Inge Amlien

• Walhovd, Kristine B; Bråthen, Anne Cecilie Sjøli; Øverbye, Knut Eiliv Ødegård; Kransberg, Jonas Moe; Sørensen, Øystein & Garrido, Pablo F. [Vis alle 19 forfattere av denne artikkelen] (2026). Feature-specific environmental contributions to human cortical architecture revealed by twin brainprints. Communications Biology. doi: 10.1038/s42003-026-10707-w. Fulltekst i vitenarkiv Vis sammendrag

  Abstract How environmental variation shapes the human cerebral cortex remains incompletely understood. Here we compare cortical brainprints – individual profiles of regional cortical morphology – in 210 twins (age 16-78 years) to distinguish prenatal, adult naturalistic and experimentally induced environmental variation from genetic contributions. Monozygotic twins showed higher brainprint similarity than dizygotic twins, consistent with genetic effects. Lasting influences of early environment were evident in lower brainprint similarity in monozygotic twin-pairs with greater birthweight discordances, driven by surface area across the cortical ribbon. In contrast, within-pair 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. Relative brainprint similarity increased in monozygotic but diverged in dizygotic pairs following training. These findings show that distinct environmental influences acting at prenatal and adult stages are reflected in different features of the human cerebral cortex.

• Pineiro, Didac Vidal; Sørensen, Øystein; Strømstad, Marie Lorentsen; Amlien, Inge; Baaré, William & Bartrés-Faz, David [Vis alle 74 forfattere av denne artikkelen] (2025). Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change. Nature Communications. 16(1). doi: 10.1038/s41467-025-66354-y. Fulltekst i vitenarkiv Vis sammendrag

  Brain atrophy is a key factor behind episodic memory loss in aging, but the nature and ubiquity of this relationship remains poorly understood. This study leverages 13 longitudinal datasets, including 3737 cognitively healthy adults (10,343 MRI scans; 13,460 memory assessments), to determine whether brain change-memory change associations are more pronounced with age and genetic risk for Alzheimer’s Disease. Both factors are associated with accelerated brain decline, yet it remains unclear whethermemory loss is exacerbated beyond what atrophy alone would predict. Additionally, we assess whether memory decline aligns with a global pattern of atrophy or stems from distinct regional contributions. Our mega-analysis reveals a nonlinear relationship between memory decline and brain atrophy, primarily affecting individuals with above-average brain structural decline. The associations are stronger in the hippocampus but also spread across diverse cortical and subcortical regions. The associations strengthen with age, reachingmoderate associations in participants in their eighties. While APOE ε4 carriers exhibit steeper brain and memory loss, genetic risk has no effect on the change-change associations. These findings support the presence of common biological macrostructural substrates underlying memory function in older age which are vulnerable to multiple age-related factors, even in the absence of overt pathological changes.

• Fjell, Anders Martin; Røgeberg, Ole Jørgen; Sørensen, Øystein; Amlien, Inge; Bartrés-Faz, David & Brandmaier, Andreas M. [Vis alle 23 forfattere av denne artikkelen] (2025). Reevaluating the role of education on cognitive decline and brain aging in longitudinal cohorts across 33 Western countries. Nature Medicine. ISSN 1078-8956. 31, s. 2967–2976. doi: 10.1038/s41591-025-03828-y. Fulltekst i vitenarkiv Vis sammendrag

  Why education is linked to higher cognitive function in aging is fiercely debated. Leading theories propose that education reduces brain decline in aging and enhances tolerance to brain pathology or that it does not affect cognitive decline but, rather, reflects higher early-life cognitive function. To test these theories, we analyzed 407,356 episodic memory scores from 170,795 participants older than 50 years, alongside 15,157 brain magnetic resonance imaging scans from 6,472 participants across 33 Western countries. More education was associated with better memory, larger intracranial volume and slightly larger volume of memory-sensitive brain regions. However, education did not protect against age-related decline or weakened effects of brain decline on cognition. The most parsimonious explanation for the results is that the associations reflect factors present early in life, including propensity of individuals with certain traits to pursue more education. Although education has numerous benefits, the notion that it provides protection against cognitive or brain decline is not supported. In a large cross-national study, education was linked to better memory and larger brain volumes but not to slower cognitive or brain decline with age, suggesting that the association reflects early-life factors rather than neuroprotective effects in aging.

• Vidal-Piñeiro, Didac; Sørensen, Øystein; Strømstad, Marie Lorentsen; Amlien, Inge; Anderson, Micael & Baaré, William F.C. [Vis alle 25 forfattere av denne artikkelen] (2025). Reliability of structural brain change in cognitively healthy adult samples. Imaging Neuroscience. 3, s. 1–25. doi: 10.1162/imag_a_00547. Fulltekst i vitenarkiv Vis sammendrag

  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 2 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 ≈2.7 and ≈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 than cortical area, thickness, and volume. The reliability estimates were comparable with those estimated from empirical data. The reliability estimates were affected by both the cohort’s age where younger adults had lower reliability of change and the preprocessing pipeline where the FreeSurfer’s longitudinal stream was notably superior than the cross-sectional stream. 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.

• Grydeland, Håkon; Sneve, Markus Handal; Roe, James Michael; Raud, Liisa; Ness, Hedda Tvedten & Folvik, Line [Vis alle 12 forfattere av denne artikkelen] (2025). Network segregation during episodic memory shows age-invariant relations with memory performance from 7 to 82 years. Neurobiology of Aging. ISSN 0197-4580. 148, s. 1–15. doi: 10.1016/j.neurobiolaging.2025.01.004. Fulltekst i vitenarkiv Vis sammendrag

  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 and were mainly present in the largest dataset,. 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.

• Fjell, Anders Martin; Sneve, Markus Handal; Amlien, Inge; Grydeland, Håkon; Mowinckel, Athanasia Monika & Vidal-Piñeiro, Didac [Vis alle 8 forfattere av denne artikkelen] (2025). Stable hippocampal correlates of high episodic memory function across adulthood. Scientific Reports. 15(1). doi: 10.1038/s41598-025-92278-0. Fulltekst i vitenarkiv
• Walhovd, Kristine B; Krogsrud, Stine Kleppe; Amlien, Inge; Sørensen, Øystein; Wang, Yunpeng & Bråthen, Anne Cecilie Sjøli [Vis alle 14 forfattere av denne artikkelen] (2024). Fetal influence on the human brain through the lifespan. eLIFE. 12. doi: 10.7554/eLife.86812. Fulltekst i vitenarkiv
• Grødem, Edvard Olaf Sætersdal; Leonardsen, Esten Høyland; MacIntosh, Bradley; Bjørnerud, Atle; SCHELLHORN, TILL & Sørensen, Øystein [Vis alle 8 forfattere av denne artikkelen] (2024). A minimalistic approach to classifying Alzheimer's disease using simple and extremely small convolutional neural networks. Journal of Neuroscience Methods. ISSN 0165-0270. 411. doi: 10.1016/j.jneumeth.2024.110253. Fulltekst i vitenarkiv
• Pal, Zarah van der; Walhovd, Kristine B; Amlien, Inge; Guichelaar, Carlijn Jamila; Kaiser, Antonia & Bottelier, Marco A. [Vis alle 9 forfattere av denne artikkelen] (2024). Stimulant medication use and apparent cortical thickness development in attention-deficit/hyperactivity disorder: a prospective longitudinal study. Frontiers in Psychiatry. 15. doi: 10.3389/fpsyt.2024.1365159. Fulltekst i vitenarkiv
• Iakunchykova, Olena; Pan, Mengyu; Amlien, Inge; Roe, James Michael; Walhovd, Kristine B & Fjell, Anders Martin [Vis alle 9 forfattere av denne artikkelen] (2024). Genetic evidence for the causal effects of C–reactive protein on self-reported habitual sleep duration. Brain, Behavior, and Immunity - Health (BBI - Health). 37. doi: 10.1016/j.bbih.2024.100754. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Sørensen, Øystein; Wang, Yunpeng; Amlien, Inge; Baaré, William F. C. & Bartrés-Faz, David [Vis alle 24 forfattere av denne artikkelen] (2023). No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy. Nature Human Behaviour. 7, s. 2008–2022. doi: 10.1038/s41562-023-01707-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration—which is shorter than current recommendations.

• Roe, James Michael; Vidal-Piñeiro, Didac; Amlien, Inge; Pan, Mengyu; Sneve, Markus Handal & Schotten, Michel Thiebaut de [Vis alle 14 forfattere av denne artikkelen] (2023). Tracing the development and lifespan change of population-level structural asymmetry in the cerebral cortex. eLIFE. 12, s. 1–32. doi: 10.7554/eLife.84685. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Sørensen, Øystein; Wang, Yunpeng; Amlien, Inge; Baaré, William F C & Bartrés-Faz, David [Vis alle 21 forfattere av denne artikkelen] (2023). Is Short Sleep Bad for the Brain? Brain Structure and Cognitive Function in Short Sleepers. Journal of Neuroscience. ISSN 0270-6474. 43(28), s. 5241–5250. doi: 10.1523/JNEUROSCI.2330-22.2023. Fulltekst i vitenarkiv Vis sammendrag

  Many sleep less than recommended without experiencing daytime sleepiness. 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 using a cross-sectional and longitudinal sample of 47,029 participants of both sexes (20–89 years) from the Lifebrain consortium, Human Connectome project (HCP) and UK Biobank (UKB), with measures of self-reported sleep, including 51,295 MRIs of the brain and cognitive tests. A total of 740 participants who reported to sleep <6 h did not experience daytime sleepiness or sleep problems/disturbances interfering with falling or staying asleep. These short sleepers showed significantly larger regional brain volumes than both short sleepers with daytime sleepiness and sleep problems ( n = 1742) and participants sleeping the recommended 7–8 h ( n = 3886). However, both groups of short sleepers showed slightly lower general cognitive function (GCA), 0.16 and 0.19 SDs, respectively. Analyses using accelerometer-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 associations with brain morphometry and that sleepiness and sleep problems may be more related to brain structural differences than duration. However, the slightly lower performance on tests of general cognitive abilities warrants closer examination in natural settings. SIGNIFICANCE STATEMENT Short habitual sleep is prevalent, with unknown consequences for brain health and cognitive performance. Here, we show that daytime sleepiness and sleep problems are more strongly related to regional brain volumes than sleep duration. However, participants sleeping ≤6 h had slightly lower scores on tests of general cognitive function (GCA). This indicates that sleep need is individual and that sleep duration per se is very weakly if at all related brain health, while daytime sleepiness and sleep problems may show somewhat stronger associations. The association between habitual short sleep and lower scores on tests of general cognitive abilities must be further scrutinized in natural settings.

• Walhovd, Kristine B; Nyberg, Lars; Lindenberger, Ulman; Amlien, Inge; Sørensen, Øystein & Wang, Yunpeng [Vis alle 20 forfattere av denne artikkelen] (2022). Brain aging differs with cognitive ability regardless of education. Scientific Reports. 12(1). doi: 10.1038/s41598-022-17727-6. Fulltekst i vitenarkiv
• Vidal-Piñeiro, Didac; Wang, Yunpeng; Krogsrud, Stine Kleppe; Amlien, Inge; Baaré, William FC & Bartres-Faz, David [Vis alle 31 forfattere av denne artikkelen] (2021). Individual variations in ‘brain age’ relate to early-life factors more than to longitudinal brain change. eLIFE. 10. doi: 10.7554/eLife.69995. Fulltekst i vitenarkiv Vis sammendrag

  Brain age is a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher-than-expected brain age is thought partially to reflect above-average rate of brain aging. Here, we explicitly tested this assumption in two independent large test datasets (UK Biobank [main] and Lifebrain [replication]; longitudinal observations ≈ 2750 and 4200) by assessing the relationship between cross-sectional and longitudinal estimates of brain age. Brain age models were estimated in two different training datasets (n ≈ 38,000 [main] and 1800 individuals [replication]) based on brain structural features. The results showed no association between cross-sectional brain age and the rate of brain change measured longitudinally. Rather, brain age in adulthood was associated with the congenital factors of birth weight and polygenic scores of brain age, assumed to reflect a constant, lifelong influence on brain structure from early life. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.

• Sun, Jiangming; Wang, Yunpeng; Folkersen, Lasse; Borne, Yan; Amlien, Inge & Buil, Alfonso [Vis alle 13 forfattere av denne artikkelen] (2021). Translating polygenic risk scores for clinical use by estimating the confidence bounds of risk prediction. Nature Communications. doi: 10.1038/s41467-021-25014-7. Fulltekst i vitenarkiv Vis sammendrag

  A promise of genomics in precision medicine is to provide individualized genetic risk pre- dictions. Polygenic risk scores (PRS), computed by aggregating effects from many genomic variants, have been developed as a useful tool in complex disease research. However, the application of PRS as a tool for predicting an individual’s disease susceptibility in a clinical setting is challenging because PRS typically provide a relative measure of risk evaluated at the level of a group of people but not at individual level. Here, we introduce a machine-learning technique, Mondrian Cross-Conformal Prediction (MCCP), to estimate the confidence bounds of PRS-to-disease-risk prediction. MCCP can report disease status conditional probability value for each individual and give a prediction at a desired error level. Moreover, with a user-defined prediction error rate, MCCP can estimate the proportion of sample (coverage) with a correct prediction.

• Wang, Yunpeng; Grydeland, Håkon; Roe, James Michael; Pan, Mengyu; Magnussen, Fredrik & Amlien, Inge [Vis alle 17 forfattere av denne artikkelen] (2021). Associations of circulating C-reactive proteins, APOE ε4, and brain markers for Alzheimer’s disease in healthy samples across the lifespan. Brain, Behavior, and Immunity. ISSN 0889-1591. 100. doi: 10.1016/j.bbi.2021.12.008. Fulltekst i vitenarkiv Vis sammendrag

  The apolipoprotein E gene ε4 allele (APOE ε4) and higher circulating level of C-reactive protein (CRP) have been extensively investigated as risk factors for Alzheimer’s disease (AD). Paradoxically, APOE ε4 has been associated with lower levels of blood CRP in middle-aged and older populations. However, few studies have investigated this intriguing relation and its impact on neurological markers for AD in younger ages, nor across the whole lifespan. Here, we examine associations of blood CRP levels, APOE ε4, and biomarkers for AD in a cognitively healthy lifespan cohort (N up to 749; 20–81 years of age) and replicate the findings in UK Biobank (N = 304 322; 37–72 years of age), the developmental ABCD study (N = 10 283; 9–11 years of age), and a middle-aged sample (N = 339; 40–65 years of age). Hippocampal volume, brain amyloid-β (Aβ) plaque levels, cerebrospinal fluid (CSF) levels of Aβ and tau species, and neurofilament protein light protein (NFL) were used as AD biomarkers in subsamples. In addition, we examined the genetic contribution to the variation of CRP levels over different CRP ranges using polygenic scores for CRP (PGS-CRP). Our results show APOE ε4 consistently associates with low blood CRP levels across all age groups (p < 0.05). Strikingly, both ε4 and PGS-CRP associated mainly with blood CRP levels within the low range (<5mg/L). We then show both APOE ε4 and high CRP levels associate with smaller hippocampus volumes across the lifespan (p < 0.025). APOE ε4 was associated with high Aβ plaque levels in the brain (FDR-corrected p = 8.69x10-4), low levels of CSF Aβ42 (FDR-corrected p = 6.9x10-2), and lower ratios of Aβ42 to Aβ40 (FDR-corrected p = 5.08x10-5). Blood CRP levels were weakly correlated with higher ratio of CSF Aβ42 to Aβ40 (p = 0.03, FDR-corrected p = 0.4). APOE ε4 did not correlate with blood concentrations of another 9 inflammatory cytokines, and none of these cytokines correlated with AD biomarkers.

• Fjell, Anders Martin; Grydeland, Håkon; Wang, Yunpeng; Amlien, Inge; Bartrés-Faz, David & Brandmaier, Andreas M. [Vis alle 24 forfattere av denne artikkelen] (2021). The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan running title: Genetics of subcortical lifespan change. eLIFE. 10, s. 1–22. doi: 10.7554/eLife.66466. Fulltekst i vitenarkiv Vis sammendrag

  Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single-nucleotide polymorphisms-based analyses of 38,127 cross-sectional MRIs showed a similar pattern of genetic volume–volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.

• Krogsrud, Stine Kleppe; Mowinckel, Athanasia Monika; Sederevicius, Donatas; Vidal-Piñeiro, Didac; Amlien, Inge Kasbohm & Wang, Yunpeng [Vis alle 9 forfattere av denne artikkelen] (2021). Relationships between apparent cortical thickness and working memory across the lifespan - Effects of genetics and socioeconomic status. Developmental Cognitive Neuroscience. ISSN 1878-9293. 51, s. 1–11. doi: 10.1016/j.dcn.2021.100997. Fulltekst i vitenarkiv
• Walhovd, Kristine Beate; Fjell, Anders Martin; Wang, Yunpeng; Amlien, Inge; Mowinckel, Athanasia Monika & Lindenberger, Ulman [Vis alle 29 forfattere av denne artikkelen] (2021). Education and income show heterogeneous relationships to lifespan brain and cognitive differences across European and US cohorts. Cerebral Cortex. ISSN 1047-3211. 32(4), s. 839–854. doi: 10.1093/cercor/bhab248. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4–97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained 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. The relatively stronger SES–ICV associations rather are compatible with SES–brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.

• Grasby, Katrina L.; Jahanshad, Neda; Painter, Jodie N; Colodro-Conde, Lucía; Bralten, Janita & Hibar, DP [Vis alle 50 forfattere av denne artikkelen] (2020). The genetic architecture of the human cerebral cortex. Science. ISSN 0036-8075. 367(6484). doi: 10.1126/science.aay6690. Fulltekst i vitenarkiv Vis sammendrag

  INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function.

• Hofer, Edith; Roshchupkin, Gennady V.; Adams, Hieab H H; Knol, Maria J.; Lin, Honghuang & Li, Shuo [Vis alle 51 forfattere av denne artikkelen] (2020). Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults. Nature Communications. 11. doi: 10.1038/s41467-020-18367-y. Fulltekst i vitenarkiv Vis sammendrag

  Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

• Esteban, Oscar; Ciric, Rastko; Finc, Karolina; Blair, Ross W.; Markiewicz, Christopher J. & Moodie, Craig A. [Vis alle 27 forfattere av denne artikkelen] (2020). Analysis of task-based functional MRI data preprocessed with fMRIPrep. Nature Protocols. ISSN 1754-2189. 15(7), s. 2186–2202. doi: 10.1038/s41596-020-0327-3. Fulltekst i vitenarkiv
• Langnes, Espen; Sneve, Markus Handal; Sederevicius, Donatas; Amlien, Inge Kasbohm; Walhovd, Kristine B & Fjell, Anders Martin (2020). Anterior and posterior hippocampus macro‐ and microstructure across the lifespan in relation to memory—A longitudinal study. Hippocampus. ISSN 1050-9631. s. 1–15. doi: 10.1002/hipo.23189. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Fjell, Anders Martin; Sørensen, Øystein; Amlien, Inge Kasbohm; Bartrés-Faz, David; Brandmaier, Andreas M. & Buchmann, Nikolaus [Vis alle 32 forfattere av denne artikkelen] (2020). Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium. Cerebral Cortex. ISSN 1047-3211. s. 1–17. doi: 10.1093/cercor/bhaa332. Fulltekst i vitenarkiv Vis sammendrag

  We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations 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). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. “PSQI # 1 Subjective sleep quality” and “PSQI #5 Sleep disturbances” were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with “PSQI #5 Sleep disturbances” emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.

• Walhovd, Kristine B; Amlien, Inge Kasbohm; Schrantee, Anouk; Rohani, Darius Adam; Groote, Inge Rasmus & Bjørnerud, Atle [Vis alle 8 forfattere av denne artikkelen] (2020). Methylphenidate effects on cortical thickness in children and adults with attention-deficit/hyperactivity disorder: A randomized clinical trial. American Journal of Neuroradiology. ISSN 0195-6108. 41(5), s. 758–765. doi: 10.3174/AJNR.A6560. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Background and purpose: Although methylphenidate is frequently used to treat children with attention-deficit/hyperactivity disorder, it is currently unknown how methylphenidate affects brain development. In a randomized controlled trial, we investigated whether the cortical effects of methylphenidate are modulated by age. Materials and methods: Between June 1, 2011, and June 15, 2015, we conducted a randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) in 99 males with attention-deficit/hyperactivity disorder (according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria) from referral centers in the greater Amsterdam area in the Netherlands. The trial was registered on March 24, 2011 (identifier NL34509.000.10) and subsequently at the Netherlands National Trial Register (identifier NTR3103). Participants (first enrolled October 13, 2011) were 10-12 years or 23-40 years of age and randomized to treatment with either methylphenidate or a placebo for 16 weeks. Our main outcome was a change in cortical thickness in predefined ROIs as measured by MR imaging pre- and posttreatment. Results: We observed a time × medication × age interaction (F[1,88.825] = 4.316, P < .05) for the right medial cortex ROI, where methylphenidate treatment yielded less cortical thinning in children, but not in adults or the placebo groups. Conclusions: Our finding that the effects of methylphenidate on right medial cortical thickness differ between children and adults infers that the drug affects gray matter development in this brain region. This warrants replication in larger groups with longer follow-up to determine whether this effect can also be observed in other cortical brain regions and whether it may have long-term consequences.

• Vidal-Piñeiro, Didac; Sneve, Markus Handal; Amlien, Inge Kasbohm; Grydeland, Håkon; Mowinckel, Athanasia Monika & Roe, James Michael [Vis alle 10 forfattere av denne artikkelen] (2020). The Functional Foundations of Episodic Memory Remain Stable Throughout the Lifespan. Cerebral Cortex. ISSN 1047-3211. doi: 10.1093/cercor/bhaa348. Fulltekst i vitenarkiv Vis sammendrag

  Abstract 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.

• Fjell, Anders Martin; Sørensen, Øystein; Amlien, Inge Kasbohm; Bartrés-Faz, David; Bros, Didac Macia & Buchmann, Nikolaus [Vis alle 28 forfattere av denne artikkelen] (2019). Self-reported sleep relates to hippocampal atrophy across the adult lifespan – results from the Lifebrain consortium. Sleep. ISSN 0161-8105. doi: 10.1093/sleep/zsz280. Fulltekst i vitenarkiv Vis sammendrag

  Objectives Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan. Methods Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18-90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21390 participants from the UK Biobank. Results No cross-sectional sleep – hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses. Conclusions Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.

• Amlien, Inge Kasbohm; Sneve, Markus Handal; Vidal-Piñeiro, Didac; Walhovd, Kristine B & Fjell, Anders Martin (2019). Elaboration Benefits Source Memory Encoding Through Centrality Change. Scientific Reports. 9(1), s. 1–13. doi: 10.1038/s41598-019-39999-1. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Fjell, Anders Martin; Chen, Chi-Hua Chen; Sederevicius, Donatas; Sneve, Markus Handal; Grydeland, Håkon & Krogsrud, Stine Kleppe [Vis alle 17 forfattere av denne artikkelen] (2019). Continuity and discontinuity in human cortical development and change from embryonic stages to old age. Cerebral Cortex. ISSN 1047-3211. 29(9), s. 3879–3890. doi: 10.1093/cercor/bhy266. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Amlien, Inge Kasbohm; Sneve, Markus Handal; Vidal-Piñeiro, Didac; Walhovd, Kristine B & Fjell, Anders Martin (2018). The lifespan trajectory of the encoding-retrieval flip: A multimodal examination of medial parietal cortex contributions to episodic memory. Journal of Neuroscience. ISSN 0270-6474. 38(40), s. 8666–8679. doi: 10.1523/JNEUROSCI.1702-17.2018. Fulltekst i vitenarkiv Vis sammendrag

  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 thePMCcoincide with the fine tuning of the episodicmemorysystem 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.

• Langnes, Espen; Vidal-Piñeiro, Didac; Sneve, Markus Handal; Amlien, Inge Kasbohm; Walhovd, Kristine B & Fjell, Anders Martin (2018). Development and decline of the hippocampal long-axis specialization and differentiation during encoding and retrieval of episodic memories. Cerebral Cortex. ISSN 1047-3211. s. 1–17. doi: 10.1093/cercor/bhy209. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Sneve, Markus Handal; Grydeland, Håkon; Storsve, Andreas Berg; Amlien, Inge Kasbohm & Yendiki, Anastasia [Vis alle 7 forfattere av denne artikkelen] (2017). Relationship between structural and functional connectivity change across the lifespan – a longitudinal investigation. Human Brain Mapping. ISSN 1065-9471. 38(1), s. 561–573. doi: 10.1002/hbm.23403. Fulltekst i vitenarkiv Vis sammendrag

  Extensive efforts are devoted to understand the functional (FC) and structural connections (SC) of the brain. FC is usually measured by functional magnetic resonance imaging (fMRI), and conceptualized as degree of synchronicity in brain activity between different regions. SC is typically indexed by measures of white matter (WM) properties, for example, by diffusion weighted imaging (DWI). FC and SC are intrinsically related, in that coordination of activity across regions ultimately depends on fast and efficient transfer of information made possible by structural connections. Convergence between FC and SC has been shown for specific networks, especially the default mode network (DMN). However, it is not known to what degree FC is constrained by major WM tracts and whether FC and SC change together over time. Here, 120 participants (20–85 years) were tested at two time points, separated by 3.3 years. Resting-state fMRI was used to measure FC, and DWI to measure WM microstructure as an index of SC. TRACULA, part of FreeSurfer, was used for automated tractography of 18 major WM tracts. Cortical regions with tight structural couplings defined by tractography were only weakly related at the functional level. Certain regions of the DMN showed a modest relationship between change in FC and SC, but for the most part, the two measures changed independently. The main conclusions are that anatomical alignment of SC and FC seems restricted to specific networks and tracts, and that changes in SC and FC are not necessarily strongly correlated. This is the peer reviewed version of the following article: Relationship between structural and functional connectivity change across the adult lifespan: A longitudinal investigation, which has been published in final form at Hum Brain Mapp. 2016 Sep 22. doi: 10.1002/hbm.23403. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

• Sneve, Markus Handal; Grydeland, Håkon; Amlien, Inge Kasbohm; Langnes, Espen; Walhovd, Kristine B & Fjell, Anders Martin (2017). Decoupling of large-scale brain networks supports the consolidation of durable episodic memories. NeuroImage. ISSN 1053-8119. 153, s. 336–345. doi: 10.1016/j.neuroimage.2016.05.048. Fulltekst i vitenarkiv Vis sammendrag

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

• Walhovd, Kristine B; Krogsrud, Stine Kleppe; Amlien, Inge Kasbohm; Bartsch, Hauke; Bjørnerud, Atle & Due-Tønnessen, Paulina [Vis alle 22 forfattere av denne artikkelen] (2016). Neurodevelopmental origins of lifespan changes in brain and cognition. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 113(33), s. 9357–9362. doi: 10.1073/pnas.1524259113. Fulltekst i vitenarkiv Vis sammendrag

  Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4–88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother–Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain–cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

• Amlien, Inge; Fjell, Anders Martin; Tamnes, Christian Krog; Grydeland, Håkon; Krogsrud, Stine Kleppe & Chaplin, Tristan A. [Vis alle 8 forfattere av denne artikkelen] (2016). Organizing Principles of Human Cortical Development - Thickness and Area from 4 to 30 Years: Insights from Comparative Primate Neuroanatomy. Cerebral Cortex. ISSN 1047-3211. 26(1), s. 257–267. doi: 10.1093/cercor/bhu214. Fulltekst i vitenarkiv
• Sneve, Markus Handal; Grydeland, Håkon; Nyberg, Lars; Bowles, Ben; Amlien, Inge Kasbohm & Langnes, Espen [Vis alle 8 forfattere av denne artikkelen] (2015). Mechanisms underlying encoding of short-lived versus durable episodic memories. Journal of Neuroscience. ISSN 0270-6474. 35(13), s. 5202–5212. doi: 10.1523/JNEUROSCI.4434-14.2015. Fulltekst i vitenarkiv Vis sammendrag

  We continuously encounter and process novel events in the surrounding world, but only some episodes will leave detailed memory traces that can be recollected after weeks and months. Here, our aim was to monitor brain activity during encoding of events that eventually transforms into long-term stable memories. Previous functional magnetic resonance imaging (fMRI) studies have shown that the degree of activation of different brain regions during encoding is predictive of later recollection success. However, most of these studies tested participants' memories the same day as encoding occurred, whereas several lines of research suggest that extended post-encoding processing is of crucial importance for long-term consolidation. Using fMRI, we tested whether the same encoding mechanisms are predictive of recollection success after hours as after a retention interval of several weeks. Seventy-eight participants were scanned during an associative encoding task and given a source memory test the same day or after ∼6 weeks. We found a strong link between regional activity levels during encoding and recollection success over short time intervals. However, results further showed that durable source memories, i.e., events recollected after several weeks, were not simply the events associated with the highest activity levels at encoding. Rather, strong levels of connectivity between the right hippocampus and perceptual areas, as well as with parts of the self-referential default-mode network, seemed instrumental in establishing durable source memories. Thus, we argue that an initial intensity-based encoding is necessary for short-term encoding of events, whereas additional processes involving hippocampal–cortical communication aid transformation into stable long-term memories.

• Fjell, Anders Martin; Sneve, Markus Handal; Grydeland, Håkon; Storsve, Andreas Berg; Lange, Ann-Marie Glasø de & Amlien, Inge Kasbohm [Vis alle 8 forfattere av denne artikkelen] (2015). Functional connectivity change across multiple cortical networks relates to episodic memory changes in aging. Neurobiology of Aging. ISSN 0197-4580. 36(12), s. 3255–3268. doi: 10.1016/j.neurobiolaging.2015.08.020. Fulltekst i vitenarkiv Vis sammendrag

  A major task of contemporary cognitive neuroscience of aging is to explain why episodic memory declines. Change in resting-state functional connectivity (rsFC) could be a mechanism accounting for reduced function. We addressed this through 3 studies. In study 1, 119 healthy participants (20–83 years) were followed for 3.5 years with verbal recall testing and magnetic resonance imaging. Independent of atrophy, recall change was related to change in rsFC in anatomically widespread areas. Striking age-effects were observed in that a positive relationship between rsFC and memory characterized older participants while a negative relationship was seen among the younger and middle-aged. This suggests that cognitive consequences of rsFC change are not stable across age. In study 2 and 3, the age-dependent differences in rsFC-memory relationship were replicated by use of a simulation model (study 2) and by a cross-sectional experimental recognition memory task (study 3). In conclusion, memory changes were related to altered rsFC in an age-dependent manner, and future research needs to detail the mechanisms behind age-varying relationships.

• Fjell, Anders Martin; Westlye, Lars Tjelta; Amlien, Inge; Tamnes, Christian Krog; Grydeland, Håkon & Engvig, Andreas [Vis alle 11 forfattere av denne artikkelen] (2015). High-expanding cortical regions in human development and evolution are related to higher intellectual abilities. Cerebral Cortex. ISSN 1047-3211. 25, s. 26–34. doi: 10.1093/cercor/bht201. Fulltekst i vitenarkiv Vis sammendrag

  Cortical surface area has tremendously expanded during human evolution, and similar patterns of cortical expansion have been observed during childhood development. An intriguing hypothesis is that the high-expanding cortical regions also show the strongest correlations with intellectual function in humans. However, we do not know how the regional distribution of correlations between intellectual function and cortical area maps onto expansion in development and evolution. Here, in a sample of 1048 participants, we show that regions in which cortical area correlates with visuospatial reasoning abilities are generally high expanding in both development and evolution. Several regions in the frontal cortex, especially the anterior cingulate, showed high expansion in both development and evolution. The area of these regions was related to intellectual functions in humans. Low-expanding areas were not related to cognitive scores. These findings suggest that cortical regions involved in higher intellectual functions have expanded the most during development and evolution. The radial unit hypothesis provides a common framework for interpretation of the findings in the context of evolution and prenatal development, while additional cellular mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and intracortical myelination, likely impact area expansion in later childhood. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cerebral Cortex following peer review. The version of record [insert complete citation information here] is available online at: http://dx.doi.org/10.1093/cercor/bht201

• Tamnes, Christian Krog; Zeller, Bernward; Amlien, Inge; Kanellopoulos, Adriani; Andersson, Stein & Due-Tønnessen, Paulina [Vis alle 9 forfattere av denne artikkelen] (2015). Cortical surface area and thickness in adult survivors of pediatric acute lymphoblastic leukemia. Pediatric Blood & Cancer. ISSN 1545-5009. 62(6), s. 1027–1034. doi: 10.1002/pbc.25386. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Grydeland, Håkon; Krogsrud, Stine Kleppe; Amlien, Inge Kasbohm; Rohani, Darius Adam & Ferschmann, Lia [Vis alle 21 forfattere av denne artikkelen] (2015). Development and aging of cortical thickness correspond to genetic organization patterns. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 112(50), s. 15462–15467. doi: 10.1073/pnas.1508831112. Fulltekst i vitenarkiv Vis sammendrag

  There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demon- strated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically progr ammed neurodevel opmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organi- zational principles of co rtical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age- related changes in cortical thick- ness followed closely the genetic organization of the cerebral cortex, with change rates varying as a functi on of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated development al and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrap- olated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective i n research aimed at identifying the genetic and environmental determinants of cortical development and aging.

• Fjell, Anders Martin; Amlien, Inge; Sneve, Markus Handal; Grydeland, Håkon; Tamnes, Christian Krog & Chaplin, Tristan [Vis alle 8 forfattere av denne artikkelen] (2015). The roots of Alzheimer's disease: Are high-expanding cortical areas preferentially targeted? Cerebral Cortex. ISSN 1047-3211. 25(9), s. 2556–2565. doi: 10.1093/cercor/bhu055. Fulltekst i vitenarkiv Vis sammendrag

  Alzheimer's disease (AD) is regarded a human-specific condition, and it has been suggested that brain regions highly expanded in humans compared with other primates are selectively targeted. We calculated shared and unique variance in the distribution of AD atrophy accounted for by cortical expansion between macaque and human, affiliation to the default mode network (DMN), ontogenetic development and normal aging. Cortical expansion was moderately related to atrophy, but a critical discrepancy was seen in the medial temporo-parietal episodic memory network. Identification of “hotspots” and “coldspots” of expansion across several primate species did not yield compelling evidence for the hypothesis that highly expanded regions are specifically targeted. Controlling for distribution of atrophy in aging substantially attenuated the expansion–AD relationship. A path model showed that all variables explained unique variance in AD atrophy but were generally mediated through aging. This supports a systems-vulnerability model, where critical networks are subject to various negative impacts, aging in particular, rather than being selectively targeted in AD. An alternative approach is suggested, focused on the interplay of the phylogenetically old and preserved medial temporal lobe areas with more highly expanded association cortices governed by different principles of plasticity and stability. This is a pre-copyedited, author-produced PDF of an article accepted for publication in Cerebral Cortex following peer review. The version of record is available online at: http://dx.doi.org/10.1093/cercor/bhu055

• Amlien, Inge & Fjell, Anders Martin (2014). Diffusion tensor imaging of white matter degeneration in Alzheimer's disease and mild cognitive impairment. Neuroscience. ISSN 0306-4522. 276, s. 206–215. doi: 10.1016/j.neuroscience.2014.02.017. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Westlye, Lars Tjelta; Grydeland, Håkon; Amlien, Inge; Espeseth, Thomas & Reinvang, Ivar [Vis alle 9 forfattere av denne artikkelen] (2014). Accelerating cortical thinning: Unique to dementia or universal in aging? Cerebral Cortex. ISSN 1047-3211. 24(4), s. 919–934. doi: 10.1093/cercor/bhs379. Fulltekst i vitenarkiv
• Krogsrud, Stine Kleppe; Tamnes, Christian Krog; Fjell, Anders Martin; Amlien, Inge; Grydeland, Håkon & Sulutvedt, Unni [Vis alle 12 forfattere av denne artikkelen] (2014). Development of hippocampal subfield volumes from 4 to 22 years. Human Brain Mapping. ISSN 1065-9471. 35(11), s. 5646–5657. doi: 10.1002/hbm.22576. Fulltekst i vitenarkiv Vis sammendrag

  The hippocampus supports several important cognitive functions known to undergo substantial development during childhood and adolescence, e.g. encoding and consolidation of vivid personal memories. However, diverging developmental effects on hippocampal volume have been observed across studies. It is possible that the inconsistent findings may attribute to varying developmental processes and functions related to different hippocampal subregions. Most studies to date have measured global hippocampal volume. We aimed to explore early hippocampal development both globally and regionally within subfields. Using cross-sectional 1.5T MRI data from 244 healthy participants aged 4-22 years, we performed automated hippocampal segmentation of seven subfield volumes; cornu ammonis (CA) 1, CA2/3, CA4/dentate gyrus (DG), presubiculum, subiculum, fimbria and hippocampal fissure. For validation purposes, seven subjects were scanned at both 1.5T and 3T, and all subfields except fimbria showed strong correlations across field strengths. Effects of age, left and right hemisphere, sex and their interactions were explored. Nonparametric local smoothing models (smoothing spline) were used to depict age-trajectories. Results suggested non-linear age functions for most subfields where volume increases until 13-15 years, followed by little age-related changes during adolescence. Further, the results showed greater right than left hippocampal volumes that seemed to be augmenting in older age. Sex differences were also found for subfields; CA2/3, CA4/DG, presubiculum, subiculum and CA1, mainly driven by participants under 13 years. These results provide a detailed characterization of hippocampal subfield development from early childhood.

• Strømmen, Kenneth; Blakstad, Elin Wahl; Moltu, Sissel; Almaas, Astrid; Westerberg, Ane Cecilie & Amlien, Inge [Vis alle 16 forfattere av denne artikkelen] (2014). Enhanced Nutrient Supply to Very Low Birth Weight Infants is Associated with Improved White Matter Maturation and Head Growth. Neonatology. ISSN 1661-7800. 107(1), s. 68–75. doi: 10.1159/000368181. Fulltekst i vitenarkiv
• Amlien, Inge; Fjell, Anders Martin; Walhovd, Kristine B; Selnes, Per; Stenset, Vidar & Grambaite, Ramune [Vis alle 12 forfattere av denne artikkelen] (2013). Mild cognitive impairment: cerebrospinal fluid tau biomarker pathologic levels and longitudinal changes in white matter integrity. Radiology. ISSN 0033-8419. 266(1), s. 295–303. doi: 10.1148/radiol.12120319. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Westlye, Lars Tjelta; Grydeland, Håkon; Amlien, Inge; Espeseth, Thomas & Reinvang, Ivar [Vis alle 10 forfattere av denne artikkelen] (2013). Critical ages in the life course of the adult brain: nonlinear subcortical aging. Neurobiology of Aging. ISSN 0197-4580. 34(10), s. 2239–2247. doi: 10.1016/j.neurobiolaging.2013.04.006. Fulltekst i vitenarkiv Vis sammendrag

  Age-related changes in brain structure result from a complex interplay among various neurobiological processes, which may contribute to more complex trajectories than what can be described by simple linear or quadratic models. We used a nonparametric smoothing spline approach to delineate cross-sectionally estimated age trajectories of the volume of 17 neuroanatomic structures in 1100 healthy adults (18–94 years). Accelerated estimated decline in advanced age characterized some structures, for example hippocampus, but was not the norm. For most areas, 1 or 2 critical ages were identified, characterized by changes in the estimated rate of change. One-year follow-up data from 142 healthy older adults (60–91 years) confirmed the existence of estimated change from the cross-sectional analyses for all areas except 1 (caudate). The cross-sectional and the longitudinal analyses agreed well on the rank order of age effects on specific brain structures (Spearman ρ = 0.91). The main conclusions are that most brain structures do not follow a simple path throughout adult life and that accelerated decline in high age is not the norm of healthy brain aging.

• Zeller, Bernward; Tamnes, Christian Krog; Kanellopoulos, Adriani; Amlien, Inge; Andersson, Stein & Due-Tønnessen, Paulina [Vis alle 10 forfattere av denne artikkelen] (2013). Reduced Neuroanatomic Volumes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia. Journal of Clinical Oncology. ISSN 0732-183X. 31, s. 2078–2085. doi: 10.1200/JCO.2012.47.4031. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Westlye, Lars Tjelta; Grydeland, Håkon; Amlien, Inge; Espeseth, Thomas & Reinvang, Ivar [Vis alle 9 forfattere av denne artikkelen] (2012). Accelerating cortical thinning: Unique to dementia or universal in aging? Cerebral Cortex. ISSN 1047-3211. doi: 10.1093/cercor/bhs379. Fulltekst i vitenarkiv
• Walhovd, Kristine B; Watts, Richard; Amlien, Inge & Woodward, Lianne J. (2012). Neural Tract Development of Infants Born to Methadone-Maintained Mothers. Pediatric Neurology. ISSN 0887-8994. 47(1), s. 1–6. doi: 10.1016/j.pediatrneuro1.2012.04.008. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Westlye, Lars Tjelta; Amlien, Inge & Walhovd, Kristine B (2012). A multi-modal investigation of behavioral adjustment: Post-error slowing is associated with white matter characteristics. NeuroImage. ISSN 1053-8119. 61(1), s. 195–205. doi: 10.1016/j.neuroimage.2012.03.007. Fulltekst i vitenarkiv Vis sammendrag

  When people make mistakes in speeded cognitive tasks, their response time on the next trial will typically be slower. This is referred to as post-error slowing (PES), and is important for optimization of performance, but its exact function remains to be decided. However, although PES is relatively stable over time, we have almost no knowledge about how PES is affected by structural brain characteristics. The aim of this study was to test to what extent white matter (WM) macro- and microstructure can account for individual differences in PES. PES was calculated for 255 healthy participants who performed a modified version of the Eriksen flanker task and underwent structural magnetic resonance imaging and diffusion tensor imaging (DTI). PES was positively related to WM volume in the caudal and rostral middle and superior frontal, medial orbitofrontal gyri and pars orbitalis. DTI analyses with tract-based spatial statistics (TBSS) showed that mean diffusivity in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus and anterior thalamic radiation, as well as axial diffusivity in the corpus callosum, was negatively related to PES. Path analysis demonstrated that WM micro- and macrostructure were complementary in accounting for PES. It is concluded that individual differences in WM characteristics can partly explain why some people are better at adjusting their behavior in response to poor performance than others.

• Fjell, Anders Martin; Westlye, Lars Tjelta; Amlien, Inge & Walhovd, Kristine B (2011). Reduced white matter integrity is related to cognitive instability. Journal of Neuroscience. ISSN 0270-6474. 31(49), s. 18060–18072. doi: 10.1523/JNEUROSCI.4735-11.2011. Fulltekst i vitenarkiv Vis sammendrag

  Increased performance variability has been demonstrated in several groups and conditions, including aging and cognitive decline. Structural brain characteristics underlying this phenomenon have so far been elusive. However, there is reason to expect that dis-connectivity in associative pathways, whether caused by immature or degraded white matter (WM) tracts, will increase performance variability by neural noise. The aim of this study was to test whether the quality of WM, measured by diffusion tensor imaging, is related to performance variability in healthy adults. Intra-individual standard deviation of the reaction time (sdRT) across trials and median reaction time (mRT) from 270 participants were obtained from a speeded continuous performance task (Eriksen flanker task) with two conditions (congruent, incongruent). Tract-based spatial statistics was used to test the relationship with diffusion characteristics [fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), axial diffusion (AD)]. Robust relationships between sdRT and all diffusion measures were found in most WM areas, independently of mRT, age, and sex. The effects were anatomically more widespread in the congruent than the incongruent condition, covering almost 50% of the voxels for RD and MD, and >25% of the voxels for FA and AD. Partial betas were in the range 0.45- 0.55, and the strength of the relationships increased significantly with age. For mRT, the effects were smaller and unstable across condition. We concluded that performance variability is a likely consequence of individual differences in WM integrity, and that it is a promising behavioral correlate of individual differences in WM microstructure.

• Walhovd, Kristine B; Westlye, Lars Tjelta; Amlien, Inge; Espeseth, Thomas; Reinvang, Ivar & Raz, Naftali [Vis alle 12 forfattere av denne artikkelen] (2011). Consistent neuroanatomical age-related volume differences across multiple samples. Neurobiology of Aging. ISSN 0197-4580. 32(5), s. 916–932. doi: 10.1016/j.neurobiolaging.2009.05.013. Fulltekst i vitenarkiv Vis sammendrag

  Magnetic resonance imaging (MRI) is the principal method for studying structural age-related brain changes in vivo. However, previous research has yielded inconsistent results, precluding understanding of structural changes of the aging brain. This inconsistency is due to methodological differences and/or different aging patterns across samples. To overcome these problems, we tested age effects on 17 different neuroanatomical structures and total brain volume across five samples, of which one was split to further investigate consistency (883 participants). Widespread age-related volume differences were seen consistently across samples. In four of the five samples, all structures, except the brainstem, showed age-related volume differences. The strongest and most consistent effects were found for cerebral cortex, pallidum, putamen and accumbens volume. Total brain volume, cerebral white matter, caudate, hippocampus and the ventricles consistently showed non-linear age functions. Healthy aging appears associated with more widespread and consistent age-related neuroanatomical volume differences than previously believed.

• Fjell, Anders Martin; Amlien, Inge; Westlye, Lars Tjelta; Stenset, Vidar; Fladby, Tormod & Skinningsrud, Anders [Vis alle 9 forfattere av denne artikkelen] (2010). CSF biomarker pathology correlates with a medial temporo-parietal network affected by very mild to moderate Alzheimer's disease but not a fronto-striatal network affected by healthy aging. NeuroImage. ISSN 1053-8119. 49(2), s. 1820–1830. doi: 10.1016/j.neuroimage.2009.09.029. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Amlien, Inge; Westlye, Lars Tjelta & Walhovd, Kristine B (2009). Mini-Mental State Examination Is Sensitive to Brain Atrophy in Alzheimer's Disease. Dementia and Geriatric Cognitive Disorders. ISSN 1420-8008. 28(3), s. 252–258. doi: 10.1159/000241878. Fulltekst i vitenarkiv
• Walhovd, Kristine B; Fjell, Anders Martin; Amlien, Inge; Grambaite, Ramune; Stenset, Vidar Tveit Vasfaret & Bjørnerud, Atle [Vis alle 11 forfattere av denne artikkelen] (2009). Multimodal imaging in mild cognitive impairment: Metabolism, morphometry and diffusion of the temporal-parietal memory network. NeuroImage. ISSN 1053-8119. 45(1), s. 215–223. doi: 10.1016/j.neuroimage.2008.10.053. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Westlye, Lars Tjelta; Amlien, Inge; Espeseth, Thomas; Reinvang, Ivar & Raz, Naftali [Vis alle 12 forfattere av denne artikkelen] (2009). High Consistency of Regional Cortical Thinning in Aging across Multiple Samples. Cerebral Cortex. ISSN 1047-3211. 19(9), s. 2001–2012. doi: 10.1093/cercor/bhn232. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Westlye, Lars Tjelta; Amlien, Inge; Espeseth, Thomas; Reinvang, Ivar & Raz, Naftali [Vis alle 12 forfattere av denne artikkelen] (2009). Minute Effects of Sex on the Aging Brain: A Multisample Magnetic Resonance Imaging Study of Healthy Aging and Alzheimer's Disease. Journal of Neuroscience. ISSN 0270-6474. 29(27), s. 8774–8783. doi: 10.1523/JNEUROSCI.0115-09.2009. Fulltekst i vitenarkiv
• Fjell, Anders Martin; Walhovd, Kristine B; Amlien, Inge; Bjørnerud, Atle; Reinvang, Ivar & Gjerstad, Leif [Vis alle 13 forfattere av denne artikkelen] (2008). Morphometric changes in the episodic memory network and tau pathologic features correlate with memory performance in patients with mild cognitive impairment. American Journal of Neuroradiology. ISSN 0195-6108. 29, s. 1183–1189. doi: 10.3174/ajnr.A1059. Fulltekst i vitenarkiv
• Walhovd, Kristine B; Fjell, Anders Martin; Amlien, Inge; Grambaite, Ramune; Stenset, Vidar Tveit Vasfaret & Bjørnerud, Atle [Vis alle 11 forfattere av denne artikkelen] (2008). Multimodal imaging in mild cognitive impairment: Metabolism. morphometry and diffusion of the temporal-parietal memory network. NeuroImage. ISSN 1053-8119. doi: 10.1016/j.neuroimage.2008.10.053. Fulltekst i vitenarkiv

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• Zeller, Bernward; Tamnes, Christian Krog; Kanellopoulos, Adriani; Amlien, Inge Kasbohm; Andersson, Stein & Due-Tønnessen, Paulina [Vis alle 10 forfattere av denne artikkelen] (2014). Response to A.A.M. van der Veldt et al. Journal of Clinical Oncology. ISSN 0732-183X. 32(8), s. 852–853. doi: 10.1200/JCO.2013.52.5725. Fulltekst i vitenarkiv
• Strømmen, Kenneth; Blakstad, Elin Wahl; Moltu, Sissel; Almaas, Astrid; Amlien, Inge & Rønnestad, Arild Erlend [Vis alle 13 forfattere av denne artikkelen] (2013). Enhanced Nutrition to very low birth weight infants improves nutrition of cerebral connective tracts. Fulltekst i vitenarkiv
• Strømmen, Kenneth; Blakstad, Elin Wahl; Moltu, Sissel; Almaas, Astrid; Westerberg, Ane Cecilie & Amlien, Inge [Vis alle 16 forfattere av denne artikkelen] (2012). Enhanced Nutrition to Very Low Birth Weight Infants Improves Maturation of Cerebral Connective Tracts. Fulltekst i vitenarkiv
• Kanellopoulos, Adriani; Andersson, Stein; Zeller, Bernward; Fjell, Anders Martin; Walhovd, Kristine B & Westlye, Lars Tjelta [Vis alle 10 forfattere av denne artikkelen] (2012). Neurocognitive function is reduced in long-term survivors of acute lymphoblastic leukemia treated with chemotherapy only - but poorer performance is not associated with higher treatment burden. Pediatric Blood & Cancer. ISSN 1545-5009. 59(6), s. 1106–1106. Fulltekst i vitenarkiv

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