Ischaemic stroke, a leading cause of death and disability, critically relies on neuroimaging for characterising the anatomical pattern of injury. Diffusion-weighted imaging (DWI) provides the highest expressivity in ischemic stroke but poses substantial challenges for automated lesion segmentation: susceptibility artefacts, morphological heterogeneity, age-related comorbidities, time-dependent signal dynamics, instrumental variability, and limited labelled data. Current U-Net-based models therefore underperform, a problem accentuated by inadequate evaluation metrics that focus on mean performance, neglecting anatomical, subpopulation, and acquisition-dependent variability. Here, we present a high-performance DWI lesion segmentation tool addressing these challenges through optimized vision transformer-based architectures, integration of 3563 annotated lesions from multi-site data, and algorithmic enhancements, achieving state-of-the-art results. We further propose a novel evaluative framework assessing model fidelity, equity (across demographics and lesion subtypes), anatomical precision, and robustness to instrumental variability, promoting clinical and research utility. This work advances stroke imaging by reconciling model expressivity with domain-specific challenges and redefining performance benchmarks to prioritize equity and generalizability, critical for personalized medicine and mechanistic research.

The quantification of cognitive powers rests on identifying a behavioural task that depends on them. Such dependence cannot be assured, for the powers a task invokes cannot be experimentally controlled or constrained a priori, resulting in unknown vulnerability to failure of specificity and generalisability. Evaluating a compact version of Raven's Advanced Progressive Matrices (RAPM), a widely used clinical test of fluid intelligence, we show that LaMa, a self-supervised artificial neural network trained solely on the completion of partially masked images of natural environmental scenes, achieves human-level test scores a prima vista, without any task-specific inductive bias or training. Compared with cohorts of healthy and focally lesioned participants, LaMa exhibits human-like variation with item difficulty, and produces errors characteristic of right frontal lobe damage under degradation of its ability to integrate global spatial patterns. LaMa's narrow training and limited capacity -- comparable to the nervous system of the fruit fly -- suggest RAPM may be open to computationally simple solutions that need not necessarily invoke abstract reasoning.

Causal mapping of the functional organisation of the human brain requires evidence of \textit{necessity} available at adequate scale only from pathological lesions of natural origin. This demands inferential models with sufficient flexibility to capture both the observable distribution of pathological damage and the unobserved distribution of the neural substrate. Current model frameworks -- both mass-univariate and multivariate -- either ignore distributed lesion-deficit relations or do not model them explicitly, relying on featurization incidental to a predictive task. Here we initiate the application of deep generative neural network architectures to the task of lesion-deficit inference, formulating it as the estimation of an expressive hierarchical model of the joint lesion and deficit distributions conditioned on a latent neural substrate. We implement such deep lesion deficit inference with variational convolutional volumetric auto-encoders. We introduce a comprehensive framework for lesion-deficit model comparison, incorporating diverse candidate substrates, forms of substrate interactions, sample sizes, noise corruption, and population heterogeneity. Drawing on 5500 volume images of ischaemic stroke, we show that our model outperforms established methods by a substantial margin across all simulation scenarios, including comparatively small-scale and noisy data regimes. Our analysis justifies the widespread adoption of this approach, for which we provide an open source implementation: https://github.com/guilherme-pombo/vae_lesion_deficit

Deep generative models are rapidly gaining traction in medical imaging. Nonetheless, most generative architectures struggle to capture the underlying probability distributions of volumetric data, exhibit convergence problems, and offer no robust indices of model uncertainty. By comparison, the autoregressive generative model PixelCNN can be extended to volumetric data with relative ease, it readily attempts to learn the true underlying probability distribution and it still admits a Bayesian reformulation that provides a principled framework for reasoning about model uncertainty. Our contributions in this paper are two fold: first, we extend PixelCNN to work with volumetric brain magnetic resonance imaging data. Second, we show that reformulating this model to approximate a deep Gaussian process yields a measure of uncertainty that improves the performance of semi-supervised learning, in particular classification performance in settings where the proportion of labelled data is low. We quantify this improvement across classification, regression, and semantic segmentation tasks, training and testing on clinical magnetic resonance brain imaging data comprising T1-weighted and diffusion-weighted sequences.