Biology subjects

Merisaari, H.

Publications and source records attributed to Merisaari, H..

16 recordsLinked to original sources

bioRxiv2026

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

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bioRxiv2026

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.

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bioRxiv2026

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.

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bioRxiv2025

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.

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bioRxiv2025

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.

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bioRxiv2025

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.

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bioRxiv2024

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.

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bioRxiv2024

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.

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bioRxiv2024

The FinnBrain Multimodal Neonatal Template and Atlas Collection: T1, T2, and DTI brain templates, and accompanying cortical and subcortical atlases

The accurate processing of neonatal and infant brain MRI data is crucially important for developmental neuroscience, but presents challenges that child and adult data do not. Tissue segmentation and image coregistration accuracy can be improved by optimizing template images and / or related segmentation procedures. Here, we describe the construction of the FinnBrain Neonate (FBN-125) template; a multi-contrast template with T1- and T2-weighted as well as diffusion tensor imaging derived fractional anisotropy and mean diffusivity images. The template is symmetric and aligned to the Talairach-like MNI 152 template and has high spatial resolution (0.5 mm3). In addition, we provide atlas labels, constructed from manual segmentations, for cortical grey matter, white matter, cerebrospinal fluid, brainstem, and cerebellum as well as the bilateral hippocampi, amygdalae, caudate nuclei, putamina, globi pallidi, and thalami. We provide this multi-contrast template along with the labelled atlases for the use of the neuroscience community in the hope that it will prove useful in advancing developmental neuroscience, for example, by helping to achieve reliable means for spatial normalization and measures of neonate brain structure via automated computational methods. Additionally, we provide standard co-registration files that will enable investigators to reliably transform their statistical maps to the adult MNI space, which has the potential to improve the consistency and comparability of neonatal studies or the use of adult MNI space atlases in neonatal neuroimaging.

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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.

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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.

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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.

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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

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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.

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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.

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bioRxiv2019

The Impact of Edema and Fiber Crossing on Diffusion MRI Metrics: DBSI vs. Diffusion ODF

PurposeDiffusion tensor imaging (DTI) has been employed for over two decades to noninvasively quantify central nervous system (CNS) diseases/injuries. However, DTI is an inadequate simplification of diffusion modeling in the presence of co-existing inflammation, edema, and crossing nerve fibers.\n\nMethodsWe employed a tissue phantom using fixed mouse trigeminal nerves coated with various amounts of agarose gel to mimic crossing fibers in the presence of vasogenic edema. Diffusivity measures derived by DTI and diffusion basis spectrum imaging (DBSI) were compared at increasing levels of simulated edema and degrees of fiber crossing. Further, we assessed the ability of DBSI, diffusion kurtosis imaging (DKI), generalized q-sampling imaging (GQI), q-ball imaging (QBI), and neurite orientation dispersion and density imaging (NODDI) to resolve fiber crossing, in reference to the gold standard angles measured from structural images.\n\nResultsDTI-computed diffusivities and fractional anisotropy (FA) were significantly confounded by gelmimicked edema and crossing fibers. Conversely, DBSI calculated accurate diffusivities of individual fibers regardless of the extent of simulated edema and degrees of fiber crossing angles. Additionaly, DBSI accurately and consistently estimated crossing angles in various conditions of gel-mimicked edema when comparing with gold standard (r2=0.92, p=1.9x10-9, bias=3.9{degrees}). Small crossing angles and edema sinficantly impact dODF, making DKI, GQI and QBI less accurate in detecting and estimating fibers corrsing angles. Lastly, we demonstrate DBSIs superiority over DTI for recovering and delineating white matter tracts in peritumoral edema for preoperative planning of surgical resection.\n\nConclusionsDBSI is able to separate two crossing fibers and accurately recover their diffusivities in a complex environment characterized by increasing crossing angles and amounts of gel-mimicked edema. DBSI also indicated better angular resolution capability compared with DKI, QBI and GQI.

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