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Karlsson, H.

Publications and source records attributed to Karlsson, H..

At least 19 recordsLinked to original sources

Epigenetic and brain age across development: Performance and associations in the MIND consortium

Understanding how biological age measures perform across development lays the groundwork for investigations into lifespan trajectories of healthy aging. We provide the most comprehensive assessment of epigenetic and brain age models across development (birth to 24 years; [≤]20,917 observations across 15 cohorts), evaluating how these models associate with chronological age and with each other, and how these associations change across development. Chronological age-prediction accuracy of epigenetic and brain age models was modest and varied substantially. Accuracy improved with age and stabilized by middle childhood. Few brain and fewer epigenetic clocks performed stably and well across all developmental stages. Performance was better when age range and tissue corresponded between training and testing data. Associations between epigenetic-brain age residuals were small, and changed little across development, tissues or clock generation. Given this developmentally dynamic system of epigenetic-brain age performances and associations, we give key recommendations to improve developmental research in this field.

neuroscience↗

Universal 3D Motif dynamics in RNA: The A-minor Switch

A-minor motifs consist of adenosines docking into adjacent RNA minor grooves, are the most prevalent 3D interaction stabilizing RNA structures, and widely considered as being static. NMR spectroscopy reveals a secondary structure equilibrium of these motifs between engaged and disengaged states, which we term the A-minor switch. A switch in E.coli ribosome helix 44 consists of a sparsely populated, transient single-nucleotide register shift that sequesters adenosines from their 3D structural A-minor contacts. Mutational trapping of the NMR-defined, A-minor-engaged ground and-disengaged excited state, combined with cryo-electron microscopy, visualizes this dynamic switch mechanism. Additionally, A-minor switches were identified using secondary structure ensemble analysis and mutational trapping was found to impair bacterial growth, directly linking RNA dynamics and function. Because A-minor motifs are widespread in structured RNAs, these findings establish A-minor switches as a general regulatory layer between secondary structure dynamics and tertiary contacts, exposing a new therapeutic target class.

biophysics↗

Cortical gray matter density at age five associated with preceding early longitudinal language profiles: A Voxel-based morphometry analysis of the FinnBrain Birth Cohort Study

Previous studies exploring the connection between early language development and brain anatomy have shown that cortical areas relating to individual differences in language skills are diverse and vary depending on the age of child. However, due to lack of large longitudinal samples, current literature is limited in answering the extent to which individual differences in language development prior to school age are reflected in areas of the cortex. To fill this gap, we compared gray matter density between participants that belonged to different longitudinally defined language profiles from 14 months to five years of age in a large population-based sample. Participants were 166 children from the FinnBrain Birth Cohort Study who had longitudinal language data from 14 months to five years of age and magnetic resonance imaging data at five years of age. Three groups of language development were used as per our prior study: persistent low, stable average, and stable high. Voxel-based morphometry metrics were calculated using SPM12 and the three language profile groups were compared to one another. Covariates included sex and age at brain scan. The statistics were thresholded at p < 0.01 and false discovery rate corrected at the cluster level. Of the three longitudinal language profiles, the stable high group had higher gray matter density than the persistent low group in the right superior frontal gyrus. No differences were found between the stable average and stable high groups, nor persistent low and stable average groups. The identified superior frontal cortical area belongs to executive functions neural network. This finding adds to the cumulating evidence that individual differences in language development are reflected in growth of gray matter supporting general processing ability rather than specialized language regions. The results suggest that cognitive development and early language development are linked through shared principles of neural growth, identifiable already at age five. Key pointsO_LIAn association between early language development from 14 months to five years of age and gray matter density differences of the right superior frontal gyrus was found at the age of five years. Children following the strongest language trajectory were more likely to exhibit higher gray matter density of the right superior frontal gyrus than children following the weakest trajectory. C_LIO_LIAs the superior frontal gyrus is part of executive functions network, we propose that individual differences in early language development are more defined by general learning mechanisms supported by those networks, rather than language specific pathways. C_LI

neuroscience↗

Functional connectome harmonics capture early brain organization and maturity in neonates

The functional organization of the human brain is established early, yet the ontogeny of its large-scale functional gradients remains unclear. Using resting-state fMRI data from 714 neonates in the Developing Human Connectome Project, we mapped neonatal brain gradients via functional connectome harmonics (FCH). We identified adult-like sensory-to-multimodal and cognitive gradient patterns present at birth. Applying three FCH-derived metrics--entropy, power, and energy--we found that power and energy were higher in term-born compared to preterm neonates, while entropy was elevated in preterms. These metrics predicted up to ~30% of postmenstrual age, indicating their biological relevance. Our findings reveal that the neonatal brain possesses a robust gradient architecture underpinning early functional organization, offering novel biomarkers for assessing brain maturity and the impact of prematurity on neurodevelopment.

neuroscience↗

Functional connectome harmonics and dynamic connectivity maps of the preadolescent brain

The maturation of large-scale functional brain networks during preadolescence underpins critical cognitive and behavioral development. However, the spatial and temporal organization of these networks in this age group remains incompletely characterized. Here we applied Functional Connectome Harmonics (FCH) and Leading Eigenvector Dynamics Analysis (LEiDA) to resting-state fMRI data from over 11,000 children aged 9-10 years in the ABCD Study. FCH revealed hierarchical spatial gradients spanning cortical and subcortical regions, while LEiDA identified recurrent dynamic brain states aligned with canonical intrinsic connectivity networks. Linking these spatial and temporal components, we established a low-dimensional harmonic scaffold constraining brain dynamics during this developmental window. These findings provide a large-scale spatiotemporal reference framework of preadolescent functional brain organization, offering a foundation for characterizing neurodevelopmental benchmarks and early neural markers relevant to adolescent mental health.

neuroscience↗

Exposure to Maternal Pre- and Postnatal Psychological Distress: Associations with Brain Structure in 5-year-old Children

BackgroundMaternal mental health is an important contributor to child neurodevelopment. While there are multiple studies on prenatal exposure, early postnatal exposure has received little attention in neuroimaging research. Methods5-year-old children (n = 173) were recruited from the FinnBrain Birth Cohort study. Maternal distress was assessed using questionnaires on depressive and anxiety symptoms at 14, 24 and 34 gestational weeks and postnatally at 3, 6 and 24 months. T1-weighted structural images were processed using a voxel-based morphometry pipeline to map associations between maternal distress exposure and regional gray matter (GM) volumes, while accounting for potential confounders. ResultsWe found widespread associations between maternal distress symptoms and offspring brain morphology. Higher prenatal distress at 14 gestational weeks was positively associated with regional GM volume in the right superior parietal lobe and precuneus. In contrast, postnatal distress at 3 months was negatively associated with GM volumes in multiple motor regions, the left anterior insula, right superior frontal areas and supramarginal gyrus. Postnatal distress at 6 months demonstrated a positive relationship with GM volumes in the right calcarine and lingual gyri, while distress at 24 months was negatively associated with GM volumes in the left supramarginal and right superior frontal gyri. ConclusionsThis study provides support for hypotheses proposing that fetal and early life exposure to maternal distress can influence the structural development of the brain. Furthermore, it highlights the role of early postnatal period and calls for further research into this so far overlooked period and pathways that explain the associations.

neuroscience↗

Temporal Associations Between Human Milk Metabolites and the Infant Gut Microbiome and metabolome

IntroductionHuman milk is vital in establishing a healthy infant gut microbiome. Gut microbes and their metabolites are important for host development. However, our understanding of how milk metabolites are connected to the gut microbiome and metabolome in early-life remains limited. We aimed to investigate associations between the human milk metabolome and the gut microbiome in infancy. MethodsThe fecal and milk samples were collected at 2.5 (n=283), 6 (n=129) and 14 (n=65) months of age. Gut microbiota was analyzed with amplicon sequencing, the gut metabolome was analyzed with gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and milk metabolites were analyzed with proton nuclear magnetic resonance. ResultsBifidobacterium and other butyrate producers were associated with ethanolamine and methionine level in the milk, in a time-dependent manner. Elevated milk fucosylated oligosaccharide, LNFP-I and caprylate concentrations were positively associated with secondary bile acid levels following the introduction of solid foods. Additionally, acidic oligosaccharides 3-SL and 6-SL were positively associated with long-chain carbohydrates prior to solid food introduction, however negatively associated thereafter. ConclusionOur results highlight that milk metabolites are associated with biologically relevant gut microbial metabolites. Only limited associations were observed between milk composition and the microbiome, which differed between early and late infancy. This suggests milk metabolome may differentially influence microbial metabolism depending on dietary diversity and/or the maturity of the microbiome. ImportanceIts essential to raise awareness about breastfeeding and its variety of health benefits. Expanding our understanding of how human milk small molecules with potential bioactivity interact with the gut microbiome can help highlight these positive effects. Exploratory studies of human milk composition with gut microbial metabolites may support achieving this goal. Furthermore, understanding of biological effects of different components in human milk is important, and it can help to develop strategies to ensure optimal growth and development of an infant regardless of the breastfeeding status of the child.

microbiology↗

skiftiTools: An R package for reading, writing, analysing, and visualising, tract-based spatial statistics (TBSS) derived diffusion MR images

skiftiTools processes three- and four-dimensional neuroimaging data, facilitating advanced statistical modelling with voxelwise data in any software of choice. Tract-Based Spatial Statistics (TBSS) is a conventionally used tool to make statistical calculations in voxel space for brain imaging data. While pre-existing software packages provide support for general linear model based statistics, there is a clear need for more sophisticated modeling. skiftiTools writes subject-per-volume NIfTI files as tab-separated value ASCII files, which are easily readable by most commonly used statistical tools such as R language (RStudio), SPSS, SAS, and GraphPad Prism. This facilitates a wide range of voxel-level statistical analyses from TBSS data, including estimation of standardised effect sizes, clustering, dimensionality reduction, non-linear and machine learning predictive modelling, which we showcase in this article using FinnBrain and developing Human Connectome Project diffusion MRI data. After statistical processing, the resulting ASCII data can then be read again for visualization. The package supports NIfTI image format, tab-separated ASCII format, and its own stand-alone format for efficient disk usage. It is open source (https://github.com/haanme/skiftiTools), built on R-language and has easy installation from Rs CRAN package repository. In addition, we provide basic functions available in Docker containers for further platform independence. HighlightsO_LIThe skiftiTools R package is an open-source, user-friendly interface for analysing voxelwise diffusion tensor imaging (DTI) data following tract-based spatial statistics (TBSS) processing C_LIO_LIIt supports reading, writing, visualization, mathematical operations, and data manipulation and thus allows comprehensive conventional and advanced statistics, including machine learning C_LIO_LIskiftiTools bridges a critical gap between statistical tools in R and voxelwise neuroimaging data - including comparable means to perform multiple comparison corrections and much needed possibility to use non-linear statistics C_LI

neuroscience↗

Faecal transplantation from exuberant toddlers increases exploratory behaviour in rats

BackgroundBehavioural phenotypes have previously been transferred via faecal microbiota transplantation (FMT) from patients with psychiatric disorders to rodents. Studies indicate that the gut microbiota composition may be linked to certain temperament traits, defined as biologically-based differences in emotional reactivity and self-regulation. Here, we aimed to determine if the gut microbiota plays a role in temperament using an FMT approach. We focused on the temperament traits of exuberance, defined as positive reactivity, decreased behavioural inhibition, and high behavioural approach tendencies. MethodsFaeces from 2.5-year-old toddlers from FinnBrain Birth Cohort Study with high exuberance/approach or high behavioural inhibition in the LabTAB bubbles-episode was transferred to juvenile male Sprague Dawley rats (age 22/23 days). Behaviour of the rat recipients (n=53) was assessed using the novel non-social arena, novel social arena, hole board test for exploratory behaviour, social approach-avoidance test, and forced swim test. The faecal pellets collected from the rodents were analyzed with 16s rRNA sequencing and faecal samples from the sample of toddlers (which included the donors, n=176) were analysed using short-read metagenomic sequencing. The striatum and prefrontal cortex from the rodents brains were analysed post-mortem using RNAseq. ResultsMicrobiome from toddlers with high exuberance traits induced increased exploratory behaviour compared to vehicle-controls and rats receiving faeces from inhibited toddlers. Locomotor activity, social, and depressive-like behaviour remained unaffected. We noted a downregulation of the dopamine synapse pathway within the striatum of the rats that received faeces from the inhibited trait donors compared with vehicle-controls. Faecal microbiota of rats receiving faeces from the same donor resembled more each other than rats from a different cage. Clostridium species AM29 11AC in toddler microbiome was positively related to exuberance, but there were no cross-sectional associations between faecal metabolites in the human sample. ConclusionsFMT from exuberant toddlers lead to altered exploratory-related behaviour in rats.

microbiology↗

Structural Brain Correlates of Speech Disfluency in Early Childhood: A Dimensional Analysis in a Non-Clinical Cohort

Most neuroimaging studies of speech disfluency have compared individuals who stutter with fluent controls. However, treating speech disfluency as a continuous, dimensional trait offers new insights into the neural basis of fluency during early childhood. This study aimed to investigate whether naturally occurring variation in speech disfluency is associated with grey matter structure in a non-clinical, population-based sample of 5-year-old children. The study included 120 participants (65M, 55F) from the FinnBrain Birth Cohort study. Speech disfluency was evaluated as a continuous measure from audiovisual speech samples, with transcription and analysis conducted using the SALT software. Ambrose & Yairi (1999) classification system was used to categorize speech disfluencies into stuttering-like (SLD) and other disfluency types. T1-weighted images obtained through magnetic resonance imaging were analyzed using voxel-based morphometry (VBM) with the CAT12 toolbox and complemented by surface-based morphometry with FreeSurfer. Whole-brain statistical analysis was employed to examine the association between grey matter metrics and speech disfluency. We found that VBM-derived proportional grey matter volume in the left middle frontal gyrus, left posterior cerebellum, and right superior frontal gyrus was positively associated with speech disfluency, specifically SLD, in children (p <.001; p=.002; p <.001, FDR corrected). No significant associations were found for cortical thickness or surface area. Additionally, no notable sex differences were observed. Our findings suggest that speech disfluency in early childhood is linked to localized structural differences in regions supporting motor planning and cognitive control, without broader changes in cortical thickness or surface area. Importantly, similar brain regions have been implicated in studies comparing children who stutter to those who do not, suggesting that normal variation in disfluency captures meaningful neurobiological differences even in non-clinical populations. This supports the value of treating speech disfluency as a spectrum and underscores the importance of longitudinal, multimodal research to clarify how these structural features evolve and influence later fluency outcomes.

neuroscience↗

Neonatal White Matter Microstructure Predicts Infant Attention Disengagement from Fearful Faces

Infants develop an attentional bias towards faces already at birth, with further specification towards fearful faces emerging at 6 months and diminishing around 11 months of age. However, the neurobiological origins of attentional bias to fear are still poorly understood. To understand the neural structures underlying perception of facial expressions, the current study utilized newborn diffusion magnetic resonance images (N = 86; 41 females; = 27.15 days) and eye tracking from the same infants at 8-months ( = 8.75 months) as a behavioural measure. An overlap paradigm was used to measure attention disengagement from fearful, happy, and neutral faces. Tract-based spatial statistics revealed that higher white matter (WM) mean diffusivity in widespread regions across the brain was associated with lower attention disengagement from fearful faces. The same association was found with happy faces but was limited to only the splenium of the corpus callosum and sensorimotor pathways. Variance in neonatal WM microstructure may reflect individual differences in growth that is related to attentional bias development later in infancy.

neuroscience↗

Effortful control and cortical brain structure in 5-year-old children: findings from the FinnBrain birth cohort study

The aim of this study was to explore the associations between an aspect of self-regulation (SR), effortful control (EC), and cortical brain structure in 5-year-old children. Efficient EC is a predictor of many attributes and important outcomes in life, such as social-emotional functioning, psychiatric and somatic health, finance, and criminal activity. The early brain correlates of EC are not widely studied, while a better understanding of them would aid in recognizing individuals at risk for maladaptive outcomes. Participants (N = 155) were a part of the FinnBrain Birth Cohort Study in Finland. T1-weighted brain magnetic resonance images were processed using FreeSurfer. The data was statistically analysed with a vertex-wise general linear model. At the age of 5 years, EC and its subscales, Attentional focusing, Inhibitory control (INH), Low intensity pleasure (LIP) and perceptual sensitivity, were assessed via parental report using The Childrens Behaviour Questionnaire. We found positive associations between overall EC and cortical volume in the left superior parietal region and in the right inferior temporal region. We also found positive associations between EC and surface area on the left hemisphere in the superior parietal region. The findings were driven by the EC subscales of INH and LIP with INH linking positively with left surface area and volume, and LIP linking with left cortical volume. We extended the previous literature by shedding light on early structural brain correlates of EC in a large sample of typically developing 5-year-olds. The results differed significantly from previous findings in older children, highlighting the need for longitudinal studies to better understand the neural underpinnings of SR throughout development.

neuroscience↗

Association between maternal depressive symptoms and hair cortisol concentration during pregnancy with corpus callosum integrity in newborns

BackgroundMaternal prenatal depressive symptoms are linked to neurodevelopmental impairments in offspring. Maternal cortisol levels are hypothesized to moderate this association, but its relationship with depressive symptoms is inconsistent. This study examined how maternal prenatal depressive symptoms and cortisol levels predict infant brain development, focusing on neonatal corpus callosum (CC) integrity. MethodsUsing data from the FinnBrain Birth Cohort Study, we analyzed 37 mother-infant dyads. MRI data were collected from 2 to 5 weeks old infants, and DTI imaging estimated fractional anisotropy (FA) in CC regions (Genu, Body, and Splenium). Maternal cortisol levels were assessed through hair cortisol concentration (HCC) from a 5cm hair segment, reflecting cortisol over the last five months of pregnancy. A factor score of maternal depressive symptoms was computed from EPDS questionnaire data collected at gestational weeks 14, 24, and 34. We employed multivariate regression models with a Bayesian approach for statistical testing, controlling for maternal and infant attributes. ResultsResults indicated that maternal prenatal depressive symptoms and HCC interact negatively in predicting infants FA across all CC regions. Infants exposed to high prenatal depressive symptoms and low HCC (1 SD below the mean) showed higher FA in all CC regions. ConclusionsThese findings highlight the complex dynamics between maternal prenatal cortisol levels and depressive symptoms, revealing a nuanced impact of those factors on the structural integrity of infants CC.

neuroscience↗

Reward responses to vicarious feeding depend on BMI

Eating is inherently social for humans. Yet, most neuroimaging studies of appetite and food-induced reward have focused on studying brain responses to food intake or viewing pictures of food alone. Here we used functional magnetic resonance imaging (fMRI) to measure haemodynamic responses to "vicarious" feeding. The subjects (n=97) viewed series of short videos representing naturalistic episodes of social eating intermixed with videos without feeding / appetite related content. Viewing the vicarious feeding (versus control) videos activated motor and premotor cortices, thalamus, and dorsolateral prefrontal cortices, consistent with somatomotor and affective engagement. Responses to the feeding videos were also downregulated as a function of the participants BMI. Altogether these results suggest that seeing others eating engages the corresponding motor and affective programs in the viewers brain, potentially increasing appetite and promoting mutual feeding.

neuroscience↗

Pre- and postnatal maternal depressive symptoms associate with localconnectivity of the left amygdala in 5-year-olds.

BackgroundMaternal depressive symptoms can influence brain development in offspring, prenatally through intrauterine programming, and postnatally through caregiving related mother-child interaction. MethodsThe participants were 5-year-old mother-child dyads from the FinnBrain Birth Cohort Study (N = 68; 28 boys, 40 girls). Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at gestational week 24, 3 months, 6 months, and 12 months postnatal. Childrens brain imaging data were acquired with task-free functional magnetic resonance imaging (fMRI) at the age of 5 years in 7 min scans while watching the Inscapes movie. The derived brain metrics included whole brain regional homogeneity (ReHo) and seed-based connectivity maps of the bilateral amygdalae. ResultsWe found that maternal depressive symptoms were positively associated with ReHo values of the left amygdala. The association was highly localised and strongest with the maternal depressive symptoms at three months postnatal. Seed-based connectivity analysis did not reveal associations between distal connectivity of the left amygdala region and maternal depressive symptoms. ConclusionsThese results suggest that maternal depressive symptoms soon after birth may influence offsprings neurodevelopment in the local functional coherence in the left amygdala. They underline the potential relevance of postnatal maternal distress exposure on neurodevelopment that has received much less attention than prenatal exposures. These results offer a possible thus far understudied pathway of intergenerational effects of perinatal depression that should be further explored in future studies.

neuroscience↗

Fecal microbiota and metabolite composition associates with stool consistency in young children

Transit time, fluid intake, diet, and overall gut health influence stool consistency. However, the relationships between the gut metabolome (microbial metabolites) and stool consistency in infants and young children remain poorly understood. Here, we analyzed the metabolome and microbiota of 618 stool samples from children aged 2.5 months (n = 360), 6 months (n = 229), 14 months (n = 274), and 30 months (n = 169) from the FinnBrain Birth Cohort Study, and related these data to stool water content and parent-reported stool consistency. Breastfeeding showed the strongest association with both stool consistency and fecal water content. Concentrations of newly identified microbial bile acid amidates were associated with constipation and stool water content, while bile salt hydrolase, an enzyme involved in bile acid deconjugation and conjugation was predicted to be negatively associated with stool water content. In addition, short-chain fatty acids, particularly acetate, were positively associated with stool water content, whereas branched-chain short-chain fatty acids showed negative associations. These findings suggest that longer gut transit time permits more extensive microbial metabolism, including the transformation of bile acid amidates. We also found that microbial taxonomic richness, diversity, and community composition were primarily associated with stool water content, with only weak associations with stool consistency. Overall, our results highlight the importance of documenting stool consistency in fecal metabolomics and microbiome research, and provide new insights into how breastfeeding, microbial metabolism, and gut transit time shape early-life gut development.

systems biology↗

Pleasurable music activates cerebral μ-opioid receptors: A combined PET-fMRI study

The -opioid receptor (MOR) system mediates incentive motivation and the hedonic component of primary rewards such as food and sex. However, there is no direct in vivo evidence for the involvement of the MOR system in pleasure derived from aesthetic rewards such as music. We measured MOR activation with positron emission tomography (PET) and the agonist radioligand [11C] carfentanil with high affinity for MORs during the listening of pleasurable music and neutral baseline condition. Haemodynamic responses to pleasurable music were measured using functional magnetic resonance imaging (fMRI). The PET results revealed that pleasurable music increased [11C]carfentanil binding in several cortical and subcortical regions, including ventral striatum and orbitofrontal cortex, known to contain "hedonic hotspots". Individual variation in baseline MOR tone influenced pleasure-dependent haemodynamic responses during music listening in regions associated with interoceptive, sensorimotor, and reward processing. Our results provide the first-ever neuroimaging evidence that listening to pleasurable music modulates MOR system activation and indicate that the -opioid system governs complex aesthetic rewards in addition to biologically salient primary rewards.

neuroscience↗

Neonatal Amygdala Mean Diffusivity: A Potential Predictor of Emotional Face Perception

The ability to differentiate between different facial expressions is an important part of human social and emotional development that begins in infancy. Studies have shown that within the first year of life, infants develop a distinctive attentional bias towards fearful facial expressions. Investigations into the neural basis for this bias have highlighted the significance of the amygdala. The amygdalas role in directing attention towards fearful facial expressions underscores its importance in early emotional development, significantly influencing how infants interpret and react to facial expressions. To date, no studies have been conducted to investigate the associations between the amygdala microstructure and infants perception of emotional faces. This study aimed to elucidate this relationship while also investigating whether this association is sex specific. We measured the amygdala microstructural properties using diffusion tensor imaging mean diffusivity (MD) measurements in 40 healthy infants aged 2 to 5 weeks. Eye tracking was used to assess attention disengagement from fearful vs. non-fearful (happy and neutral) facial expressions as well as scrambled non-face control picture at 8 months. Generally, infants were age-typically less likely to disengage from fearful faces than from non-fearful faces towards salient distractors. A significant negative association was observed between the right amygdala MD measures and disengagement probability from fearful faces in the overall sample. Moreover, there was a positive association between the bilateral amygdala MD measures and the disengagement probability from scrambled non-face control picture in girls. These results indicate that the amygdala MD is associated with attention disengagement processes already in infancy, both in fear processing and in non-emotional conditions. Specifically, these findings highlight the role of the amygdala microstructure in modulating attentional processes, which may have implications for emotional regulation and susceptibility to emotional dysregulation later in life.

neuroscience↗