Errors of attention adaptively warp spatial cognition
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Smartwatch- and smartphone-based remote assessment of brain health and detection of mild cognitive impairment
Consumer-grade mobile devices are used by billions worldwide. Their ubiquity provides opportunities to robustly capture everyday cognition. ‘Intuition’ was a remote observational study that enrolled 23,004 US adults, collecting 24 months of longitudinal multimodal data via their iPhones and Apple Watches using a custom research application that captured routine device use, self-reported health information and cognitive assessments. The study objectives were to classify mild cognitive impairment (MCI), characterize cognitive trajectories and develop tools to detect and track cognitive health at scale. The study addresses sources of bias in current cognitive health research, including limited representativeness (for example, racial/ethnic, geographic) and accuracy of cognitive measurement tools. We describe study design and provide baseline cohort characteristics. Next, we present foundational proof-of-concept MCI classification modeling results using interactive cognitive assessment data. Initial findings support the reliability and validity of remote MCI detection and the usefulness of such data in describing at-risk cognitive health trajectories in demographically diverse aging populations. ClinicalTrials.gov identifier: NCT05058950.
Spatially resolved transcriptomics and graph-based deep learning improve accuracy of routine CNS tumor diagnostics
The diagnostic landscape of brain tumors integrates comprehensive molecular markers alongside traditional histopathological evaluation. DNA methylation and next-generation sequencing (NGS) have become a cornerstone in central nervous system (CNS) tumor classification. A limiting requirement for NGS and methylation profiling is sufficient DNA quality and quantity, which restrict its feasibility. Here we demonstrate NePSTA (neuropathology spatial transcriptomic analysis) for comprehensive morphological and molecular neuropathological diagnostics from single 5-µm tissue sections. NePSTA uses spatial transcriptomics with graph neural networks for automated histological and molecular evaluations. Trained and evaluated across 130 participants with CNS malignancies and healthy donors across four medical centers, NePSTA predicts tissue histology and methylation-based subclasses with high accuracy. We demonstrate the ability to reconstruct immunohistochemistry and genotype profiling on tissue with minimal requirements, inadequate for conventional molecular diagnostics, demonstrating the potential to enhance tumor subtype identification with implications for fast and precise diagnostic workup.
A spatiotemporal style transfer algorithm for dynamic visual stimulus generation
Understanding how visual information is encoded in biological and artificial systems often requires the generation of appropriate stimuli to test specific hypotheses, but available methods for video generation are scarce. Here we introduce the spatiotemporal style transfer (STST) algorithm, a dynamic visual stimulus generation framework that allows the manipulation and synthesis of video stimuli for vision research. We show how stimuli can be generated that match the low-level spatiotemporal features of their natural counterparts, but lack their high-level semantic features, providing a useful tool to study object recognition. We used these stimuli to probe PredNet, a predictive coding deep network, and found that its next-frame predictions were not disrupted by the omission of high-level information, with human observers also confirming the preservation of low-level features and lack of high-level information in the generated stimuli. We also introduce a procedure for the independent spatiotemporal factorization of dynamic stimuli. Testing such factorized stimuli on humans and deep vision models suggests a spatial bias in how humans and deep vision models encode dynamic visual information. These results showcase potential applications of the STST algorithm as a versatile tool for dynamic stimulus generation in vision science.
Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma
Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis. We discovered two functional units, one is the intratumor inflammatory hub featured by CAF-FAP plus CD8_PDCD1 proximity and the other is the marginal wound-healing hub with CAF-C7 plus Macrophage_SPP1 co-localization. Inhibiting CAF-FAP combined with anti-PD-1 in orthotopic HCC models led to improved tumor regression than either monotherapy. Collectively, our findings suggest stroma-targeted strategies for HCC based on defined stromal archetypes, raising the concept that CAFs change their transcriptional program and intercellular crosstalk according to the spatial context.
Curiosity shapes spatial exploration and cognitive map formation in humans
Cognitive maps are thought to arise, at least in part, from our intrinsic curiosity to explore unknown places. However, it remains untested how curiosity shapes aspects of spatial exploration in humans. Combining a virtual reality task with indices of exploration complexity, we found that pre-exploration curiosity states predicted how much individuals spatially explored environments, whereas markers of visual exploration determined post-exploration feelings of interest. Moreover, individual differences in curiosity traits, particularly Stress Tolerance, modulated the relationship between curiosity and spatial exploration, suggesting the capacity to cope with uncertainty enhances the curiosity-exploration link. Furthermore, both curiosity and spatial exploration predicted how precisely participants could recall spatial-relational details of the environment, as measured by a sketch map task. These results provide new evidence for a link between curiosity and exploratory behaviour, and how curiosity might shape cognitive map formation.
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