradually lower activity from childhood to adulthood, followed by positive age-relationships until 70 years. Interestingly, this pattern characterized task engagement regardless of memory success or failure. Children engaged posterior hippocampus more than anterior, while anterior hippocampus was more activated relative to posterior already in teenagers. Intra-hippocampal connectivity increased during task, and this increase declined with age. In sum, the results suggest that hippocampal long-axis differentiation and communication during episodic memory tasks develop rapidly during childhood and adolescence, are markedly different in older compared to younger adults, and are related to task engagement, not the successful completion of the task.

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