Biology subjects

Luby, J. L.

Publications and source records attributed to Luby, J. L..

7 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2025

Commonality and Variability in Functional Networks In Young Children Under 5 Years Old

Functional brain networks support human cognition, yet how individualized network architecture emerges in early childhood remains poorly understood. Averaging across participants can obscure age-specific organization and person-to-person differences, particularly in slowly developing association cortices. We developed an age-appropriate functional reference that captured common structure across toddlers without averaging away individual variability, enabling estimation of each childs networks from resting-state fMRI. Across cohorts of 8-60-month-old children, we found individualized network organization--including finer-scale subdivisions and emerging language lateralization--well before age five. Network layouts showed longitudinal stability, with greater consistency in sensory than association regions. Within-network connectivity was stronger and explained age-related variance when networks were defined using individualized rather than group-consensus topography. Left-lateralization of language networks tracked age-normalized verbal ability, linking early functional architecture to emerging cognition. These findings show that behaviorally relevant brain networks arise far earlier than previously recognized, providing a foundation for studying typical development and early biomarkers.

neuroscience↗

bioRxiv2025

Replicable, Transdiagnostic Behavioral and Neural Correlates of Sensory Over-responsivity

ObjectiveSensory over-responsivity (SOR), characterized by strong negative reactions to typically innocuous stimuli, is considered a symptom of autism spectrum disorder. However, SOR also affects 15-20% of children overall, including a majority of children with common psychiatric conditions. Despite its prevalence, the clinical specificity and neurobiological bases of SOR remain poorly understood. Our study aims to determine the specific clinical significance of SOR across diverse child samples and establish whether SOR is associated with replicable patterns of functional connectivity (FC). MethodWe analyzed data from 15,728 children (ages 6-17.9 years) across five datasets: three community samples, including the Adolescent Brain Cognitive Development [ABCD] and Healthy Brain Network [HBN] studies, and two autism-enriched samples. Bivariate and multivariate models examined associations between SOR and symptoms of anxiety, attention-deficit/hyperactivity disorder, depression, conduct disorder, and oppositional defiant disorder, as well as autistic traits. Analysis of resting-state functional MRI (fMRI) data from the ABCD study (n=4195) identified candidate brain-wide and circuit-specific FC correlates of mild SOR and tested replication of effects in an independent ABCD subsample (n=4190). Additional analyses tested extension to children with severe SOR in ABCD and replication in smaller samples [HBN (n=356), ABCD subset (n=356)]. ResultsMultivariate analyses revealed that SOR is associated with a remarkably consistent profile across samples: greater levels of both autistic traits and anxiety symptoms and, in community samples, lower levels of conduct disorder symptoms. Across samples, SOR is not reliably associated with symptoms of any other analyzed psychiatric conditions. Mild SOR is associated with brain-wide FC patterns and, specifically, reduced FC between cingulo-parietal network and bilateral caudate nucleus; these patterns show robust replication across independent ABCD subsamples and extension to severe SOR in ABCD but are not significant in smaller samples, indicating that large sample size is needed to reliably detect brain effects. ConclusionResults suggest that SOR may constitute a latent trait associated with both specific clinical risk and protection, and with replicable cortico-subcortical neural correlates. These findings advance our understanding of the neurobiology and clinical relevance of SOR. They may also inform clinical practice and future research aimed at understanding and supporting individuals with sensory challenges.

neuroscience↗

bioRxiv2024

Early Life Neuroimaging: The Generalizability of Cortical Area Parcellations Across Development

The cerebral cortex consists of distinct areas that develop through intrinsic embryonic patterning and postnatal experiences. Accurate parcellation of these areas in neuroimaging studies improves statistical power and cross-study comparability. Given significant brain changes in volume, microstructure, and connectivity during early life, we hypothesized that cortical areas in 1- to 3-year-olds would differ markedly from neonates and increasingly resemble adult patterns as development progresses. Here, we parcellated the cerebral cortex into putative areas using local functional connectivity gradients in 92 toddlers at 2 years old. We demonstrate high reproducibility of these cortical regions across 1- to 3-year-olds in two independent datasets. The area boundaries in 1- to 3-year-olds were more similar to those in adults than those in neonates. While the age-specific group area parcellation better fit the underlying functional connectivity in individuals during the first 3 years, adult area parcellations might still have some utility in developmental studies, especially in children older than 6 years. Additionally, we provide connectivity-based community assignments of the parcels, showing fragmented anterior and posterior components based on the strongest connectivity, yet alignment with adult systems when weaker connectivity was included.

neuroscience↗

bioRxiv2023

Functional parcellation of the neonatal brain

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that adult- and older infant-derived parcels are a poor fit with neonatal data, emphasizing the need for neonatal-specific parcels. We next derive a set of 283 cortical surface parcels from a sample of n=261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies. HIGHLIGHTSO_LINeonatal cortical surface parcels derived based on abrupt changes in functional connectivity (FC) were highly homogenous and were validated in external neonatal datasets. C_LIO_LIBorders between cortical parcels were smoother (less abrupt) in group-average neonatal data compared to adults, likely due to increased heterogeneity in boundary location across individual neonates. C_LIO_LIParcels derived from adults and older infants show poor fit with neonatal resting-state FC data, underscoring the need for a neonatal-specific parcellation. C_LI

neuroscience↗

bioRxiv2023

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↗

bioRxiv2022

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↗