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Nov 10

Explainable AI Methods for Neuroimaging: Systematic Failures of Common Tools, the Need for Domain-Specific Validation, and a Proposal for Safe Application

Trustworthy interpretation of deep learning models is critical for neuroimaging applications, yet commonly used Explainable AI (XAI) methods lack rigorous validation, risking misinterpretation. We performed the first large-scale, systematic comparison of XAI methods on ~45,000 structural brain MRIs using a novel XAI validation framework. This framework establishes verifiable ground truth by constructing prediction tasks with known signal sources - from localized anatomical features to subject-specific clinical lesions - without artificially altering input images. Our analysis reveals systematic failures in two of the most widely used methods: GradCAM consistently failed to localize predictive features, while Layer-wise Relevance Propagation generated extensive, artifactual explanations that suggest incompatibility with neuroimaging data characteristics. Our results indicate that these failures stem from a domain mismatch, where methods with design principles tailored to natural images require substantial adaptation for neuroimaging data. In contrast, the simpler, gradient-based method SmoothGrad, which makes fewer assumptions about data structure, proved consistently accurate, suggesting its conceptual simplicity makes it more robust to this domain shift. These findings highlight the need for domain-specific adaptation and validation of XAI methods, suggest that interpretations from prior neuroimaging studies using standard XAI methodology warrant re-evaluation, and provide urgent guidance for practical application of XAI in neuroimaging.

  • 6 authors
·
Aug 4

fastHDMI: Fast Mutual Information Estimation for High-Dimensional Data

In this paper, we introduce fastHDMI, a Python package designed for efficient variable screening in high-dimensional datasets, particularly neuroimaging data. This work pioneers the application of three mutual information estimation methods for neuroimaging variable selection, a novel approach implemented via fastHDMI. These advancements enhance our ability to analyze the complex structures of neuroimaging datasets, providing improved tools for variable selection in high-dimensional spaces. Using the preprocessed ABIDE dataset, we evaluate the performance of these methods through extensive simulations. The tests cover a range of conditions, including linear and nonlinear associations, as well as continuous and binary outcomes. Our results highlight the superiority of the FFTKDE-based mutual information estimation for feature screening in continuous nonlinear outcomes, while binning-based methods outperform others for binary outcomes with nonlinear probability preimages. For linear simulations, both Pearson correlation and FFTKDE-based methods show comparable performance for continuous outcomes, while Pearson excels in binary outcomes with linear probability preimages. A comprehensive case study using the ABIDE dataset further demonstrates fastHDMI's practical utility, showcasing the predictive power of models built from variables selected using our screening techniques. This research affirms the computational efficiency and methodological strength of fastHDMI, significantly enriching the toolkit available for neuroimaging analysis.

  • 5 authors
·
Oct 13, 2024

Cascaded Multi-Modal Mixing Transformers for Alzheimer's Disease Classification with Incomplete Data

Accurate medical classification requires a large number of multi-modal data, and in many cases, different feature types. Previous studies have shown promising results when using multi-modal data, outperforming single-modality models when classifying diseases such as Alzheimer's Disease (AD). However, those models are usually not flexible enough to handle missing modalities. Currently, the most common workaround is discarding samples with missing modalities which leads to considerable data under-utilization. Adding to the fact that labeled medical images are already scarce, the performance of data-driven methods like deep learning can be severely hampered. Therefore, a multi-modal method that can handle missing data in various clinical settings is highly desirable. In this paper, we present Multi-Modal Mixing Transformer (3MAT), a disease classification transformer that not only leverages multi-modal data but also handles missing data scenarios. In this work, we test 3MT for AD and Cognitively normal (CN) classification and mild cognitive impairment (MCI) conversion prediction to progressive MCI (pMCI) or stable MCI (sMCI) using clinical and neuroimaging data. The model uses a novel Cascaded Modality Transformer architecture with cross-attention to incorporate multi-modal information for more informed predictions. We propose a novel modality dropout mechanism to ensure an unprecedented level of modality independence and robustness to handle missing data scenarios. The result is a versatile network that enables the mixing of arbitrary numbers of modalities with different feature types and also ensures full data utilization missing data scenarios. The model is trained and evaluated on the ADNI dataset with the SOTRA performance and further evaluated with the AIBL dataset with missing data.

  • 6 authors
·
Oct 1, 2022

BRAINS: A Retrieval-Augmented System for Alzheimer's Detection and Monitoring

As the global burden of Alzheimer's disease (AD) continues to grow, early and accurate detection has become increasingly critical, especially in regions with limited access to advanced diagnostic tools. We propose BRAINS (Biomedical Retrieval-Augmented Intelligence for Neurodegeneration Screening) to address this challenge. This novel system harnesses the powerful reasoning capabilities of Large Language Models (LLMs) for Alzheimer's detection and monitoring. BRAINS features a dual-module architecture: a cognitive diagnostic module and a case-retrieval module. The Diagnostic Module utilizes LLMs fine-tuned on cognitive and neuroimaging datasets -- including MMSE, CDR scores, and brain volume metrics -- to perform structured assessments of Alzheimer's risk. Meanwhile, the Case Retrieval Module encodes patient profiles into latent representations and retrieves similar cases from a curated knowledge base. These auxiliary cases are fused with the input profile via a Case Fusion Layer to enhance contextual understanding. The combined representation is then processed with clinical prompts for inference. Evaluations on real-world datasets demonstrate BRAINS effectiveness in classifying disease severity and identifying early signs of cognitive decline. This system not only shows strong potential as an assistive tool for scalable, explainable, and early-stage Alzheimer's disease detection, but also offers hope for future applications in the field.

BrainFLORA: Uncovering Brain Concept Representation via Multimodal Neural Embeddings

Understanding how the brain represents visual information is a fundamental challenge in neuroscience and artificial intelligence. While AI-driven decoding of neural data has provided insights into the human visual system, integrating multimodal neuroimaging signals, such as EEG, MEG, and fMRI, remains a critical hurdle due to their inherent spatiotemporal misalignment. Current approaches often analyze these modalities in isolation, limiting a holistic view of neural representation. In this study, we introduce BrainFLORA, a unified framework for integrating cross-modal neuroimaging data to construct a shared neural representation. Our approach leverages multimodal large language models (MLLMs) augmented with modality-specific adapters and task decoders, achieving state-of-the-art performance in joint-subject visual retrieval task and has the potential to extend multitasking. Combining neuroimaging analysis methods, we further reveal how visual concept representations align across neural modalities and with real world object perception. We demonstrate that the brain's structured visual concept representations exhibit an implicit mapping to physical-world stimuli, bridging neuroscience and machine learning from different modalities of neural imaging. Beyond methodological advancements, BrainFLORA offers novel implications for cognitive neuroscience and brain-computer interfaces (BCIs). Our code is available at https://github.com/ncclab-sustech/BrainFLORA.

  • 5 authors
·
Jul 13

Machine Learning Workflow to Explain Black-box Models for Early Alzheimer's Disease Classification Evaluated for Multiple Datasets

Purpose: Hard-to-interpret Black-box Machine Learning (ML) were often used for early Alzheimer's Disease (AD) detection. Methods: To interpret eXtreme Gradient Boosting (XGBoost), Random Forest (RF), and Support Vector Machine (SVM) black-box models a workflow based on Shapley values was developed. All models were trained on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset and evaluated for an independent ADNI test set, as well as the external Australian Imaging and Lifestyle flagship study of Ageing (AIBL), and Open Access Series of Imaging Studies (OASIS) datasets. Shapley values were compared to intuitively interpretable Decision Trees (DTs), and Logistic Regression (LR), as well as natural and permutation feature importances. To avoid the reduction of the explanation validity caused by correlated features, forward selection and aspect consolidation were implemented. Results: Some black-box models outperformed DTs and LR. The forward-selected features correspond to brain areas previously associated with AD. Shapley values identified biologically plausible associations with moderate to strong correlations with feature importances. The most important RF features to predict AD conversion were the volume of the amygdalae, and a cognitive test score. Good cognitive test performances and large brain volumes decreased the AD risk. The models trained using cognitive test scores significantly outperformed brain volumetric models (p<0.05). Cognitive Normal (CN) vs. AD models were successfully transferred to external datasets. Conclusion: In comparison to previous work, improved performances for ADNI and AIBL were achieved for CN vs. Mild Cognitive Impairment (MCI) classification using brain volumes. The Shapley values and the feature importances showed moderate to strong correlations.

  • 2 authors
·
May 12, 2022

Homogenized $\textit{C. elegans}$ Neural Activity and Connectivity Data

There is renewed interest in modeling and understanding the nervous system of the nematode Caenorhabditis elegans (C. elegans), as this small model system provides a path to bridge the gap between nervous system structure (connectivity) and function (physiology). However, existing physiology datasets, whether involving passive recording or stimulation, are in distinct formats, and connectome datasets require preprocessing before analysis can commence. Here we compile and homogenize datasets of neural activity and connectivity. Our neural activity dataset is derived from 11 C. elegans neuroimaging experiments, while our connectivity dataset is compiled from 9 connectome annotations based on 3 primary electron microscopy studies and 1 signal propagation study. Physiology datasets, collected under varying protocols, measure calcium fluorescence in labeled subsets of the worm's 300 neurons. Our preprocessing pipeline standardizes these datasets by consistently ordering labeled neurons and resampling traces to a common sampling rate, yielding recordings from approximately 900 worms and 250 uniquely labeled neurons. The connectome datasets, collected from electron microscopy reconstructions, represent the entire nervous system as a graph of connections. Our collection is accessible on HuggingFace, facilitating analysis of the structure-function relationship in biology using modern neural network architectures and enabling cross-lab and cross-animal comparisons.

  • 4 authors
·
Nov 18, 2024