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Alexopoulos, D.

Publications and source records attributed to Alexopoulos, D..

7 recordsLinked to original sources

Functional Organization of the Neonatal Basal Ganglia and Thalamus

The basal ganglia and thalamus are key nodes in subcortico-cortical loops involved in sensory, motor, and cognitive function. In adults, posterior regions of the subcortex link to cortical sensorimotor networks and anterior regions link to association networks. Alterations in the size, strength, and selectivity of these subcortical regional network representations are implicated in several neuropsychiatric disorders, many of which originate early in development. However, the organization of these network representations at birth remains incompletely understood, limiting our ability to devise normative and atypical developmental models of subcortico-cortical interactions. Using resting-state fMRI, we characterized the size, strength, and selectivity of cortical network representations in the basal ganglia and thalamus in a set of neonates (n=261) and compared results to children (age range 9-11 years, n=69) and adults (n=120). We found that the broad anterior-posterior organization of the subcortex is present at birth, yet representations of somatomotor networks were larger at birth compared to children and adults (p<0.001). The strength and selectivity of subcortico-cortical functional connectivity (FC) exhibited interactions between age group and network (all p<0.001), such that subcortical representations of sensorimotor networks exhibited stronger FC and higher selectivity in neonates, while subcortical representations of association networks exhibited stronger FC and higher selectivity in older cohorts. In parallel, data-driven clustering revealed areas with integration of multiple networks in the neonatal subcortex. These results suggest that subcortico-cortical FC evolves over development largely in a sensorimotor-association manner and provide a baseline for normative and disordered subcortical development. HIGHLIGHTSO_LIThe basic anterior-posterior layout of association to sensorimotor network representation in the basal ganglia and thalamus is present at term birth. C_LIO_LISensorimotor systems are overrepresented in neonates compared to children and adults. C_LIO_LISensorimotor representations exhibit greater functional connectivity strength and selectivity than association representations at birth, while association representations are stronger and more selective than sensorimotor representations in adults. C_LIO_LIThe neonatal subcortex exhibits substantial integration of multiple cortical networks. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/736181v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1d3bfa3org.highwire.dtl.DTLVardef@ca904dorg.highwire.dtl.DTLVardef@c7c219org.highwire.dtl.DTLVardef@983020_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

fMRIPrep Lifespan: Extending A Robust Pipeline for Functional MRI Preprocessing to Developmental Neuroimaging

The adoption of a standardized preprocessing workflow is vital for fostering community, sharing, and reproducibility. fMRIPrep has been a critical advancement towards this end, however, it is limited in its capacity to be applied to data across the lifespan, starting from infancy. Here, we introduce fMRIPrep Lifespan, an extension of fMRIPrep that extends the standardized processing from childhood to senescence to include neonatal, infant, and toddler structural and functional MRI data preprocessing. This effort involves a NiPreps integration of 1) a workflow akin to fMRIPrep optimized for MRI data in the first years of life (previously NiBabies) and 2) upstream enhancements to the entire NiPreps suite, including multi-echo data processing, modularization of workflow components, and convergence of processing with other popular workflows (ABCD-BIDS, Human Connectome Project Pipelines). Using data from the Baby Connectome Project (participants 1-43 months of age), we demonstrate that fMRIPrep Lifespan produces high-quality outputs across a wide age range. Moving forward, the scalable, modular infrastructure of fMRIPrep Lifespan will ensure adaptability to data from birth to old age while maintaining robust and reproducible frameworks for functional MRI research across the lifespan.

bioinformatics↗

Baby Open Brains: An Open-Source Repository of Infant Brain Segmentations

Reproducibility of neuroimaging research on infant brain development remains limited due to highly variable protocols and processing approaches. Progress towards reproducible pipelines is limited by a lack of benchmarks such as gold standard brain segmentations. Addressing this core limitation, we constructed the Baby Open Brains (BOBs) Repository, an open source resource comprising manually curated and expert-reviewed infant brain segmentations. Markers and expert reviewers manually segmented anatomical MRI data from 71 infant imaging visits across 51 participants, using both T1w and T2w images per visit. Anatomical images showed dramatic differences in myelination and intensities across the 1 to 9 month age range, emphasizing the need for densely sampled gold standard manual segmentations in these ages. The BOBs repository is publicly available through the Masonic Institute for the Developing Brain (MIDB) Open Data Initiative, which links S3 storage, Datalad for version control, and BrainBox for visualization. This repository represents an open-source paradigm, where new additions and changes can be added, enabling a community-driven resource that will improve over time and extend into new ages and protocols. These manual segmentations and the ongoing repository provide a benchmark for evaluating and improving pipelines dependent upon segmentations in the youngest populations. As such, this repository provides a vitally needed foundation for early-life large-scale studies such as HBCD.

neuroscience↗

Prenatal environment is associated with the pace of cortical network development over the first three years of life

Environmental influences on brain structure and function during early development have been well-characterized. In pre-registered analyses, we test the theory that socioeconomic status (SES) is associated with differences in trajectories of intrinsic brain network development from birth to three years (n = 261). Prenatal SES is associated with developmental increases in cortical network segregation, with neonates and toddlers from lower-SES backgrounds showing a steeper increase in cortical network segregation with age, consistent with accelerated network development. Associations between SES and cortical network segregation occur at the local scale and conform to a sensorimotor-association hierarchy of cortical organization. SES-associated differences in cortical network segregation are associated with language abilities at two years, such that lower segregation is associated with improved language abilities. These results yield key insight into the timing and directionality of associations between the early environment and trajectories of cortical development.

neuroscience↗

BIBSNet: A Deep Learning Baby Image Brain Segmentation Network for MRI Scans

ObjectivesBrain segmentation of infant magnetic resonance (MR) images is vitally important for studying typical and atypical brain development. The infant brain undergoes many changes throughout the first years of postnatal life, making tissue segmentation difficult for most existing algorithms. Here we introduce a deep neural network BIBSNet (Baby and Infant Brain Segmentation Neural Network), an open-source, community-driven model for robust and generalizable brain segmentation leveraging data augmentation and a large sample size of manually annotated images. Experimental DesignIncluded in model training and testing were MR brain images from 90 participants with an age range of 0-8 months (median age 4.6 months). Using the BOBs repository of manually annotated real images along with synthetic segmentation images produced using SynthSeg, the model was trained using a 10-fold procedure. Model performance of segmentations was assessed by comparing BIBSNet, joint label fusion (JLF) inferred segmentation to ground truth segmentations using Dice Similarity Coefficient (DSC). Additionally, MR data along with the FreeSurfer compatible segmentations were processed with the DCAN labs infant-ABCD-BIDS processing pipeline from ground truth, JLF, and BIBSNet to further assess model performance on derivative data, including cortical thickness, resting state connectivity and brain region volumes. Principal ObservationsBIBSNet segmentations outperforms JLF across all regions based on DSC comparisons. Additionally, with processed derived metrics, BIBSNet segmentations outperforms JLF segmentations across nearly all metrics. ConclusionsBIBSNet segmentation shows marked improvement over JLF across all age groups analyzed. The BIBSNet model is 600x faster compared to JLF, produces FreeSurfer-compatible segmentation labels, and can be easily included in other processing pipelines. BIBSNet provides a viable alternative for segmenting the brain in the earliest stages of development.

neuroscience↗

Neurodevelopmental Patterns of Early Postnatal White Matter Maturation Represent Distinct Underlying Microstructure and Histology

During the early postnatal period, cerebral white matter undergoes rapid maturation through a complex series of interrelated cellular and histogenetic processes. Accurately quantifying these processes is important for improving understanding of early brain development, developmental abnormalities related to prematurity, and neurodevelopmental diseases. Past efforts have used magnetic resonance imaging (MRI) to track these developmental processes in vivo. However, most previous studies have relied on single imaging modality data and have often been limited by small samples and analytics that do not evaluate complex multivariate imaging patterns. Here, we applied an advanced unsupervised multivariate pattern analysis technique, non-negative matrix factorization (NMF), to T2w/T1w signal ratio maps from a large cohort of newborns (Developing Human Connectome Project [dHCP], n=342), revealing patterns of synchronous white matter maturation. These patterns showed divergent age-related maturational trajectories and differential susceptibility to premature birth, which were replicated in an independent large sample of newborns (Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders [eLABE], n=239). Furthermore, we showed that T2w/T1w signal variations in white matter maturational patterns are explained by differential contributions of white matter microstructure indices (i.e., free water content and neurite density index) derived from neurite orientation dispersion and density imaging (NODDI) modeling of diffusion-weighted MRI. Finally, we demonstrated how white matter maturation patterns relate to distinct histological features by comparing our findings with postmortem late fetal/early postnatal brain tissue staining. Together, these results delineate a novel MRI representation of white matter microstructural and histological reorganization during the early postnatal development.

neuroscience↗

Dynamic patterns of cortical expansion during folding of the preterm human brain

During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggests that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a new method to estimate local growth from sequential cortical reconstructions. Using anatomically-constrained Multimodal Surface Matching (aMSM), we obtain accurate, physically-guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned 2-4 times during the period of rapid cortical expansion (28 to 38 weeks postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with patterns of active folding. Furthermore, these growth patterns shift over the course of development, with non-injured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully-automated surface analysis, based on tools freely available to the brain mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.\n\nSignificance StatementThe human brain exhibits complex folding patterns that emerge during the third trimester of fetal development. Minor folds are quasi-randomly shaped and distributed. Major folds, in contrast, are more conserved and form important landmarks. Disruption of cortical folding is associated with devastating disorders of cognition and emotion. Despite decades of study, the processes that produce normal and abnormal folding remain unresolved, although the relatively rapid tangential expansion of the cortex has emerged as a driving factor. Accurate and precise measurement of cortical growth patterns during the period of folding has remained elusive. Here, we illuminate the spatiotemporal dynamics of cortical expansion by analyzing MRI-derived surfaces of preterm infant brains, using a novel strain energy minimization approach.

neuroscience↗