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Teufel, C.

Publications and source records attributed to Teufel, C..

11 recordsLinked to original sources

Delusions Emerge from Generative Model Reorganisation rather than Faulty Inference: Insights from Hybrid Predictive Coding

Predictive coding has influenced many conceptual accounts of delusions, the bizarre and distressing beliefs that accompany a range of neuropsychiatric conditions. However, these explanations remain incomplete and have rarely been tested directly using formal modelling. Here, we present a formal account of delusional beliefs based on hybrid predictive coding, which sheds light on the computational mechanisms underpinning the core features of delusions: thematic recurrence and imperviousness to contradictory evidence. In simulation experiments, we demonstrate that a combination of contextually inadequate initialisation of beliefs and excessive certainty (a hallmark of psychosis), triggers a reorganisation of the generative model relating observed events to hidden causes. This reorganisation enables the maintenance of delusional beliefs that are thematically stable, internally consistent with external inputs, and impervious to contradictory evidence, all without an increase in prediction error. Overall, our results suggest that delusions may arise not from faulty inference, as previously argued, but as an adaptive consequence of generative models learned under atypical conditions. These findings provide mechanistic insights into the computations underpinning delusions and have important implications for a novel therapeutic strategy in terms of re-training generative models.

neuroscience↗

Lymphoid-tissue-on-chip recapitulates human antibody responses in vitro

In the past decades, vaccine development has made great strides. Nevertheless, more often than not, vaccine candidates fail in advanced stages of development and clinical trials. A key reason is the poor predictive value of non-clinical in vivo and in vitro models, due to either species-specific differences in the immune response or insufficient reflection of physiological vaccine mechanisms. Reliable modeling of human adaptive immune responses is a prerequisite to understand processes leading to vaccine-induced protective immunization and to drive informed decisions in vaccine development pipelines. Here, we present a centrifugal microfluidics based organ-on-chip approach to generate an organotypic high density lymphoid tissue on-chip. The model enables long-term culture of lymphoid tissue and raised antigen-specific antibody responses against influenza vaccines even after four weeks on-chip. Antibody response of different magnitude and quality could be induced both by direct antigen exposure as well as by recruitment of antigen-presenting cells from the periphery. The model represents an attractive approach to evaluate the impact of the mode of antigen delivery on adaptive immune responses. Beyond applications in vaccine development, the lymphoid-tissue-on-chip provides a platform to study cellular interactions during homeostasis, immune responses and long-term impact of immunomodulators over several weeks.

bioengineering↗

Solid tumor-on-chip model for efficacy and safety assessment of CAR-T cell therapy

The non-clinical assessment of CAR-T cells demands innovative models that are capable of predicting safety and efficacy in the clinical setting. Here, we present a novel solid tumor-on-chip model that allows CAR-T cell perfusion and integrates the vasculature and tumor lesions to recapitulate key events of CAR-T cell performance including extravasation, tumor infiltration and cytokine release. We assessed CAR-T cells targeting the ROR1 antigen against tumor aggregates that were derived from a breast cancer cell line and primary breast cancer organoids. The data show the temporal kinetic of ROR1 CAR-T cell migration and expansion, lytic activity and cytokine production over the course of 8 days, and reveal a correlation between anti-tumor efficacy and ROR1 antigen density on tumor cells. CAR-modified T cells extravasated faster, infiltrated tumor lesions stronger, persisted longer and in higher numbers than non-CAR modified T cells. Intriguingly, we detected cytokine release levels and kinetics typically observed in patients who developed cytokine release syndrome, and administered dasatinib as a pharmacologic OFF switch to control this inflammatory response. The data illustrate the ability of this tumor-on-chip platform to assess parameters associated withherapeutic outcome and the potential to aid in patient stratification and monitoring of CAR-T cell therapy.

bioengineering↗

Characterising modulatory effects of transcranial random noise stimulation using the perceptual template model.

Neural noise is an inherent property of all nervous systems. However, the mechanisms by which such random and fluctuating neural activity influences perception are still unclear. To elucidate the relationship between neural noise and perceptual performance we require techniques that can safely manipulate neural noise in humans. Transcranial random noise stimulation (tRNS), a form of electrical brain stimulation, has been proposed to increase neural noise according to principles of stochastic resonance (SR); where small to moderate intensities of tRNS improve performance, while higher intensities are detrimental. To date, high intensity (i.e., >2mA) tRNS effects on neural noise levels have not been directly quantified, nor have the detrimental effects proposed by SR been demonstrated in early visual processing. For this purpose, we applied a maximum current intensity of 3mA high-frequency tRNS to the visual cortex (V1) during an orientation discrimination task across increasing external visual noise levels, and fit the perceptual template model to contrast thresholds to quantify intrinsic mechanisms related to noise underlying changes in perceptual performance. We found that tRNS generally worsened perceptual performance by increasing observers internal noise and reducing the ability to filter external noise compared to sham. While most observers experienced detrimental effects, others demonstrated improved perceptual performance (i.e., reduced internal noise and better noise filtering). Preliminary evidence suggests that individual baseline internal noise levels may drive the observed beneficial or detrimental observer responses to tRNS. These findings have important implications for the application of tRNS to investigate the impact of internal noise and noise filtering processes on perception.

neuroscience↗

White matter microstructure in face and body networks predicts facial expression and body posture perception across development

Facial expression and body posture recognition have protracted developmental trajectories. Interactions between face and body perception, such as the influence of body posture on facial expression perception, also change with development. While the brain regions underpinning face and body processing are well-defined, little is known about how white-matter tracts linking these regions relate to perceptual development. Here, we obtained complementary diffusion magnetic resonance imaging (MRI) measures (fractional anisotropy FA, spherical mean [Formula]), and a quantitative MRI myelin-proxy measure (R1), within white-matter tracts of face- and body-selective networks in children and adolescents and related these to perceptual development. In tracts linking occipital and fusiform face areas, facial expression perception was predicted by age-related microstructural development, as measured by [Formula] and R1, as well as age-independent individual differences in microstructure, as measured by FA. Tract microstructure linking the body region in posterior superior temporal sulcus with anterior temporal lobe (ATL) was related to the influence of body on facial expression perception, supporting ATL as a site of face and body network convergence. Overall, our results highlight age-dependent and age-independent constraints that white-matter microstructure poses on perceptual abilities during development and the importance of complementary microstructural measures in linking brain structure and behaviour.

neuroscience↗

Knowledge-driven perceptual organization reshapes information sampling via eye movements

Humans constantly move their eyes to explore the environment and obtain information. Competing theories of gaze guidance consider the factors driving eye movements within a dichotomy between low-level visual features and high-level object representations. However, recent developments in object perception indicate a complex and intricate relationship between features and objects. Specifically, image-independent object-knowledge can generate objecthood by dynamically reconfiguring how feature space is carved up by the visual system. Here, we adopt this emerging perspective of object perception, moving away from the simplifying dichotomy between features and objects in explanations of gaze guidance. We recorded eye movements in response to stimuli that appear as meaningless patches on initial viewing but are experienced as coherent objects once relevant object-knowledge has been acquired. We demonstrate that gaze guidance differs substantially depending on whether observers experienced the same stimuli as meaningless patches or organized them into object representations. In particular, fixations on identical images became object-centred, less dispersed, and more consistent across observers once exposed to relevant prior object-knowledge. Observers gaze behaviour also indicated a shift from exploratory information-sampling to a strategy of extracting information mainly from selected, object-related image areas. These effects were evident from the first fixations on the image. Importantly, however, eye-movements were not fully determined by object representations but were best explained by a simple model that integrates image-computable features and high-level, knowledge-dependent object representations. Overall, the results show how information sampling via eye-movements in humans is guided by a dynamic interaction between image-computable features and knowledge-driven perceptual organization.

neuroscience↗

Autologous human immunocompetent white adipose tissue-on-chip

Obesity and associated diseases, such as diabetes, have reached epidemic proportions globally. In the era of diabesity and due to its central role for metabolic and endocrine processes, adipose tissue (specifically white adipose tissue; WAT) has become a target of high interest for therapeutic strategies. To gain insights in cellular and molecular mechanisms of adipose (patho-)physiology, researchers traditionally relied on animal models since in vitro studies on human WAT are challenging due to the large size, buoyancy, and fragility of mature white adipocytes. Leveraging the Organ-on-Chip technology, we introduce a next-generation microphysiological in vitro model of human WAT based on a tailored microfluidic platform featuring vasculature-like perfusion. The platform integrates a 3D tissue comprising all major WAT-associated cellular components in an autologous manner, including not only mature adipocytes but also organotypic endothelial barriers and stromovascular cells featuring tissue-resident innate immune cells, specifically adipose tissue macrophages. This microphysiological tissue model recapitulates pivotal WAT functions, such as energy storage and mobilization as well as endocrine and immunomodulatory activities. The combination of all individual cell types with extra cellular matrix-like hydrogels in a precisely controllable bottom-up approach enables the generation of a multitude of replicates from the same donors circumventing issues of inter-donor variability and paving the way for personalized medicine. Moreover, it allows to adjust the models degree of complexity to fit a specific purpose via a flexible mix- and-match approach with different cell component modules. This novel WAT-on-chip system constitutes a human-based, autologous and immunocompetent in vitro model of adipose tissue that recapitulates almost full tissue heterogeneity. In the future, the new WAT-on-chip model can become a powerful tool for human-relevant research in the field of metabolism and its associated diseases as well as for compound testing and personalized- and precision medicine applications.

bioengineering↗

Semantic object-scene inconsistencies affect eye movements, but not in the way predicted by contextualized meaning maps

Semantic information is important in eye-movement control. An important semantic influence on gaze guidance relates to object-scene relationships: objects that are semantically inconsistent with the scene attract more fixations than consistent objects. One interpretation of this effect is that fixations are driven towards inconsistent objects because they are semantically more informative. We tested this explanation using contextualized meaning maps, a method that is based on crowd-sourced ratings to quantify the spatial distribution of context-sensitive meaning in images. In Experiment 1, we compared gaze data and contextualized meaning maps for images, in which objects-scene consistency was manipulated. Observers fixated more on inconsistent vs. consistent objects. However, contextualized meaning maps did not assigned higher meaning to image regions that contained semantic inconsistencies. In Experiment 2, a large number of raters evaluated the meaningfulness of a set of carefully selected image-regions. The results suggest that the same scene locations were experienced as slightly less meaningful when they contained inconsistent compared to consistent objects. In summary, we demonstrated that - in the context of our rating task - semantically inconsistent objects are experienced as less meaningful than their consistent counterparts, and that contextualized meaning maps do not capture prototypical influences of image meaning on gaze guidance.

neuroscience↗

Low-level, prediction-based sensory and motor processesare unimpaired in Autism

A new promising account of human brain function suggests that sensory cortices try to optimise information processing via predictions that are based on prior experiences. The brain is thus likened to a probabilistic prediction machine. There has been a growing - though inconsistent - literature to suggest that features of autism spectrum conditions (ASCs) are associated with a deficit in modelling the world through such prediction-based inference. However empirical evidence for differences in low-level sensorimotor predictions in autism is still lacking. One approach to examining predictive processing in the sensorimotor domain is in the context of self-generated (predictable) as opposed to externally-generated (less predictable) effects. We employed two complementary tasks - force-matching and intentional binding - which examine self-versus externally-generated action effects in terms of sensory attenuation and attentional binding respectively in adults with and without autism. The results show that autism was associated with normal levels of sensory attenuation of internally-generated force and with unaltered temporal attraction of voluntary actions and their outcomes. Thus, our results do not support a general deficit in predictive processing in autism.

neuroscience↗

Meaning maps and saliency models based on deep convolutional neural networks are insensitive to image meaning when predicting human fixations

Eye movements are vital for human vision, and it is therefore important to understand how observers decide where to look. Meaning maps (MMs), a technique to capture the distribution of semantic importance across an image, have recently been proposed to support the hypothesis that meaning rather than image features guide human gaze. MMs have the potential to be an important tool far beyond eye-movements research. Here, we examine central assumptions underlying MMs. First, we compared the performance of MMs in predicting fixations to saliency models, showing that DeepGaze II - a deep neural network trained to predict fixations based on high-level features rather than meaning - outperforms MMs. Second, we show that whereas human observers respond to changes in meaning induced by manipulating object-context relationships, MMs and DeepGaze II do not. Together, these findings challenge central assumptions underlying the use of MMs to measure the distribution of meaning in images.

neuroscience↗

Inability to improve performance with control shows limited access to inner states

Any repeatedly performed action is characterised by endogenous variability, affecting both speed and accuracy - for a large part presumably caused by fluctuations in underlying brain and body states. The current research questions were: 1) whether such states are accessible to us, and 2) whether we can act upon this information to reduce variability. For example, when playing a game of darts, there is an implicit assumption that people can wait to throw until they are in the right perceptual-attentional state. If this is true, taking away the ability to self-pace the game should worsen performance. We first tested precisely this assumption asking participants to play darts in a self-paced and a fixed-paced condition. There was no benefit of self-pacing, showing that participants were unable to use such control to improve their performance and reduce their variability. Next, we replicated these findings in two computer-based tasks, in which participants performed a rapid action-selection and a visual detection task in one self-paced and three forced-paced conditions. Over four different empirical tests, we show that the self-paced condition did not lead to improved performance or reduced variability, nor to reduced temporal dependencies in the reaction time series. Overall, it seems that, if people have any access to their fluctuating performance-relevant inner states, this access is limited and not relevant for upcoming performance.

neuroscience↗