• Roe, James Michael; Vidal-Piñeiro, Didac; Sørensen, Øystein; Mowinckel, Athanasia Monika; Walhovd, Kristine B; Fjell, Anders Martin & Westerhausen, Rene (2021). Asymmetric thinning of the cerebral cortex across the adult lifespan is accelerated in Alzheimer’s Disease. Nature Communications.  ISSN 2041-1723. . doi: https://doi.org/10.1101/2020.06.18.158980 Vis sammendrag

  Normal aging and Alzheimer’s Disease (AD) are accompanied by large-scale alterations in brain organization that undermine brain function. Although hemispheric asymmetry is a global organizing feature of cortex thought to promote brain efficiency, current descriptions of cortical thinning in aging and AD have largely overlooked cortical asymmetry. Consequently, the foundational question of whether and where the cerebral hemispheres change at different rates in aging and AD remains open. First, applying vertex-wise data-driven clustering in a longitudinal discovery sample (aged 20-89; 2577 observations; 1851 longitudinal) we identified cortical regions exhibiting similar age-trajectories of asymmetry across the adult lifespan. Next, we sought replication in 4 independent longitudinal aging cohorts. We show that higher-order regions of cortex that exhibit pronounced asymmetry at age ~20 also show asymmetry change in aging. Results revealed that both leftward and rightward asymmetry is progressively lost on a similar time-scale across adult life. Hence, faster thinning of the (previously) thicker homotopic hemisphere is a feature of aging. This simple organizational principle showed high consistency across multiple aging cohorts in the Lifebrain consortium, and both the topological patterns and temporal dynamics of asymmetry-loss were markedly similar across replicating samples. Finally, we show that regions exhibiting gradual asymmetry-loss over healthy adult life exhibit faster asymmetry-change in AD. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.18.158980; this version posted June 20, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Overall, our results suggest a system-wide breakdown in the adaptive asymmetric organization of cortex across adult life which is further accelerated in AD, and may implicate thickness asymmetry as a viable marker for declining hemispheric specialization in aging and AD.

• Sørensen, Øystein; Brandmaier, Andreas M.; Macià, Dídac; Ebmeier, Klaus; Ghisletta, Paolo; Kievit, Rogier A.; Mowinckel, Athanasia Monika; Walhovd, Kristine B; Westerhausen, Rene & Fjell, Anders Martin (2021). Meta-analysis of generalized additive models in neuroimaging studies. NeuroImage.  ISSN 1053-8119.  224 . doi: 10.1016/j.neuroimage.2020.117416 Fulltekst i vitenarkiv.
• Sørensen, Øystein; Mowinckel, Athanasia Monika; Walhovd, Kristine B; Westerhausen, Rene & Fjell, Anders Martin (2021). Meta-analysis of generalized additive models in neuroimaging studies. NeuroImage.  ISSN 1053-8119. . doi: https://doi.org/10.1016/j.neuroimage.2020.117416 Vis sammendrag

  Analyzing data from multiple neuroimaging studies has great potential in terms of increasing statistical power, enabling detection of effects of smaller magnitude than would be possible when analyzing each study separately and also allowing to systematically investigate between-study differences. Restrictions due to privacy or proprietary data as well as more practical concerns can make it hard to share neuroimaging datasets, such that analyzing all data in a common location might be impractical or impossible. Meta-analytic methods provide a way to overcome this issue, by combining aggregated quantities like model parameters or risk ratios. Most meta-analytic tools focus on parametric statistical models, and methods for meta-analyzing semi-parametric models like generalized additive models have not been well developed. Parametric models are often not appropriate in neuroimaging, where for instance age-brain relationships may take forms that are difficult to accurately describe using such models. In this paper we introduce meta-GAM, a method for meta-analysis of generalized additive models which does not require individual participant data, and hence is suitable for increasing statistical power while upholding privacy and other regulatory concerns. We extend previous works by enabling the analysis of multiple model terms as well as multivariate smooth functions. In addition, we show how meta-analytic p-values can be computed for smooth terms. The proposed methods are shown to perform well in simulation experiments, and are demonstrated in a real data analysis on hippocampal volume and self-reported sleep quality data from the Lifebrain consortium. We argue that application of meta-GAM is especially beneficial in lifespan neuroscience and imaging genetics. The methods are implemented in an accompanying R package metagam, which is also demonstrated.

• Danielsen, Vilde Marie; Vidal-Piñeiro, Didac; Mowinckel, Athanasia Monika; Sederevicius, Donatas; Fjell, Anders Martin; Walhovd, Kristine B & Westerhausen, Rene (2020). Lifespan trajectories of relative corpus callosum thickness: Regional differences and cognitive relevance. Cortex.  ISSN 0010-9452.  130, s 127- 141 . doi: https://doi.org/10.1016/j.cortex.2020.05.020 Vis sammendrag

  The cerebral hemispheres are specialized for different cognitive functions and receive divergent information from the sensory organs, so that the interaction between the hemispheres is a crucial aspect of perception and cognition. At the same time, the major fiber tract responsible for this interaction, the corpus callosum, shows a structural development across the lifespan which is over-proportional. That is, compared to changes in overall forebrain volume, the corpus callosum shows an accentuated growth during childhood, adolescence, and early adulthood, as well as pronounced decline in older age. However, this over-proportionality of growth and decline along with potential consequences for cognition, have been largely overlooked in empirical research. In the present study we systematically address the proportionality of callosal development in a large mixed cross-sectional and longitudinal sample (1867 datasets from 1014 unique participants), covering the human lifespan (age range 4–93 years), and examine the cognitive consequences of the observed changes. Relative corpus callosum thickness was measured at 60 segments along the midsagittal surface, and lifespan trajectories were clustered to identify callosal subsections of comparable lifespan development. While confirming the expected inverted u-shaped lifespan trajectories, we also found substantial regional variation. Compared with anterior clusters, the most posterior sections exhibited an accentuated growth during development which extends well into the third decade of life, and a protracted decline in older age which is delayed by about 10 years (starting mid to late 50s). We further showed that the observed longitudinal changes in relative thickness of the mid splenium significantly mediates age-related changes in tests assessing verbal knowledge and non-verbal visual-spatial abilities across the lifespan. In summary, we demonstrate that analyzing the proportionality of callosal growth and decline offers valuable insight into lifespan development of structural connectivity between the hemispheres, and suggests consequences for the cognitive development of perception and cognition.

• Fjell, Anders Martin; Sørensen, Øystein; Amlien, Inge Kasbohm; Bartrés-Faz, David; Brandmaier, Andreas M.; Buchmann, Nikolaus; Demuth, Ilja; Drevon, Christian A; Düzel, Sandra; Ebmeier, Klaus; Ghisletta, Paolo; Idland, Ane-Victoria; Kietzmann, Tim C; Kievit, Rogier A.; Kühn, Simone; Lindenberger, Ulman; Magnussen, Fredrik; Macià Bros, Didac; Mowinckel, Athanasia Monika; Nyberg, Lars Erik; Sexton, Claire E; Sole-Padulles, Cristina; Pudas, Sara; Roe, James Michael; Sederevicius, Donatas; Suri, Sana; Vidal-Piñeiro, Didac; Wagner, Gerd; Watne, Leiv Otto; Westerhausen, Rene; Zsoldos, Eniko & Walhovd, Kristine B (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 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.

• Gorbach, Tetiana; Pudas, Sara; Bartrés-Faz, David; Brandmaier, Andreas M.; Düzel, Sandra; Henson, Rik; Idland, Ane-Victoria; Lindenberger, Ulman; Macià Bros, Didac; Mowinckel, Athanasia Monika; Solé-Padullés, Cristina; Sørensen, Øystein; Walhovd, Kristine B; Watne, Leiv Otto; Westerhausen, Rene; Fjell, Anders Martin & Nyberg, Lars Erik (2020). Longitudinal association between hippocampus atrophy and episodic‐memory decline in non‐demented APOE ε4 carriers. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring.  ISSN 2352-8729.  12(1) . doi: https://doi.org/10.1002/dad2.12110 Vis sammendrag

  Introduction The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic‐memory decline in non‐demented individuals remains unclear. Methods We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium. Results The change‐change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non‐carriers: N = 467, r = 0.073, P = .117). The linear relationship was significantly steeper for the carriers [t(629) = 2.4, P = .013]. A similar trend toward a stronger change‐change relation for carriers was seen in a subsample with more than two assessments. Discussion These findings provide evidence for a difference in hippocampus‐memory association between ε4 carriers and non‐carriers, thus highlighting how genetic factors modulate the translation of the AD‐related pathophysiological cascade into cognitive deficits.

• Ljøsne, Isabelle Sylvie Budin; Friedman, Barbara Bodorkos; Suri, Sana; Solé-Padullés, Cristina; Düzel, Sandra; Drevon, Christian A; Baaré, William F.C.; Mowinckel, Athanasia Monika; Zsoldos, Enikő; Madsen, Kathrine Skak; Carver, Rebecca Bruu; Ghisletta, Paolo; Arnesen, Mari; Bartrés Faz, David; Brandmaier, Andreas M.; Fjell, Anders Martin; Kvalbein, Aud; Henson, Richard N.; Kievit, Rogier A.; Nawijn, Laura; Pochet, Roland; Schnitzler, Alfons; Walhovd, Kristine B & Zasiekina, Larysa (2020). The global brain health survey: Development of a multi-language survey of public views on brain health. Frontiers In Public Health.  ISSN 2296-2565.  8:387, s 1- 13 . doi: 10.3389/fpubh.2020.00387 Fulltekst i vitenarkiv.
• Mowinckel, Athanasia Monika & Vidal-Piñeiro, Didac (2020). Visualization of Brain Statistics With R Packages ggseg and ggseg3d. Advances in Methods and Practices in Psychological Science (AMPPS).  ISSN 2515-2459. . doi: https://doi.org/10.1177/2515245920928009
• Vidal-Piñeiro, Didac; Parker, Nadine; Shin, Jean; French, Leon; Grydeland, Håkon; Jackowski, Andrea; Mowinckel, Athanasia Monika; Patel, Yash; Pausova, Zdenka; Salum, Giovanni; Sørensen, Øystein; Walhovd, Kristine B; Paus, Tomáš & Fjell, Anders Martin (2020). Cellular correlates of cortical thinning throughout the lifespan. Scientific Reports.  ISSN 2045-2322.  10(1), s 1- 14 . doi: 10.1038/s41598-020-78471-3 Fulltekst i vitenarkiv.
• Vidal-Piñeiro, Didac; Sneve, Markus Handal; Amlien, Inge Kasbohm; Grydeland, Håkon; Mowinckel, Athanasia Monika; Roe, James Michael; Sørensen, Øystein; Nyberg, Lars; Walhovd, Kristine B & Fjell, Anders Martin (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.
• Walhovd, Kristine B; Bråthen, Anne Cecilie Sjøli; Panizzon, Matthew S.; Mowinckel, Athanasia Monika; Sørensen, Øystein; de Lange, Ann-Marie Glasø; Krogsrud, Stine Kleppe; Håberg, Asta; Franz, Carol E.; Kremen, William S & Fjell, Anders Martin (2020). Within-session verbal learning slope is predictive of lifespan delayed recall, hippocampal volume, and memory training benefit, and is heritable. Scientific Reports.  ISSN 2045-2322.  10, s 1- 13 . doi: 10.1038/s41598-020-78225-1 Fulltekst i vitenarkiv. Vis sammendrag

  Memory performance results from plasticity, the ability to change with experience. We show that benefit from practice over a few trials, learning slope, is predictive of long-term recall and hippocampal volume across a broad age range and a long period of time, relates to memory training benefit, and is heritable. First, in a healthy lifespan sample (n = 1825, age 4–93 years), comprising 3483 occasions of combined magnetic resonance imaging (MRI) scans and memory tests over a period of up to 11 years, learning slope across 5 trials was uniquely related to performance on a delayed free recall test, as well as hippocampal volume, independent from first trial memory or total memory performance across the five learning trials. Second, learning slope was predictive of benefit from memory training across ten weeks in an experimental subsample of adults (n = 155). Finally, in an independent sample of male twins (n = 1240, age 51–50 years), learning slope showed significant heritability. Within-session learning slope may be a useful marker beyond performance per se, being heritable and having unique predictive value for long-term memory function, hippocampal volume and training benefit across the human lifespan.

• Walhovd, Kristine B; Fjell, Anders Martin; Sørensen, Øystein; Mowinckel, Athanasia Monika; Reinbold, Céline Sonja; Idland, Ane-Victoria; Watne, Leiv; Franke, Andre; Dobricic, Valerija; Kilpert, Fabian; Bertram, Lars & Wang, Yunpeng (2020). Genetic risk for Alzheimer disease predicts hippocampal volume through the human lifespan. Neurology: Genetics.  ISSN 2376-7839.  6(5) . doi: doi:10.1212/NXG.0000000000000506 Fulltekst i vitenarkiv.
• Fjell, Anders Martin; Chen, Chi-Hua Chen; Sederevicius, Donatas; Sneve, Markus Handal; Grydeland, Håkon; Krogsrud, Stine Kleppe; Amlien, Inge Kasbohm; Ferschmann, Lia; Ness, Hedda; Folvik, Line; Beck, Dani; Mowinckel, Athanasia Monika; Tamnes, Christian Krog; Westerhausen, René; Håberg, Asta; Dale, Anders M & Walhovd, Kristine B (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.
• Fjell, Anders Martin; Sneve, Markus Handal; Sederevicius, Donatas; Sørensen, Øystein; Krogsrud, Stine Kleppe; Mowinckel, Athanasia Monika & Walhovd, Kristine B (2019). Volumetric and microstructural regional changes of the hippocampus underlying development of recall performance after extended retention intervals. Developmental Cognitive Neuroscience.  ISSN 1878-9293.  40:100723, s 1- 12 . doi: 10.1016/j.dcn.2019.100723 Fulltekst i vitenarkiv.
• Fjell, Anders Martin; Sørensen, Øystein; Amlien, Inge Kasbohm; Bartrés-Faz, David; Bros, Didac Macia; Buchmann, Nikolaus; Demuth, Ilja; Drevon, Christian A; duzel, Sandra; Ebmeier, K P; Idland, Ane-Victoria; Kietzmann, Tim C; Kievit, Rogier; Kühn, Simone; Lindenberger, Ulman; Mowinckel, Athanasia Monika; Nyberg, Lars Erik; Price, Darren; Sexton, Claire; Sole-Padulles, Cristina; Pudas, Sara; Sederevicius, Donatas; Suri, Sana; Wagner, Gerd; Watne, Leiv Otto; Westerhausen, René; Zsoldos, Eniko & Walhovd, Kristine B (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.
• Vidal-Piñeiro, Didac; Sneve, Markus Handal; Nyberg, Lars; Mowinckel, Athanasia Monika; Sederevicius, Donatas; Walhovd, Kristine B & Fjell, Anders Martin (2019). Maintained Frontal Activity Underlies High Memory Function Over 8 Years in Aging. Cerebral Cortex.  ISSN 1047-3211.  29(7), s 3111- 3123 . doi: 10.1093/cercor/bhy177 Fulltekst i vitenarkiv.
• Mowinckel, Athanasia Monika; Alnæs, Dag; Pedersen, Mads Lund; Ziegler, Sigurd; Fredriksen, Mats; Kaufmann, Tobias; Sonuga-Barke, Edmund J.S.; Endestad, Tor; Westlye, Lars Tjelta & Biele, Guido (2017). Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD. NeuroImage: Clinical.  ISSN 2213-1582.  16, s 369- 382 . doi: 10.1016/j.nicl.2017.03.008 Fulltekst i vitenarkiv.
• Ziegler, Sigurd; Pedersen, Mads Lund; Mowinckel, Athanasia Monika & Biele, Guido (2016). Modelling ADHD: A review of ADHD theories through their predictions for computational models of decision-making and reinforcement learning. Neuroscience and Biobehavioral Reviews.  ISSN 0149-7634.  71, s 633- 656 . doi: 10.1016/j.neubiorev.2016.09.002
• Mowinckel, Athanasia Monika; Pedersen, Mads Lund; Eilertsen, Espen Moen & Biele, Guido (2015). A Meta-Analysis of Decision-Making and Attention in Adults With ADHD. Journal of Attention Disorders.  ISSN 1087-0547.  19(5), s 355- 367 . doi: 10.1177/1087054714558872 Vis sammendrag

  Abstract Objective: Deficient reward processing has gained attention as an important aspect of ADHD, but little is known about reward-based decision-making (DM) in adults with ADHD. This article summarizes research on DM in adult ADHD and contextualizes DM deficits by comparing them to attention deficits. Method: Meta-analytic methods were used to calculate average effect sizes for different DM domains and continuous performance task (CPT) measures. Results: None of the 59 included studies (DM: 12 studies; CPT: 43; both: 4) had indications of publication bias. DM and CPT measures showed robust, small to medium effects. Large effect sizes were found for a drift diffusion model analysis of the CPT. Conclusion: The results support the existence of DM deficits in adults with ADHD, which are of similar magnitude as attention deficits. These findings warrant further examination of DM in adults with ADHD to improve the understanding of underlying neurocognitive mechanisms

• Mowinckel, Athanasia Monika; Espeseth, Thomas & Westlye, Lars Tjelta (2012). Network-specific effects of age and in-scanner subject motion: A resting-state fMRI study of 238 healthy adults. NeuroImage.  ISSN 1053-8119.  63(3), s 1364- 1373 . doi: 10.1016/j.neuroimage.2012.08.004 Vis sammendrag

  Cognitive aging is accompanied by a range of structural and functional differences in the brain, even in the absence of neurodegenerative disease. Functional magnetic resonance imaging (fMRI) studies have reported increased bilateral activation during task performance in elderly participants compared to their younger counterparts, particularly in frontal regions. Alterations have also been observed in the functional architecture of the resting brain, suggesting that aging is associated with changes in the organization of the networks of the brain. However, previous studies have largely focused on the default mode network, and little is known about the effects of age on other resting state-networks (RSNs). The aim of the present study was to investigate age-differences in resting state functional connectivity (RSFC) using fMRI data obtained during rest from 238 healthy participants aged 21–80 years. Using independent component analysis (ICA) and dual-regression, the results revealed age-related increases in RSFC across a range of RSNs, including task-positive networks in frontal and parietal regions. In contrast, age-related reductions in the default mode network and occipital visual networks were observed. Furthermore, whereas the effects of age on the various RSNs were found independent of age-related decreases in gray matter volume, sex and subject motion, we report strong positive and widespread effects of estimated subject motion on the RSFC across RSNs. The results provide support for the notion of network-specific effects in aging, manifested as increased tonic activation of task-positive networks, supporting higher-order cognitive functions and cognitive control, along with reduced task-negative default mode network and sensory visual networks during rest. The present results also corroborate recent evidence of strong influence of subject motion on estimated functional connectivity measures and strongly suggest that studies using RSFC measures as imaging phenotypes should adjust for individual differences in in-scanner subject motion.

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• Mowinckel, Athanasia Monika (2016). Re: Kronisk utmattelsessyndrom og erfaring med Lightning Process. Tidsskrift for Den norske legeforening.  ISSN 0029-2001.  136(7), s 588

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