Biology subjects

Karlsson, L.

Publications and source records attributed to Karlsson, L..

34 records · Page 2Linked to original sources

bioRxiv2023

Attentional bias toward fearful faces is associated with maternal postnatal distress and alterations in white matter microstructure in 5-year-old females

The development of face processing system is paramount for social interaction and communication skills. Eye-tracking provides a viable means to investigate face processing even in very young children and can be used to derive indices of affective processing biases that are adaptive in supporting preparedness for emotional encoding. The neural correlates of early-emerging attentional biases have not been explored. In the current study, we gathered diffusion tensor imaging (DTI) and eye-tracking data (attention disengagement from neutral, happy, fearful faces, and control pictures towards distractor stimuli) to investigate the association of white matter (WM) microstructural alterations and attentional biases in 117 (55 female) typically developing 5-year-old children. We estimated fractional anisotropy (FA) and used tract-based spatial statistics (TBSS) before conducting voxel-wise analyses testing associations between attentional biases and brain diffusivity. We found that reduced WM integrity (indexed as decrease in FA) in widespread WM regions, including the splenium of corpus callosum, left anterior limb of internal capsule (ALIC), left posterior limb of internal capsule (PLIC), left posterior thalamic radiation and optic tract, predicted higher attentional bias toward fearful expressions in females (adjusted for potential confounders). Further, maternal postnatal anxiety and depressive symptoms were detected to associate positively with attentional bias toward fearful expression, but only in females. Based on these findings and prior results on association between maternal distress and reduced WM integrity in female offspring, it is possible that alterations in WM microstructure may transmit the long-term effects of maternal mental distress during early life to increased vigilance towards negative emotional expressions. These hypotheses and sexual dimorphism in the observed associations require replication and are potential focus areas for future studies.

neuroscience↗

bioRxiv2023

Personalised Regional Modelling Predicts Tau Progression in the Human Brain

Aggregation of the hyperphosphorylated tau protein is a central driver of Alzheimers disease, and its accumulation exhibits a rich spatio-temporal pattern that unfolds during the course of the disease, sequentially progressing through the brain across axonal connections. It is unclear how this spatio-temporal process is orchestrated - namely, to what extent the spread of pathologic tau is governed by transport between brain regions, local production or both. To address this, we develop a mechanistic model from tau PET data to describe tau dynamics along the Alzheimers disease timeline. Our analysis reveals longitudinal changes in production and transport dynamics on two independent cohorts, with subjects in early stage of the disease exhibiting transport-dominated spread, consistent with an initial spread of pathologic tau seeds, and subjects in late stage disease (Braak stage 3/4 onwards) characterised primarily by local production of tau. Furthermore, we demonstrate that the model can accurately predict subject-specific longitudinal tau accumulation at a regional level, potentially providing a new clinical tool to monitor and classify patient disease progression. TeaserA mechanistic model reveals tau protein dynamics in Alzheimers, showing stage-specific shifts in transport and local production.

neuroscience↗

bioRxiv2023

Associations between maternal pre-pregnancy BMI and infant striatal mean diffusivity

Background/ObjectivesIt is well-established that parental obesity is a strong risk factor for associates with offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring brain during in utero development. MethodsWe used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 mean gestational weeks at birth 39.88, SD = 1.14; and at scan 43.56, SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index and infant striatal mean diffusivity. ResultsA strong positive association was found between the maternal pre-pregnancy body mass index and newborn left caudate nucleus mean diffusivity. Results remained unchanged after the adjustment for covariates. ConclusionsIn utero exposure to maternal adiposity might have a growth impairing impact on the mean diffusivity of infant left caudate nucleus. Considering the involvement of caudate nucleus in regulating eating behaviour and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early life caudate development and weight trajectories of the offspring.

neuroscience↗

bioRxiv2023

Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimers disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related mechanisms which vary between individuals, such as CSF production and clearance rates. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our novel reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.

neuroscience↗

bioRxiv2023

Exposure to childhood maltreatment is associated with changes in sperm small non-coding RNA and DNA methylation profiles

BackgroundChildhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the paternal germ line. The contribution of paternal early life stress on the health of the next generation in humans is not fully elucidated. MethodsIn this study, we measured paternal CME using the Trauma and Distress Scale (TADS) questionnaire and mapped sperm-borne sncRNAs expression by small RNA sequencing (small RNA-seq) and DNA methylation (DNAme) in spermatozoa by reduced-representation bisulfite sequencing (RRBS-seq) in males from the FinnBrain Birth Cohort Study. The study design was a (nested) case-control study, high-TADS (TADS [≥] 39, n = 25 for DNAme and n = 14 for small RNA-seq) and low-TADS (TADS [≤] 10, n = 30 for DNAme and n = 16 for small RNA-seq)). Groups were compared to identify specific epigenetic signatures associated with TADS levels in the spermatozoa of participants. ResultsCompared to the control group, high CME was associated with altered sperm sncRNA expression and DNAme profiles. Particularly, we identified several tRNA-derived small RNAs (tsRNAs) and miRNAs with markedly changed levels in males with high CME. DNA methylation analysis identified several genomic regions with differentially methylated CpGs between groups. Notably, we identified two epigenetic marks related to brain development with distinct profiles between CME and controls, the miRNA hsa-mir-34c-5p and differential methylation of the region in proximity of FSCN1. ConclusionsThis study provides further evidence that early life stress influences the paternal germ line epigenome and supports a possible contribution in the development of the central nervous system of the next generation.

molecular biology↗

bioRxiv2023

Infant Left Amygdala Volume Is Negatively Associated with Fecal Microbiota Diversity

IntroductionRodent studies have addressed the importance of early life gut microbiota in the development of emotional and social functioning. Studies in human infants are still scarce, but associations with cognition and temperament have been reported. Neuroimaging studies have linked the amygdala with fecal microbiota diversity in infants, but crucially these studies have not covered the neonatal period, and the current study addressed this gap. MethodsThe study population included 65 infants drawn from the ongoing, general population based FinnBrain Birth Cohort Study. Brain MRI was performed around the age of one month (mean age 25 days). Fecal microbiota profiles (mean 68 days) were assessed by 16s rRNA amplicon sequencing at the age of 2.5 months. ResultsWe found a negative association between infant left amygdala volume and alpha diversity (n=52, beta =-0.0043, p=0.034, adjusted for infant sex, breastfeeding, delivery mode, age during fecal sampling, age from conception during scan, and intracranial volume, Fig.1). Amygdala volumes were not associated with beta diversity (p=0.21), nor with the abundances of individual genera when adjusted for the same covariates and multiple testing. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/537273v1_fig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@bf1304org.highwire.dtl.DTLVardef@798edeorg.highwire.dtl.DTLVardef@92c040org.highwire.dtl.DTLVardef@8bc2a9_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure. 1.C_FLOATNO Gut microbiota alpha diversity associates negatively with left (A), but not with right (B) amygdala volume. The grey areas depict 95% confidence intervals. C_FIG ConclusionOur results provide first evidence for associations between the brain and fecal microbiota in human neonates. Although the reported data do not allow investigation of underlying mechanisms, i.e. about the directionality of the hypothesized gut-brain connection, the reported connection encourages for future investigations of manifestations of gut-brain axis in early life.

neuroscience↗

bioRxiv2023

Impact of prenatal synthetic glucocorticoid exposure on the adolescent brain

Synthetic Glucocorticoids (sGC) are commonly prescribed in preterm risk pregnancies in order to improve fetal organ maturation. This administration greatly reduces perinatal and neonatal mortality and respiratory distress syndrome associated with prematurity, but preclinical evidence warns for an adverse effect of sGC in the developing brain. In this work we evaluated the long-term effects of prenatal exposure to sGC in the brain of 17 years-old adolescents using multimodal MRI. From 4607 birth registrations from Hospital de Braga - Portugal, we selected participants that were born with similar gestational age, but that were either exposed during pregnancy to sGC (n=21) or non-exposed (n=24). After obtaining a detailed clinical history, participants were subjected to an extensive neuropsychological evaluation, followed by structural and functional MRI. No differences were found in the performance on neuropsychological tests between sGC-exposed and non-exposed participants. Moreover, no differences were found in regional brain volumes. However, the sGC-exposed group presented reduced functional connectivity at rest in a network involving primarily sub-cortical, cerebellar and frontal nodes in comparison to the non-exposed group, even after controlling for confounding factors such as gestational age at birth, birth weight, and sex. Our results suggest that prenatal sGC-exposed adolescents present no significant deviations in neuropsychological performance in the dimensions that we evaluated, although they presented altered functional connectivity, highlighting the need for additional studies to understand the impact of these changes in brain functioning and in behavior. HighlightsPrenatal synthetic glucocorticoid exposure does not lead to structural changes in the adolescent brain. Adolescents prenatally exposed to synthetic glucocorticoids present altered resting state network.

neuroscience↗

bioRxiv2023

Effect of number of diffusion encoding directions in Neonatal Diffusion Tensor Imaging using Tract-Based Spatial Statistical analysis

Diffusion Tensor Imaging (DTI) has been used to study the developing brain in early childhood, infants and in utero studies. In infants, number of used diffusion encoding directions has traditionally been smaller in earlier studies down to the minimum of 6 orthogonal directions. While the more recent studies often involve more directions, number of used directions remains an issue when acquisition time is optimized without compromising on data quality and in retrospective studies. Variability in the number of used directions may introduce bias and uncertainties to the DTI scalar estimates that affect cross-sectional and longitudinal study of the brain. We analyzed DTI images of 133 neonates, each data having 54 directions after quality control, to evaluate the effect of number of diffusion weighting directions from 6 to 54 with interval of 6 to the DTI scalars with Tract-based spatial statistics (TBSS) analysis. The TBSS analysis was applied to DTI scalar maps, and the mean Region of Interest (ROI) values were extracted using JHU atlas. We found significant bias in ROI mean values when only 6 directions were used (positive in FA, negative in MD, AD, RD), while when using 24 directions and above, the difference to scalar values calculated from 54 direction DTI was negligible. Using DTI measurements from data with at least 24 directions may be used in comparisons with DTI measurements from data with higher numbers of directions.

neuroscience↗

bioRxiv2023

Parental childhood maltreatment associates with offspring left amygdala volume at early infancy

BackgroundChildhood maltreatment exposure (CME) and related trauma could be considered some of psychiatrys greatest public health challenges. CME and early adversity have been associated with increased amygdala volume in exposed individuals. Emerging evidence implies that CME could also affect prenatal development of the offspring. MethodsAs part of the FinnBrain Birth Cohort Study, we measured bilateral amygdala volumes from MR images in 76 healthy infants at 2-5 weeks of gestation corrected age and obtained the Trauma and Distress Scale (TADS) questionnaire from both parents. The associations between neonatal amygdala volumes and TADS scores were examined in stepwise regression models. ResultsWe found that maternal CME associated positively with infant left amygdala volume (p = .045) while the positive association for the paternal trauma score was only marginally significant (p = .099). Similar associations were not observed for the right amygdala. In the exploratory analyses, we used age ranges (0-6, 7-12, and 13-18 years) as estimate of the timing of the CME and included all three time points from both parents using left amygdala volume into the stepwise regression models. We found that maternal TADS scores from 13-18 years of age associated positively with infant left amygdala volumes (p = .008). Correspondingly, paternal TADS scores from 0-6 years of age associated positively with the infant left amygdala volumes (p = .014). ConclusionsOur link the infant offspring amygdala volume with parental CME with some agreement with prior findings, and they also imply links paternal CME to infant amygdala volumes. Amygdala is one of the key brain structures associated with both early life exposures and later psychiatric health, which makes it crucially important to elucidate both the underlying mechanisms and the later relevance of these associations in future studies.

neuroscience↗

bioRxiv2023

Structural brain correlates of non-verbal cognitive ability in 5-year-old children: findings from the FinnBrain Birth Cohort study

Non-verbal cognitive ability predicts multiple important life outcomes, e.g., school and job performance. It has been associated with parieto-frontal cortical anatomy in prior studies in adult and adolescent populations, while young children have received relatively little attention. We explored the associations between cortical anatomy and non-verbal cognitive ability in 165 5-year-old participants (mean scan age 5.40 years, SD 0.13; 90 males) from the FinnBrain Birth Cohort study. T1-weighted brain magnetic resonance images were processed using FreeSurfer. Non-verbal cognitive ability was measured using the Performance Intelligence Quotient (PIQ) estimated from the Block Design and Matrix Reasoning subtests from the Wechsler Preschool And Primary Scale Of Intelligence (WPPSI-III). In vertex-wise general linear models, PIQ scores associated positively with volumes in left caudal middle frontal and right pericalcarine regions, as well as surface area in left caudal middle frontal, left inferior temporal, and right lingual regions. There were no associations between PIQ and cortical thickness. To the best of our knowledge, this is the first study to examine structural correlates of non-verbal cognitive ability in a large sample of typically developing 5-year-olds. The findings are generally in line with prior findings from older age groups.

neuroscience↗

bioRxiv2023

Sex differences, asymmetry and age-related white matter development in infants and 5-year-olds as assessed with Tract-Based Spatial Statistics

The rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of five years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tractbased spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seems to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry. HighlightsO_LIWhite matter tract integrity shows widespread sex differences at the age of 5 years. C_LIO_LIWhite matter structure is highly lateralized during early childhood, and changes in asymmetry occur between the birth and 5 years of age. C_LIO_LIThe white matter lateralization pattern of 5-year-olds, unlike of infants, resembles asymmetry observed in adults. C_LI

neuroscience↗

bioRxiv2023

Maternal prenatal distress exposure negatively associates with the stability of neonatal frontoparietal network

Maternal prenatal distress (PD), frequently defined as in utero prenatal stress exposure (PSE) to the developing fetus, influences the developing brain and numerous associations between PSE and brain structure have been described both in neonates and in older children. Previous studies addressing PSE-linked alterations in neonates brain activity have focused on connectivity analyses from predefined seed regions, but the effects of PSE at the level of distributed functional networks remains unclear. In this study, we investigated the impact of prenatal distress on the spatial and temporal properties of functional networks detected in functional MRI data from 20 naturally sleeping, term-born (age 25.85 {+/-} 7.72 days, 11 males), healthy neonates. First, we performed group level independent component analysis (GICA) to evaluate an association between PD and the spatial configuration of the functional networks. Second, we search for an association with PD at the level of the stability of functional networks over time using leading eigenvector dynamics analysis (LEiDA). No statistically significant associations were detected at the spatial level for the GICA-derived networks. However, at the dynamic level, LEiDA revealed that maternal PD significantly decreased the stability of a frontoparietal network. These results imply that maternal PD may influence the stability of frontoparietal connections in neonatal brain network dynamics and adds to the cumulating evidence that frontal areas are especially sensitive to PSE.

neuroscience↗

bioRxiv2022

Associations of Cumulative Paternal and Maternal Childhood Maltreament Exposure with Neonate Brain Anatomy

BackgroundChildhood maltreatment exposure (CME) can lead to adverse long-term consequences for the exposed individual. Emerging evidence suggests that the long-term effect of CME may be transmitted across generations, starting already during prenatal development. MethodsIn this study, we measured brain grey and white matter volumes from MR images in 62 healthy neonates at 2-5 weeks of gestation corrected age and obtained Trauma and Distress Scale (TADS) questionnaire data from both parents. ResultsWe found that paternal CME associated positively with neonate supratentorial grey matter volumes while the association for the maternal TADS scores was not statistically significant. Maternal pre-pregnancy BMI associated with supratentorial white matter volumes, but not with parental CME. ConclusionsWe are the first to report that paternal CME is linked with variation in newborn cortical volume. Our results imply an intergenerational transmission of paternal CME to offspring. Elucidating the later relevance of these associations and mechanisms involved remains an enticing avenue for future studies.

neuroscience↗

bioRxiv2022

Genomic characterization of Francisella tularensis and other diverse Francisella species from complex samples

Francisella tularensis, the bacterium that causes the zoonosis tularemia, and its genetic near neighbor species, can be difficult or impossible to cultivate from complex samples. Thus, there is a lack of genomic information for these species that has, among other things, limited the development of robust detection assays for F. tularensis that are both specific and sensitive. The objective of this study was to develop and validate approaches to capture, enrich, sequence, and analyze Francisella DNA present in DNA extracts generated from complex samples. RNA capture probes were designed based upon the known pan genome of F. tularensis and other diverse species in the family Francisellaceae. Probes that targeted genomic regions also present in non-Francisellaceae species were excluded, and probes specific to particular Francisella species or phylogenetic clades were identified. The capture-enrichment system was then applied to diverse, complex DNA extracts containing low-level Francisella DNA, including human clinical tularemia samples, environmental samples (i.e., animal tissue and air filters), and whole ticks/tick cell lines, which was followed by sequencing of the enriched samples. Analysis of the resulting data facilitated rigorous and unambiguous confirmation of the detection of F. tularensis or other Francisella species in complex samples, identification of mixtures of different Francisella species in the same sample, analysis of gene content (e.g., known virulence and antimicrobial resistance loci), and high-resolution whole genome-based genotyping. The benefits of this capture-enrichment system include: even very low target DNA can be amplified; it is culture-independent, reducing exposure for research and/or clinical personnel and allowing genomic information to be obtained from samples that do not yield isolates; and the resulting comprehensive data not only provide robust means to confirm the presence of a target species in a sample, but also can provide data useful for source attribution, which is important from a genomic epidemiology perspective.

genomics↗

bioRxiv2021

Subcortical brain segmentation in 5-year-old children: validation of FSL-FIRST and FreeSurfer against manual segmentation

Developing accurate subcortical volumetric quantification tools is crucial for neurodevelopmental studies, as they could reduce the need for challenging and time-consuming manual segmentation. In this study the accuracy of two automated segmentation tools, FSL-FIRST (with three different boundary correction settings) and FreeSurfer were compared against manual segmentation of subcortical nuclei, including the hippocampus, amygdala, thalamus, putamen, globus pallidus, caudate and nucleus accumbens, using volumetric and correlation analyses in 80 5-year-olds. Both FSL-FIRST and FreeSurfer overestimated the volume on all structures except the caudate, and the accuracy varied depending on the structure. Small structures such as the amygdala and nucleus accumbens, which are visually difficult to distinguish, produced significant overestimations and weaker correlations with all automated methods. Larger and more readily distinguishable structures such as the caudate and putamen produced notably lower overestimations and stronger correlations. Overall, the segmentations performed by FSL-FIRSTs Default pipeline were the most accurate, while FreeSurfers results were weaker across the structures. In line with prior studies, the accuracy of automated segmentation tools was imperfect with respect to manually defined structures. However, apart from amygdala and nucleus accumbens, FSL-FIRSTs agreement could be considered satisfactory (Pearson correlation > 0.74, Intraclass correlation coefficient (ICC) > 0.68 and Dice Score coefficient (DSC) > 0.87) with highest values for the striatal structures (putamen, globus pallidus and caudate) (Pearson correlation > 0.77, ICC > 0.87 and DSC > 0.88, respectively). Overall, automated segmentation tools do not always provide satisfactory results, and careful visual inspection of the automated segmentations is strongly advised.

neuroscience↗

bioRxiv2021

Feasibility of FreeSurfer processing for T1-weighted brain images of 5-year-olds: semiautomated protocol of FinnBrain Neuroimaging Lab

Pediatric neuroimaging is a quickly developing field that still faces important methodological challenges. One key challenge is the use of many different atlases, automated segmentation tools, manual edits in semiautomated protocols, and quality control protocols, which complicates comparisons between studies. In this article, we present our semiautomated segmentation protocol using FreeSurfer v6.0, ENIGMA consortium software, and the quality control protocol that was used in FinnBrain Birth Cohort Study. We used a dichotomous quality rating scale for inclusion and exclusion of images, and then explored the quality on a region of interest level to exclude all regions with major segmentation errors. The effects of manual edits on cortical thickness values were minor: less than 2% in all regions. Supplementary materials cover registration and additional edit options in FreeSurfer and comparison to the computational anatomy toolbox (CAT12). Overall, we conclude that despite minor imperfections FreeSurfer can be reliably used to segment cortical metrics from T1-weighted images of 5-year-old children with appropriate quality assessment in place. However, custom templates may be needed to optimize the results for the subcortical areas. Our semiautomated segmentation protocol provides high quality pediatric neuroimaging data and could help investigators working with similar data sets.

neuroscience↗