Biology subjects

Braem, S.

Publications and source records attributed to Braem, S..

8 recordsLinked to original sources

bioRxiv2026

Parallel control of conjunctive and compositional representations supports dynamic task preparation

People can dynamically and adaptively update task goals in the face of task uncertainty. In this fMRI study, we aimed to investigate the modulation of neural task representations that subserve such flexible task control. On each trial, we asked people to perform one of nine image categorization tasks. During task preparation, participants had to actively infer varying levels of task uncertainty and dynamically modulate their task preparation accordingly. Multivariate pattern analyses demonstrated dissociable uncertainty-driven modulations of conjunctive and compositional task representations in the right frontoparietal network. Specifically, different sub-regions showed diminished conjunctive task representations when task uncertainty increased during task preparation. At the same time, we observed an active maintenance of compositional task representations, suggesting an adaptive cognitive strategy in facilitating compositional task reconfiguration. These findings suggest a mechanism of parallel control on conjunctive and compositional representations that allows for maximizing the advantages of both representational formats, offering new insights into the neural mechanisms underpinning human flexible task preparation.

neuroscience↗

bioRxiv2025

Two time scales of adaptation in human learning rates

Different situations may require radically different information updating speeds (i.e., learning rates). Some demand fast learning rates, while others benefit from using slower ones. To adjust learning rates, decision makers could rely on either global, meta-learned differences between environments, or faster but transient adaptations to locally experienced prediction errors. Here, we introduce a new paradigm that allows researchers to measure and empirically disentangle both forms of adaptations. Participants performed short blocks of trials of a continuous estimation task - fishing for crabs - on six different islands that required different optimal (initial) learning rates. Across two experiments, participants showed fast adaptations in learning rate within a block. Critically, participants also learned global environment-specific learning rates over the time course of the experiment, as evidenced by computational modelling and by the learning rates calculated on the very first trial when revisiting an environment (i.e., unconfounded by transient adaptations). Using representational similarity analyses of fMRI data, we found that differences in voxel pattern responses in the central orbitofrontal cortex correlated with differences in these global environment-specific learning rates. Our findings show that humans adapt learning rates at both slow and fast time scales, and that the central orbitofrontal cortex may support meta-learning by representing environment-specific task-relevant features such as learning rates.

neuroscience↗

bioRxiv2024

A hollow fiber membrane-based liver organoid-on-a-chip model for examining drug metabolism and transport

Liver-on-a-chip models predictive for both metabolism as well as canalicular and blood transport of drug candidates in humans are lacking. Here, we established an advanced, bioengineered and animal component-free hepatocyte-like millifluidic system based on 3D hollow fiber membranes (HFMs), recombinant human laminin 332 coating and adult human stem cell-derived organoids. Organoid fragments formed polarized and tight monolayers on HFMs with improved hepatocyte-like maturation, as compared to standard 3D organoid cultures in Matrigel from matched donors. Gene expression profiling and immunofluorescence revealed that hepatocyte-like monolayers expressed a broad panel of phase I (e.g., CYP3A4, CYP2D6) and II (UGTs, SULTs) drug-metabolizing enzymes and drug transporters (e.g., OATP1B3, MDR1 and MRP3). Moreover, statically cultured monolayers displayed phase I and II metabolism of a cocktail of six relevant compounds, including midazolam and 7-hydroxycoumarin. We also demonstrated the disposition of midazolam in the basal/blood-like circulation and apical/canalicular-like compartment of the millifluidic chip. Finally, we connected the system to the other two PK/ADME-most relevant organ systems, i.e. small intestine- and kidney proximal tubule-like to study the bioavailability of midazolam and coumarin, and excretion of metformin. In conclusion, we generated a proof-of-concept liver organoid-on-a-chip model for examining metabolism and transport of drugs, which can be further developed to predict PK/ADME profiles in humans.

pharmacology and toxicology↗

bioRxiv2023

The Temporal Dynamics of Metacognitive Experiences Track Rational Adaptations in Task Performance

Human task performance elicits diverse subjective metacognitive experiences, such as boredom, effort, fatigue and frustration, which are thought to play important roles in the monitoring and regulation of cognitive processes. Yet, their specific contributions to task performance remain poorly understood. Therefore, we investigated the temporal dynamics underlying these metacognitive experiences and the latent cognitive processes supporting task performance. We used a time-on-task design using a conflict Flanker task, and analyzed the data using a comprehensive approach encompassing behavioral, model-based, subjective, and neural measures. Our results show that the temporal dynamics in cognitive processes can be understood as a rational attempt to optimize task performance and that distinct metacognitive experiences track different aspects of this rational endeavor. These findings suggest that metacognitive experiences act as tools for humans to gain insights into the optimality of their cognitive performance.

neuroscience↗

bioRxiv2023

Hebbian learning of stimulus-response associations using transcranial magnetic stimulation

Classical conditioning states that the systematic co-occurrence of a neutral stimulus with an unconditioned stimulus can cause the neutral stimulus to, over time, evoke the same response as the unconditioned stimulus. On a neural level, Hebbian learning suggests that this type of learning occurs through changes in synaptic plasticity when two neurons are simultaneously active, resulting in increased connectivity between them. Inspired by learning theories, we here investigated whether the mere co-activation of visual stimuli and stimulation of the primary motor cortex using transcranial magnetic stimulation (TMS) would result in stimulus-response associations that can impact future behaviour. During a learning phase, we repeatedly paired the presentation of a specific colour (but not other colours) with a TMS pulse over the motor cortex. Next, participants performed a two-alternative forced choice task where they had to categorize simple shapes and we studied whether the shapes task-irrelevant colour (and its potentially associated involuntary motor activity) affected the required motor response. Participants showed more errors on incongruent trials for stimuli that were previously paired with high intensity TMS pulses, but only when tested on the same day. Using a drift diffusion model for conflict tasks, we further demonstrate that this interference occurred early, and gradually increased as a function of associated TMS intensity. Taken together, our findings show that the human brain can learn stimulus-response associations using externally induced motor cortex stimulation.

neuroscience↗

bioRxiv2022

Effects of experiencing CS-US pairings on instructed fear reversal

Fear learning allows us to identify and anticipate aversive events, and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms where an initially neutral conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (US), eventually leading to the CS also being perceived as aversive and threatening. Importantly, however, humans also show verbal fear learning. Namely, they have the ability to change their responses to stimuli rapidly through verbal instructions about CS-US pairings. Past research on the link between experience-based and verbal fear learning indicated that verbal instructions about a reversal of CS-US pairings can fully override the effects of previously experienced CS-US pairings, as measured through fear ratings, skin conductance, and fear-potentiated startle. However, it remains an open question whether such instructions can also annul memory traces in the brain. Here, we used a fear reversal paradigm in conjunction with representational similarity analysis of fMRI data to test whether verbal instructions fully override the effects of experienced CS-US pairings in fear-related brain regions or not. Previous research suggests that only the right amygdala should show lingering representations of previously experienced threat (a so-called "Pavlovian trace"). Unexpectedly, we found evidence for the residual effect of prior CS-US experience to be much more widespread than anticipated, in the amygdala but also cortical regions like the dorsal anterior cingulate or dorso-lateral prefrontal cortex. This finding shines a new light on the interaction of different fear learning mechanisms, at times with unexpected consequences.

neuroscience↗

bioRxiv2020

Faster model updating in autism during early sensory processing

BackgroundRecent theories of autism propose that a core deficit in autism would be a less context-sensitive weighting of prediction errors. There is also first support for this hypothesis on an early sensory level. However, an open question is whether this decreased context-sensitivity is caused by faster updating of ones model of the world (i.e. higher weighting of new information), proposed by predictive coding theories, or slower model updating. Here, we differentiated between these two hypotheses by investigating how first impressions shape the mismatch negativity (MMN), reflecting early sensory prediction error processing. MethodsAn autism and matched control group (both n=27) were compared on the multi-timescale MMN paradigm, in which tones were presented that were either standard (frequently occurring) or deviant (rare), and these roles reversed every block. A well-replicated observation is that the initial model (i.e. the standard and deviant sound in the first block) influences MMN amplitudes in later blocks. If autism is characterized by faster model updating, we hypothesized that their MMN amplitudes would be less influenced by the initial context. ResultsWe found that MMN responses in the autism group did not differ between the initial deviant and initial standard sounds as they did in the control group. ConclusionsThese results show that individuals with autism are less influenced by initial contexts, confirming that autism is characterized by faster updating of sensory models, as proposed by predictive coding accounts of autism.

neuroscience↗

bioRxiv2019

Shared Neural Representations of Cognitive Conflict and Negative Affect in the Dorsal Anterior Cingulate Cortex

Influential theories of medial frontal cortex (MFC) function suggest that the MFC registers cognitive conflict as an aversive signal, but no study directly tested this idea. Instead, recent studies suggested that non-overlapping regions in the MFC process conflict and affect. In this pre-registered human fMRI study, we used multivariate pattern analyses to identify which regions respond similarly to conflict and aversive signals. The results reveal that, of all conflict- and value-related regions, the ventral pre-supplementary motor area (or dorsal anterior cingulate cortex) showed a shared neural pattern response to different conflict and affect tasks. These findings challenge recent conclusions that conflict and affect are processed independently, and provide support for integrative views of MFC function.

neuroscience↗