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Biology subjects

Wurm, F.

Publications and source records attributed to Wurm, F..

5 recordsLinked to original sources

The unique value of zero prediction errors in reinforcement learning

Updating beliefs when necessary is at the cornerstone of learning. A fundamental problem is to describe under which conditions humans update their internal models of the world. The general assumption across animal, human, and artificial learning models1-3 has been that updates occur when outcomes deviate from expectations. Perfectly predicted outcomes cause no learning. As a result, no research has examined cases in which predictions are surprisingly perfect. Here, we empirically test this assumption and find that zero prediction errors are psychologically unique. We show that after zero prediction errors, momentary happiness is the highest, and belief updates do indeed occur in a pattern that cannot be reproduced by a benchmark model. We present a new model that captures this non-linear pattern in belief updating by postulating that zero prediction errors elicit a distinct latent belief state, guiding subsequent updating. This latent state then tracks neural activity patterns measured with EEG precisely when zero prediction errors occur, exactly as the model would predict. Crucially, the strength of the neural activity during this time window exhibits a dissociation in predicting the next belief update depending on whether feedback was a zero prediction error or a regular prediction error. Overall, we provide strong evidence that surprisingly perfect predictions are treated in a unique, non-linear fashion at affective, behavioral and neural levels. Being surprisingly accurate can function as a distinct belief updating signal, conforming trial-and-hit learning.

neuroscience↗

A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should aim to elicit broad-protection, provide long-lasting immunity and facilitate equitable access for all populations. In this study, a panel of chimeric, full-length spike antigens were developed that incorporate mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was obtained from a high-yield production process in stable CHO cells with purity of >95%, long-term stability and elicitation of broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced protein vaccine (NVX-CoV2373), CoVEXS5 could boost T cell immunity, as well as neutralising antibodies levels against viruses from three sarbecoviruses clades. The breadth of sarbecovirus cross-reactivity elicited by CoVEXS5 exceeded that observed after boosting with the NVX-CoV2373 vaccine. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.

immunology↗

Phasic alertness generates urgency and amplifies competition between evidence accumulators

Although phasic alertness generally benefits cognitive performance, it often increases the interference caused by distracting information, resulting in impaired decision-making and cognitive control. However, it is unclear why phasic alertness has these negative effects. Here, we present a novel, biologically-informed account, according to which phasic alertness generates an evidence-independent urgency signal. This urgency signal shortens overall response times, but also amplifies competition between evidence accumulators, thus slowing down decision-making and impairing cognitive control. The key assumptions of this account are supported with pupil measurements and electrophysiological data from human decision-makers performing an arrow flanker task. We also show that a computational model of the flanker task that incorporates time-varying urgency can reproduce the behavioral effects of phasic alertness, but only when the evidence accumulators compete with each other through lateral inhibition. Our results reveal a close interplay between dynamic changes in urgency, cognitive control and evidence accumulation.

neuroscience↗

Short-term transcutaneous vagus nerve stimulation increases pupil size but does not affect EEG alpha power: a replication

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) is a promising brain stimulation method for the treatment of pharmaco-resistant epilepsy and depression. Its clinical efficacy is thought to depend on taVNS-induced activation of the locus coeruleus. However, unlike for invasive VNS, there is little evidence for an effect of taVNS on noradrenergic activity. ObjectiveWe attempted to replicate recently published findings by Sharon et al. (2021), showing that short bursts of taVNS transiently increased pupil size and decreased EEG alpha power, two correlates of central noradrenergic activity. MethodsFollowing the original study, we used a single-blind, sham-controlled, randomized cross-over design. We applied short-term (3.4 s) taVNS in healthy human volunteers (n=29), while collecting resting-state pupil-size and EEG data. To analyze the data, we used scripts provided by Sharon and colleagues. ResultsConsistent with Sharon et al. (2021), pupil dilation was significantly larger during taVNS than during sham stimulation (p = .009; Bayes factor supporting the difference = 7.45). However, we failed to replicate the effect of taVNS on EEG alpha power (p = .37); the data were four times more likely under the null hypothesis (BF10 = 0.28). ConclusionOur findings support the effectiveness of short-term taVNS in inducing transient pupil dilation, a correlate of phasic noradrenergic activity. However, we failed to replicate the recent finding by Sharon et al. (2021) that taVNS attenuates EEG alpha activity. Overall, this study highlights the need for continued research on the neural mechanisms underlying taVNS efficacy and its potential as a treatment option for pharmaco-resistant conditions. It also highlights the need for direct replications of influential taVNS studies.

neuroscience↗

Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens

Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.

microbiology↗