Biology subjects

Park, S. A.

Publications and source records attributed to Park, S. A..

9 recordsLinked to original sources

bioRxiv2026

A cognitive map of subjective value space for human risky choice

Individuals are thought to make choices based on subjective valuations of options that integrate multiple attributes into a unified subjective value signal in the brains "value coding system." How these attributes are transformed into a subjective valuation remains poorly understood. One candidate is the "cognitive mapping system," which efficiently represents relational, multi-dimensional information and has been proposed to afford novel inferences. We develop a risky decision-making task and use fMRI to show that a two-dimensional (2D) subjective value space of reward probability and amount is represented in the cognitive mapping system as both a grid-like representation of decision vectors and a 2D "positional" code in entorhinal cortex (EC) and medial prefrontal cortex (mPFC). The strength of grid-like and subjective value representations are positively correlated, suggesting the cognitive mapping and value coding systems work in tandem. These findings bridge these systems and support a new framework for how the brain constructs values.

neuroscience↗

bioRxiv2025

Spatial Analysis of Malignant-Immune Cell Interactions in the Tumor Microenvironment Using Topological Data Analysis

The spatial interactions between malignant and immune cells in the tumor microenvironment (TME) play a crucial role in cancer biology and treatment response. Understanding these interactions is critical for predicting prognosis and assessing immunotherapy effectiveness. Conventional methods, which focus on local spatial features, often struggle to achieve robust analysis due to the complex and heterogeneous cellular distributions. We propose a Topological Data Analysis (TDA)-based framework using both global and local spatial features between malignant and immune cells. For the global aspects, we introduce Topological Malignant Clusters (TopMC), a method utilizing persistence diagrams in TDA to capture the global spatial shapes of malignant cell distributions. It quantifies tumor-immune cell infiltration at a global scale by computing distances from the boundaries of the TopMC. Local interactions are evaluated through the density of malignant cells. Using high-resolution multiplex immunofluorescence (mIF) imaging in Diffuse Large B Cell Lymphoma, we integrate distance and density measures into a distance-density space to analyze patterns of malignant-immune cell interactions in TME. This study shows the robustness of the proposed approach to variations in cell distribution, enabling consistent analysis irrespective of whether images are acquired from malignant-enriched or border regions of the tumors. Furthermore, we elucidate the correlation between spatial patterns of immune phenotypes and patient survival probability.

bioinformatics↗

bioRxiv2023

The representational geometry of cognitive maps under dynamic cognitive control

Recent work has shown that the brain abstracts non-spatial relationships between entities or task states into representations called cognitive maps. Here, we investigate how cognitive control enables flexible top-down selection of goal-relevant information from multidimensional cognitive maps retrieved from memory. We examine the relationship between cognitive control and representational geometry by conducting parallel analyses of functional magnetic resonance imaging data and recurrent neural network models trained to perform the same task. We find both stable map-like representations in a medial temporal lobe and orbitofrontal cortical network that reflect both task-relevant and irrelevant dimensions and context-dependent, orthogonal representations of only task-relevant dimensions in a frontoparietal network. These representational motifs also emerge with distinct temporal profiles over the course of training in the recurrent neural network, with map-like representations appearing first. We further show that increasing control demands due to incongruence (conflicting responses) between current task-relevant and irrelevant dimensions impact the geometry of subjective representations, and the degree of this effect further accounts for individual differences in cognitive control. Taken together, our findings show how complementary representational geometries balance stability and behavioral flexibility, and reveal an intricate relationship between cognitive control and cognitive map geometry.

neuroscience↗

bioRxiv2022

The Phytophthora capsici RxLR effector CRISIS2 has roles in suppression of PTI and triggering cell death in host plant

Pathogen effectors can suppress various plant immune responses, suggesting that they have multiple targets in the host. To understand the mechanisms underlying plasma membrane-associated and effector-mediated immunity, we performed Phytophthora capsici RxLR cell death Inducer Suppressing Immune System (CRISIS) screening. In Nicotiana benthamiana, the cell death induced by the RxLR effector CRISIS2 is inhibited by the irreversible plasma membrane H+-ATPase (PMA) activator fusicoccin. Biochemical and gene silencing analyses revealed that CRISIS2 physically and functionally associates with PMAs and induces host cell death independent of immune receptors. CRISIS2 induces apoplastic alkalization by suppressing PMA activity via its association with the C-terminal regulatory domain of PMA. In planta expression of CRISIS2 significantly enhanced the virulence of P. capsici, whereas host-induced gene silencing of CRISIS2 compromised disease symptom and biomass of P. capsici. Furthermore, co-immunoprecipitation assays revealed that CRISIS2 constitutively associates with BAK1, the co-receptor of pattern recognition receptors (PRRs). CRISIS2 interferes with the FLS2-BAK1 complex induced by flagellin perception and impairs downstream signaling from the PRR complex. Proteomics and gene silencing assays identified putative PRRs that negatively regulate the virulence of P. capsici in N. benthamiana as interactors of CRISIS2 and BAK1. Our study identified a novel RxLR effector playing multiple roles in the suppression of plant defense and induction of cell death to support the pathogen hemibiotrophic life cycle in the host plant.

plant biology↗

bioRxiv2021

Neural mechanisms of credit assignment for inferred relationships in a structured world

Animals have been proposed to abstract compact representations of a tasks structure that could, in principle, support accelerated learning and flexible behavior. Whether and how such abstracted representations may be used to assign credit for inferred, but unobserved, relationships in structured environments are unknown. Here, we develop a novel hierarchical reversal-learning task and Bayesian learning model to assess the computational and neural mechanisms underlying how humans infer specific choice-outcome associations via structured knowledge. We find that the medial prefrontal cortex (mPFC) efficiently represents hierarchically related choice-outcome associations governed by the same latent cause, using a generalized code to assign credit for both experienced and inferred outcomes. Furthermore, mPFC and lateral orbital frontal cortex track the inferred current "position" within a latent association space that generalizes over stimuli. Collectively, these findings demonstrate the importance both of tracking the current position in an abstracted task space and efficient, generalizable representations in prefrontal cortex for supporting flexible learning and inference in structured environments.

neuroscience↗

bioRxiv2021

An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies

In addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based on in vitro data, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.

molecular biology↗

bioRxiv2020

Novel Inferences in a Multidimensional Social Network Use a Grid-like Code

Generalizing experiences to guide decision making in novel situations is a hallmark of flexible behavior. It has been hypothesized such flexibility depends on a cognitive map of an environment or task, but directly linking the two has proven elusive. Here, we find that discretely sampled abstract relationships between entities in an unseen two-dimensional (2-D) social hierarchy are reconstructed into a unitary 2-D cognitive map in the hippocampus and entorhinal cortex. We further show that humans utilize a grid-like code in several brain regions, including entorhinal cortex and medial prefrontal cortex, for inferred direct trajectories between entities in the reconstructed abstract space during discrete decisions. Moreover, these neural grid-like codes in the entorhinal cortex are associated with neural decision value computations in the medial prefrontal cortex and temporoparietal junction area during choice. Collectively, these findings show that grid-like codes are used by the human brain to infer novel solutions, even in abstract and discrete problems, and suggest a general mechanism underpinning flexible decision making and generalization.

neuroscience↗

bioRxiv2019

Map making: Constructing, combining, and navigating abstract cognitive maps

Cognitive maps are thought to enable model-based inferences from limited experience that can guide novel decisions-a hallmark of behavioral flexibility. We tested whether the hippocampus (HC), entorhinal cortex (EC), and ventromedial prefrontal cortex (vmPFC)/medial orbitofrontal cortex (mOFC) organize abstract and discrete relational information into a cognitive map to guide novel inferences. Subjects learned the status of people in two separate unseen 2-D social hierarchies defined by competence and popularity piecemeal from binary comparisons, with each dimension learned on a separate day. Although only one dimension was ever behaviorally relevant, multivariate activity patterns in HC, EC and vmPFC/mOFC were linearly related to the Euclidean distance between people in the mentally reconstructed 2-D space. Hubs created unique comparisons between the two hierarchies, enabling inferences between novel pairs of people. We found that both behavior and neural activity in EC and vmPFC/mOFC reflected the Euclidean distance to the retrieved hub, which was reinstated in HC. These findings reveal how abstract and discrete relational structures are represented, combined, and enable novel inferences in the human brain.

neuroscience↗

bioRxiv2018

Bayesian Inference of Other Minds Explains Human Decisions in a Group Decision Making Task

To make decisions in a social context, humans have to predict the behavior of others, an ability that is thought to rely on having a model of other minds known as theory of mind. Such a model becomes especially complex when the number of people one simultaneously interacts is large and the actions are anonymous. Here, we show that in order to make decisions within a large group, humans employ Bayesian inference to model the \"mind of the group,\" making predictions of others decisions while also considering the effects of their own actions on the group as a whole. We present results from a group decision making task known as the Volunteers Dilemma and demonstrate that a Bayesian model based on partially observable Markov decision processes outperforms existing models in quantitatively explaining human behavior. Our results suggest that in group decision making, rather than acting based solely on the rewards received thus far, humans maintain a model of the group and simulate the groups dynamics into the future in order to choose an action as a member of the group.

neuroscience↗