Dani Beck

• Beck, Dani; Carrick, Chloe; Aksnes, Eira Ranheim; MacSweeney, Niamh Anne; Westlye, Lars Tjelta & Fuhrmann, Delia [Show all 7 contributors for this article] (2026). Synchrony between brain age and internalising and externalising symptoms across adolescence. Communications Biology. doi: 10.1038/s42003-026-10722-x. Full text in Research Archive Show summary

  Abstract Adolescence is a period of rapid neurobiological and behavioural change, yet how brain maturation deviations relate to psychopathology remains unclear. Here, we show, using data from the Adolescent Brain Cognitive Development Study, that deviations in brain age are coupled with internalising and externalising symptom development across adolescence. Combining multimodal brain age prediction across four waves (ages ~8.3–17.5) with bivariate latent growth curve models of ten symptom waves, we found coordinated nonlinear development between brain maturation and symptoms: adolescents whose brains increasingly diverged from age-expected maturation showed increasing symptoms. Effects were most consistent for internalising symptoms in females ( r  = 0.15–0.23) and broader for externalising symptoms in both sexes ( r  = 0.15–0.32); intercept-level associations were weaker ( r  = 0.08–0.09). Sex differences were not robust after correction. Vulnerability to adolescent psychopathology appears more closely linked to changes in brain maturational tempo than to fixed differences in brain age.

• Beck, Dani; Westlye, Lars Tjelta & Tamnes, Christian Krog (2026). Cardiometabolic Risk and Structural Brain Development in a Large Community-Based US Cohort. Human Brain Mapping. ISSN 1065-9471. 47(8). doi: 10.1002/hbm.70575. Full text in Research Archive
• Brieant, Alexis; Chaku, Natasha; Beck, Dani; MacSweeney, Niamh Anne; Rakesh, Divyangana & Tamnes, Christian Krog (2026). Timing and tempo of puberty and neurodevelopment following adversity: A registered report. Developmental Cognitive Neuroscience. ISSN 1878-9293. 79. doi: 10.1016/j.dcn.2026.101738. Full text in Research Archive
• Gurholt, Tiril Pedersen; Beck, Dani; Voldsbekk, Irene; Parker, Nadine; Askeland-Gjerde, Daniel E. & Lange, Ann-Marie Glasø de [Show all 13 contributors for this article] (2026). Linking obesity with white matter microstructure highlights the importance of brainstem tracts and sex differences. Brain Communications. 8(1), p. 1–15. doi: 10.1093/braincomms/fcag026. Full text in Research Archive Show summary

  While obesity (body mass index ≥ 30) has been consistently associated with white matter diffusion magnetic resonance imaging (MRI) phenotypes, the contributions of common obesity phenotypes on various diffusion metrics, and the moderating effects of sex and age, require further clarification. This study aims to elucidate these body–brain connections to enhance our understanding of the comorbid link between obesity and body anthropometrics and the brain using a large-scale dataset. We analysed cross-sectional data from 40 040 participants from the UK Biobank (52.2% female; ages 44–83 years) using multiple linear regression to evaluate how obesity and body anthropometrics relate to regional white matter diffusion tensor imaging metrics (fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity). We also examined interactions with age and sex. Our analyses revealed significant associations between individual obesity phenotypes (i.e. obesity and body anthropometrics) and diffusion tensor imaging metrics of small effects, with partial correlation coefficient |r| effect sizes ranging from 0.02 to 0.20 for most regions of interest with largest effects in brainstem tracts. We observed more widespread sex-by-obesity phenotypes than age-by-obesity phenotypes interaction effects on diffusion tensor imaging metrics. Our results link obesity and body anthropometrics with white matter phenotypes and suggests that shared body fat-related pathways link physical and brain health that may vary based on sex and age. Understanding these body–brain relationships, and the role of age and sex, could enhance the development and evaluation of targeted, personalized, treatment strategies for brain disorders that co-occur with obesity, although further longitudinal and intervention studies are needed to map the causal dynamics of these associations.

• Karl, Valerie; Bjørndal, Ludvig Daae; Aksnes, Eira Ranheim; Teulings, Irene Johanna Elisabeth; MacSweeney, Niamh Anne & Beck, Dani [Show all 9 contributors for this article] (2026). Symptom-specific links between internalizing problems and functional connectivity in adolescents: a network analysis. European Child and Adolescent Psychiatry. ISSN 1018-8827. doi: 10.1007/s00787-026-02989-6. Full text in Research Archive
• Slapø, Nora Berz; Jørgensen, Kjetil Nordbø; Nerland, Stener; Mørch-Johnsen, Lynn Egeland; Pettersen, Johanne Hagen & Roelfs, Daniel [Show all 23 contributors for this article] (2026). Relationship between N100 amplitude and T1w/T2w-ratio in the auditory cortex in schizophrenia spectrum disorders. Schizophrenia. doi: 10.1038/s41537-025-00715-w. Full text in Research Archive Show summary

  Schizophrenia spectrum disorders (SCZspect) are associated with altered function in the auditory cortex (AC), indicated by lower N100 amplitude of the auditory evoked potential (AEP). Although the neural substrate behind lower N100 amplitude remains elusive, myelination in the AC may play a role. This study compared N100 amplitude and magnetic resonance imaging (MRI) T1 weighted and T2 weighted ratio (T1w/T2w-ratio), as a proxy of myelination, in the primary AC (AC1) and secondary AC (AC2) between SCZspect (n = 33, 48% women) and healthy controls (HC, n = 144, 49% women). We also examined the associations between N100 amplitude and T1w/T2w-ratios across groups. We finally explored N100 amplitude and T1w/T2w-ratios and the N100-T1w/T2w-ratio associations between male and female SCZspect and HC. N100 amplitude was significantly lower in male SCZspect compared to male HC (p = 0.01) and nominally lower in SCZspect compared to HC (p = 0.03). However, T1w/T2w-ratios in AC1/AC2 did not differ between groups, and no association was found between N100 amplitude and T1w/T2w-ratio in either group. These findings suggest that sex-specific effects should be considered in SCZspect neurophysiology research. Our results do not support the hypothesis of an association between lower N100 amplitude and lower T1w/T2w-ratio in the AC1/AC2 in SCZspect. More precise assessments of intracortical myelin are needed to understand the relationship between N100 amplitude and cortical myelination in the AC in SCZspect and in healthy controls.

• Beck, Dani; Westlye, Lars Tjelta & Tamnes, Christian Krog (2025). Cardiometabolic risk and structural brain development in a large community-based U.S. cohort. medRxiv. doi: 10.1101/2025.10.23.25338683. Full text in Research Archive Show summary

  Abstract Objective Cardiometabolic risk factors are already detectable in childhood and adolescence, but their relations to the developing brain remains unclear. The current study tested whether poorer cardiometabolic health is associated with brain structure and microstructure development in 10–17-year-old youth. Methods Using the Adolescent Brain Cognitive Development Study, we analysed data from 3,527 participants with 4,433 observations across three waves. We related anthropometric (body-mass index, waist circumference), cardiovascular (systolic and diastolic blood pressure, resting heart rate), and metabolic (haemoglobin A1c, high-density lipoprotein cholesterol) indices to global cortical thickness and surface area, and to white matter fractional anisotropy and mean diffusivity. Bayesian multilevel models were fitted to estimate main and time-interaction effects, and sensitivity analyses tested within-person change, prospective prediction to the next wave, and replaced chronological age with puberty status. Results Higher body-mass index was associated with thinner cortex, and higher resting heart rate was associated with higher mean diffusivity, an association that strengthened over time. Other cardiometabolic measures favoured the null, and sensitivity analyses provided little evidence that wave-to-wave changes in cardiometabolic health tracked contemporaneous brain change or predicted subsequent brain structure. Conclusion Across late childhood and adolescence, brain architecture appears largely insensitive to variation in cardiometabolic risk indices.

• Tamnes, Christian K.; Bekkhus, Mona; Eilertsen, Maja; Nes, Ragnhild Bang; Prydz, Monica Beer & Ystrom, Eivind [Show all 63 contributors for this article] (2025). The nature of the relation between mental well-being and ill-being. Nature Human Behaviour. 9(12), p. 2431–2440. doi: 10.1038/s41562-025-02319-x. Full text in Research Archive
• Aksnes, Eira R.; Birkeland, Marianne Skogbrott; Ebrahimi, Omid V.; Bekkhus, Mona; Ferschmann, Lia & Beck, Dani [Show all 12 contributors for this article] (2025). Developmental dynamics of symptoms of emotional problems in childhood and adolescence: A longitudinal network analysis. JCPP Advances. doi: 10.1002/jcv2.70079. Full text in Research Archive Show summary

  Abstract Background Epidemiological studies document increasing incident rates of mental disorders across childhood and adolescence, with mood and anxiety disorders particularly increasing among adolescent females. Research also indicates that these emotional problems have become more prevalent in recent decades. Yet, there is still a lack of understanding of the interrelated development of distinct emotional symptoms from childhood to adolescence. Methods Here, we investigate and compare symptom dynamics in males and females. To accomplish this, we leveraged longitudinal data from the Avon Longitudinal Study of Parents and Children study ( N  = 11,120, 50.1% males at baseline). We used five items ( worries , unhappy , nervous , fearful , somatic complaints ) derived from the parent‐reported Strength and Difficulties Questionnaire emotional problems scale, measured at up to seven timepoints (mean age = 9.52, range = 4.0–18.3 years old). We estimated a panel Graphical Vector Autoregressive network model (GVAR) and statistically compared the networks of males and females. Results The temporal network revealed largely reciprocal associations among symptoms, with the strongest edges between fearful–nervous and unhappy–worries ( β  = 0.04–0.06). The contemporaneous and between‐person networks showed similar structures, although the between‐person network exhibited fewer but stronger associations, reflecting more stable individual differences. Somatic complaints were weakly connected in the temporal network but more strongly associated in contemporaneous and between‐person networks. Network invariance testing indicated no significant sex differences in average network structure. Conclusion The study delineates the developmental dynamics of emotional symptoms across childhood and adolescence, highlighting bidirectional influences between core symptoms of depression and anxiety, but did not find support for sex differences in their developmental interrelatedness.

• Lindseth, Linn Renate Sjøveian; Beck, Dani; Westlye, Lars Tjelta; Tamnes, Christian K. & Fridman, Linn Bonaventure (2025). Linking pregnancy- and birth-related risk factors to a multivariate fusion of child cortical structure. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 122(25). doi: 10.1073/pnas.2422281122. Full text in Research Archive Show summary

  Pregnancy- and birth-related factors affect offspring brain development, emphasizing the importance of early life exposures. While most previous studies have focused on a few variables in isolation, here we investigated associations between a broad range of pregnancy- and birth-related variables and multivariate cortical brain MRI features. Our sample consisted of 8,396 children aged 8.9 to 11.1 y from the Adolescent Brain Cognitive Development Study. Through multiple correspondence analysis and factor analysis of mixed data, we distilled numerous pregnancy and birth variables into four overarching dimensions; maternal pregnancy complications, maternal substance use, low birth weight and prematurity, and newborn birth complications. Vertex-wise measures of cortical thickness (CT), surface area (SA), and curvature were fused using linked independent component analysis. Linear mixed-effects models showed that maternal pregnancy complications and low birth weight and prematurity were associated with smaller global SA. Additionally, low birth weight and prematurity was associated with complex regional cortical patterns reflecting bidirectional variations in both SA and CT. Newborn birth complications showed multivariate patterns reflecting smaller occipital- and larger temporal area, bidirectional frontal area variations, and reduced CT across the cortex. Maternal substance use showed no associations with child cortical structure. By employing a multifactorial and multivariate morphometric fusion approach, we connected complications during pregnancy and fetal size and prematurity to global SA and specific regional signatures across child cortical MRI features.

• Whitmore, Lucy & Beck, Dani (2025). Current challenges and future directions for brain age prediction in children and adolescents. Nature Communications. 16(1). doi: 10.1038/s41467-025-63222-7. Full text in Research Archive Show summary

  Abstract Advancements in computational techniques have enhanced our understanding of human brain development, particularly through high-dimensional data from magnetic resonance imaging (MRI). One notable approach is the brain-age prediction framework, which predicts biological age from neuroimaging data and calculates the brain age gap (BAG), a marker of deviation from chronological age. Most commonly applied to adult samples, this approach is now increasingly used in children and adolescents. However, several considerations must be taken into account when applying brain-age prediction in youth. In this Perspective, we outline important challenges and provide recommendations for researchers as well as future directions for the field.

• MacSweeney, Niamh; Beck, Dani; Whitmore, Lucy; Mills, Kathryn L.; Westlye, Lars Tjelta & Soest, Tilmann Martin von [Show all 8 contributors for this article] (2025). Multimodal Brain Age Indicators of Internalizing Problems in Early Adolescence: A Longitudinal Investigation. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. ISSN 2451-9022. doi: 10.1016/j.bpsc.2024.11.003. Full text in Research Archive
• Naseri, Nasimeh; Beck, Dani; Ferschmann, Lia; Aksnes, Eira Ranheim; Havdahl, Alexandra & Jalbrzikowski, Maria [Show all 8 contributors for this article] (2025). MRI-based cortical gray/white matter contrast in young adults who endorse psychotic experiences or are at genetic risk for psychosis. Psychiatry Research : Neuroimaging. ISSN 0925-4927. 349. doi: 10.1016/j.pscychresns.2025.111981. Full text in Research Archive
• Tamnes, Christian K.; Bekkhus, Mona; Eilertsen, Maja; Nes, Ragnhild B.; Prydz, Monica Beer & Ystrom, Eivind [Show all 63 contributors for this article] (2024). The nature of the relation between mental illbeing and wellbeing. Nature Human Behaviour. 9, p. 2431–2440. doi: 10.31234/osf.io/9jk2x. Full text in Research Archive Show summary

  Research on mental health has traditionally separated the study of illbeing—disorder and problems—and wellbeing—life satisfaction and positive affect. While previous reviews of studies primarily employing self-report scales indicate that illbeing and wellbeing are distinct yet interconnected constructs, a deeper examination of their relationship is lacking. This perspective article from the PROMENTA Research Center offers a review and synthesis of findings on the joint and distinct nature of illbeing and wellbeing across multiple levels of analysis. Adopting an interdisciplinary approach, we integrate genetic, biological, developmental, psychosocial, societal, cultural, and intervention-based perspectives. Our review reveals substantial genetic overlap and some similar biological underpinnings for illbeing and wellbeing. In contrast, environmental factors and societal changes often have divergent impacts. We propose that future research should systematically assess both positive and negative aspects of mental health to discern their shared and unique determinants, predictors, mechanisms, and consequences.

• Karl, Valerie Christine; Beck, Dani; Eilertsen, Espen Moen; Morawetz, Carmen; Wiker, Thea & Aksnes, Eira Ranheim [Show all 15 contributors for this article] (2024). Associations between parental psychopathology and youth functional emotion regulation brain networks. Developmental Cognitive Neuroscience. ISSN 1878-9293. 70. doi: 10.1016/j.dcn.2024.101476. Full text in Research Archive Show summary

  Parental mental health is associated with children’s emotion regulation (ER) and risk for psychopathology. The relationship between parental psychopathology and children’s functional ER networks and whether connectivity patterns mediate the relationship between parent and youth psychopathology remains unexplored. Using resting-state functional magnetic resonance imaging data from the Adolescent Brain Cognitive Development Study (N = 4202, mean age = 10.0) and a multilevel approach, we analyzed the relationship between self-reported parental psychopathology and their offsprings’ connectivity of four ER networks, as well as associations with self-reported youth psychopathology at a 3-year follow-up. Parental internalizing and total problems were associated with 1) higher connectivity between a subcortical-cortical integrative and ventrolateral prefrontal cortical (PFC) network, 2) lower connectivity between dorsolateral and ventrolateral PFC networks involved in cognitive aspects of ER, and 3) lower connectivity within a subcortical ER network (β = −0.05–0.04). Parental externalizing and total problems were associated with lower connectivity within the integrative network (βext = −0.05; βtot = −0.04). Mediation analyses yielded direct effects of parental to youth psychopathology, but no mediation effect of ER network connectivity. Overall, our results show that ER network connectivity in youth is related to parental psychopathology, yet do not explain intergenerational transmission of psychopathology.

• Nerland, Stener; Slapø, Nora Berz; Barth, Claudia; Mørch-Johnsen, Lynn Egeland; Jørgensen, Kjetil Nordbø & Beck, Dani [Show all 13 contributors for this article] (2024). Current Auditory Hallucinations Are Not Associated With Specific White Matter Diffusion Alterations in Schizophrenia. Schizophrenia Bulletin Open. 5(1). doi: 10.1093/schizbullopen/sgae008. Full text in Research Archive Show summary

  Background and Hypothesis Studies have linked auditory hallucinations (AH) in schizophrenia spectrum disorders (SCZ) to altered cerebral white matter microstructure within the language and auditory processing circuitry (LAPC). However, the specificity to the LAPC remains unclear. Here, we investigated the relationship between AH and DTI among patients with SCZ using diffusion tensor imaging (DTI). Study Design We included patients with SCZ with (AH+; n = 59) and without (AH−; n = 81) current AH, and 140 age- and sex-matched controls. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were extracted from 39 fiber tracts. We used principal component analysis (PCA) to identify general factors of variation across fiber tracts and DTI metrics. Regression models adjusted for sex, age, and age2 were used to compare tract-wise DTI metrics and PCA factors between AH+, AH−, and healthy controls and to assess associations with clinical characteristics. Study Results Widespread differences relative to controls were observed for MD and RD in patients without current AH. Only limited differences in 2 fiber tracts were observed between AH+ and controls. Unimodal PCA factors based on MD, RD, and AD, as well as multimodal PCA factors, differed significantly relative to controls for AH−, but not AH+. We did not find any significant associations between PCA factors and clinical characteristics. Conclusions Contrary to previous studies, DTI metrics differed mainly in patients without current AH compared to controls, indicating a widespread neuroanatomical distribution. This challenges the notion that altered DTI metrics within the LAPC is a specific feature underlying AH.

• Ferschmann, Lia; Grydeland, Håkon; MacSweeney, Niamh; Beck, Dani; Bos, Marieke G.N. & Norbom, Linn Bonaventure [Show all 12 contributors for this article] (2024). The importance of timing of socioeconomic disadvantage throughout development for depressive symptoms and brain structure. Developmental Cognitive Neuroscience. ISSN 1878-9293. 69. doi: 10.1016/j.dcn.2024.101449. Full text in Research Archive Show summary

  Prior studies have reported associations between socioeconomic disadvantage, brain structure and mental health outcomes, but the timing of these relations is not well understood. Using prospective longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC), this preregistered study examined whether socioeconomic disadvantage related differentially to depressive symptoms (n=3012–3530) and cortical and subcortical structures (n=460–733) in emerging adults, depending on the timing of exposure to socioeconomic disadvantage. Family income in early childhood and own income measured concurrently were both significantly related to depressive symptoms in emerging adulthood. Similar results were observed for perceived financial strain. In contrast, only family income in early childhood was associated with brain structure in emerging adulthood, with positive associations with intracranial volume and total and regional cortical surface area. The findings suggest that both objective and subjective aspects of one’s financial standing throughout development relate to depressive symptoms in adulthood, but that specifically early life family income is related to brain structural features in emerging adulthood. This suggests that associations between socioeconomic disadvantage and brain structure originate early in neurodevelopment, highlighting the role of timing of socioeconomic disadvantage.

• Beck, Dani; Whitmore, Lucy; MacSweeney, Niamh; Brieant, Alexis; Karl, Valerie & Lange, Ann-Marie Glasø de [Show all 9 contributors for this article] (2024). Dimensions of Early-Life Adversity Are Differentially Associated With Patterns of Delayed and Accelerated Brain Maturation. Biological Psychiatry. ISSN 0006-3223. 97(1), p. 64–72. doi: 10.1016/j.biopsych.2024.07.019. Full text in Research Archive
• Beck, Dani; Lange, Ann-Marie Glasø de; Gurholt, Tiril Pedersen; Voldsbekk, Irene; Maximov, Ivan & Subramaniapillai, Sivaniya [Show all 19 contributors for this article] (2024). Dissecting unique and common variance across body and brain health indicators using age prediction. Human Brain Mapping. ISSN 1065-9471. 45(6). doi: 10.1002/hbm.26685. Full text in Research Archive Show summary

  Ageing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses inter-individual heterogeneity in the multisystem ageing process. Using machine-learning regression models on the UK Biobank data set (N = 32,593, age range 44.6–82.3, mean age 64.1 years), we first estimated tissue-specific brain age for white and gray matter based on diffusion and T1-weighted magnetic resonance imaging (MRI) data, respectively. Next, bodily health traits, including cardiometabolic, anthropometric, and body composition measures of adipose and muscle tissue from bioimpedance and body MRI, were combined to predict ‘body age’. The results showed that the body age model demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. The correlation between body age and brain age predictions was 0.62 for the T1 and 0.64 for the diffusion-based model, indicating a degree of unique variance in brain and bodily ageing processes. Bayesian multilevel modelling carried out to quantify the associations between health traits and predicted age discrepancies showed that higher systolic blood pressure and higher muscle-fat infiltration were related to older-appearing body age compared to brain age. Conversely, higher hand-grip strength and muscle volume were related to a younger-appearing body age. Our findings corroborate the common notion of a close connection between somatic and brain health. However, they also suggest that health traits may differentially influence age predictions beyond what is captured by the brain imaging data, potentially contributing to heterogeneous ageing rates across biological systems and individuals.

• Norbom, Linn Bonaventure; Rokicki, Jaroslav; Eilertsen, Espen Moen; Wiker, Thea; Hanson, Jamie & Dahl, Andreas [Show all 13 contributors for this article] (2024). Parental education and income are linked to offspring cortical brain structure and psychopathology at 9–11 years. JCPP Advances. 4(1). doi: 10.1002/jcv2.12220. Full text in Research Archive Show summary

  Background A child's socioeconomic environment can shape central aspects of their life, including vulnerability to mental disorders. Negative environmental influences in youth may interfere with the extensive and dynamic brain development occurring at this time. Indeed, there are numerous yet diverging reports of associations between parental socioeconomic status (SES) and child cortical brain morphometry. Most of these studies have used single metric- or unimodal analyses of standard cortical morphometry that downplay the probable scenario where numerous biological pathways in sum account for SES-related cortical differences in youth. Methods To comprehensively capture such variability, using data from 9758 children aged 8.9–11.1 years from the ABCD Study®, we employed linked independent component analysis (LICA) and fused vertex-wise cortical thickness, surface area, curvature and grey-/white-matter contrast (GWC). LICA revealed 70 uni- and multimodal components. We then assessed the linear relationships between parental education, parental income and each of the cortical components, controlling for age, sex, genetic ancestry, and family relatedness. We also assessed whether cortical structure moderated the negative relationships between parental SES and child general psychopathology. Results Parental education and income were both associated with larger surface area and higher GWC globally, in addition to local increases in surface area and to a lesser extent bidirectional GWC and cortical thickness patterns. The negative relation between parental income and child psychopathology were attenuated in children with a multimodal pattern of larger frontal- and smaller occipital surface area, and lower medial occipital thickness and GWC. Conclusion Structural brain MRI is sensitive to SES diversity in childhood, with GWC emerging as a particularly relevant marker together with surface area. In low-income families, having a more developed cortex across MRI metrics, appears beneficial for mental health.

• Korbmacher, Max; Meer, Dennis van der; Beck, Dani; Askeland-Gjerde, Daniel E.; Eikefjord, Eli Nina Hølleland & Lundervold, Arvid [Show all 9 contributors for this article] (2024). Distinct Longitudinal Brain White Matter Microstructure Changes and Associated Polygenic Risk of Common Psychiatric Disorders and Alzheimer's Disease in the UK Biobank. Biological Psychiatry: Global Open Science. 4(4). doi: 10.1016/j.bpsgos.2024.100323. Full text in Research Archive Show summary

  Background: During the course of adulthood and aging, white matter (WM) structure and organization are characterized by slow degradation processes such as demyelination and shrinkage. An acceleration of such aging processes has been linked to the development of a range of diseases. Thus, an accurate description of healthy brain maturation, particularly in terms of WM features, is fundamental to the understanding of aging. Methods: We used longitudinal diffusion magnetic resonance imaging to provide an overview of WM changes at different spatial and temporal scales in the UK Biobank (UKB) (n = 2678; agescan 1 = 62.38 ± 7.23 years; agescan 2 = 64.81 ± 7.1 years). To examine the genetic overlap between WM structure and common clinical conditions, we tested the associations between WM structure and polygenic risk scores for the most common neurodegenerative disorder, Alzheimer’s disease, and common psychiatric disorders (unipolar and bipolar depression, anxiety, obsessive-compulsive disorder, autism, schizophrenia, attention-deficit/hyperactivity disorder) in longitudinal (n = 2329) and cross-sectional (n = 31,056) UKB validation data. Results: Our findings indicate spatially distributed WM changes across the brain, as well as distributed associations of polygenic risk scores with WM. Importantly, brain longitudinal changes reflected genetic risk for disorder development better than the utilized cross-sectional measures, with regional differences giving more specific insights into gene-brain change associations than global averages. Conclusions: We extend recent findings by providing a detailed overview of WM microstructure degeneration on different spatial levels, helping to understand fundamental brain aging processes. Further longitudinal research is warranted to examine aging-related gene-brain associations.

• Korbmacher, Max; Meer, Dennis van der; Beck, Dani; Lange, Ann-Marie Glasø de; Eikefjord, Eli Nina Hølleland & Lundervold, Arvid [Show all 9 contributors for this article] (2024). Brain asymmetries from mid- to late life and hemispheric brain age. Nature Communications. 15. doi: 10.1038/s41467-024-45282-3. Full text in Research Archive Show summary

  The human brain demonstrates structural and functional asymmetries which have implications for ageing and mental and neurological disease development. We used a set of magnetic resonance imaging (MRI) metrics derived from structural and diffusion MRI data in N=48,040 UK Biobank participants to evaluate age-related differences in brain asymmetry. Most regional grey and white matter metrics presented asymmetry, which were higher later in life. Informed by these results, we conducted hemispheric brain age (HBA) predictions from left/right multimodal MRI metrics. HBA was concordant to conventional brain age predictions, using metrics from both hemispheres, but offers a supplemental general marker of brain asymmetry when setting left/right HBA into relationship with each other. In contrast to WM brain asymmetries, left/right discrepancies in HBA are lower at higher ages. Our findings outline various sex-specific differences, particularly important for brain age estimates, and the value of further investigating the role of brain asymmetries in brain ageing and disease development.

• Karl, Valerie Christine; Engen, Haakon Gabrielsen; Beck, Dani; Norbom, Linn Bonaventure; Ferschmann, Lia & Aksnes, Eira Ranheim [Show all 13 contributors for this article] (2024). The role of functional emotion circuits in distinct dimensions of psychopathology in youth. Translational Psychiatry. 14(1). doi: 10.1038/s41398-024-03036-1. Full text in Research Archive Show summary

  Several mental disorders emerge during childhood or adolescence and are often characterized by socioemotional difficulties, including alterations in emotion perception. Emotional facial expressions are processed in discrete functional brain modules whose connectivity patterns encode emotion categories, but the involvement of these neural circuits in psychopathology in youth is poorly understood. This study examined the associations between activation and functional connectivity patterns in emotion circuits and psychopathology during development. We used task-based fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC, N = 1221, 8–23 years) and conducted generalized psycho-physiological interaction (gPPI) analyses. Measures of psychopathology were derived from an independent component analysis of questionnaire data. The results showed positive associations between identifying fearful, sad, and angry faces and depressive symptoms, and a negative relationship between sadness recognition and positive psychosis symptoms. We found a positive main effect of depressive symptoms on BOLD activation in regions overlapping with the default mode network, while individuals reporting higher levels of norm-violating behavior exhibited emotion-specific lower functional connectivity within regions of the salience network and between modules that overlapped with the salience and default mode network. Our findings illustrate the relevance of functional connectivity patterns underlying emotion processing for behavioral problems in children and adolescents.

• Korbmacher, Max; Lange, Ann-Marie Glasø de; Meer, Dennis van der; Beck, Dani; Eikefjord, Eli Nina & Lundervold, Arvid [Show all 9 contributors for this article] (2023). Brain‐wide associations between white matter and age highlight the role of fornix microstructure in brain ageing. Human Brain Mapping. ISSN 1065-9471. 44, p. 4101–4119. doi: 10.1002/hbm.26333. Full text in Research Archive Show summary

  Unveiling the details of white matter (WM) maturation throughout ageing is a fundamental question for understanding the ageing brain. In an extensive comparison of brain age predictions and age-associations of WM features from different diffusion approaches, we analyzed UK Biobank diffusion magnetic resonance imaging (dMRI) data across midlife and older age (N = 35,749, 44.6–82.8 years of age). Conventional and advanced dMRI approaches were consistent in predicting brain age. WM-age associations indicate a steady microstructure degeneration with increasing age from midlife to older ages. Brain age was estimated best when combining diffusion approaches, showing different aspects of WM contributing to brain age. Fornix was found as the central region for brain age predictions across diffusion approaches in complement to forceps minor as another important region. These regions exhibited a general pattern of positive associations with age for intra axonal water fractions, axial, radial diffusivities, and negative relationships with age for mean diffusivities, fractional anisotropy, kurtosis. We encourage the application of multiple dMRI approaches for detailed insights into WM, and the further investigation of fornix and forceps as potential biomarkers of brain age and ageing.

• Wiker, Thea; Pedersen, Mads Lund; Ferschmann, Lia; Beck, Dani; Norbom, Linn Christin Bonaventure & Dahl, Andreas [Show all 13 contributors for this article] (2023). Assessing the Longitudinal Associations Between Decision-Making Processes and Attention Problems in Early Adolescence. Research on Child and Adolescent Psychopathology. ISSN 2730-7166. 52, p. 803–817. doi: 10.1007/s10802-023-01148-8. Full text in Research Archive Show summary

  Abstract Cognitive functions and psychopathology develop in parallel in childhood and adolescence, but the temporal dynamics of their associations are poorly understood. The present study sought to elucidate the intertwined development of decision-making processes and attention problems using longitudinal data from late childhood (9–10 years) to mid-adolescence (11–13 years) from the Adolescent Brain Cognitive Development (ABCD) Study (n = 8918). We utilised hierarchical drift-diffusion modelling of behavioural data from the stop-signal task, parent-reported attention problems from the Child Behavior Checklist (CBCL), and multigroup univariate and bivariate latent change score models. The results showed faster drift rate was associated with lower levels of inattention at baseline, as well as a greater reduction of inattention over time. Moreover, baseline drift rate negatively predicted change in attention problems in females, and baseline attention problems negatively predicted change in drift rate. Neither response caution (decision threshold) nor encoding- and responding processes (non-decision time) were significantly associated with attention problems. There were no significant sex differences in the associations between decision-making processes and attention problems. The study supports previous findings of reduced evidence accumulation in attention problems and additionally shows that development of this aspect of decision-making plays a role in developmental changes in attention problems in youth.

• Wierenga, Lara M.; Ruigrok, Amber; Aksnes, Eira Ranheim; Barth, Claudia; Beck, Dani & Burke, Sarah M. [Show all 21 contributors for this article] (2023). Recommendations for a Better Understanding of Sex and Gender in the Neuroscience of Mental Health. Biological Psychiatry: Global Open Science. 4(2). doi: 10.1016/j.bpsgos.2023.100283. Full text in Research Archive Show summary

  There are prominent sex/gender differences in the prevalence, expression, and life span course of mental health and neurodiverse conditions. However, the underlying sex- and gender-related mechanisms and their interactions are still not fully understood. This lack of knowledge has harmful consequences for those with mental health problems. Therefore, we set up a cocreation session in a 1-week workshop with a multidisciplinary team of 25 researchers, clinicians, and policy makers to identify the main barriers in sex and gender research in the neuroscience of mental health. Based on this work, here we provide recommendations for methodologies, translational research, and stakeholder involvement. These include guidelines for recording, reporting, analysis beyond binary groups, and open science. Improved understanding of sex- and gender-related mechanisms in neuroscience may benefit public health because this is an important step toward precision medicine and may function as an archetype for studying diversity.

• Schindler, Louise S; Subramaniapillai, Sivaniya; Ambikairajah, Ananthan; Barth, Claudia; Crestol, Arielle & Voldsbekk, Irene [Show all 15 contributors for this article] (2023). Cardiometabolic health across menopausal years is linked to white matter hyperintensities up to a decade later. Frontiers in Global Women’s Health. 4. doi: 10.3389/fgwh.2023.1320640. Full text in Research Archive Show summary

  Introduction: The menopause transition is associated with several cardiometabolic risk factors. Poor cardiometabolic health is further linked to microvascular brain lesions, which can be detected as white matter hyperintensities (WMHs) using T2-FLAIR magnetic resonance imaging (MRI) scans. Females show higher risk for WMHs post-menopause, but it remains unclear whether changes in cardiometabolic risk factors underlie menopause-related increase in brain pathology. Methods: In this study, we assessed whether cross-sectional measures of cardiometabolic health, including body mass index (BMI) and waist-to-hip ratio (WHR), blood lipids, blood pressure, and long-term blood glucose (HbA1c), as well as longitudinal changes in BMI and WHR, differed according to menopausal status at baseline in 9,882 UK Biobank females (age range 40–70 years, n premenopausal = 3,529, n postmenopausal = 6,353). Furthermore, we examined whether these cardiometabolic factors were associated with WMH outcomes at the follow-up assessment, on average 8.78 years after baseline. Results: Postmenopausal females showed higher levels of baseline blood lipids (HDL β = 0.14, p < 0.001, LDL β = 0.20, p < 0.001, triglycerides β = 0.12, p < 0.001) and HbA1c (β = 0.24, p < 0.001) compared to premenopausal women, beyond the effects of age. Over time, BMI increased more in the premenopausal compared to the postmenopausal group (β = −0.08, p < 0.001), while WHR increased to a similar extent in both groups (β = −0.03, p = 0.102). The change in WHR was however driven by increased waist circumference only in the premenopausal group. While the group level changes in BMI and WHR were in general small, these findings point to distinct anthropometric changes in pre- and postmenopausal females over time. Higher baseline measures of BMI, WHR, triglycerides, blood pressure, and HbA1c, as well as longitudinal increases in BMI and WHR, were associated with larger WMH volumes (β range = 0.03–0.13, p ≤ 0.002). HDL showed a significant inverse relationship with WMH volume (β = −0.27, p < 0.001). Discussion: Our findings emphasise the importance of monitoring cardiometabolic risk factors in females from midlife through the menopause transition and into the postmenopausal phase, to ensure improved cerebrovascular outcomes in later years.

• Pieciak, Tomasz; Paris, Guillem; Beck, Dani; Maximov, Ivan; Tristan-Vega, Antonio & Luis-Garcia, Rodrigo de [Show all 8 contributors for this article] (2023). Spherical means-based free-water volume fraction from diffusion MRI increases non-linearly with age in the white matter of the healthy human brain. NeuroImage. ISSN 1053-8119. 279. doi: 10.1016/j.neuroimage.2023.120324. Full text in Research Archive Show summary

  The term free-water volume fraction (FWVF) refers to the signal fraction that could be found as the cerebrospinal fluid of the brain, which has been demonstrated as a sensitive measure that correlates with cognitive performance and various neuropathological processes. It can be quantified by properly fitting the isotropic component of the magnetic resonance (MR) signal in diffusion-sensitized sequences. Using healthy subjects (178F/109M) aged 25-94, this study examines in detail the evolution of the FWVF obtained with the spherical means technique from multi-shell acquisitions in the human brain white matter across the adult lifespan, which has been previously reported to exhibit a positive trend when estimated from single-shell data using the bi-tensor signal representation. We found evidence of a noticeably non-linear gain after the sixth decade of life, with a region-specific variate and varying change rate of the spherical means-based multi-shell FWVF parameter with age, at the same time, a heteroskedastic pattern across the adult lifespan is suggested. On the other hand, the FW corrected diffusion tensor imaging (DTI) leads to a region-dependent flattened age-related evolution of the mean diffusivity (MD) and fractional anisotropy (FA), along with a considerable reduction in their variability, as compared to the studies conducted over the standard (single-component) DTI. This way, our study provides a new perspective on the trajectory-based assessment of the brain and explains the conceivable reason for the variations observed in FA and MD parameters across the lifespan with previous studies under the standard diffusion tensor imaging.

• Sanders, Anne-Marthe; Richard, Geneviève; Kolskår, Knut-Kristian; Ulrichsen, Kristine Moe; Alnæs, Dag & Beck, Dani [Show all 14 contributors for this article] (2023). Associations between everyday activities and arterial spin labeling-derived cerebral blood flow: A longitudinal study in community-dwelling elderly volunteers. Human Brain Mapping. ISSN 1065-9471. 44, p. 3377–3393. doi: 10.1002/hbm.26287. Full text in Research Archive Show summary

  Cerebral blood flow (CBF) is critical for brain metabolism and function. Age-related changes in CBF are associated with increased risk of neurocognitive disorders and vascular events such as stroke. Identifying correlates and positive modifiers of age- related changes in CBF before the emergence of incipient clinical decline may inform public health advice and clinical practice. Former research has been inconclusive regarding the association between regular physical activity and CBF, and there is a lack of studies on the association between level of everyday activities and CBF, in older adults. To investigate these relationships, 118 healthy community-dwelling adults (65–89 years) underwent pseudo-continuous arterial spin labeling (ASL) MRI, neurocognitive, physical, and activity assessments at baseline. Eighty-six participants completed a follow-up ASL MRI, on average 506 (SD = 113) days after the baseline scan. Cross-sectional analysis revealed credible evidence for positive associations between time spent on low intensity physical activity and CBF in multiple cortical and subcortical regions, time spent on moderate to vigorous intensity physical activity and accumbens CBF, participation in social activity and CBF in multiple cortical regions, and between reading and thalamic CBF, indicating higher regional CBF in more active adults. Longitudinal analysis revealed anecdotal evidence for an interac- tion between time and baseline level of gardening on occipital and parietal CBF, and baseline reading on pallidum CBF, indicating more change in CBF in adults with lower level of activity. The findings support that malleable lifestyle factors contribute to healthy brain aging, with relevance for public health guidelines.

• Beck, Dani; Ferschmann, Lia; MacSweeney, Niamh; Norbom, Linn Christin Bonaventure; Wiker, Thea & Aksnes, Eira Ranheim [Show all 15 contributors for this article] (2023). Puberty differentially predicts brain maturation in male and female youth: A longitudinal ABCD Study. Developmental Cognitive Neuroscience. ISSN 1878-9293. 61. doi: 10.1016/j.dcn.2023.101261. Full text in Research Archive Show summary

  Research has demonstrated associations between pubertal development and brain maturation. However, existing studies have been limited by small samples, cross-sectional designs, and inconclusive findings regarding directionality of effects and sex differences. We examined the longitudinal temporal coupling of puberty status assessed using the Pubertal Development Scale (PDS) and magnetic resonance imaging (MRI)-based grey and white matter brain structure. Our sample consisted of 8896 children and adolescents at baseline (mean age = 9.9) and 6099 at follow-up (mean age = 11.9) from the Adolescent Brain and Cognitive Development (ABCD) Study cohort. Applying multigroup Bivariate Latent Change Score (BLCS) models, we found that baseline PDS predicted the rate of change in cortical thickness among females and rate of change in cortical surface area for both males and females. We also found a correlation between baseline PDS and surface area and co-occurring changes over time in males. Diffusion tensor imaging (DTI) analyses revealed correlated change between PDS and fractional anisotropy (FA) for both males and females, but no significant associations for mean diffusivity (MD). Our results suggest that pubertal status predicts cortical maturation, and that the strength of the associations differ between sex. Further research spanning the entire duration of puberty is needed to understand the extent and contribution of pubertal development on the youth brain.

• Dijsselhof, Mathijs; Barboure, Michelle; Stritt, Michael; Nordhøy, Wibeke; Wink, Alle Meije & Beck, Dani [Show all 11 contributors for this article] (2023). The value of arterial spin labelling perfusion MRI in brain age prediction. Human Brain Mapping. ISSN 1065-9471. 44(7), p. 2754–2766. doi: 10.1002/hbm.26242. Full text in Research Archive Show summary

  Abstract Current structural MRI‐based brain age estimates and their difference from chronological age—the brain age gap (BAG)—are limited to late‐stage pathological brain‐tissue changes. The addition of physiological MRI features may detect early‐stage pathological brain alterations and improve brain age prediction. This study investigated the optimal combination of structural and physiological arterial spin labelling (ASL) image features and algorithms. Healthy participants ( n = 341, age 59.7 ± 14.8 years) were scanned at baseline and after 1.7 ± 0.5 years follow‐up ( n = 248, mean age 62.4 ± 13.3 years). From 3 T MRI, structural (T1w and FLAIR) volumetric ROI and physiological (ASL) cerebral blood flow (CBF) and spatial coefficient of variation ROI features were constructed. Multiple combinations of features and machine learning algorithms were evaluated using the Mean Absolute Error (MAE). From the best model, longitudinal BAG repeatability and feature importance were assessed. The ElasticNetCV algorithm using T1w + FLAIR+ASL performed best (MAE = 5.0 ± 0.3 years), and better compared with using T1w + FLAIR (MAE = 6.0 ± 0.4 years, p &lt; .01). The three most important features were, in descending order, GM CBF, GM/ICV, and WM CBF. Average baseline and follow‐up BAGs were similar (−1.5 ± 6.3 and − 1.1 ± 6.4 years respectively, ICC = 0.85, 95% CI: 0.8–0.9, p = .16). The addition of ASL features to structural brain age, combined with the ElasticNetCV algorithm, improved brain age prediction the most, and performed best in a cross‐sectional and repeatability comparison. These findings encourage future studies to explore the value of ASL in brain age in various pathologies.

• Slapø, Nora Berz; Nerland, Stener; Jørgensen, Kjetil Nordbø; Mørch-Johnsen, Lynn Egeland; Pettersen, Johanne Hagen & Roelfs, Daniel [Show all 22 contributors for this article] (2023). Auditory Cortex Thickness Is Associated With N100 Amplitude in Schizophrenia Spectrum Disorders. Schizophrenia Bulletin Open. 4(1). doi: 10.1093/schizbullopen/sgad015. Full text in Research Archive Show summary

  Background and Hypothesis: The auditory cortex (AC) may play a central role in the pathophysiology of schizophrenia and auditory hallucinations (AH). Previous schizophrenia studies report thinner AC and impaired AC function, as indicated by decreased N100 amplitude of the auditory evoked potential. However, whether these structural and functional alterations link to AH in schizophrenia remain poorly understood. Study Design: Patients with a schizophrenia spectrum disorder (SCZspect), including patients with a lifetime experience of AH (AH+), without (AH−), and healthy controls underwent magnetic resonance imaging (39 SCZ spect, 22 AH+, 17 AH−, and 146 HC) and electroencephalography (33 SCZ spect, 17 AH+, 16 AH−, and 144 HC). Cortical thickness of the primary (AC1, Heschl’s gyrus) and secondary (AC2, Heschl’s sulcus, and the planum temporale) AC was compared between SCZ spect and controls and between AH+, AH−, and controls. To examine if the association between AC thickness and N100 amplitude differed between groups, we used regression models with interaction terms. Study Results: N100 amplitude was nominally smaller in SCZ spect (P = .03, d = 0.42) and in AH− (P = .020, d = 0.61), while AC2 was nominally thinner in AH+ (P = .02, d = 0.53) compared with controls. AC1 thickness was positively associated with N100 amplitude in SCZspect (t = 2.56, P = .016) and AH− (t= 3.18, P = .008), while AC2 thickness was positively associated with N100 amplitude in SCZspect (t = 2.37, P = .024) and in AH+ (t = 2.68, P = .019). Conclusions: The novel indings of positive associations between AC thickness and N100 amplitude in SCZ spect, suggest that a common neural substrate may underlie AC thickness and N100 amplitude alterations.

• Wiker, Thea; Norbom, Linn B.; Beck, Dani; Agartz, Ingrid; Andreassen, Ole A. & Alnæs, Dag [Show all 14 contributors for this article] (2023). Reaction Time Variability in Children Is Specifically Associated With Attention Problems and Regional White Matter Microstructure. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. ISSN 2451-9022. 8(8), p. 832–840. doi: 10.1016/j.bpsc.2023.03.010. Full text in Research Archive Show summary

  Background Increased intraindividual variability (IIV) in reaction times (RTs) has been suggested as a key cognitive and behavioral marker of attention problems, but findings for other dimensions of psychopathology are less consistent. Moreover, while studies have linked IIV to brain white matter microstructure, large studies testing the robustness of these associations are needed. Methods We used data from the Adolescent Brain Cognitive Development (ABCD) Study baseline assessment to test the associations between IIV and psychopathology (n = 8622, age = 8.9–11.1 years) and IIV and white matter microstructure (n = 7958, age = 8.9–11.1 years). IIV was investigated using an ex-Gaussian distribution analysis of RTs in correct response go trials in the stop signal task. Psychopathology was measured by the Child Behavior Checklist and a bifactor structural equation model was performed to extract a general p factor and specific factors reflecting internalizing, externalizing, and attention problems. To investigate white matter microstructure, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were examined in 23 atlas-based tracts. Results Increased IIV in both short and long RTs was positively associated with the specific attention problems factor (Cohen’s d = 0.13 and d = 0.15, respectively). Increased IIV in long RTs was also positively associated with radial diffusivity in the left and right corticospinal tract (both tracts, d = 0.12). Conclusions Using a large sample and a data-driven dimensional approach to psychopathology, the results provide novel evidence for a small but specific association between IIV and attention problems in children and support previous findings on the relevance of white matter microstructure for IIV.

• Slapø, Nora Berz; Jørgensen, Kjetil Nordbø; Elvsåshagen, Torbjørn; Nerland, Stener; Roelfs, Daniel & Valstad, Mathias [Show all 18 contributors for this article] (2023). Relationship between function and structure in the visual cortex in healthy individuals and in patients with severe mental disorders. Psychiatry Research : Neuroimaging. ISSN 0925-4927. 332. doi: 10.1016/j.pscychresns.2023.111633. Full text in Research Archive Show summary

  Patients with schizophrenia spectrum disorders (SCZspect) and bipolar disorders (BD) show impaired function in the primary visual cortex (V1), indicated by altered visual evoked potential (VEP). While the neural substrate for altered VEP in these patients remains elusive, altered V1 structure may play a role. One previous study found a positive relationship between the amplitude of the P100 component of the VEP and V1 surface area, but not V1 thickness, in a small sample of healthy individuals. Here, we aimed to replicate these findings in a larger healthy control (HC) sample (n = 307) and to examine the same relationship in patients with SCZspect (n = 30) or BD (n = 45). We also compared the mean P100 amplitude, V1 surface area and V1 thickness between controls and patients and found no significant group differences. In HC only, we found a significant positive P100-V1 surface area association, while there were no significant P100-V1 thickness relationships in HC, SCZspect or BD. Together, our results confirm previous findings of a positive P100-V1 surface area association in HC, whereas larger patient samples are needed to further clarify the function-structure relationship in V1 in SCZspect and BD.

• Holm, Madelene Christin; Leonardsen, Esten Høyland; Beck, Dani; Dahl, Andreas; Kjelkenes, Rikka & Lange, Ann-Marie Glasø de [Show all 7 contributors for this article] (2023). Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort. Developmental Cognitive Neuroscience. ISSN 1878-9293. 60. doi: 10.1016/j.dcn.2023.101220. Full text in Research Archive Show summary

  The temporal characteristics of adolescent neurodevelopment are shaped by a complex interplay of genetic, biological, and environmental factors. Using a large longitudinal dataset of children aged 9–13 from the Adolescent Brain Cognitive Development (ABCD) study we tested the associations between pubertal status and brain maturation. Brain maturation was assessed using brain age prediction based on convolutional neural networks and minimally processed T1-weighted structural MRI data. Brain age prediction provided highly accurate and reliable estimates of individual age, with an overall mean absolute error of 0.7 and 1.4 years at the two timepoints respectively, and an intraclass correlation of 0.65. Linear mixed effects (LME) models accounting for age and sex showed that on average, a one unit increase in pubertal maturational level was associated with a 2.22 months higher brain age across time points (β = 0.10, p < .001). Moreover, annualized change in pubertal development was weakly related to the rate of change in brain age (β = .047, p = 0.04). These results demonstrate a link between sexual development and brain maturation in early adolescence, and provides a basis for further investigations of the complex sociobiological impacts of puberty on life outcomes.

• Korbmacher, Max; Gurholt, Tiril Pedersen; Lange, Ann-Marie Glasø de; Meer, Dennis van der; Beck, Dani & Eikefjord, Eli Nina [Show all 10 contributors for this article] (2023). Bio-psycho-social factors’ associations with brain age: a large-scale UK Biobank diffusion study of 35,749 participants. Frontiers in Psychology. 14. doi: 10.3389/fpsyg.2023.1117732. Full text in Research Archive Show summary

  Kontrollert for godkjenning av Elise Davis-Keaveny

• Meer, Dennis van der; Gurholt, Tiril Pedersen; Sønderby, Ida Elken; Shadrin, Alexey; Hindley, Guy Frederick Lanyon & Rahman, Zillur [Show all 18 contributors for this article] (2022). The link between liver fat and cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition. Communications Biology. 5(1). doi: 10.1038/s42003-022-04237-4. Full text in Research Archive Show summary

  Abstract Obesity and associated morbidities, metabolic associated fatty liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting genome-wide association studies (GWAS) of these MRI-derived measures. We ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 33,588 White European UK Biobank participants (mean age of 64.5 years, 51.4% female). Through multivariate analysis, we discovered 100 loci with distributed effects across the body composition measures and 241 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h 2  = .25 vs. .13, p  = 1.8x10 −7 ). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (r g  = .49, p  = 2.7x10 −22 ). These findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.

• Nerland, Stener; Stokkan, Therese; Jørgensen, Kjetil Nordbø; Wortinger, Laura Anne; Richard, Geneviève & Beck, Dani [Show all 11 contributors for this article] (2022). A comparison of intracranial volume estimation methods and their cross-sectional and longitudinal associations with age. Human Brain Mapping. ISSN 1065-9471. doi: 10.1002/hbm.25978. Full text in Research Archive Show summary

  Intracranial volume (ICV) is frequently used in volumetric magnetic resonance imaging (MRI) studies, both as a covariate and as a variable of interest. Findings of associations between ICV and age have varied, potentially due to differences in ICV estimation methods. Here, we compared five commonly used ICV estimation methods and their associations with age. T1-weighted cross-sectional MRI data was included for 651 healthy individuals recruited through the NORMENT Centre (mean age = 46.1 years, range = 12.0–85.8 years) and 2410 healthy individuals recruited through the UK Biobank study (UKB, mean age = 63.2 years, range = 47.0–80.3 years), where longitudinal data was also available. ICV was estimated with FreeSurfer (eTIV and sbTIV), SPM12, CAT12, and FSL. We found overall high correlations across ICV estimation method, with the lowest observed correlations between FSL and eTIV (r = .87) and between FSL and CAT12 (r = .89). Widespread proportional bias was found, indicating that the agreement between methods varied as a function of head size. Body weight, age, sex, and mean ICV across methods explained the most variance in the differences between ICV estimation methods, indicating possible confounding for some estimation methods. We found both positive and negative cross-sectional associations with age, depending on dataset and ICV estimation method. Longitudinal ICV reductions were found for all ICV estimation methods, with annual percentage change ranging from −0.293% to −0.416%. This convergence of longitudinal results across ICV estimation methods offers strong evidence for age-related ICV reductions in mid- to late adulthood.

• Winterton, Adriano; Bettella, Francesco; Beck, Dani; Gurholt, Tiril Pedersen; Steen, Nils Eiel & Rødevand, Linn Nilsen [Show all 9 contributors for this article] (2022). The oxytocin signalling gene pathway contributes to the association between loneliness and cardiometabolic health. Psychoneuroendocrinology. ISSN 0306-4530. 144. doi: 10.1016/j.psyneuen.2022.105875. Full text in Research Archive Show summary

  Increasing evidence has shown adverse effects of loneliness on cardiometabolic health. The neuromodulator and hormone oxytocin has traditionally been linked with social cognition and behaviour. However, recent implications of the oxytocin system in energy metabolism and the overrepresentation of metabolic issues in psychiatric illness suggests that oxytocin may represent a mechanism bridging mental and somatic traits. To clarify the role of the oxytocin signalling system in the link between cardiometabolic risk factors and loneliness, we calculated the contribution of single nucleotide polymorphisms (SNPs) in the oxytocin signalling pathway gene-set (154 genes) to the polygenic architecture of loneliness and body mass index (BMI). We investigated the associations of these oxytocin signalling pathway polygenic scores with body composition measured using body magnetic resonance imaging (MRI), bone mineral density (BMD), haematological markers, and blood pressure in a sample of just under half a million adults from the UK Biobank (BMD subsample n = 274,457; body MRI subsample n = 9796). Our analysis revealed significant associations of the oxytocin signalling pathway polygenic score for BMI with abdominal subcutaneous fat tissue, HDL cholesterol, lipoprotein(a), triglycerides, and BMD. We also found an association between the oxytocin signalling pathway polygenic score for loneliness and apolipoprotein A1, the major protein component of HDL. Altogether, these results provide additional evidence for the oxytocin signalling pathway’s role in energy metabolism, lipid homoeostasis, and bone density, and support oxytocin’s complex pleiotropic effects.

• Schindler, Louise S; Subramaniapillai, Sivaniya; Barth, Claudia; Meer, Dennis van der; Pedersen, Mads Lund & Kaufmann, Tobias [Show all 18 contributors for this article] (2022). Associations between abdominal adipose tissue, reproductive span, and brain characteristics in post-menopausal women. NeuroImage: Clinical. 36. doi: 10.1016/j.nicl.2022.103239. Full text in Research Archive Show summary

  The menopause transition involves changes in oestrogens and adipose tissue distribution, which may influence female brain health post-menopause. Although increased central fat accumulation is linked to risk of cardiometabolic diseases, adipose tissue also serves as the primary biosynthesis site of oestrogens post-menopause. It is unclear whether different types of adipose tissue play diverging roles in female brain health post-menopause, and whether this depends on lifetime oestrogen exposure, which can have lasting effects on the brain and body even after menopause. Using the UK Biobank sample, we investigated associations between brain characteristics and visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) in 10,251 post-menopausal females, and assessed whether the relationships varied depending on length of reproductive span (age at menarche to age at menopause). To parse the effects of common genetic variation, we computed polygenic scores for reproductive span. The results showed that higher VAT and ASAT were both associated with higher grey and white matter brain age, and greater white matter hyperintensity load. The associations varied positively with reproductive span, indicating more prominent associations between adipose tissue and brain measures in females with a longer reproductive span. The effects were in general small, but could not be fully explained by genetic variation or relevant confounders. Our findings indicate that associations between abdominal adipose tissue and brain health post-menopause may partly depend on individual differences in cumulative oestrogen exposure during reproductive years, emphasising the complexity of neural and endocrine ageing processes in females.

• Beck, Dani; Lange, Ann-Marie Glasø de; Alnæs, Dag; Maximov, Ivan; Pedersen, Mads Lund & Leinhard, Olof Dahlqvist [Show all 20 contributors for this article] (2022). Adipose tissue distribution from body MRI is associated with cross-sectional and longitudinal brain age in adults. NeuroImage: Clinical. 33. doi: 10.1016/j.nicl.2022.102949. Full text in Research Archive Show summary

  There is an intimate body-brain connection in ageing, and obesity is a key risk factor for poor cardiometabolic health and neurodegenerative conditions. Although research has demonstrated deleterious effects of obesity on brain structure and function, the majority of studies have used conventional measures such as waist-to-hip ratio, waist circumference, and body mass index. While sensitive to gross features of body composition, such global anthropometric features fail to describe regional differences in body fat distribution and composition. The sample consisted of baseline brain magnetic resonance imaging (MRI) acquired from 790 healthy participants aged 18–94 years (mean ± standard deviation (SD) at baseline: 46.8 ± 16.3), and follow-up brain MRI collected from 272 of those individuals (two time-points with 19.7 months interval, on average (min = 9.8, max = 35.6). Of the 790 included participants, cross-sectional body MRI data was available from a subgroup of 286 participants, with age range 19–86 (mean = 57.6, SD = 15.6). Adopting a mixed cross-sectional and longitudinal design, we investigated cross-sectional body magnetic resonance imaging measures of adipose tissue distribution in relation to longitudinal brain structure using MRI-based morphometry (T1) and diffusion tensor imaging (DTI). We estimated tissue-specific brain age at two time points and performed Bayesian multilevel modelling to investigate the associations between adipose measures at follow-up and brain age gap (BAG) – the difference between actual age and the prediction of the brain’s biological age – at baseline and follow-up. We also tested for interactions between BAG and both time and age on each adipose measure. The results showed credible associations between T1-based BAG and liver fat, muscle fat infiltration (MFI), and weight-to-muscle ratio (WMR), indicating older-appearing brains in people with higher measures of adipose tissue. Longitudinal evidence supported interaction effects between time and MFI and WMR on T1-based BAG, indicating accelerated ageing over the course of the study period in people with higher measures of adipose tissue. The results show that specific measures of fat distribution are associated with brain ageing and that different compartments of adipose tissue may be differentially linked with increased brain ageing, with potential to identify key processes involved in age-related transdiagnostic disease processes.

• Subramaniapillai, Sivaniya; Suri, Sana; Barth, Claudia; Maximov, Ivan; Voldsbekk, Irene & Meer, Dennis van der [Show all 13 contributors for this article] (2022). Sex- and age-specific associations between cardiometabolic risk and white matter brain age in the UK Biobank cohort. Human Brain Mapping. ISSN 1065-9471. 43(12), p. 3759–3774. doi: 10.1002/hbm.25882. Full text in Research Archive Show summary

  Cardiometabolic risk (CMR) factors are associated with accelerated brain aging and increased risk for sex-dimorphic illnesses such as Alzheimer's disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E-ϵ4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi-shell diffusion-weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied (i) between males and females, (ii) according to age at menopause in females, and (iii) across different age groups in males and females. We report sex differences in associations between BAG and all three CMRs, with stronger positive associations among males compared to females. Independent of APOE4 status, higher BAG (older brain age relative to chronological age) was associated with greater BMI, WHR, and BF% in males, whereas in females, higher BAG was associated with greater WHR, but not BMI and BF%. These divergent associations were most prominent within the oldest group of females (66–81 years), where greater BF% was linked to lower BAG. Earlier menopause transition was associated with higher BAG, but no interactions were found with CMRs. In conclusion, the findings point to sex- and age-specific associations between CMRs and brain age. Incorporating sex as a factor of interest in studies addressing CMR may promote sex-specific precision medicine, consequently improving health care for both males and females.

• Voldsbekk, Irene; Barth, Claudia; Maximov, Ivan I.; Kaufmann, Tobias; Beck, Dani & Richard, Genevive [Show all 9 contributors for this article] (2021). A history of previous childbirths is linked to women's white matter brain age in midlife and older age. Human Brain Mapping. ISSN 1065-9471. 42(13), p. 1–15. doi: 10.1002/hbm.25553. Full text in Research Archive Show summary

  Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter and white matter ageing trajectories later in life. Utilising global and regional brain age prediction based on multi-shell diffusion-weighted imaging data, we investigated the association between previous childbirths and white matter brain age in 8,895 women in the UK Biobank cohort (age range = 54–81 years). The results showed that number of previous childbirths was negatively associated with white matter brain age, potentially indicating a protective effect of parity on white matter later in life. Both global white matter and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global white matter association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain white matter characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women's white matter trajectories across the lifespan.

• Valstad, Mathias; Roelfs, Daniel; Slapø, Nora Berz; Timpe, Clara Marie Fides; Rai, Ahsan & Matziorinis, Anna Maria [Show all 24 contributors for this article] (2021). Evidence for Reduced Long-Term Potentiation-Like Visual Cortical Plasticity in Schizophrenia and Bipolar Disorder. Schizophrenia Bulletin. ISSN 0586-7614. 47(6), p. 1751–1760. doi: 10.1093/schbul/sbab049. Full text in Research Archive Show summary

  Several lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. We measured the VEP of patients with SZ spectrum disorders (n = 31), BDI (n = 34), BDII (n = 33), and other BD spectrum disorders (n = 2), and age-matched healthy control (HC) participants (n = 200) before and after prolonged visual stimulation. Compared to HCs, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum (χ 2 = 35.1, P = 3.1 × 10−9) and BD spectrum (χ 2 = 7.0, P = 8.2 × 10−3), including BDI (χ 2 = 6.4, P = .012), but not BDII (χ 2 = 2.2, P = .14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients (χ 2 = 14.2, P = 1.7 × 10−4). N1b modulation was not significantly associated with Positive and Negative Syndrome Scale (PANSS) negative or positive symptoms scores, number of psychotic episodes, Montgomery and Åsberg Depression Rating Scale (MADRS) scores, or Young Mania Rating Scale (YMRS) scores after multiple comparison correction, although a nominal association was observed between N1b modulation and PANSS negative symptoms scores among SZ spectrum patients. These results suggest that LTP-like plasticity is impaired in SZ and BD. Adding to previous genetic, pharmacological, and electrophysiological evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

• Sanders, Anne-Marthe; Richard, Geneviève; Kolskår, Knut-Kristian; Ulrichsen, Kristine Moe; Kaufmann, Tobias & Alnæs, Dag [Show all 11 contributors for this article] (2021). Linking objective measures of physical activity and capability with brain structure in healthy community dwelling older adults. NeuroImage: Clinical. 31. doi: 10.1016/j.nicl.2021.102767. Full text in Research Archive Show summary

  Maintaining high levels of daily activity and physical capability have been proposed as important constituents to promote healthy brain and cognitive aging. Studies investigating the associations between brain health and physical activity in late life have, however, mainly been based on self-reported data or measures designed for clinical populations. In the current study, we examined cross-sectional associations between physical activity, recorded by an ankle-positioned accelerometer for seven days, physical capability (grip strength, postural control, and walking speed), and neuroimaging based surrogate markers of brain health in 122 healthy older adults aged 65–88 years. We used a multimodal brain imaging approach offering complementary structural MRI based indicators of brain health: global white matter fractional anisotropy (FA) and mean diffusivity (MD) based on diffusion tensor imaging, and subcortical and global brain age based on brain morphology inferred from T1-weighted MRI data. In addition, based on the results from the main analysis, follow-up regression analysis was performed to test for association between the volume of key subcortical regions of interest (hippocampus, caudate, thalamus and cerebellum) and daily steps, and a follow-up voxelwise analysis to test for associations between walking speed and FA across the white matter Tract-Based Spatial Statistics (TBSS) skeleton. The analyses revealed a significant association between global FA and walking speed, indicating higher white matter integrity in people with higher pace. Voxelwise analysis supported widespread significant associations. We also found a significant interaction between sex and subcortical brain age on number of daily steps, indicating younger-appearing brains in more physically active women, with no significant associations among men. These results provide insight into the intricate associations between different measures of brain and physical health in old age, and corroborate established public health advice promoting physical activity.

• Beck, Dani; Lange, Ann-Marie G. de; Pedersen, Mads L.; Alnæs, Dag; Maximov, Ivan & Voldsbekk, Irene [Show all 18 contributors for this article] (2021). Cardiometabolic risk factors associated with brain age and accelerate brain ageing. Human Brain Mapping. ISSN 1065-9471. p. 1–21. doi: 10.1002/hbm.25680. Full text in Research Archive Show summary

  The structure and integrity of the ageing brain is interchangeably linked to physical health, and cardiometabolic risk factors (CMRs) are associated with dementia and other brain disorders. In this mixed cross-sectional and longitudinal study (interval mean = 19.7 months), including 790 healthy individuals (mean age = 46.7 years, 53% women), we investigated CMRs and health indicators including anthropometric measures, lifestyle factors, and blood biomarkers in relation to brain structure using MRI-based morphometry and diffusion tensor imaging (DTI). We performed tissue specific brain age prediction using machine learning and performed Bayesian multilevel modeling to assess changes in each CMR over time, their respective association with brain age gap (BAG), and their interaction effects with time and age on the tissue-specific BAGs. The results showed credible associations between DTI-based BAG and blood levels of phosphate and mean cell volume (MCV), and between T1-based BAG and systolic blood pressure, smoking, pulse, and C-reactive protein (CRP), indicating older-appearing brains in people with higher cardiometabolic risk (smoking, higher blood pressure and pulse, low-grade inflammation). Longitudinal evidence supported interactions between both BAGs and waist-to-hip ratio (WHR), and between DTI-based BAG and systolic blood pressure and smoking, indicating accelerated ageing in people with higher cardiometabolic risk (smoking, higher blood pressure, and WHR). The results demonstrate that cardiometabolic risk factors are associated with brain ageing. While randomized controlled trials are needed to establish causality, our results indicate that public health initiatives and treatment strategies targeting modifiable cardiometabolic risk factors may also improve risk trajectories and delay brain ageing.

• Valstad, Mathias; Moberget, Torgeir; Roelfs, Daniël Thomas Heimen; Slapø, Nora Berz; Timpe, Clara Marie Fides & Beck, Dani [Show all 18 contributors for this article] (2020). Experience-dependent modulation of the visual evoked potential: Testing effect sizes, retention over time, and associations with age in 415 healthy individuals. NeuroImage. ISSN 1053-8119. doi: 10.1016/j.neuroimage.2020.117302. Full text in Research Archive Show summary

  Experience-dependent modulation of the visual evoked potential (VEP) is a promising proxy measure of synaptic plasticity in the cerebral cortex. However, existing studies are limited by small to moderate sample sizes as well as by considerable variability in how VEP modulation is quantified. In the present study, we used a large sample (n = 415) of healthy volunteers to compare different quantifications of VEP modulation with regards to effect sizes and retention of the modulation effect over time. We observed significant modulation for VEP components C1 (Cohen's d = 0.53), P1 (d = 0.66), N1 (d=-0.27), N1b (d=-0.66), but not P2 (d = 0.08), and in three clusters of total power modulation, 2–4 min after 2 Hz prolonged visual stimulation. For components N1 (d=-0.21) and N1b (d=-0.38), as well for the total power clusters, this effect was retained after 54–56 min, by which time also the P2 component had gained modulation (d = 0.54). Moderate to high correlations (0.39≤ρ≤0.69) between modulation at different postintervention blocks revealed a relatively high temporal stability in the modulation effect for each VEP component. However, different VEP components also showed markedly different temporal retention patterns. Finally, participant age correlated negatively with C1 (χ2=30.4), and positively with P1 modulation (χ2=13.4), whereas P2 modulation was larger for female participants (χ2=15.4). There were no effects of either age or sex on N1 and N1b potentiation. These results provide strong support for VEP modulation, and especially N1b modulation, as a robust measure of synaptic plasticity, but underscore the need to differentiate between components, and to control for demographic confounders.

• Tønnesen, Siren; Kaufmann, Tobias; Lange, Ann-Marie Glasø de; Richard, Geneviève; Doan, Nhat Trung & Alnæs, Dag [Show all 33 contributors for this article] (2020). Brain age prediction reveals aberrant brain white matter in schizophrenia and bipolar disorder: A multisample diffusion tensor imaging study. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. ISSN 2451-9022. 5(12), p. 1095–1103. doi: 10.1016/j.bpsc.2020.06.014. Full text in Research Archive Show summary

  Background Schizophrenia (SZ) and bipolar disorder (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, patients with BD, and healthy control (HC) subjects across 10 cohorts. Methods We trained 6 cross-validated models using different combinations of DTI data from 927 HC subjects (18–94 years of age) and applied the models to the test sets including 648 patients with SZ (18–66 years of age), 185 patients with BD (18–64 years of age), and 990 HC subjects (17–68 years of age), estimating the brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results. Results Tenfold cross-validation revealed high accuracy for all models. Compared with HC subjects, the model including all feature sets significantly overestimated the age of patients with SZ (Cohen’s d = −0.29) and patients with BD (Cohen’s d = 0.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy–based models showed larger group differences than the models based on other DTI-derived metrics. Conclusions Brain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.

• Beck, Dani; Lange, Ann-Marie Glasø de; Maximov, Ivan; Richard, Geneviève; Andreassen, Ole Andreas & Nordvik, Jan E. [Show all 7 contributors for this article] (2020). White matter microstructure across the adult lifespan: A mixed longitudinal and cross-sectional study using advanced diffusion models and brain-age prediction. NeuroImage. ISSN 1053-8119. 224:117441, p. 1–14. doi: 10.1016/j.neuroimage.2020.117441. Full text in Research Archive Show summary

  The macro- and microstructural architecture of human brain white matter undergoes substantial alterations throughout development and ageing. Most of our understanding of the spatial and temporal characteristics of these lifespan adaptations come from magnetic resonance imaging (MRI), including diffusion MRI (dMRI), which enables visualisation and quantification of brain white matter with unprecedented sensitivity and detail. However, with some notable exceptions, previous studies have relied on cross-sectional designs, limited age ranges, and diffusion tensor imaging (DTI) based on conventional single-shell dMRI. In this mixed cross-sectional and longitudinal study (mean interval: 15.2 months) including 702 multi-shell dMRI datasets, we combined complementary dMRI models to investigate age trajectories in healthy individuals aged 18 to 94 years (57.12% women). Using linear mixed effect models and machine learning based brain age prediction, we assessed the age-dependence of diffusion metrics, and compared the age prediction accuracy of six different diffusion models, including diffusion tensor (DTI) and kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), restriction spectrum imaging (RSI), spherical mean technique multi-compartment (SMT-mc), and white matter tract integrity (WMTI). The results showed that the age slopes for conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) were largely consistent with previous research, and that the highest performing advanced dMRI models showed comparable age prediction accuracy to conventional DTI. Linear mixed effects models and Wilk's theorem analysis showed that the ‘FA fine’ metric of the RSI model and ‘orientation dispersion’ (OD) metric of the NODDI model showed the highest sensitivity to age. The results indicate that advanced diffusion models (DKI, NODDI, RSI, SMT mc, WMTI) provide sensitive measures of age-related microstructural changes of white matter in the brain that complement and extend the contribution of conventional DTI.

• Fjell, Anders Martin; Chen, Chi-Hua Chen; Sederevicius, Donatas; Sneve, Markus Handal; Grydeland, Håkon & Krogsrud, Stine Kleppe [Show all 17 contributors for this article] (2019). Continuity and discontinuity in human cortical development and change from embryonic stages to old age. Cerebral Cortex. ISSN 1047-3211. 29(9), p. 3879–3890. doi: 10.1093/cercor/bhy266. Full text in Research Archive Show summary

  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.

• Maglanoc, Luigi Angelo; Kaufmann, Tobias; Jonassen, Rune; Hilland, Eva; Beck, Dani & Landrø, Nils Inge [Show all 7 contributors for this article] (2019). Multimodal fusion of structural and functional brain imaging in depression using linked independent component analysis. Human Brain Mapping. ISSN 1065-9471. doi: 10.1002/hbm.24802. Full text in Research Archive Show summary

  Previous structural and functional neuroimaging studies have implicated distributed brain regions and networks in depression. However, there are no robust imaging biomarkers that are specific to depression, which may be due to clinical heterogeneity and neurobiological complexity. A dimensional approach and fusion of imaging modalities may yield a more coherent view of the neuronal correlates of depression. We used linked independent component analysis to fuse cortical macrostructure (thickness, area, gray matter density), white matter diffusion properties and resting‐state functional magnetic resonance imaging default mode network amplitude in patients with a history of depression (n = 170) and controls (n = 71). We used univariate and machine learning approaches to assess the relationship between age, sex, case–control status, and symptom loads for depression and anxiety with the resulting brain components. Univariate analyses revealed strong associations between age and sex with mainly global but also regional specific brain components, with varying degrees of multimodal involvement. In contrast, there were no significant associations with case–control status, nor symptom loads for depression and anxiety with the brain components, nor any interaction effects with age and sex. Machine learning revealed low model performance for classifying patients from controls and predicting symptom loads for depression and anxiety, but high age prediction accuracy. Multimodal fusion of brain imaging data alone may not be sufficient for dissecting the clinical and neurobiological heterogeneity of depression. Precise clinical stratification and methods for brain phenotyping at the individual level based on large training samples may be needed to parse the neuroanatomy of depression.

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• Beck, Dani (2025). Early life adversity and the developing brain. Full text in Research Archive
• Beck, Dani; Whitmore, Lucy; MacSweeney, Niamh; Brieant, Alexis; Lange, Ann-Marie Glasø de & Westlye, Lars Tjelta [Show all 8 contributors for this article] (2024). Dimensions of early life adversity are differentially associated with patterns of delayed and accelerated brain maturation. Full text in Research Archive
• Meer, Dennis van der; Beck, Dani; Askeland-Gjerde, Daniel E.; Eikefjord, Eli; Lundervold, Arvid & Andreassen, Ole A. [Show all 8 contributors for this article] (2024). Distinct longitudinal brain white matter microstructure changes and associated polygenic risk of common psychiatric disorders and Alzheimer’s disease in the UK Biobank. Full text in Research Archive
• Meer, Dennis van der; Beck, Dani; Lange, Ann-Marie Glasø de; Eikefjord, Eli Nina Hølleland; Lundervold, Arvid & Andreassen, Ole A. [Show all 8 contributors for this article] (2024). Brain asymmetries from mid-to late life and hemispheric brain age. Full text in Research Archive
• Beck, Dani; Whitmore, Lucy; MacSweeney, Niamh; Brieant, Alexis; Lange, Ann-Marie G. de & Westlye, Lars Tjelta [Show all 8 contributors for this article] (2024). Dimensions of early life adversity links to trimodal brain age in youth. Full text in Research Archive
• Wierenga, Lara M. & Beck, Dani (2024). Sex/gender associated mechanisms in the (human) brain: Sex hormones, sex chromosomes, and social-cultural gender factors, Encyclopedia of the Human Brain. Elsevier Science, USA. doi: 10.1016/B978-0-12-820480-1.00173-X. Full text in Research Archive
• Beck, Dani (2023). Puberty differentially predicts brain maturation in male and female youth. Full text in Research Archive
• Korbmacher, Max; Gurholt, Tiril Pedersen; Lange, Ann-Marie Glasø de; Meer, Dennis van der; Beck, Dani & Eikefjord, Eli Nina Hølleland [Show all 10 contributors for this article] (2023). Brain age estimates from different white matter microstructure features associate concordantly with bio-psycho-social factors. Full text in Research Archive
• Korbmacher, Max; Lange, Ann-Marie Glasø de; Meer, Dennis van der; Beck, Dani; Eikefjord, Eli Nina Hølleland & Lundervold, Arvid [Show all 9 contributors for this article] (2023). Fornix and forceps are key regions of white matter brain age. Full text in Research Archive
• Korbmacher, Max; Gurholt, Tiril Pedersen; Lange, Ann-Marie Glasø de; Meer, Dennis van der; Beck, Dani & Eikefjord, Eli Nina Hølleland [Show all 10 contributors for this article] (2023). White matter microstructure is predictive of cardiometabolic health. Full text in Research Archive
• Korbmacher, Max; Lange, Ann-Marie Glasø de; Meer, Dennis van der; Beck, Dani; Eikefjord, Eli Nina Hølleland & Lundervold, Arvid [Show all 9 contributors for this article] (2023). Regional grey and white matter asymmetry decreases at higher ages. Full text in Research Archive
• Beck, Dani; Ferschmann, Lia; MacSweeney, Niamh; Fridman, Linn Bonaventure; Wiker, Thea & Aksnes, Eira Ranheim [Show all 15 contributors for this article] (2023). Puberty differentially predicts brain maturation in males and females: A longitudinal ABCD Study. Full text in Research Archive
• Beck, Dani; Whitmore, Lucy; MacSweeney, Niamh; Westlye, Lars Tjelta; Mills, Kathryn L. & Tamnes, Christian Krog (2023). Associations between early life trauma and gray and white matter brain age during childhood and adolescence. Full text in Research Archive
• Beck, Dani (2022). Cardiometabolic risk and the ageing brain: Using brain and body MRI to elucidate the body-brain axis in healthy adults. Full text in Research Archive
• Beck, Dani (2022). Brain age prediction as a method for measuring brain maturation. Full text in Research Archive
• Sanders, Anne-Marthe; Richard, Geneviève; Kolskår, Knut K.; Ulrichsen, Kristine Moe; Alnæs, Dag & Beck, Dani [Show all 14 contributors for this article] (2022). Associations between everyday activities and arterial spin labelling-derived cerebral blood flow: A longitudinal study in community-dwelling elderly volunteers. medRxiv. doi: 10.1101/2022.09.22.22280237. Full text in Research Archive

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