Biology subjects

Keding, T. J.

Publications and source records attributed to Keding, T. J..

3 recordsLinked to original sources

bioRxiv2026

Bridging Cotyledon Pathology and Perfusion in Healthy Primate Pregnancy

IntroductionHealthy and diseased placentae alike often display some degree of pathology. However, quantitative techniques to characterize common pathologies and their relationship to local maternal hemodynamics in healthy primate placentae are currently limited. MethodsPlacentae from seven rhesus macaques were imaged by MRI at three time points across mid-to late-gestation, to quantify placental blood volume, flow, and perfusion from maternal spiral arteries across pregnancy. Near term, we collected placental cotyledons, digitized hematoxylin/eosin-stained slides, then segmented and annotated sub-tissues and major pathologies (intervillous gaps, fibrin deposition, villous agglutination, inflammatory agglutination, and stromal mineralization) within each cotyledon. Individual pathologies were assessed in relation to each other and MRI perfusion metrics, in a cotyledon-specific manner. Parallel analyses were performed to investigate both basic (Spearman correlation) and animal variance-negated (dimensionality-reduction) relationships. ResultsCotyledons with increased stromal mineralization demonstrated low blood perfusion across pregnancy, alongside significant compensatory changes. Mineralization was further associated with decreased fetal weight, across all sub-tissues. Dimensionality reduction revealed maternal vascular malperfusion-associated pathologies as the largest contributor to dataset variance. Additionally, pathologies commonly associated with healthy placental function demonstrated low cotyledon blood flow and volume at all timepoints, with no evidence of compensatory changes across gestation. ConclusionsComprehensive digital annotation revealed several relationships connecting pathology and maternal blood perfusion in the healthy primate pregnancy, at the smallest functional unit of the placenta. This methodological framework embeds pathologist-refined morphological expertise into a quantitative, spatially resolved format that can ground, rather than be replaced by, unsupervised computational approaches to placental analysis.

pathology↗

bioRxiv2025

Corticolimbic structure-function coupling is sensitive to childhood adversity and buffers adversity-related symptoms during development

Childhood adversity is a potent predictor of mental health problems across the lifespan, and a rich cross-species literature implicates stress-sensitive corticolimbic circuits in adversity-related psychopathology. Structure-function coupling (SFC) is a promising multimodal marker that is sensitive to developmental plasticity. While emerging evidence suggests cortical SFC is sensitive to adversity exposure during early childhood, it is unknown how SFC in stress-sensitive corticolimbic circuits links adversity exposure with mental health across development. We examined associations between adversity exposure, transdiagnostic symptomatology, and both amygdala-cortical and hippocampal-cortical SFC across development in a large sample of youth (N = 607, 39% F). Results revealed that adversity exposure moderated age-related change in amygdala-vmPFC SFC (p = .007), such that youth exposed to higher, but not lower, levels of adversity showed an age-related increase in amygdala-vmPFC SFC. Further, amygdala-vmPFC SFC buffered the effect of adversity on internalizing symptoms (p = .012), such that those youth with higher adversity exposure who had stronger amygdala-vmPFC SFC also displayed lower internalizing symptoms. Separately, higher adversity exposure was associated with lower hippocampal-limbic network SFC (p = .037), which moderated the effect of adversity on internalizing symptoms (p = .010). These findings highlight that structural and functional neurodevelopment of amygdala-vmPFC and hippocampal-limbic network connections may adapt in distinct ways to support mental health following adversity, with implications for risk and resilience against internalizing psychopathology. Significance StatementDelineating how childhood adversity alters neurodevelopment is critical to understanding the origins of adversity-related risk for mental health disorders. Here, we leverage a multimodal marker of the correspondence between brain structure and function to test how corticolimbic circuits are jointly shaped by adversity exposure. Results reveal that the structure-function coupling of amygdala-vmPFC and hippocampal-limbic networks is associated with adversity exposure and differentially moderate risk for internalizing psychopathology. These findings suggest key roles for neural stress regulation and memory circuits in adapting to support optimal functioning following adversity exposure, and highlight the concordance of neural structure and function as an important indicator of individual-level risk and resilience.

neuroscience↗

bioRxiv2023

Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.

neuroscience↗