Stroke Lesions as a Rosetta Stone for Language Model Interpretability

Large language models (LLMs) have achieved remarkable capabilities, yet methods to verify which model components are truly necessary for language function remain limited. Current interpretability approaches rely on internal metrics and lack external validation. Here we present the Brain-LLM Unified Model (BLUM), a framework that leverages lesion-symptom mapping, the gold standard for establishing causal brain-behavior relationships for over a century, as an external reference structure for evaluating LLM perturbation effects. Using data from individuals with chronic post-stroke aphasia (N = 410), we trained symptom-to-lesion models that predict brain damage location from behavioral error profiles, applied systematic perturbations to transformer layers, administered identical clinical assessments to perturbed LLMs and human patients, and projected LLM error profiles into human lesion space. LLM error profiles were sufficiently similar to human error profiles that predicted lesions corresponded to actual lesions in error-matched humans above chance in 67% of picture naming conditions (p < 10^{-23}) and 68.3% of sentence completion conditions (p < 10^{-61}), with semantic-dominant errors mapping onto ventral-stream lesion patterns and phonemic-dominant errors onto dorsal-stream patterns. These findings open a new methodological avenue for LLM interpretability in which clinical neuroscience provides external validation, establishing human lesion-symptom mapping as a reference framework for evaluating artificial language systems and motivating direct investigation of whether behavioral alignment reflects shared computational principles.

MindGrab for BrainChop: Fast and Accurate Skull Stripping for Command Line and Browser

We developed MindGrab, a parameter- and memory-efficient deep fully-convolutional model for volumetric skull-stripping in head images of any modality. Its architecture, informed by a spectral interpretation of dilated convolutions, was trained exclusively on modality-agnostic synthetic data. MindGrab was evaluated on a retrospective dataset of 606 multimodal adult-brain scans (T1, T2, DWI, MRA, PDw MRI, EPI, CT, PET) sourced from the SynthStrip dataset. Performance was benchmarked against SynthStrip, ROBEX, and BET using Dice scores, with Wilcoxon signed-rank significance tests. MindGrab achieved a mean Dice score of 95.9 with standard deviation (SD) 1.6 across modalities, significantly outperforming classical methods (ROBEX: 89.1 SD 7.7, P < 0.05; BET: 85.2 SD 14.4, P < 0.05). Compared to SynthStrip (96.5 SD 1.1, P=0.0352), MindGrab delivered equivalent or superior performance in nearly half of the tested scenarios, with minor differences (<3% Dice) in the others. MindGrab utilized 95% fewer parameters (146,237 vs. 2,566,561) than SynthStrip. This efficiency yielded at least 2x faster inference, 50% lower memory usage on GPUs, and enabled exceptional performance (e.g., 10-30x speedup, and up to 30x memory reduction) and accessibility on a wider range of hardware, including systems without high-end GPUs. MindGrab delivers state-of-the-art accuracy with dramatically lower resource demands, supported in brainchop-cli (https://pypi.org/project/brainchop/) and at brainchop.org.

State-of-the-Art Stroke Lesion Segmentation at 1/1000th of Parameters

Efficient and accurate whole-brain lesion segmentation remains a challenge in medical image analysis. In this work, we revisit MeshNet, a parameter-efficient segmentation model, and introduce a novel multi-scale dilation pattern with an encoder-decoder structure. This innovation enables capturing broad contextual information and fine-grained details without traditional downsampling, upsampling, or skip-connections. Unlike previous approaches processing subvolumes or slices, we operate directly on whole-brain $256^3$ MRI volumes. Evaluations on the Aphasia Recovery Cohort (ARC) dataset demonstrate that MeshNet achieves superior or comparable DICE scores to state-of-the-art architectures such as MedNeXt and U-MAMBA at 1/1000th of parameters. Our results validate MeshNet's strong balance of efficiency and performance, making it particularly suitable for resource-limited environments such as web-based applications and opening new possibilities for the widespread deployment of advanced medical image analysis tools.

Heteroscedastic sparse high-dimensional linear regression with a partitioned empirical Bayes ECM algorithm

Sparse linear regression methods for high-dimensional data often assume that residuals have constant variance. When this assumption is violated, it can lead to bias in estimated coefficients, prediction intervals (PI) with improper length, and increased type I errors. We propose a heteroscedastic high-dimensional linear regression model through a partitioned empirical Bayes Expectation Conditional Maximization (H-PROBE) algorithm. H-PROBE is a computationally efficient maximum a posteriori estimation approach based on a Parameter-Expanded Expectation-Conditional-Maximization algorithm. It requires minimal prior assumptions on the regression parameters through plug-in empirical Bayes estimates of hyperparameters. The variance model uses a multivariate log-Gamma prior on coefficients that can incorporate covariates hypothesized to impact heterogeneity. The motivation of our approach is a study relating Aphasia Quotient (AQ) to high-resolution T2 neuroimages of brain damage in stroke patients. AQ is a vital measure of language impairment and informs treatment decisions, but it is challenging to measure and subject to heteroscedastic errors. It is, therefore, of clinical importance -- and the goal of this paper -- to use high-dimensional neuroimages to predict and provide PIs for AQ that accurately reflect the heterogeneity in residual variance. Our analysis demonstrates that H-PROBE can use markers of heterogeneity to provide narrower PI widths than standard methods without sacrificing coverage. Through extensive simulation studies, we exhibit that H-PROBE results in superior prediction, variable selection, and predictive inference than competing methods.