Biology subjects

Heim, C.

Publications and source records attributed to Heim, C..

6 recordsLinked to original sources

bioRxiv2026

Multimodal longitudinal prediction of alcohol-use trajectories in adolescents and young adults: Social context, real-life social affective benefit, and fronto-striatal involvement

Escalating alcohol use during adolescence and young adulthood confers substantial risk for later substance misuse and adverse mental health outcomes, yet the factors that determine early drinking trajectories remain poorly understood. Here, we examined alcohol use across social, affective, and neural domains in a cohort of 378 community-based young drinkers using a combination of longitudinal phenotyping, ecological momentary assessment (EMA) and functional neuroimaging. Across different levels of analysis, higher baseline alcohol consumption (standard drinks per week) was associated with immediate substance-use social context, greater social-affective benefit in daily life, and heightened engagement of the fronto-striatal reward circuitry. In a one-year longitudinal follow-up, individual social-affective benefit and substance-related social environmental factors showed the strongest predictive value for drinking trajectories in a follow-up of 219 individuals after one year. Our findings identify key social and neural reward-related determinants of youth drinking behavior, informing the development of evidence-based risk detection and prevention measures.

neuroscience↗

bioRxiv2026

Neurostructural correlates of real-life social drinking risk in alcohol use disorder

The social context of alcohol consumption is increasingly recognized as an important factor in the development of alcohol use disorder (AUD). However, individuals with AUD may differ in how strongly alcohol use by people around them is associated with their own drinking, and the neurostructural basis of this variation remains unclear. Here we studied 83 individuals with AUD (53 men, 30 women; mean [SD] age, 37.20 [12.42] years; median DSM-5 AUD criteria, 4) using six weeks of ecological momentary assessment and structural magnetic resonance imaging (n = 80). Across 5,221 non-solitary observations, greater exposure to surrounding drinkers was associated with increased odds of momentary drinking (odds ratio, 4.23; 95% CI, 3.60-4.97), with significant between-person variation that we quantified as social drinking risk (SDR). Higher SDR was associated with lower gray matter volume in the pregenual anterior cingulate cortex (T = 5.40; P < .001) and weaker pregenual anterior cingulate cortex-ventral striatum structural covariance (T = 3.15; P = .032). These findings support SDR as an ecologically grounded phenotype linking daily-life social-context sensitivity to cingulostriatal structure, with potential relevance for mechanistic and interventional research in AUD.

neuroscience↗

bioRxiv2026

Epigenetic and brain age across development: Performance and associations in the MIND consortium

Understanding how biological age measures perform across development lays the groundwork for investigations into lifespan trajectories of healthy aging. We provide the most comprehensive assessment of epigenetic and brain age models across development (birth to 24 years; [≤]20,917 observations across 15 cohorts), evaluating how these models associate with chronological age and with each other, and how these associations change across development. Chronological age-prediction accuracy of epigenetic and brain age models was modest and varied substantially. Accuracy improved with age and stabilized by middle childhood. Few brain and fewer epigenetic clocks performed stably and well across all developmental stages. Performance was better when age range and tissue corresponded between training and testing data. Associations between epigenetic-brain age residuals were small, and changed little across development, tissues or clock generation. Given this developmentally dynamic system of epigenetic-brain age performances and associations, we give key recommendations to improve developmental research in this field.

neuroscience↗

bioRxiv2025

PKC Promotes T-Tubule Membrane Loss by Activating a PKD-NFκB Endocytic Pathway

BackgroundIn heart disease, the membrane of the cardiomyocyte transverse-axial tubular system (TATS) deteriorates. This impairs contractility, hinders recovery and predisposes to arrhythmia. However, the key signals and cellular processes driving TATS loss are not understood. We investigated protein kinase C (PKC) and its downstream signals in animal and human cardiomyocytes. MethodsVentricular cardiomyocytes were isolated from healthy adult rat, rabbit and failing human hearts and treated with the PKC activator phorbol 12-myristat 13-acetat (PMA) or receptor-mediated agonists, alongside inhibitors targeting PKC, PKD, NF{kappa}B, MKK1-ERK1/2, NFAT, or endocytic pathways. TATS density was analyzed by confocal microscopy using lipophilic membrane dyes. Signaling pathway activation was determined by Western blotting and RNA sequencing. Ca2+ signals and contractility were assessed in rat cells. Mechanisms of TATS loss were studied using endocytosis assays involving fixable dextran. ResultsPMA induced severe TATS loss, which was prevented by inhibiting PKC, PKD, NF{kappa}B or MKK1, but not by blocking NFAT or p38 MAPK. Receptor-mediated PKC activation also decreased TATS density. All effective inhibitors suppressed I{kappa}B expression. RNA sequencing indicated PMA-mediated activation of the NF{kappa}B and MAPK/ERK pathways and genes related to endocytosis. NF{kappa}B inhibition did not suppress the MAPK pathway, but MKK inhibition suppressed NF{kappa}B. PMA decreased Ca2+ transient amplitudes and contractility, whereas NF{kappa}B inhibitors preserved both. Dextran assays revealed that TATS membranes were internalized via a macropinocytic process that followed saturation kinetics was upregulated by PMA, downregulated by NF{kappa}B inhibition, and required PI3K, myosin I, and clathrin-independent endocytosis and correlated with the rate of TATS loss. Key findings were consistent in human cardiomyocytes and in ex-vivo rat and rabbit myocardial slice culture. ConclusionsPKC activation drives TATS loss in human and animal myocytes via PKC-PKD-NF{kappa}B, T-tubules are degraded by endocytic internalization, offering a new perspective on how cardiomyocyte membranes may deteriorate in heart disease.

cell biology↗

bioRxiv2023

Longitudinal Changes in Value-based Learning in Middle Childhood: Distinct Contributions of Hippocampus and Striatum

The hippocampal-dependent memory system and striatal-dependent memory system modulate reinforcement learning depending on feedback timing in adults, but their contributions during development remain unclear. In a 2-year longitudinal study, 6-to-7-year-old children performed a reinforcement learning task in which they received feedback immediately or with a short delay following their response. Childrens learning was found to be sensitive to feedback timing modulations in their reaction time and inverse temperature parameter, which quantifies value-guided decision-making. They showed longitudinal improvements towards more optimal value-based learning, and their hippocampal volume showed protracted maturation. Better delayed model-derived learning covaried with larger hippocampal volume longitudinally, in line with the adult literature. In contrast, a larger striatal volume in children was associated with both better immediate and delayed model-derived learning longitudinally. These findings show, for the first time, an early hippocampal contribution to the dynamic development of reinforcement learning in middle childhood, with neurally less differentiated and more cooperative memory systems than in adults.

neuroscience↗

bioRxiv2021

Longitudinal developmental trajectories do not follow cross-sectional age associations in hippocampal subfield and memory development

Many cross-sectional findings suggest that volumes of specific hippocampal subfields increase in middle childhood and early adolescence. In contrast, a small number of available longitudinal studies observed decreased volumes in most subfields over this age range. Further, it remains unknown whether structural changes in development are associated with corresponding gains in childrens memory. Here we report cross-sectional age differences in childrens hippocampal subfield volumes together with longitudinal developmental trajectories and their relationships with memory performance. In two waves, 109 healthy participants aged 6 to 10 years (wave 1: MAge=7.25, wave 2: MAge=9.27) underwent high-resolution magnetic resonance imaging to assess hippocampal subfield volumes, and completed cognitive tasks assessing hippocampus dependent memory processes. We found that cross-sectional age-associations and longitudinal developmental trends in hippocampal subfield volumes were highly discrepant, both by subfields and in direction. Further, volumetric changes were largely unrelated to changes in memory, with the exception that increase in subiculum volume was associated with gains in spatial memory. Importantly, the observed longitudinal patterns of brain-cognition coupling could not be inferred from cross-sectional findings. We discuss potential sources of these discrepancies. This study underscores that childrens structural brain development and its relationship to cognition cannot be inferred from cross-sectional age comparisons. HighlightsO_LIThe subiculum undergoes volumetric increase between 6-10 years of age C_LIO_LIChange across two years in CA1-2 and DG-CA3 was not observed in this age window C_LIO_LIChange across two years did not reflect age differences spanning two years C_LIO_LICross-sectional and longitudinal slopes in stark contrast for hippocampal subfields C_LIO_LILongitudinal brain-cognition coupling cannot be inferred from cross-sectional data C_LI

neuroscience↗