Biology subjects

Heinzel, S.

Publications and source records attributed to Heinzel, S..

6 recordsLinked to original sources

bioRxiv2025

Executive control in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium

ObjectiveObsessive-compulsive disorder (OCD) is associated with impaired executive function and altered activity in associated neural circuits, contributing to reduced goal-directed behavior. To investigate neural activation during executive control, we conducted a mega-analysis in the ENIGMA-OCD consortium pooling individual participant data from 475 individuals with OCD and 345 healthy controls across 15 fMRI tasks collected worldwide. MethodsIndividual participant data was uniformly processed using HALFpipe to construct voxelwise statistical images of executive control and task load contrasts. Parameter estimates extracted from regions of interest were entered into multilevel Bayesian models to examine regional and whole-brain effects of diagnosis, and, within OCD, the influence of medication status, symptom severity, and age of onset on task activation. ResultsWe observed a robust task activation pattern across individuals with OCD and control participants in executive control regions across tasks. Relative to controls, individuals with OCD showed moderate to very strong evidence of weaker activation of the dorsolateral prefrontal cortex, precuneus, frontal eye fields, and inferior parietal lobule during executive control (all positive posterior probabilities [P+]<0.1). Individuals with OCD also showed stronger activation in regions of the default mode network during executive function relative to controls. We found little evidence for differential activation during executive control in task- positive regions related to disease onset, severity and medication status. ConclusionIn the first mega-analysis of fMRI studies of executive function in OCD, we found strong evidence of weaker frontoparietal activation during executive control tasks. Our findings also suggest a failure of default mode network regions to appropriately disengage during task performance in OCD.

neuroscience↗

bioRxiv2025

Functional immune profiling reveals CD4+ T cell dysregulation associated with celiac disease

T cells integrate signals from antigen and co-stimulatory receptors to calibrate the strength and quality of their responses. This signal integration is influenced by genetic background, which can modulate thresholds for immune tolerance and strength of responses to threat. Celiac disease (CeD) is an autoimmune disorder driven by well-defined genetic risk and characterised by immune dysregulation in response to dietary gluten. However, whether sensitivity or response differences in naive T cell programming contributes to disease susceptibility is not known. To investigate such variation, we developed a sensitive quantitative platform, the momentum assay, which combines standardised, T cell activation with subsequent stimulus withdrawal, enabling measurement of T cell proliferation and survival over time. This assay is integrated with the Cyton2 mathematical model to infer underlying cellular timer programs from population-level dynamics. We applied this method to assess whether naive T cells from individuals with celiac disease (CeD) exhibited altered responses compared to healthy donors (HDs). We found that CD4+ but not CD8+ T cells from CeD patients showed a hypo-proliferative response following stimulation, associated with impaired secretion of the proliferative and pro-survival cytokine IL-2. Moreover, surface expression of early activation marker, CD69 remained elevated for longer on CD4+ T cells from CeD donors after stimulus withdrawal, suggesting prolonged activation and subtle alterations in regulatory feedback mechanisms. These findings reveal previously unrecognised quantitative alterations in naive T cell programming in CeD and underscore the utility of model-based analytical frameworks for detecting subtle functional perturbations in complex immune-mediated diseases.

immunology↗

bioRxiv2025

Network Neuroscience of Human Multitasking: Local Features Matter

The neural basis of multitasking costs is subject to continuing debate. Cognitive theories assume that overlap of task representations may lead to between-task crosstalk in concurrent task processing and thus requires cognitive control. Recent research suggests that modality-based crosstalk contributes to multitasking costs, involving central overlap of modality-specific representations. Consistently increased costs for specific modality pairings (visual-vocal and auditory-manual vs. visual-manual and auditory-vocal) were demonstrated (modality-compatibility effect), which were recently linked to representational overlap in the auditory cortex. However, it remains unclear whether modality-based crosstalk emerges from overlapping patterns of global brain connectivity and whether resolving it requires additional involvement of cognitive control as reflected in the fronto-parietal control network. This preregistered functional imaging study investigates these questions in 64 healthy, young human adults. Specifically, we focus on the modality-compatibility effect in multitasking by employing functional connectivity (FC) analysis. First, we tested the FC similarity between the single-task networks. Second, we compared the strength of the control network in whole-brain FC between dual tasks. We found no evidence for different FC similarities of single-task networks between modality pairings and no additional involvement of the control network during dual tasks. However, post-hoc connectivity analysis revealed a brain-behavior correlation for the modality-compatibility effect in dual tasks. This effect was locally restricted to FC between lateral frontal and sensory auditory regions, providing evidence for the modality-based crosstalk theory. More generally, the findings suggest that robust behavioral differences in multitasking are not necessarily related to global functional connectivity differences but to local connectivity changes. SignificanceOur lives are dominated by multitasking. Understanding the neurocognitive mechanisms of multitasking and its associated limitations is relevant for safety-relevant consequences. Here, we investigate functional brain-connectivity patterns associated with modality-based crosstalk in multitasking, describing unintentional exchange of information between two tasks, leading to robust dual-task costs. Our network analyses revealed no significant difference between single or dual tasks with varying degrees of modality overlap on the whole-brain level. However, specific connections between cognitive control-related frontal and sensory-related regions were associated with individual multitasking performance, emphasizing that behavioral differences can arise from specific neural interactions rather than from widespread network reconfigurations. These findings advance our understanding of the underlying mechanisms responsible for modality-based crosstalk, providing practical implications for human-machine interactions.

neuroscience↗

bioRxiv2024

Multitasking practice eliminates modality-based interference by separating task representations in sensory brain regions

The debate on the neural basis of multitasking costs evolves around neural overlap between concurrently performed tasks. Recent evidence suggests that training-related reductions in representational overlap in fronto-parietal brain regions predict multitasking improvements. Cognitive theories assume that overlap of task representations may lead to unintended information exchange between tasks (i.e., crosstalk). Modality-based crosstalk was suggested as a source for multitasking costs in multisensory settings. Robust findings of increased costs for certain modality mappings may be explained by crosstalk between the stimulus modality in one task and sensory action consequences in the concurrently performed task. Whether modality-based crosstalk emerges from representational overlap in general fronto-parietal multitasking regions or modality-specific regions is not known yet. In this functional neuroimaging study, we investigate neural overlap in multitasking performance, focusing on modality compatibility by employing multivariate pattern analysis and modality-specific practice interventions in three groups (total N = 54). We observed significant differences between modality compatible and modality incompatible single-task representations, specifically in the auditory cortex but not in fronto-parietal regions. Notably, improved auditory decoding accuracy related to modality incompatible tasks was predictive of performance gains in the corresponding dual task along with complete elimination of modality-specific dual-task costs. This predictive relationship was evident only in the group practicing modality incompatible mappings, suggesting that specific practice on task sets with modality overlap influenced both neural representations and subsequent multitasking performance. This study contributes to the integration of cognitive theory and neuroscience and the role of task representations in dual-task interference. SignificanceIn a society dominated by multitasking, understanding its neurocognitive basis and plasticity is crucial for key aspects of work-related and everyday tasks. We investigate the neural mechanisms behind multitasking limitations, offering insights for targeted cognitive interventions. The study builds upon established theories of cognitive multitasking and imaging research, addressing the concept of modality-based crosstalk - the unintended exchange of modality-based information between tasks. Through functional brain imaging and pattern analysis, we examined how neural task representations contribute to performance costs in dual tasks with varying degrees of modality overlap. Notably, our findings demonstrate a practice-related decrease in neural overlap which is associated with substantial multitasking improvements, specifically in the auditory cortex, emphasizing the contribution of sensory regions to flexible multidimensional task representations.

neuroscience↗

bioRxiv2023

Molecular control of the lymphocyte death timer

When stimulated, individual lymphocytes program times for division and death that are inherited within families, revealing a common timing mechanism transmitted over generations. Here we describe a threshold-based mechanism for the time to die. By comparing protein levels in control and apoptosis disabled cells, we show that death can be predicted by a cooperating ensemble of BCL-2 family proteins falling below a critical threshold. Single cell measurements predict the time of death with a simple formula, where an additional inhibition factor explains accelerated death induced by BH3 mimetic compounds. Thus, we identify the death timer as a protein-threshold device that underlies signal integration machinery. Together these results reveal that predicting lymphocyte behavior at single cell level, in complex environments, is possible with modular multiscale models that incorporate timers and heritability features of critical proteins.

immunology↗

bioRxiv2019

Gut microbiome signatures of risk and prodromal markers of Parkinson's disease

ObjectivesAlterations of the gut microbiome in Parkinsons disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. MethodsEstablished risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial -/{beta}-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants. ResultsAmong risk and prodromal markers, physical inactivity, constipation and age showed associations with - and {beta}-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with {beta}-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations. InterpretationSeveral risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.

neuroscience↗