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Biology subjects

Lundervold, A.

Publications and source records attributed to Lundervold, A..

9 recordsLinked to original sources

Run or glide: muscles are indifferent while the tendon takes the strain

Conventional diagonal stride skiing traditionally includes a glide phase, characterised by a period of relatively passive gliding on one ski. While the glide phase may take advantage of low ski-snow friction, it does not exhibit the same whole-cycle mechanical energy fluctuations seen in running or walking on foot. A new sub-technique, known as running style, substantially reduces the glide phase and may alter the role of elastic tissues, making the movement pattern more similar to uphill running on foot in its temporal organisation. We examined knee extensor and plantar flexor muscle-tendon behaviour in eight competitive skiers performing conventional diagonal and running techniques on a treadmill inclined at 10{degrees}. Using synchronised ultrasonography, 3D kinematics, ski forces and EMG, we quantified gastrocnemius medialis and vastus lateralis fascicle and muscle-tendon unit (MTU) dynamics in both the running (RUN) and conventional (CON) styles. Shorter glide and total cycle durations during RUN shifted MTU peak length and velocity earlier during the kick phase. Fascicles in both muscles operated at similar velocities across techniques, showing MTU-fascicle decoupling. Vastus lateralis fascicles shortened at higher absolute peak velocities than gastrocnemius in both conditions, while normalised velocities were similar. RUN increased preactivation and advanced EMG timing, while integrated EMG during the kick was lower compared to CON. These findings suggest that, despite large shifts in external mechanics between glide-based and more running-like skiing, elastic tissues may help stabilise fascicle behaviour and preserve a similar contractile strategy across muscles and techniques.

synthetic biology↗

Brain asymmetries from midlife to old adulthood and hemispheric brain age

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.

neuroscience↗

Muscle function during locomotion on skis at varying speed and incline conditions

The human musculoskeletal system is well adapted to use energy efficient muscle-tendon mechanics during walking and running but muscle behaviour during on-snow locomotion is unknown. Therefore, we examined muscle and muscle-tendon unit behaviour during diagonal style roller skiing at three speed and incline conditions. We assessed lower leg muscle and muscle-tendon unit mechanics and muscle activity in thirteen high-level skiers during treadmill roller skiing using synchronised ultrasound, motion capture, electromyography and ski-binding force measurements. Participants skied using diagonal style at 2.5 and 3.5 m{middle dot}s-1 at 5{degrees}, and at 2.5 m{middle dot}s-1 at 10{degrees}. We found an uncoupling of muscle and joint behaviour during most parts of the propulsive kick phase in all conditions (P<0.01). Gastrocnemius muscle fascicles actively shortened ~9 mm during the kick phase, while the muscle-tendon unit went through a stretch-shortening cycle. Peak muscle-tendon unit shortening velocity was five times higher than fascicle velocity (375 vs 74 mm{middle dot}s-1, P<0.01). Increased incline was met by greater muscle activity (24%, P=0.04) and slower fascicle shortening velocities (34 vs. 45 mm{middle dot}s-1, P<0.01). Increased speed was met by greater peak muscle activity (23%, P<0.01) and no change in fascicle shortening velocity. Our data show that muscle behaviour was uncoupled from the joint movement, which enables beneficial contractile conditions and energy utilisation during diagonal style at different slopes and speeds. Active preloading in the end of the glide phase may benefit the mechanisms. Summary statementWe examined muscle function during diagonal style cross country skiing in competitive cross-country skiers. Our data show an uncoupling of muscle and joint behaviour in the lower leg during skiing.

physiology↗

Brain-wide associations between white matter and agehighlight the role of fornix microstructure in brain age

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 analysed UK Biobank diffusion Magnetic Resonance Imaging (dMRI) data across midlife and older age (N = 35,749, 44.6 to 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.

neuroscience↗

Longitudinal stability of the brain functional connectome is associated with episodic memory performance in aging

The brain functional connectome forms a relatively stable and idiosyncratic backbone that can be used for identification or \"fingerprinting\" of individuals with a high level of accuracy. While previous cross-sectional evidence has demonstrated increased stability and distinctiveness of the brain connectome during the course of childhood and adolescence, less is known regarding the longitudinal stability in middle and old age. Here we collected structural and resting state functional MRI data at two time-points separated by 2-3 years in 75 middle-aged and older adults (age 49-80, SD = {+/-} 6.91 years) which allowed us to assess the long-term stability of the functional connectome. We show that the connectome backbone generally remains stable over a 2-3 year time frame in middle- and old age. Independent of age, cortical volume was associated with the connectome stability of several canonical resting-state networks, suggesting that the connectome backbone relates to the structural integrity of the cortex. Moreover, individual longitudinal stability of subcortical and default mode networks were associated with differences in cross-sectional and longitudinal measures of episodic memory performance, supporting the functional relevance. The findings encourage the use of connectome stability analyses for understanding individual differences in cognitive aging. Furthermore, the observation that age-related changes in episodic memory performance relates to the stability of subcortical and default mode networks, provides new longitudinal evidence for the importance of these networks in maintaining mnemonic processing in old age.

neuroscience↗

Shared genetic background between children and adults with attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

genetics↗

Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways

Liability to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published GWAS in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected (\"Concordant\") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants demonstrating the counterintuitive (\"Discordant\") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education and/or schizophrenia at p<5x10-8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs, and many of these have been validated by larger, more recent single-phenotype GWAS. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms: early neurodevelopmental pathways that characterize concordant allelic variation, and adulthood synaptic pruning pathways that were linked to the paradoxical positive genetic association between education and schizophrenia. Further, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia, but also to the broader biological dimensions that are implicated in both general health outcomes and psychiatric illness.

genetics↗

Lateral ventricle volume trajectories predict response inhibition in older age - a longitudinal brain imaging and machine learning approach

ObjectiveIn a three-wave ~6 yrs longitudinal study we investigated if expansion of lateral ventricle (LV) volumes (regarded as a proxy for brain parenchyma loss) predicts performance on a test of response inhibition.\n\nParticipants and MethodsAnatomical trajectories of left (LH) and right (RH) lateral ventricle volumes across the three study-waves were quantified using the Longitudinal Stream in Freesurfer 5.3 and modelled using a linear mixed-effects (LME) algorithm. All participants (N = 74, mean age 60.7 yrs at inclusion, 48 females) performed the Color-Word Interference Test (CWIT). Response time on the third condition was used as a measure of response inhibition (RI) and divided into three classes (fast, medium and slow). The Extreme Gradient Boosting (XGBoost) algorithm was used for calculating the relative importance of selected LV volume features from the LME model in predicting RI class. Finally, the two most important extracted features were fed into a 10-fold cross-validation framework, estimating the accuracy, precision and recall of the RI class prediction.\n\nResultsFour LME based features were selected to characterize LV volume trajectories: steepness of LV volume change and the LV volume at the time of inclusion, each from the right and left hemisphere. The XGBoost procedure selected the steepness measure from the right and the volume at inclusion from the left hemisphere as the two most important features to predict RI performance. The 10-fold cross validation procedure showed a recall, precision and accuracy score (.40 - .50) that were clearly above chance level.\n\nConclusionMeasures of the LV volume trajectories gave a fairly good prediction of response inhibition performance, confirming the role of LV volume as a biomarker of cognitive function in older adults. Future studies should investigate the value of the lateral ventricle volume trajectories as predictors of cognitive preservation or decline into older age.

neuroscience↗

Brain scans from 21297 individuals reveal the genetic architecture of hippocampal subfield volumes

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimers disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields genetic architecture. T1-weighted brain scans (n=21297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, covarying for total hippocampal volume. We further calculated the single nucleotide polymorphism (SNP)-based heritability of twelve subfields, as well as their genetic correlation with each other, with other structural brain features, and with AD and schizophrenia. All outcome measures were corrected for age, sex, and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from .14 to .27, all p< 1x10-16) and clustered together based on their genetic correlations compared to other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

genetics↗