Danilo Bzdok

Xinxu Wei, Kaifu Yang, Danilo Bzdok et al.

Most of the existing deep learning based methods for vessel segmentation neglect two important aspects of retinal vessels, one is the orientation information of vessels, and the other is the contextual information of the whole fundus region. In this paper, we propose a robust Orientation and Context Entangled Network (denoted as OCE-Net), which has the capability of extracting complex orientation and context information of the blood vessels. To achieve complex orientation aware, a Dynamic Complex Orientation Aware Convolution (DCOA Conv) is proposed to extract complex vessels with multiple orientations for improving the vessel continuity. To simultaneously capture the global context information and emphasize the important local information, a Global and Local Fusion Module (GLFM) is developed to simultaneously model the long-range dependency of vessels and focus sufficient attention on local thin vessels. A novel Orientation and Context Entangled Non-local (OCE-NL) module is proposed to entangle the orientation and context information together. In addition, an Unbalanced Attention Refining Module (UARM) is proposed to deal with the unbalanced pixel numbers of background, thick and thin vessels. Extensive experiments were performed on several commonly used datasets (DRIVE, STARE and CHASEDB1) and some more challenging datasets (AV-WIDE, UoA-DR, RFMiD and UK Biobank). The ablation study shows that the proposed method achieves promising performance on maintaining the continuity of thin vessels and the comparative experiments demonstrate that our OCE-Net can achieve state-of-the-art performance on retinal vessel segmentation.

Robert Carruthers, Isabel Straw, James K Ruffle et al.

Equity is widely held to be fundamental to the ethics of healthcare. In the context of clinical decision-making, it rests on the comparative fidelity of the intelligence -- evidence-based or intuitive -- guiding the management of each individual patient. Though brought to recent attention by the individuating power of contemporary machine learning, such epistemic equity arises in the context of any decision guidance, whether traditional or innovative. Yet no general framework for its quantification, let alone assurance, currently exists. Here we formulate epistemic equity in terms of model fidelity evaluated over learnt multi-dimensional representations of identity crafted to maximise the captured diversity of the population, introducing a comprehensive framework for Representational Ethical Model Calibration. We demonstrate use of the framework on large-scale multimodal data from UK Biobank to derive diverse representations of the population, quantify model performance, and institute responsive remediation. We offer our approach as a principled solution to quantifying and assuring epistemic equity in healthcare, with applications across the research, clinical, and regulatory domains.

Sonia Joseph, Praneet Suresh, Lorenz Hufe et al.

Robust tooling and publicly available pre-trained models have helped drive recent advances in mechanistic interpretability for language models. However, similar progress in vision mechanistic interpretability has been hindered by the lack of accessible frameworks and pre-trained weights. We present Prisma (Access the codebase here: https://github.com/Prisma-Multimodal/ViT-Prisma), an open-source framework designed to accelerate vision mechanistic interpretability research, providing a unified toolkit for accessing 75+ vision and video transformers; support for sparse autoencoder (SAE), transcoder, and crosscoder training; a suite of 80+ pre-trained SAE weights; activation caching, circuit analysis tools, and visualization tools; and educational resources. Our analysis reveals surprising findings, including that effective vision SAEs can exhibit substantially lower sparsity patterns than language SAEs, and that in some instances, SAE reconstructions can decrease model loss. Prisma enables new research directions for understanding vision model internals while lowering barriers to entry in this emerging field.

Chen Liu, Ke Xu, Liangbo L. Shen et al.

Advances in medical imaging technologies have enabled the collection of longitudinal images, which involve repeated scanning of the same patients over time, to monitor disease progression. However, predictive modeling of such data remains challenging due to high dimensionality, irregular sampling, and data sparsity. To address these issues, we propose ImageFlowNet, a novel model designed to forecast disease trajectories from initial images while preserving spatial details. ImageFlowNet first learns multiscale joint representation spaces across patients and time points, then optimizes deterministic or stochastic flow fields within these spaces using a position-parameterized neural ODE/SDE framework. The model leverages a UNet architecture to create robust multiscale representations and mitigates data scarcity by combining knowledge from all patients. We provide theoretical insights that support our formulation of ODEs, and motivate our regularizations involving high-level visual features, latent space organization, and trajectory smoothness. We validate ImageFlowNet on three longitudinal medical image datasets depicting progression in geographic atrophy, multiple sclerosis, and glioblastoma, demonstrating its ability to effectively forecast disease progression and outperform existing methods. Our contributions include the development of ImageFlowNet, its theoretical underpinnings, and empirical validation on real-world datasets. The official implementation is available at https://github.com/KrishnaswamyLab/ImageFlowNet.

Sonia Joseph, Praneet Suresh, Ethan Goldfarb et al.

While vision models are highly capable, their internal mechanisms remain poorly understood -- a challenge which sparse autoencoders (SAEs) have helped address in language, but which remains underexplored in vision. We address this gap by training SAEs on CLIP's vision transformer and uncover key differences between vision and language processing, including distinct sparsity patterns for SAEs trained across layers and token types. We then provide the first systematic analysis on the steerability of CLIP's vision transformer by introducing metrics to quantify how precisely SAE features can be steered to affect the model's output. We find that 10-15\% of neurons and features are steerable, with SAEs providing thousands more steerable features than the base model. Through targeted suppression of SAE features, we then demonstrate improved performance on three vision disentanglement tasks (CelebA, Waterbirds, and typographic attacks), finding optimal disentanglement in middle model layers, and achieving state-of-the-art performance on defense against typographic attacks.

Karam Ghanem, Danilo Bzdok

Through Diffusion Models (DMs), we have made significant advances in generating high-quality images. Our exploration of these models delves deeply into their core operational principles by systematically investigating key aspects across various DM architectures: i) noise schedules, ii) samplers, and iii) guidance. Our comprehensive examination of these models sheds light on their hidden fundamental mechanisms, revealing the concealed foundational elements that are essential for their effectiveness. Our analyses emphasize the hidden key factors that determine model performance, offering insights that contribute to the advancement of DMs. Past findings show that the configuration of noise schedules, samplers, and guidance is vital to the quality of generated images; however, models reach a stable level of quality across different configurations at a remarkably similar point, revealing that the decisive factors for optimal performance predominantly reside in the diffusion process dynamics and the structural design of the model's network, rather than the specifics of configuration details. Our comparative analysis reveals that Denoising Diffusion Probabilistic Model (DDPM)-based diffusion dynamics consistently outperform the Noise Conditioned Score Network (NCSN)-based ones, not only when evaluated in their original forms but also when continuous through Stochastic Differential Equation (SDE)-based implementations.

Karan Bali, Jack Stanley, Praneet Suresh et al.

In mechanistic interpretability, recent work scrutinizes transformer "circuits" - sparse, mono or multi layer sub computations, that may reflect human understandable functions. Yet, these network circuits are rarely acid-tested for their stability across different instances of the same deep learning architecture. Without this, it remains unclear whether reported circuits emerge universally across labs or turn out to be idiosyncratic to a particular estimation instance, potentially limiting confidence in safety-critical settings. Here, we systematically study stability across-refits in increasingly complex transformer language models of various sizes. We quantify, layer by layer, how similarly attention heads learn representations across independently initialized training runs. Our rigorous experiments show that (1) middle-layer heads are the least stable yet the most representationally distinct; (2) deeper models exhibit stronger mid-depth divergence; (3) unstable heads in deeper layers become more functionally important than their peers from the same layer; (4) applying weight decay optimization substantially improves attention-head stability across random model initializations; and (5) the residual stream is comparatively stable. Our findings establish the cross-instance robustness of circuits as an essential yet underappreciated prerequisite for scalable oversight, drawing contours around possible white-box monitorability of AI systems.

Praneet Suresh, Jack Stanley, Sonia Joseph et al.

As generative AI systems become competent and democratized in science, business, and government, deeper insight into their failure modes now poses an acute need. The occasional volatility in their behavior, such as the propensity of transformer models to hallucinate, impedes trust and adoption of emerging AI solutions in high-stakes areas. In the present work, we establish how and when hallucinations arise in pre-trained transformer models through concept representations captured by sparse autoencoders, under scenarios with experimentally controlled uncertainty in the input space. Our systematic experiments reveal that the number of semantic concepts used by the transformer model grows as the input information becomes increasingly unstructured. In the face of growing uncertainty in the input space, the transformer model becomes prone to activate coherent yet input-insensitive semantic features, leading to hallucinated output. At its extreme, for pure-noise inputs, we identify a wide variety of robustly triggered and meaningful concepts in the intermediate activations of pre-trained transformer models, whose functional integrity we confirm through targeted steering. We also show that hallucinations in the output of a transformer model can be reliably predicted from the concept patterns embedded in transformer layer activations. This collection of insights on transformer internal processing mechanics has immediate consequences for aligning AI models with human values, AI safety, opening the attack surface for potential adversarial attacks, and providing a basis for automatic quantification of a model's hallucination risk.

Liam Hodgson, Danilo Bzdok

The multivariate hypergeometric distribution describes sampling without replacement from a discrete population of elements divided into multiple categories. Addressing a gap in the literature, we tackle the challenge of estimating discrete distributions when both the total population size and the sizes of its constituent categories are unknown. Here, we propose a novel solution using the hypergeometric likelihood to solve this estimation challenge, even in the presence of severe under-sampling. We develop our approach to account for a data generating process where the ground-truth is a mixture of distributions conditional on a continuous latent variable, such as with collaborative filtering, using the variational autoencoder framework. Empirical data simulation demonstrates that our method outperforms other likelihood functions used to model count data, both in terms of accuracy of population size estimate and in its ability to learn an informative latent space. We demonstrate our method's versatility through applications in NLP, by inferring and estimating the complexity of latent vocabularies in text excerpts, and in biology, by accurately recovering the true number of gene transcripts from sparse single-cell genomics data.

Marc-Andre Schulz, Bertrand Thirion, Alexandre Gramfort et al.

High-quality data accumulation is now becoming ubiquitous in the health domain. There is increasing opportunity to exploit rich data from normal subjects to improve supervised estimators in specific diseases with notorious data scarcity. We demonstrate that low-dimensional embedding spaces can be derived from the UK Biobank population dataset and used to enhance data-scarce prediction of health indicators, lifestyle and demographic characteristics. Phenotype predictions facilitated by Variational Autoencoder manifolds typically scaled better with increasing unlabeled data than dimensionality reduction by PCA or Isomap. Performances gains from semisupervison approaches will probably become an important ingredient for various medical data science applications.

Marc-Andre Schulz, Matt Chapman-Rounds, Manisha Verma et al.

Identification of disease subtypes and corresponding biomarkers can substantially improve clinical diagnosis and treatment selection. Discovering these subtypes in noisy, high dimensional biomedical data is often impossible for humans and challenging for machines. We introduce a new approach to facilitate the discovery of disease subtypes: Instead of analyzing the original data, we train a diagnostic classifier (healthy vs. diseased) and extract instance-wise explanations for the classifier's decisions. The distribution of instances in the explanation space of our diagnostic classifier amplifies the different reasons for belonging to the same class - resulting in a representation that is uniquely useful for discovering latent subtypes. We compare our ability to recover subtypes via cluster analysis on model explanations to classical cluster analysis on the original data. In multiple datasets with known ground-truth subclasses, most compellingly on UK Biobank brain imaging data and transcriptome data from the Cancer Genome Atlas, we show that cluster analysis on model explanations substantially outperforms the classical approach. While we believe clustering in explanation space to be particularly valuable for inferring disease subtypes, the method is more general and applicable to any kind of sub-type identification.

Hao-Ting Wang, Jonathan Smallwood, Janaina Mourao-Miranda et al.

Since the beginning of the 21st century, the size, breadth, and granularity of data in biology and medicine has grown rapidly. In the example of neuroscience, studies with thousands of subjects are becoming more common, which provide extensive phenotyping on the behavioral, neural, and genomic level with hundreds of variables. The complexity of such big data repositories offer new opportunities and pose new challenges to investigate brain, cognition, and disease. Canonical correlation analysis (CCA) is a prototypical family of methods for wrestling with and harvesting insight from such rich datasets. This doubly-multivariate tool can simultaneously consider two variable sets from different modalities to uncover essential hidden associations. Our primer discusses the rationale, promises, and pitfalls of CCA in biomedicine.

Arthur Mensch, Julien Mairal, Danilo Bzdok et al.

Cognitive neuroscience is enjoying rapid increase in extensive public brain-imaging datasets. It opens the door to large-scale statistical models. Finding a unified perspective for all available data calls for scalable and automated solutions to an old challenge: how to aggregate heterogeneous information on brain function into a universal cognitive system that relates mental operations/cognitive processes/psychological tasks to brain networks? We cast this challenge in a machine-learning approach to predict conditions from statistical brain maps across different studies. For this, we leverage multi-task learning and multi-scale dimension reduction to learn low-dimensional representations of brain images that carry cognitive information and can be robustly associated with psychological stimuli. Our multi-dataset classification model achieves the best prediction performance on several large reference datasets, compared to models without cognitive-aware low-dimension representations, it brings a substantial performance boost to the analysis of small datasets, and can be introspected to identify universal template cognitive concepts.

Danilo Bzdok, B. T. Thomas Yeo

Neuroscience is undergoing faster changes than ever before. Over 100 years our field qualitatively described and invasively manipulated single or few organisms to gain anatomical, physiological, and pharmacological insights. In the last 10 years neuroscience spawned quantitative big-sample datasets on microanatomy, synaptic connections, optogenetic brain-behavior assays, and high-level cognition. While growing data availability and information granularity have been amply discussed, we direct attention to a routinely neglected question: How will the unprecedented data richness shape data analysis practices? Statistical reasoning is becoming more central to distill neurobiological knowledge from healthy and pathological brain recordings. We believe that large-scale data analysis will use more models that are non-parametric, generative, mixing frequentist and Bayesian aspects, and grounded in different statistical inferences.

Danilo Bzdok

Neuroimaging research has predominantly drawn conclusions based on classical statistics, including null-hypothesis testing, t-tests, and ANOVA. Throughout recent years, statistical learning methods enjoy increasing popularity, including cross-validation, pattern classification, and sparsity-inducing regression. These two methodological families used for neuroimaging data analysis can be viewed as two extremes of a continuum. Yet, they originated from different historical contexts, build on different theories, rest on different assumptions, evaluate different outcome metrics, and permit different conclusions. This paper portrays commonalities and differences between classical statistics and statistical learning with their relation to neuroimaging research. The conceptual implications are illustrated in three common analysis scenarios. It is thus tried to resolve possible confusion between classical hypothesis testing and data-guided model estimation by discussing their ramifications for the neuroimaging access to neurobiology.