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Paul M. Thompson

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Published work

9 published item(s)

preprint2026arXiv

Anchoring the Eigengap: Cross-Modal Spectral Stabilization for Sample-Efficient Representation Learning

Deep vision models degrade sharply in low-data regimes, particularly in medical imaging where labeled samples are scarce. We show this arises not merely from overfitting but from a geometric failure: finite-sample noise corrupts the embedding covariance, collapsing the eigengap and limiting the number of recoverable signal-bearing modes. We develop a spectral theory of finite-sample representation learning that quantifies the recoverable dimension K(N), the number of eigenmodes that can be stably estimated from N samples. Using perturbation theory and concentration bounds, we show that only modes with eigenvalues above the noise floor $\|\hatΣ - Σ\|_{\mathrm{op}} \sim \sqrt{D/N}$ are reliable, yielding a truncated Mahalanobis energy that governs classification performance. Under a power-law spectral model, this energy can be approximated by a truncated Riemann zeta function, linking eigenvalue decay to data efficiency and AUC. Within this framework, multimodal learning acts as spectral stabilization: vision-language models impose low-rank constraints that suppress noise-dominated directions and preserve the eigengap, increasing K(N) under data scarcity. Across MNIST and multi-disease neuroimaging, we show that multimodal training maintains more stable modes and improves class separation, even when unimodal models achieve comparable few-shot accuracy. These results identify spectral collapse as a fundamental bottleneck in low-data learning. We use truncated Mahalanobis energy and K(N) to diagnose encoder quality, and introduce zeta-based spectral filtering as a principled approach to improve data efficiency.

preprint2021arXiv

Improved Brain Age Estimation with Slice-based Set Networks

Deep Learning for neuroimaging data is a promising but challenging direction. The high dimensionality of 3D MRI scans makes this endeavor compute and data-intensive. Most conventional 3D neuroimaging methods use 3D-CNN-based architectures with a large number of parameters and require more time and data to train. Recently, 2D-slice-based models have received increasing attention as they have fewer parameters and may require fewer samples to achieve comparable performance. In this paper, we propose a new architecture for BrainAGE prediction. The proposed architecture works by encoding each 2D slice in an MRI with a deep 2D-CNN model. Next, it combines the information from these 2D-slice encodings using set networks or permutation invariant layers. Experiments on the BrainAGE prediction problem, using the UK Biobank dataset, showed that the model with the permutation invariant layers trains faster and provides better predictions compared to other state-of-the-art approaches.

preprint2020arXiv

Overview of Scanner Invariant Representations

Pooled imaging data from multiple sources is subject to bias from each source. Studies that do not correct for these scanner/site biases at best lose statistical power, and at worst leave spurious correlations in their data. Estimation of the bias effects is non-trivial due to the paucity of data with correspondence across sites, so called "traveling phantom" data, which is expensive to collect. Nevertheless, numerous solutions leveraging direct correspondence have been proposed. In contrast to this, Moyer et al. (2019) proposes an unsupervised solution using invariant representations, one which does not require correspondence and thus does not require paired images. By leveraging the data processing inequality, an invariant representation can then be used to create an image reconstruction that is uninformative of its original source, yet still faithful to the underlying structure. In the present abstract we provide an overview of this method.

preprint2020arXiv

Scanner Invariant Representations for Diffusion MRI Harmonization

Purpose: In the present work we describe the correction of diffusion-weighted MRI for site and scanner biases using a novel method based on invariant representation. Theory and Methods: Pooled imaging data from multiple sources are subject to variation between the sources. Correcting for these biases has become very important as imaging studies increase in size and multi-site cases become more common. We propose learning an intermediate representation invariant to site/protocol variables, a technique adapted from information theory-based algorithmic fairness; by leveraging the data processing inequality, such a representation can then be used to create an image reconstruction that is uninformative of its original source, yet still faithful to underlying structures. To implement this, we use a deep learning method based on variational auto-encoders (VAE) to construct scanner invariant encodings of the imaging data. Results: To evaluate our method, we use training data from the 2018 MICCAI Computational Diffusion MRI (CDMRI) Challenge Harmonization dataset. Our proposed method shows improvements on independent test data relative to a recently published baseline method on each subtask, mapping data from three different scanning contexts to and from one separate target scanning context. Conclusion: As imaging studies continue to grow, the use of pooled multi-site imaging will similarly increase. Invariant representation presents a strong candidate for the harmonization of these data.

preprint2017arXiv

Simultaneous Matrix Diagonalization for Structural Brain Networks Classification

This paper considers the problem of brain disease classification based on connectome data. A connectome is a network representation of a human brain. The typical connectome classification problem is very challenging because of the small sample size and high dimensionality of the data. We propose to use simultaneous approximate diagonalization of adjacency matrices in order to compute their eigenstructures in more stable way. The obtained approximate eigenvalues are further used as features for classification. The proposed approach is demonstrated to be efficient for detection of Alzheimer's disease, outperforming simple baselines and competing with state-of-the-art approaches to brain disease classification.

preprint2016arXiv

An Empirical Study of Continuous Connectivity Degree Sequence Equivalents

In the present work we demonstrate the use of a parcellation free connectivity model based on Poisson point processes. This model produces for each subject a continuous bivariate intensity function that represents for every possible pair of points the relative rate at which we observe tracts terminating at those points. We fit this model to explore degree sequence equivalents for spatial continuum graphs, and to investigate the local differences between estimated intensity functions for two different tractography methods. This is a companion paper to Moyer et al. (2016), where the model was originally defined.

preprint2016arXiv

Large-scale Collaborative Imaging Genetics Studies of Risk Genetic Factors for Alzheimer's Disease Across Multiple Institutions

Genome-wide association studies (GWAS) offer new opportunities to identify genetic risk factors for Alzheimer's disease (AD). Recently, collaborative efforts across different institutions emerged that enhance the power of many existing techniques on individual institution data. However, a major barrier to collaborative studies of GWAS is that many institutions need to preserve individual data privacy. To address this challenge, we propose a novel distributed framework, termed Local Query Model (LQM) to detect risk SNPs for AD across multiple research institutions. To accelerate the learning process, we propose a Distributed Enhanced Dual Polytope Projection (D-EDPP) screening rule to identify irrelevant features and remove them from the optimization. To the best of our knowledge, this is the first successful run of the computationally intensive model selection procedure to learn a consistent model across different institutions without compromising their privacy while ranking the SNPs that may collectively affect AD. Empirical studies are conducted on 809 subjects with 5.9 million SNP features which are distributed across three individual institutions. D-EDPP achieved a 66-fold speed-up by effectively identifying irrelevant features.

preprint2015arXiv

Unifying inference on brain network variations in neurological diseases: The Alzheimer's case

There is growing interest in understanding how the structural interconnections among brain regions change with the occurrence of neurological diseases. Diffusion weighted MRI imaging has allowed researchers to non-invasively estimate a network of structural cortical connections made by white matter tracts, but current statistical methods for relating such networks to the presence or absence of a disease cannot exploit this rich network information. Standard practice considers each edge independently or summarizes the network with a few simple features. We enable dramatic gains in biological insight via a novel unifying methodology for inference on brain network variations associated to the occurrence of neurological diseases. The key of this approach is to define a probabilistic generative mechanism directly on the space of network configurations via dependent mixtures of low-rank factorizations, which efficiently exploit network information and allow the probability mass function for the brain network-valued random variable to vary flexibly across the group of patients characterized by a specific neurological disease and the one comprising age-matched cognitively healthy individuals.

preprint2012arXiv

Identification of gene pathways implicated in Alzheimer's disease using longitudinal imaging phenotypes with sparse regression

We present a new method for the detection of gene pathways associated with a multivariate quantitative trait, and use it to identify causal pathways associated with an imaging endophenotype characteristic of longitudinal structural change in the brains of patients with Alzheimer's disease (AD). Our method, known as pathways sparse reduced-rank regression (PsRRR), uses group lasso penalised regression to jointly model the effects of genome-wide single nucleotide polymorphisms (SNPs), grouped into functional pathways using prior knowledge of gene-gene interactions. Pathways are ranked in order of importance using a resampling strategy that exploits finite sample variability. Our application study uses whole genome scans and MR images from 464 subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. 66,182 SNPs are mapped to 185 gene pathways from the KEGG pathways database. Voxel-wise imaging signatures characteristic of AD are obtained by analysing 3D patterns of structural change at 6, 12 and 24 months relative to baseline. High-ranking, AD endophenotype-associated pathways in our study include those describing chemokine, Jak-stat and insulin signalling pathways, and tight junction interactions. All of these have been previously implicated in AD biology. In a secondary analysis, we investigate SNPs and genes that may be driving pathway selection, and identify a number of previously validated AD genes including CR1, APOE and TOMM40.