Biology subjects

Lindblom, J.

Publications and source records attributed to Lindblom, J..

3 recordsLinked to original sources

bioRxiv2026

The Influence of Early Life Stress on the Development of Neural Representations during Mentalizing

Early life stress (ELS) is associated with altered social cognition, but the neurodevelopmental mechanisms of this association remain understudied. In the present longitudinal study spanning 20-years, eighty-nine young adults performed the Reading the Mind in the Eyes Test (RMET) with a matched control condition during fMRI. Two ELS indices were inspected separately: a prospective cumulative risk score based on caregiver wellbeing during pregnancy and first year of life, and a retrospective self-report of adverse experiences by the participants in late adolescence. Neural outcomes were characterized by univariate activation, representational similarity analysis (RSA), and inter-subject RSA. Inter-subject RSA tested two pairwise approaches to intersubject similarity in ELS: absolute pairwise difference, and pairwise average. Prospective ELS was associated with better RMET performance, and one region survived correction across 360 cortical regions tested in RSA and IS-RSA: left anterior inferior frontal sulcus. The IS-RSA effect was pairwise average: low-exposure participants shared a more typical neural representational geometry, while high-exposure participants demonstrated increasing neural representational idiosyncrasy. Additionally, higher prospective ELS was associated with weaker RMET-versus-control separation within the same region. Retrospective ELS yielded no behavioral nor neural associations. The present study offers novel findings relating to neural representations of mentalizing using the RMET, alongside their neurodevelopmental susceptibility to ELS. The present study additionally highlights implications relating to the differentiation of mentalizing from lexical-semantic and semantic-control demands for future research.

neuroscience↗

bioRxiv2025

Assessing the Molecular Validity of Spontaneous Lupus Mouse Models and Its Implication for Human Studies

BackgroundSystemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a loss of self-tolerance, causing inflammation and tissue damage in multiple organs. Animal models have advanced our understanding of SLEs molecular basis, but the FDAs recent elimination of animal testing requirements for drug approval has raised concerns about their validity, prompting a reevaluation of their role in basic research, especially for heterogeneous diseases like SLE. MethodsFour different spontaneous SLE mouse models were studied: MRLlpr/lpr, NZB/W, BXSB.Yaa, and Tlr7.Tg6. Transcriptome sequencing from blood, spleen, and kidney, flow cytometry from the spleen, and cytokines and autoantibody measurement in plasma were performed at four time points. Similar molecular data from human SLE patients was used for the integration. ResultsThe study identified specific molecular pathways driving the phenotype in each mouse model and established optimal time points for future experimental designs. By comparing these pathways to human SLE, the most similar ones and their relationship with disease activity were identified, providing crucial insight into translational relevance. Importantly, disease severity across models was linked to the extent and timing of molecular dysregulations. As expected, MRLlpr/lpr showed the most aggressive phenotype with early immune activation and apoptosis dysregulation, while Tlr7.Tg6 presented late-onset signatures associated with interferon and inflammation. Shared molecular features with human SLE included interferon responses, T and B cell depletion, and neutrophil activation. Integration analysis revealed distinct yet overlapping immune pathways between models and species, with some signatures such as age-associated B cells and double-negative memory T cells being model-specific but potentially relevant to early disease processes. ConclusionsThese findings build a valuable framework for future SLE research, reinforcing the utility of mouse models in studying specific molecular pathways related to human SLE pathogenesis and heterogeneity. The integration of longitudinal mouse data with human transcriptomes highlights the models that best recapitulate key aspects of human disease, offering guidance for the study of specific immunopathological mechanisms or therapeutic targets.

immunology↗

bioRxiv2024

Similarity in Early Life Stress Exposure is Associated with Similarity in Neural Representations in Early Adulthood

Early life stress (ELS) has profound implications for developmental trajectories, yet the neural mechanisms underlying its long-term effects remain incompletely understood. In the present study, we examined whether interindividual similarity in ELS exposure aligns with similarity in neural representations and behavioral task performance in early adulthood. Leveraging a 20-year longitudinal dataset of Finnish families, we evaluated 87 young adults who underwent functional magnetic resonance imaging (fMRI) during an emotional go/no-go task. Intersubject representational similarity analysis (IS-RSA) was used to assess the associations between pairwise similarities in prospectively or retrospectively measured ELS, neural representations in 360 cortical regions, and task performance. We incorporated multidimensional scaling and Procrustes alignment to visualize interindividual differences in representational spaces. Prospective ELS, but not Retrospective ELS, was significantly associated with neural representational similarity across 40 cortical regions, including the anterior insula, frontal operculum, and anterior cingulate cortex. Higher Prospective ELS was also linked to reduced detection sensitivity, mediated by neural responses to angry facial expressions. These findings highlight the systematic and chronic effects of more moderate ELS on brain development and emphasize the value of prospective measurements and advanced similarity analyses in capturing the nuanced influences of ELS. By integrating spatial and shape analytical techniques, the present study provides new insights into the long-term neurobiological correlates of ELS and introduces novel methodological tools for neurodevelopmental research.

neuroscience↗