Rein, M. | bioRxiv Science

bioRxiv2025

Theory of Mind and Discourse Production in Schizotypy: An fMRI Study

BackgroundSchizotypy (ST) reflects subclinical traits linked to schizophrenia spectrum disorders and associated cognitive and social impairments. Theory of Mind (ToM) and discourse production deficits are well-documented in schizophrenia (SZ), yet the neural basis of discourse-related ToM processes in ST remains unclear. This study investigated brain activation during narrative planning and production in individuals with schizotypal traits. MethodsThirty young adults (mean age = 18.8 years) completed standardized assessments, including the Schizotypal Personality Questionnaire-Brief Revised (SPQ-BR), adverse childhood experiences (ACEs), depression (PHQ-9), and dissociation (DES-B). Participants performed a discourse task in an fMRI scanner, describing nine-panel cartoons requiring inference of character intentions. Behavioral discourse metrics included total and inferred events. fMRI analyses examined activation during planning and production phases, with SPQ-BR positive, negative, and disorganized traits entered as regressors. ResultsSchizotypal traits correlated with multiple psychosocial risk factors, including elevated depression, ACEs, and dissociation (r = .48-.82, p < .01). During planning, canonical ToM/self-referential regions (vmPFC, precuneus, insula) were recruited. Positive traits correlated with increased activation in the right temporo-parietal junction, precuneus, and lingual gyrus, whereas disorganized traits were associated with reduced activation in the precuneus and lingual gyri. During production, networks spanning vmPFC, hippocampus, right TPJ, and basal ganglia were engaged. Negative traits correlated with increased motor/premotor activation, while disorganized traits correlated with reduced activation in lingual gyrus, SMA, and cerebellum. ConclusionsFindings demonstrate distinct neural correlates of schizotypal traits during discourse planning and production, supporting models of schizophrenia-spectrum risk emphasizing disrupted inference and integration processes.

neuroscience↗

bioRxiv2024

Quantification of beta cell carrying capacity in prediabetes

Prediabetes, a subclinical state of high glucose, carries a risk of transition to diabetes. One cause of prediabetes is insulin resistance, which impairs the ability of insulin to control blood glucose. However, many individuals with high insulin resistance retain normal glucose due to compensation by enhanced insulin secretion by beta cells. Individuals seem to differ in their maximum compensation level, termed beta cell carrying capacity, such that low carrying capacity is associated with a higher risk of prediabetes and diabetes. Carrying capacity has not been quantified using a mathematical model and cannot be estimated directly from measured glucose and insulin levels in patients, unlike insulin resistance and beta cell function which can be estimated using HOMA-IR and HOMA-B formula. Here we present a mathematical model of beta cell compensation and carrying capacity, and develop a new formula called HOMA-C to estimate it from glucose and insulin measurements. HOMA-C estimates the maximal potential beta cell function of an individual, rather than the current beta cell function. We test this approach using longitudinal cohorts of prediabetic people, finding 10-fold variation in carrying capacity. Low carrying capacity is associated with higher risk of transitioning to diabetes. We estimate the timescales of beta cell compensation and insulin resistance using large datasets, showing that, unlike previous mathematical models, the new model can explain the slow rise in glucose over decades. Our mathematical understanding of beta cell carrying capacity may help to assess the risk of prediabetes in each individual.

systems biology↗