Biology subjects

Fjell, A.

Publications and source records attributed to Fjell, A..

12 recordsLinked to original sources

bioRxiv2026

Punctuated memory change: The temporal dynamics and brain basis of memory stability in aging

Are there individuals who resist episodic memory decline into older age? Analyzing 728,000 memory tests from 80,000 participants with at least 4 assessments, we introduce a simulation-calibrated framework to identify genuine memory stability. Across cohorts and models, [~]10% of adults [≥]70 years showed stable performance over a decade. In an MRI subgroup (n{approx}2,000), stable performers exhibited lower rates of brain atrophy across widespread regions, anchoring cognitive stability in structural brain maintenance. However, stability was often transient rather than trait-like: many individuals followed trajectories with extended plateaus of stable performance punctuated by episodes of accelerated decline. Accordingly, 54% showed at least one period of observed stability, averaging 10 years, whereas only 0.4% upheld stable performance over 24 years under the strictest definition. These findings are consistent with a complex-systems model of cognitive aging in which decline often reflects critical transitions rather than continuous erosion.

neuroscience↗

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.

neuroscience↗

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.

neuroscience↗

bioRxiv2022

Is short sleep bad for the brain? Brain structure and cognitive function in short sleepers

Many sleep less than recommended without experiencing daytime tiredness. According to prevailing views, short sleep increases risk of lower brain health and cognitive function. Chronic mild sleep deprivation could cause undetected sleep debt, negatively affecting cognitive function and brain health. However, it is possible that some have less sleep need and are more resistant to negative effects of sleep loss. We investigated this question using a combined cross-sectional and longitudinal sample of 47,029 participants (age 20-89 years) with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. 701 participants who reported to sleep < 6 hours did not experience daytime tiredness or sleep problems. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime tiredness and sleep problems (n = 1619) and participants sleeping the recommended 7-8 hours (n = 3754). However, both groups of short sleepers showed slightly lower general cognitive function, 0.16 and 0.19 standard deviations, respectively. Analyses using acelerometer-estimated sleep duration confirmed the findings, and the associations remained after controlling for body mass index, depression symptoms, income and education. The results suggest that some people can cope with less sleep without obvious negative consequences for brain morphometry, in line with a view on sleep need as individualized. Tiredness and sleep problems seem to be more relevant for brain structural differences than sleep duration per se. However, the slightly lower performance on tests of general cognitive function warrants closer examination by experimental designs in natural settings. Significance statementShort habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here we show that daytime tiredness and sleep problems are more important variables for regional brain volumes than sleep duration. However, participants sleeping < 6 hours had slightly lower scores on tests of general cognitive function. This indicates that sleep need is individual, and that sleep duration per se may be a less relevant variable for brain health than daytime tiredness and sleep problems. The association between habitual short sleep and lower scores on tests of general cogntitive function must be further scrutinized in natural settings.

neuroscience↗

bioRxiv2022

Sleep duration and brain structure - phenotypic associations and genotypic covariance

The question of how much sleep is best for the brain attracts scientific and public interest, and there is concern that insuficient sleep leads to poorer brain health. However, it is unknown how much sleep is sufficient and how much is too much. We analyzed 51,295 brain magnetic resonnance images from 47,039 participants, and calculated the self-reported sleep duration associated with the largest regional volumes and smallest ventricles relative to intracranial volume (ICV) and thickest cortex. 6.8 hours of sleep was associated with the most favorable brain outcome overall. Critical values, defined by 95% confidence intervals, were 5.7 and 7.9 hours. There was regional variation, with for instance the hippocampus showing largest volume at 6.3 hours. Moderately long sleep (> 8 hours) was more strongly associated with smaller relative volumes, thinner cortex and larger ventricles than even very short sleep (< 5 hours), but effect sizes were modest. People with larger ICV reported longer sleep (7.5 hours), so not correcting for ICV yielded longer durations associated with maximal volume. Controlling for socioeconomic status, body mass index and depression symptoms did not alter the associations. Genetic analyses showed that genes related to longer sleep in short sleepers were related to shorter sleep in long sleepers. This may indicate a genetically controlled homeostatic regulation of sleep duration. Mendelian randomization analyses did not suggest sleep duration to have a causal impact on brain structure in the analyzed datasets. The findings challenge the notion that habitual short sleep is negatively related to brain structure. Significance statementAccording to consensus recommendations, adults should sleep between 7 and 9 hours to optimize their health. We found that sleeping less than the recommended amount was associated with greater regional brain volumes relative to intracranial volume, and very short sleep was only weakly related to smaller volumes. Genetic analyses did not show causal effects of sleep duration on brain structure. Taken together, the results suggest that habitual short sleep is not an important contributor to lower brain volumes in adults on a group level, and that large individual dfferences in sleep need likely exist.

neuroscience↗

bioRxiv2022

Brain aging differs with cognitive ability regardless of education

Higher general cognitive ability (GCA) is associated with lower risk of neurodegenerative disorders, but neural mechanisms are unknown. GCA could be associated with more cortical tissue, from young age, i.e. brain reserve, or less cortical atrophy in adulthood, i.e. brain maintenance. Controlling for education, we investigated the relative association of GCA with reserve and maintenance of cortical volume, -area and -thickness through the adult lifespan, using multiple longitudinal brain imaging cohorts (n = 3327, 7002 MRI scans, baseline age 20-88 years, followed-up up to 11 years). There were widespread positive relationships between GCA and cortical characteristics (level-level associations). In select regions, higher baseline GCA was associated with less atrophy over time (level-change associations). Relationships remained when controlling for polygenic scores for both GCA and education. Our findings suggest that higher GCA is associated with cortical volumes by both brain reserve and -maintenance mechanisms through the adult lifespan.

neuroscience↗

bioRxiv2020

Education and income show heterogeneous relationships to lifespan brain and cognitive differences across European and US cohorts

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 {approx} 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.

neuroscience↗

bioRxiv2020

The genetic organization of subcortical volumetric change is stable throughout the lifespan

While development and aging of the cerebral cortex show a similar topographic organization and are mainly governed by the same genes, it is unclear whether the same is true for subcortical structures, which follow fundamentally different ontogenetic and phylogenetic principles than the cerebral cortex. To test the hypothesis that genetically governed neurodevelopmental processes can be traced in subcortical structures throughout life, we analyzed a longitudinal magnetic resonance imaging dataset (n = 974, age 4-89 years), identifying five clusters of longitudinal change in development. With some exceptions, these clusters followed placement along the cranial axis in embryonic brain development, suggesting continuity in the pattern of change from prenatal stages. Developmental change patterns were conserved through the lifespan and predicted general cognitive function in an age-invariant manner. The results were replicated in longitudinal data from the Lifebrain consortium (n = 756, age 19-83 years). Genetic contributions to longitudinal brain changes were calculated from the Vietnam Era Twin Study of Aging (n = 331 male twins, age 51-60 years), revealing that distinct sets of genes tended to govern change for each developmental cluster. This finding was confirmed with single nucleotide polymorphisms and cross-sectional MRI data from the UK Biobank (n = 20,588, age 40-69), demonstrating significantly higher co-heritability among structures belonging to the same developmental clusters. Together, these results suggest that coordination of subcortical change adheres to fundamental principles of lifespan continuity, genetic organization and age-invariant relationships to cognitive function. Significance statementHere we show that subcortical change during childhood development is organized in clusters. These clusters tend to follow the main gradient of embryonic brain development, and are stable across life. This means that subcortical regions changing together in childhood also change together throughout the rest of life, in accordance with a lifespan perspective on brain development and aging. Twin and single nucleotide polymorphism-based heritability analyses in middle-aged and older adults showed that volume and volume change of regions within each developmental cluster tended to be governed by the same sets of genes. Thus, volumetric changes across subcortical regions are tightly organized, and the coordinated change can be described in a lifespan perspective according to ontogenetic and genetic influences.

neuroscience↗

bioRxiv2020

Self-reported sleep problems are related to cortical thinning in aging but not memory decline and amyloid-β accumulation - results from the Lifebrain consortium

BackgroundOlder persons with poor sleep are more likely to develop neurodegenerative disease, but the causality underlying this association is unclear. To move towards explanation, we examine whether sleep quality and quantity are similarly associated with brain changes across the adult lifespan. MethodsAssociations between self-reported sleep parameters (Pittsburgh Sleep Quality Index;PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n=2205, 4363 MRIs, 18-92 years). Analyses were augmented by considering episodic memory change, gene expression from the Allen Human Brain Atlas, and amyloid-beta (A{beta}) accumulation (n=1980). ResultsPSQI components sleep problems and low sleep quality were related to thinning of the right lateral temporal cortex. The association with sleep problems emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. BMI and symptoms of depression had negligible effects. Sleep problems were neither related to longitudinal change in episodic memory function nor to A{beta} accumulation, suggesting that sleep-related cortical changes were independent of AD neuropathology and cognitive decline. ConclusionWorse self-reported sleep in later adulthood was associated with more cortical thinning in regions of high expression of genes related to oligodendrocytes and S1 pyramidal neurons, but not to A{beta} accumulation or memory decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes, except for a few restricted regions, indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

neuroscience↗

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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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.

neuroscience↗

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.

neuroscience↗