Biology subjects

Weber, C. F.

Publications and source records attributed to Weber, C. F..

5 recordsLinked to original sources

bioRxiv2026

Structural Brain Co-Maturation In The Neonatal Period

Background. The neonatal period is characterized by neurodevelopmental processes coinciding with rapid physiological transitions, however, spatial patterns of brain expansion in early life remain incompletely characterized. Here, we leverage grey matter structural covariance in term- and preterm-born neonates to study the interregional synchrony of neonatal brain maturation along principal brain organizational axes. Methods. We used structural MRI data from the developing Human Connectome Project (n=525; 435 term-born) scanned at 37-44 weeks postmenstrual age (PMA)), stratifying the sample by term status and PMA. Based on cortical thickness (CT) and surface area (SA) metrics, we computed age group- (CVg) and individual-level (CVi) structural covariance matrices. Applying surface-based linear models, we identified changes in interregional covariance with postmenstrual age (PMA) and gestational age at birth (GAB), and contextualized alterations to neonatal functional networks. Using gradient decomposition, we identified major trajectories of cortical expansion on individual and group levels, and determined their correlation to archetypal geometric, evolutionary, and functional axes. Results. We found age-related changes reflecting cortical expansion and an increased structural differentiation with age. Gradient decomposition of group-level covariance revealed that primary components followed both an posterior-anterior distribution, anchored in the visual cortex, and a sensorimotor-association gradient. Individual-level covariance gradients adhered most to geometric axes, and diverged from a sensorimotor-association pattern with increasing PMA. Term-born neonates exhibited a higher spatial correlation to functional and geometric axes than preterm-born neonates, overall pointing to different expansion patterns in neonates of the same PMA. Conclusion. We found trajectories of structural maturation in the neonatal period that appear coordinated along geometric and functional axes. On an age group level, term-born neonates appear to follow archetypal axes more than preterm-borns at term-equivalent age, underlining differential expansion patterns in preterm-born neonates.

neuroscience↗

bioRxiv2025

Associations between epilepsy-related polygenic risk and brain morphology in childhood

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated with a complex genetic architecture, but the translation from genetic risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic risk scores for HS (PRS-HS) and brain structure in a large sample of neurotypical children, and correlated these signatures with case-control findings in in multicentric cohorts of patients with TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning in temporo-parietal and fronto-central regions, strongly anchored to distinct functional and structural network epicentres. Compared to disease-related effects derived from epilepsy case-control cohorts, structural correlates of PRS-HS mirrored atrophy and epicentre patterns in patients with TLE-HS. By identifying a potential pathway between genetic vulnerability and disease mechanisms, our findings provide new insights into the genetic underpinnings of structural alterations in TLE-HS and highlight potential imaging-genetic biomarkers for early risk stratification and personalized interventions.

neuroscience↗

bioRxiv2024

Contracted Functional Connectivity Profiles in Autism

ObjectiveAutism spectrum disorder (ASD) is a pervasive neurodevelopmental condition that is associated with atypical brain network organization, with prior work suggesting differential connectivity alterations with respect to functional connection length. Here, we tested whether functional connectopathy in ASD specifically relates to disruptions in long-relative to short-range functional connectivity profiles. Our approach combined functional connectomics with geodesic distance mapping, and we studied associations to macroscale networks, microarchitectural patterns, as well as socio-demographic and clinical phenotypes. MethodsWe studied 211 males from three sites of the ABIDE-I dataset comprising 103 participants with an ASD diagnosis (mean{+/-}SD age=20.8{+/-}8.1 years) and 108 neurotypical controls (NT, 19.2{+/-}7.2 years). For each participant, we computed cortex-wide connectivity distance (CD) measures by combining geodesic distance mapping with resting-state functional connectivity profiling. We compared CD between ASD and NT participants using surface-based linear models, and studied associations with age, symptom severity, and intelligence scores. We contextualized CD alterations relative to canonical networks and explored spatial associations with functional and microstructural cortical gradients as well as cytoarchitectonic cortical types. ResultsCompared to NT, ASD participants presented with widespread reductions in CD, generally indicating shorter average connection length and thus suggesting reduced long-range connectivity but increased short-range connections. Peak reductions were localized in transmodal systems (i.e., heteromodal and paralimbic regions in the prefrontal, temporal, and parietal and temporo-parieto-occipital cortex), and effect sizes correlated with the sensory-transmodal gradient of brain function. ASD-related CD reductions appeared consistent across inter-individual differences in age and symptom severity, and we observed a positive correlation of CD to IQ scores. ConclusionsOur study showed reductions in CD as a relatively stable imaging phenotype of ASD that preferentially impacted paralimbic and heteromodal association systems. CD reductions in ASD corroborate previous reports of ASD-related imbalance between short-range overconnectivity and long-range underconnectivity.

neuroscience↗

bioRxiv2023

Connectome-wide structure-function coupling models implicate polysynaptic alterations in autism

AO_SCPLOWBSTRACTC_SCPLOWAutism spectrum disorder (ASD) is one of the most common neurodevelopmental diagnoses. Although incompletely understood, structural and functional network alterations are increasingly recognized to be at the core of the condition. We utilized multimodal imaging and connectivity modeling to study structure-function coupling in ASD, and probed mono- and polysynaptic mechanisms on structurally-governed network function. We examined multimodal magnetic resonance imaging data in 47 ASD and 37 neurotypical controls from the Autism Brain Imaging Data Exchange (ABIDE) II initiative. We predicted intrinsic functional connectivity from structural connectivity data in each participant using a Riemannian optimization procedure that varies the times that simulated signals can unfold along tractography-derived personalized connectomes. In both ASD and neurotypical controls, we observed improved structure-function prediction at longer diffusion time scales, indicating better modeling of brain function when polysynaptic mechanisms are accounted for. Prediction improvements were marked in transmodal association systems, such as the default mode network, in both controls and ASD. Improvements were, however, lower in ASD in a polysynaptic regime at higher simulated diffusion times. Regional differences followed a sensory-to-transmodal cortical hierarchy, with an increased gap between groups in transmodal compared to sensory/motor systems. Multivariate associative techniques revealed that structure-function differences reflected inter-individual differences in autistic symptoms and verbal as well as non-verbal intelligence. Our network modeling approach sheds light on atypical structure-function coupling in autism, and suggests that polysynaptic network mechanisms are implicated in the condition and can help explain its wide range of associated symptoms.

neuroscience↗

bioRxiv2021

Inhibition of select actinobacteria by the organophosphate pesticide chlorpyrifos

Organophosphorus compounds have an extensive history as both agricultural pesticides as well as chemical nerve agents. Decades of research have demonstrated numerous links between these chemicals and their direct and indirect effects on humans and other organisms. The inhibitory effects of organophosphate pesticides (OPPs) on metazoan physiology, are well-characterized; however, the effects of organophosphorus compounds on soil microbes - essential contributors to key agricultural processes - are poorly understood. Chlorpyrifos (CPF) is an OPP that is used globally for crop protection. Studies of CPF application to soils have shown transient effects on soil microbial communities with conflicting data. Here, we directly test the effect of CPF on a panel of 196 actinobacteria strains, examining the effects of CPF on their growth and in vitro phenotypes on solid media. Strains were grown and replica-plated onto media containing CPF or a vehicle control and grown at 28{degrees}C. CPF dramatically inhibited the growth of most strains and/or altered colony morphologies, with 13 strains completely inhibited by CPF. In disk diffusion assays with CPF, its degradation product 3,5,6-trichloropyridinol (TCP), malathion, parathion, monocrotophos and mevinphos, only CPF exhibited direct antimicrobial activity suggesting that the observed effects were due to CPF itself. IMPORTANCEChlorpyrifos is a globally used pesticide with documented neurological effects on non-target organisms in the environment. Finding that chlorpyrifos can inhibit the growth of some soil microbes in vitro may have implications for the composition, stability, and health of the soil microbiome. Due to the importance of soil microbes to numerous biogeochemical processes in agricultural systems, additional investigations into the non-target effects of CPF on soil microbes are clearly needed.

microbiology↗