Australian researchers teach brain cells to play'Doom' video game Scientist Brett Kagan looks at cortical and hippocampal cells on cell culture plates as they attempt to decode morse code, at Cortical Labs' Physical Containment Level 2 laboratory in Melbourne. Melbourne - Australian researchers have trained lab-grown brain cells on a silicon computer chip to play the '90s shooter game Doom and say they are just scratching the surface of what the neurons could be capable of doing. It's the science-fiction work of biotech boffins at Cortical Labs, who researched and developed the technology that harnesses the workings of the brain's networking system. Each so-called "biological computer" contains around 200,000 living human brain cells, grown from stem cells that were harvested from blood donations. In a time of both misinformation and too much information, quality journalism is more crucial than ever. By subscribing, you can help us get the story right.

Flow and diffusion generative models have established themselves as widely adopted density estimators for simulation-based inference (SBI), extending naturally from neural posterior estimation to likelihood and joint density estimation. Their principled optimization objectives and freedom from architectural constraints have driven rapid adoption across the natural sciences. Yet the most widely used SBI libraries remain PyTorch-based, leaving researchers who develop their forward models and analysis pipelines in JAX without a native option. We present GenSBI, an open-source library that implements flow matching, score matching, and denoising diffusion entirely in JAX. The library offers three transformer-based architectures -- SimFormer, Flux1, and a novel Flux1Joint that extends gate-modulated transformer blocks to joint density estimation -- all interchangeable through a unified interface that decouples generative method, neural backbone, and inference mode. GenSBI provides an end-to-end workflow from training through posterior calibration (SBC, TARP, LC2ST) and supports custom architectures with domain-specific embedding networks.

Simulation-based inference (SBI; Cranmer et al., 2020) is a powerful framework for inferring parameters of scientific models whose likelihood functions are unavailable or computationally prohibitive to evaluate, but for which simulating data is straightforward. The use of flexible neural conditional density estimators has substantially expanded the applicability of SBI to challenging problems, especially in fields such as particle physics (Brehmer, 2021), cognitive neuroscience (Fengler et al., 2021), economics (Dyer et al., 2024) and cosmology (Alsing et al., 2018; Jeffrey et al., 2021). Neural SBI methods rely on simulations from the scientific model to approximate intractable quantities such as the posterior, the likelihood, the likelihood-to-evidence ratio, or the score function; see Zammit-Mangion et al. (2024) for a recent review. In this work, we focus on the widely used neural posterior estimation (NPE) method (Papamakarios and Murray, 2016; Radev et al., 2022). A central practical limitation of NPE is the simulation budget required to train the conditional density estimator. As many scientific simulators are expensive to run, generating a sufficiently large training set is often the main computational bottleneck.

Low-dimensional embeddings are widely used as visual summaries of high-dimensional data and to enable downstream scientific discoveries. Yet, popular nonlinear dimension reduction methods, such as t-SNE and UMAP, are often selected based on visual appeal alone and without rigorous quantitative validation. A major reason is that manifold embeddings typically do not provide an out-of-sample map nor an inverse back to the original feature space; this makes held-out validation, the gold standard in supervised learning, all but impossible. To address these challenges, we develop a novel framework, MEDAL (Manifold Embedding Distillation via Autoencoder Learning), which distills a fitted manifold embedding into a reusable encoder--decoder model. MEDAL trains a constrained autoencoder whose bottleneck exactly matches any teacher embedding while the decoder reconstructs the original input; this yields an explicit map for new samples, an approximate inverse, and a pointwise reconstruction-based measure of distortion in the manifold space. This converts static manifold embeddings into models that can be evaluated on held-out data, enabling quantitative validation including comparing different dimension reduction methods as well as hyperparameter tuning. Across multiple benchmark and scientific case studies, we show that MEDAL enables held-out validation to determine optimal manifold embeddings and hyperparameters, reveals biologically coherent regions that are difficult to preserve in two dimensional embeddings, and detects distribution shift when new samples are mapped into a fixed reference manifold. MEDAL provides a general validation wrapper to any existing dimension reduction technique that will improve the rigor and

Causal discovery from multivariate time series is challenging when causal effects may occur both across time and within the same sampling interval. This issue is especially important in applications such as neuroscience, where the sampling rate may be coarse relative to the underlying dynamics and contemporaneous effects need not form an acyclic graph. We study causal discovery in linear Gaussian structural VAR models under an equal noise variance assumption, meaning that the structural noise terms have a common variance. Unlike the DAG-based cross-sectional equal noise variance setting, the time-series setting considered here does not generally yield point identification of a unique causal graph. Instead, multiple structural VAR parameterizations can induce the same stationary observed process law. We introduce a notion of observational equivalence tailored to this setting and show that the corresponding equivalence class is characterized by orthogonal transformations of the structural equations together with a global positive scale. This characterization leads to an equivalence-aware model discrepancy, the observational alignment discrepancy, which compares structural models modulo transformations that preserve the observed law. Building on this theory, we propose ENVAR, a sparsity-based procedure that searches over the induced observational equivalence class for a sparse normalized structural representative. We evaluate the proposed methodology on synthetic structural VAR data and on an fMRI dataset.

Effective medication management in Parkinson's Disease (PD) is challenging due to heterogeneous disease progression, variable patient response, and medication side effects. While AI models can forecast levodopa equivalent daily dose (LEDD) as a measure of medication needs, standard uncertainty quantification often fails to communicate the reliability of these predictions, treating high and low confidence clinical decisions identically. We introduce CASCADE (Calibrated Adaptive Scaling via Conformal And Distributional Estimation), a novel conformal prediction framework that propagates epistemic uncertainty from a screening classifier to adapt downstream predictions. Unlike standard conformal methods that rely on auxiliary residual regression, we leverage epistemic uncertainty from a primary classification task (identifying whether a medication change is needed) to dynamically scale the prediction intervals of a secondary regression task (predicting how much change). By mapping Venn-Abers multi-probabilistic uncertainty directly to non-conformity scores, our framework achieves continuous risk adaptation. We demonstrate that this ``cascade effect'' produces highly efficient intervals for confident patients (38.9% narrower than standard conformal baselines) while automatically expanding intervals to ensure robust coverage for uncertain cases, bridging the gap between discrete clinical decision-making and continuous dose forecasting in PD.

Modern matrix completion problems often involve heterogeneous data whose rows simultaneously belong to many meta-categories, such as demographic and age groups in recommendation systems, or region and recording session labels in neural electrophysiological experiments. Standard low-rank estimators impose a single global latent geometry, which can recover average structure but may smooth away subgroup-specific variation, especially when observations are unevenly distributed across groups. We introduce Group-Aware Matrix Estimation (GAME), a convex estimator for overlapping subgroup-wise low-rank matrix estimation. GAME regularizes category-specific submatrices through overlapping nuclear-norm penalties, allowing related groups to borrow information while preserving local latent structure in a shared coordinate system. We provide finite-sample guarantees for both reconstruction error and subgroup-specific subspace recovery, showing how performance depends on sampling density, subgroup rank, and overlap structure. Experiments on synthetic, recommendation, ecological, and neuroscience datasets show that GAME is most beneficial in structured missingness regimes, where subgroup-aware regularization improves both reconstruction accuracy and latent subspace fidelity. Across these benchmarks, GAME is competitive or best among global low-rank, side-information, and modern imputation baselines, with the largest gains when subgroups exhibit distinct low-rank structure.

Tensor-valued data arise naturally in neuroimaging, genomics, climate science, and spatiotemporal networks, where multilinear dependencies across modes carry information that is destroyed under vectorization. Existing approaches either impose a single low-rank structure, which can miss localized signal, or treat the tensor as a long vector, which discards its multiway geometry. We propose a *Dual-Channel Tensor Neural Network* (DC-TNN) that decomposes each tensor input into a low-rank core and a sparse refinement, and processes the two components through coupled neural channels. The framework is structure-agnostic and accommodates CP, Tucker, and tensor-train cores within a single architecture. For estimation, we establish non-asymptotic risk bounds for the DC-TNN estimator that decompose into network approximation, core estimation, and refinement-selection terms, and show that the effective dimension is determined jointly by the core rank and refinement sparsity rather than by the ambient tensor size. For inference, we develop a *structure-aware conformal ROC* procedure that calibrates within the core-refinement latent space and produces ROC and AUC confidence bands with finite-sample, distribution-free coverage. Building on this, we propose a *conformal structure selector* that, to our knowledge, is the *first distribution-free procedure* for choosing among candidate tensor decompositions with finite-sample validity. Simulations and an analysis of a protein dataset demonstrate competitive predictive accuracy, reliable uncertainty quantification, and consistent recovery of the tensor structure.

Medium-horizon Alzheimer's disease progression prediction is difficult because future clinical scores can remain tied to baseline severity, while biomarker histories are irregular and incompletely observed. We develop an anchor-based analysis of 24-month Clinical Dementia Rating Sum of Boxes (CDR-SB) change using harmonized Alzheimer's Disease Neuroimaging Initiative (ADNI) tables. Each labeled sample is anchored at a mild cognitive impairment visit, uses only clinical and biomarker history observed at or before that anchor, and defines the response as CDR-SB at the future visit closest to 24 months within an 18--30 month window minus anchor CDR-SB. The analytic cohort contains 2,600 labeled anchors from 858 participants and 7,276 longitudinal rows. We propose a residual gap-aware transformer that combines a mixed-effects statistical reference with transformer-based residual learning from pre-anchor clinical and biomarker histories. The model uses participant-level random intercepts in the mixed-effects reference, observation-level triplet tokenization for irregular histories, and a learned nonnegative time-gap penalty inside self-attention. We compare the proposed model with a Bayesian-information-criterion-selected linear mixed-effects baseline, GRU-D, and STraTS under repeated participant-level train--test splits. Across five participant-level random seeds, the proposed model achieves the best mean test performance across all reported metrics, reducing MSE by 13.1% and increasing prediction--observation correlation by 26.4% relative to the mixed-effects baseline. It also improves over both GRU-D and STraTS in mean error and correlation. These results show that statistical anchoring and gap-aware residual learning provide a useful structure for medium-horizon Alzheimer's disease progression prediction.

Learning meaningful latent representations from nonlinear fMRI data remains a fundamental challenge in neuroimaging analysis. Traditional independent component analysis, widely used due to its ability to estimate interpretable functional brain networks, relies on a linear mixing assumption for latent sources, limiting its ability to capture the inherently nonlinear and complex organization of brain dynamics. More recently, deep representation learning methods have emerged as promising alternatives for modeling nonlinear latent structure. However, many of these approaches have been evaluated primarily on simulated datasets or natural image benchmarks, with comparatively limited validation on real-world neuroimaging data such as fMRI. In this work, we are motivated by the $β$-TCVAE (Total Correlation Variational Autoencoder), a refinement of the $β$-VAE framework for learning latent representations without introducing additional hyperparameters during training. We adapt and modify this model to fMRI data for nonlinear source disentanglement, aiming to separate mixed spatial and temporal brain signals into interpretable components. We show that the $β$-TCVAE framework can recover meaningful nonlinear spatial components with biological relevance, including well-established intrinsic connectivity networks such as the default mode network. Furthermore, we evaluate the learned representations using functional network connectivity, showing that the latent structure captures coherent and interpretable brain organization patterns. This study provides a pilot investigation that bridges nonlinear representation learning and fMRI analysis.