bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical coherence tomography enables longitudinal evaluation of cell graft-directed remodeling in stroke lesions
Authors: Adewumi Honour O , Simkulet Matthew G , Küreli Gülce , Giblin John T , Lopez Arnaldo Bisbal , Erdener Şefik Evren , Jiang John , Boas David A , O’Shea Timothy M 
Published: October 2024

AbstractStem cell grafting can promote glial repair of adult stroke injuries during the subacute wound healing phase, but graft survival and glial repair outcomes are perturbed by lesion severity and mode of injury. To better understand how stroke lesion environments alter the functions of cell grafts, we employed optical coherence tomography (OCT) to longitudinally image mouse cortical photothrombotic ischemic strokes treated with allogeneic neural progenitor cell (NPC) grafts. OCT angiography, signal intensity, and signal decay resulting from optical scattering were assessed at multiple timepoints across two weeks in mice receiving an NPC graft or an injection of saline at two days after stroke. OCT scattering information revealed pronounced axial lesion contraction that naturally occurred throughout the subacute wound healing phase that was not modified by either NPC or saline treatment. By analyzing OCT signal intensity along the coronal plane, we observed dramatic contraction of the cortex away from the imaging window in the first week after stroke which impaired conventional OCT angiography but which enabled the detection of NPC graft-induced glial repair. There was moderate, but variable, NPC graft survival at photothrombotic strokes at two weeks which was inversely correlated with acute stroke lesion sizes as measured by OCT prior to treatment, suggesting a prognostic role for OCT imaging and reinforcing the dominant effect of lesion size and severity on graft outcome. Overall, our findings demonstrate the utility of OCT imaging for both tracking and predicting natural and treatment-directed changes in ischemic stroke lesion cores.
Explaining decision biases through context-dependent repetition
Authors: Wagner Ben J. , Wolf H. Benedikt , Kiebel Stefan J. 
Published: October 2024

AbstractHumans are prone to decision biases, which make behavior seemingly irrational. An important cause for decision biases is that the context in which decisions are made can later influence which choices humans prefer in new situations. Current computational models often require extensive environmental knowledge to explain these biases. Here, we tested the hypothesis that decision biases are mainly driven by a tendency to repeat context-specific actions. We implemented a series of nine value-based decision experiments on n = 351 male and female participants and reanalyzed six previously published datasets (n=350 participants). We found that higher within-context repetition of an option was associated with biased choices including higher subjective valuation and lower uncertainty for repeated actions. Next, we used a computational model based on two basic principles, learning by reward and decision repetition and tested it on all datasets. Our results show that the combination of these two basic principles is sufficient to explain biased choices. We demonstrate via hierarchical Bayesian model comparison that our model outperforms all alternative models. These results provide novel insights into human choice behavior and offer a solution to difficulties in current explanations and models.Significance StatementHuman decision-making often deviates from rational choice theory. Understanding how decision biases emerge is essential for interpreting real-world human behavior. Our study shows how repeating decisions shapes decision making in novel situations. We adapt a simple computational model that can explain decision biases based on reward learning and decision repetition. By testing the model across 15 datasets, we demonstrate that it outperforms previous models, also offering new insights into how preferences affect subjective valuation and uncertainty. In sum, these findings provide a deeper understanding of how context-dependent preferences for specific decisions emerge and persist.
Experimental short-term heatwaves negatively impact body weight gain and survival during larval development in a wild pollinator
Authors: Wögler Laura , Kurze Christoph 
Published: October 2024

AbstractClimate change-induced heatwaves threaten global biodiversity, including crucial pollinators like bumblebees. Despite alarming projections, little is known about the effects of short-term heatwaves on insect larval development. Hence, we investigated the impact of simulated heatwaves on the development of fourth instar larvae (L4) ofBombus terrestrisL. (Hymenoptera: Apidae) using anin vitrorearing method. Individual larvae were incubated at 37°C and 38°C for a period of 4 days, with a constant rearing temperature of 34°C as the control. We examined body weight gain, developmental duration, survival to adult stage, and adult body size (i.e. dry mass, ITD, and head width). A simulated heatwave of 37°C did not significantly affect larval development, but 38°C impaired larval body mass gain. While developmental duration and adult body size were unaffected, an acute heat stress of 38°C during the L4 stage reduced the probability of pupae reaching adulthood. These findings highlight the potential for heatwaves to negatively affect bee populations by impairing larval growth and reducing survival to the adult stage, which may have severe implication for colony fitness.
Unveiling the latent dynamics in social cognition with multi-agent inverse reinforcement learning
Authors: Chen Yusi , Radulescu Angela , Wu Herbert Zheng 
Published: October 2024

AbstractUnderstanding the intentions and beliefs of others, a phenomenon known as “theory of mind”, is a crucial element in social behavior. These beliefs and perceptions are inherently subjective and latent, making them often unobservable for investigation. Social interactions further complicate the matter, as multiple agents can engage in recursive reasoning about each other’s strategies with increasing levels of cognitive hierarchy. While previous research has shown promise in understanding a single agent’s belief of values through inverse reinforcement learning, extending this to model interactions among multiple agents remains an open challenge due to the computational complexity. In this work,we adopted a probabilistic recursive modeling of cognitive levels and joint value decomposition to achieve efficient multi-agent inverse reinforcement learning (MAIRL). We validated our method using simulations of a cooperative foraging task. Our algorithm revealed both the ground truth goal-directed value function and agents’ beliefs about their counter-parts’ strategies. When applied to human behavior in a cooperative hallway task, our method identified meaningful goal maps that evolved with task proficiency and an interaction map that is related to key states in the task without accessing to the task rules. Similarly, in a non-cooperative task performed by monkeys, we identified mutual predictions that correlated with the animals’ social hierarchy, highlighting the behavioral relevance of the latent beliefs we uncovered. Together, our findings demonstrate that MAIRL offers a new framework for uncovering human or animal beliefs in social behavior, thereby illuminating previously opaque aspects of social cognition.
Reward-driven cerebellar climbing fiber activity influences both neural and behavioral learning
Authors: Jin Shuyang , Hull Court 
Published: October 2024

AbstractThe cerebellum plays a key role in motor coordination and learning. In contrast with classical supervised learning models, recent work has revealed that CFs can signal reward-predictive information in some behaviors. This raises the question of whether CFs may also operate according to principles similar to those described by reinforcement learning models. To test how CFs operate during reward-guided behavior, and evaluate the role of reward-related CF activity in learning, we have measured CF responses in Purkinje cells of the lateral cerebellum during a Pavlovian task using 2-photon calcium imaging. Specifically, we have performed multi-stimulus experiments to determine whether CF activity meets the requirements of a reward prediction error (rPE) signal for transfer from an unexpected reward to a reward-predictive cue. We find that once CF activity is transferred to a conditioned stimulus, and there is no longer a response to reward, CFs cannot generate learned responses to a second conditioned stimulus that carries the same reward prediction. In addition, by expressing the inhibitory opsin GtACR2 in neurons of the inferior olive, and optically inhibiting these neurons across behavioral training at the time of unexpected reward, we find that the transfer of CF signals to the conditioned stimulus is impaired. Moreover, this optogenetic inhibition also impairs learning, resulting in a deficit in anticipatory lick timing. Together, these results indicate that CF signals can exhibit several characteristics in common with rPEs during reinforcement learning, and that the cerebellum can harness these learning signals to generate accurately timed motor behavior.
Cerebellar climbing fibers signal flexible, rapidly adapting reward predictions
Authors: Vignali Carlo , Mutersbaugh Michael , Hull Court 
Published: October 2024

AbstractClassical models of cerebellar computation posit that climbing fibers (CFs) operate according to supervised learning rules, correcting movements by signaling the occurrence of motor errors. However, recent findings suggest that in some behaviors, CF activity can exhibit features that resemble the instructional signals necessary for reinforcement learning, namely reward prediction errors (rPEs). Despite these initial observations, many key properties of reward-related CF responses remain unclear, thus limiting our understanding of how they operate to guide cerebellar learning. Here, we have measured the postsynaptic responses of CFs onto cerebellar Purkinje cells using two-photon calcium imaging to test how they respond to learned stimuli that either do or do not predict reward. We find that CFs can develop generalized responses to similar cues of the same modality, regardless of whether they are reward predictive. However, this generalization depends on temporal context, and does not extend across sensory modalities. Further, learned CF responses are flexible, and can be rapidly updated according to new reward contingencies. Together these results suggest that CFs can generate learned, reward-predictive responses that flexibly adapt to the current environment in a context-sensitive manner.
Neocortical differentiation and hippocampal integration of non-meaningful items and their spatial location
Authors: Nemecz Zsuzsanna , Homolya István , Ilyés Alex , Kis Hunor , Mező György , Varga Virág Anna , Werkle-Bergner Markus , Keresztes Attila 
Published: October 2024

AbstractResolving interference between similar inputs is a critical feature of adaptive memory systems. Computational theories of the medial temporal lobe posit that the dentate gyrus and CA3 (CA3DG) subfields of the hippocampus are ideally suited to reduce interference via a process called pattern separation. Whereas neocortical areas upstream of the hippocampus have been shown to play a role in content-specific (e.g., spatial or object-related) interference reduction, the CA3DG is traditionally viewed as a domain-general pattern separator. Recent work also drew attention to the role of frontal and parietal control areas in allocating resources according to task demands during mnemonic discrimination, exerting top-down control over the medial temporal lobe. However, extant evidence in humans is almost solely based on mnemonic discrimination tasks involving everyday items, potentially confounding retrieval processes with pattern separation. Here, we studied pattern separation in a “process-pure” manner, utilizing non-meaningful fractal images. We acquired full-brain high-resolution functional MRI data of 39 participants (mean age (SD) = 22.6 (2.4) years, 19 females) while they studied fractals with varying degrees of interference in either their spatial or object features. Building upon the idea that the repetition of a stimulus results in a diminished BOLD response in areas involved in the processing of that stimulus (repetition suppression), we expected that regions engaged in pattern separation of objects or locations would decrease their response to repetitions, but not to highly similar (interference-inducing) items. We found that the parahippocampal cortex contributes to interference reduction in the spatial domain, while the perirhinal cortex contributes to interference reduction in the object domain. The frontoparietal control network was recruited during the encoding of both object and location lures, and displayed strengthened within- and cross-network connectivity in response to lures. Contrary to our expectations, the CA3DG showed repetition suppression to both exact repetitions and highly similar lures, indicating a lack of sensitivity to small differences in interfering stimuli. Altogether, these results are in line with content-specific neocortical interference reduction in the medial temporal lobe, possibly orchestrated by the frontoparietal control network, but challenge the view of CA3DG as a universal pattern separator.
Ramping dissociates motor and cognitive sequences in the parietal and prefrontal cortices
Authors: Doyle Hannah , Yewbrey Rhys , Kornysheva Katja , Desrochers Theresa M. 
Published: October 2024

AbstractHumans complete different types of sequences as a part of everyday life. These sequences can be divided into two important categories: those that are abstract, in which the steps unfold according to a rule at super-second to minute time scale, and those that are motor, defined solely by individual movements and their order which unfold at the sub-second to second timescale. For example, the sequence of making spaghetti consists of abstract tasks (preparing the sauce and cooking the noodles) and nested motor actions (stir pasta water). Previous work shows neural activity increases (ramps) in the rostrolateral prefrontal (RLPFC) during abstract sequence execution (Desrochers et al., 2015, 2019). During motor sequence production, activity occurs in regions of the prefrontal cortex (Yewbrey et al., 2023). However, it remains unknown if ramping is a signature of motor sequence production as well or solely an attribute of abstract sequence monitoring and execution. We tested the hypothesis that significant ramping activity occurs during motor sequence production in the RLPFC. Contrary to our hypothesis, we did not observe significant ramping activity in the RLPFC during motor sequence production, but we found significant ramping activity in bilateral inferior parietal cortex, in regions distinct from those observed during an abstract sequence task. Our results suggest different prefrontal-parietal circuitry may underlie abstract versus motor sequence execution.
Causal discovery from ecological time-series with one timestamp and multiple observations
Authors: Bystrova Daria , Assaad Charles K. , Si-moussi Sara , Thuiller Wilfried 
Published: October 2024

AbstractEcologists frequently seek to establish causal relations between entities of an ecological system, such as species interactions, ecosystem functions or ecosystem services, using observational data. Despite this, many studies still primarily rely on correlation-based methods, which lack the capability for causal interpretation. Recently, causal discovery methods have gained traction in analysing ecological time-series. However, the scarcity of ecological time-series data presents a challenge due to the demanding and time-consuming nature of collecting consistent measurements over extended periods. In this paper, we delve into the applicability of causal discovery methods when applied to point-in-time (or snapshot-like) observational data obtained from ecological dynamic systems. Specifically, we examine the PC algorithm, which holds theoretical validity assuming the causal Markov condition, faithfulness and causal sufficiency. Additionally, we explore the FCI algorithm, an extension of the PC algorithm designed to handle cases where causal sufficiency is violated. Through a combination of theoretical reasoning and simulation experiments, we elucidate the scenarios in which both algorithms are expected to yield meaningful results. We demonstrate that even in situations where causal sufficiency is not satisfied, the PC algorithm - characterized by its comparatively simpler interpretability - can still deduce specific types of relationships between ecological entities. Furthermore, we illustrate our theoretical findings on simulated data as well as on real data containing records of the abundance of various bird species as well as climatic and land-cover conditions.
CRISPR/Cas9-based somatic knock-in of reporters in the avian embryo in ovo
Authors: Vargas Alciades Petit , Mida Baptiste , Goïame Rosette , Alegria-Prevot Olinda , Djelic Bojana , Fischer Evelyne , Tozer Samuel , Gros Jérôme , Manceau Marie , Morin Xavier 
Published: October 2024

AbstractGene editing and protein tagging are at the heart of modern developmental and cell biology. The advent of CRISPR/Cas9 based methods offers the possibility to develop customized approaches for genomic manipulations in non-classical experimental models. Here, we show that highly efficient somatic knock-ins of long DNA fragments can be achieved in the developing chick neural tube in ovo. We compare different types of repair matrices and different methods for the delivery of the CRISPR/Cas9 machinery, and find that an all plasmid-based approach and short arms of homology provide an easy and efficient method to achieve high frequencies of knock-in insertions with virtually no background signal. We use this method to target fluorescent reporters and dynamically monitor the subcellular distribution of endogenously expressed tagged proteins, as well as to insert the Gal4-VP16 transcription factor or the Cre recombinase at specific loci to label neural sub-populations in the chick embryonic spinal cord. Finally, we show that the method can also be applied to target the epiblast and somitic mesoderm.
A low-level Cdkn1c/p57kip2expression in spinal progenitors drives the transition from proliferative to neurogenic modes of division
Authors: Mida Baptiste , Lehman Nathalie , Coulpier Fanny , Bouhali Kamal , Goiame Rosette , Thomas-Chollier Morgane , Fischer Evelyne , Morin Xavier 
Published: October 2024

ABSTRACTDuring vertebrate neurogenesis, a progressive transition from symmetric proliferative to asymmetric neurogenic divisions is critical to balance growth and differentiation. Using single-cell RNA-seq data from chick embryonic neural tube, we identify the cell cycle regulator Cdkn1c as a key regulator of this transition. While Cdkn1 is classically associated with neuronal cell cycle exit, we show that its expression initiates at low levels in neurogenic progenitors. Functionally targeting the onset of this expression impacts the course of neurogenesis: Cdkn1c knockdown impairs neuron production by favoring proliferative symmetric divisions. Conversely, inducing a low-level CDKN1c misexpression in self-expanding progenitors forces them to prematurely undergo neurogenic divisions. CDKN1c exerts this effect primarily by inhibiting the cyclin D-CDK complex and lengthening G1 phase duration. We propose that Cdkn1c acts as a dual driver of the neurogenic transition whose low level of expression first controls the progressive entry of progenitors into neurogenic modes of division before a higher expression mediates cell cycle exit in daughter cells. This highlights that the precise control of neurogenesis regulators’ expression levels sequentially imparts distinct functions, and is essential for proper neural development.
Regional associations of sleep architecture and Alzheimer’s disease pathology
Authors: Buchal Antonia , Elmenhorst David , Doering Elena , Dzialas Verena , Giehl Kathrin , Bischof Gérard N , van Eimeren Thilo , Drzezga Alexander , Hoenig Merle C. ,   the T-POT study group
Published: October 2024

AbstractObjectiveRecent evidence suggests that disturbances of sleep architecture are linked to Alzheimer’s disease (AD) pathology. Here, we assessed the association between sleep architecture and regional amyloid and tau pathology employing a portable sleep-monitoring device in addition to PET imaging.Methods18 cognitively normal adults (CN; M(Age) = 64.06 (8.63), Sex (M/F) =6/12) and 18 patients with MCI/early AD (M(Age) = 67.33 (8.25), Sex (M/F) =9/9) were included from the “Tau Propagation Over Time” (T-POT) study. All subjects underwent amyloid ([11C]-PiB) and tau ([18F]-AV1451) PET imaging. PET images were normalized to MNI-space and intensity standardized to the whole cerebellum ([11C]-PiB) or the inferior cerebellum ([18F]-AV1451). Sleep monitoring was performed at home using the portable “Dreem” EEG-headband (Beacon Biosignal), which is a reliable and comfortable wireless alternative to the gold-standard polysomnography (PSG). Sleep recordings were performed within six months of the PET acquisitions. At least, one sufficient night had to be acquired, which was used to assess the sleep macrostructure for each individual. Total duration of sleep phases per minutes (i.e. REM, N1, N2, N3) and total sleep time were extracted. In a first step, a linear mixed model (LMM) was used to compare the groups in terms of duration of the different sleep stages across the nightly recordings. Given the results of this comparison, mean N1 and N3 duration were subsequently correlated with regional amyloid and tau pathology SUVRs of 34 cortical regions using Spearman’s correlation. The reported results are based on one-tailed tests. All analyses were corrected for age.ResultsPatients with MCI/AD showed reduced N3 duration (p= .007) compared to the CN group. A trend was observed indicating that patients with MCI/AD exhibited longer N1 durations (p= .094); however, this difference did not reach statistical significance. Shorter N3 duration was associated with higher regional amyloid load in the paracentral lobe and the posterior cingulate gyrus, whereas longer N1 duration was linked to higher amyloid pathology in several regions, including the medial temporal lobe, cingulate cortex and the occipital lobe. Moreover, associations were observed between longer N1 duration and greater tau burden in regions comprising the temporal lobe, cingulate cortex, and medial-frontal areas of the brain.ConclusionDifferences in sleep architecture between healthy controls and MCI/AD may arise from regionally-specific accumulation patterns of AD pathologies. Although it remains unknown whether disruptions in sleep architecture are a cause or a consequence, a complex relationship between AD-aggregation pathology in specific brain regions and the different phases of sleep appears to emerge.