Enforcing Conditional Independence for Fair Representation Learning and Causal Image Generation

Conditional independence (CI) constraints are critical for defining and evaluating fairness in machine learning, as well as for learning unconfounded or causal representations. Traditional methods for ensuring fairness either blindly learn invariant features with respect to a protected variable (e.g., race when classifying sex from face images) or enforce CI relative to the protected attribute only on the model output (e.g., the sex label). Neither of these methods are effective in enforcing CI in high-dimensional feature spaces. In this paper, we focus on a nascent approach characterizing the CI constraint in terms of two Jensen-Shannon divergence terms, and we extend it to high-dimensional feature spaces using a novel dynamic sampling strategy. In doing so, we introduce a new training paradigm that can be applied to any encoder architecture. We are able to enforce conditional independence of the diffusion autoencoder latent representation with respect to any protected attribute under the equalized odds constraint and show that this approach enables causal image generation with controllable latent spaces. Our experimental results demonstrate that our approach can achieve high accuracy on downstream tasks while upholding equality of odds.

Metadata-Conditioned Generative Models to Synthesize Anatomically-Plausible 3D Brain MRIs

Generative AI models hold great potential in creating synthetic brain MRIs that advance neuroimaging studies by, for example, enriching data diversity. However, the mainstay of AI research only focuses on optimizing the visual quality (such as signal-to-noise ratio) of the synthetic MRIs while lacking insights into their relevance to neuroscience. To gain these insights with respect to T1-weighted MRIs, we first propose a new generative model, BrainSynth, to synthesize metadata-conditioned (e.g., age- and sex-specific) MRIs that achieve state-of-the-art visual quality. We then extend our evaluation with a novel procedure to quantify anatomical plausibility, i.e., how well the synthetic MRIs capture macrostructural properties of brain regions, and how accurately they encode the effects of age and sex. Results indicate that more than half of the brain regions in our synthetic MRIs are anatomically accurate, i.e., with a small effect size between real and synthetic MRIs. Moreover, the anatomical plausibility varies across cortical regions according to their geometric complexity. As is, our synthetic MRIs can significantly improve the training of a Convolutional Neural Network to identify accelerated aging effects in an independent study. These results highlight the opportunities of using generative AI to aid neuroimaging research and point to areas for further improvement.

LSOR: Longitudinally-Consistent Self-Organized Representation Learning

Interpretability is a key issue when applying deep learning models to longitudinal brain MRIs. One way to address this issue is by visualizing the high-dimensional latent spaces generated by deep learning via self-organizing maps (SOM). SOM separates the latent space into clusters and then maps the cluster centers to a discrete (typically 2D) grid preserving the high-dimensional relationship between clusters. However, learning SOM in a high-dimensional latent space tends to be unstable, especially in a self-supervision setting. Furthermore, the learned SOM grid does not necessarily capture clinically interesting information, such as brain age. To resolve these issues, we propose the first self-supervised SOM approach that derives a high-dimensional, interpretable representation stratified by brain age solely based on longitudinal brain MRIs (i.e., without demographic or cognitive information). Called Longitudinally-consistent Self-Organized Representation learning (LSOR), the method is stable during training as it relies on soft clustering (vs. the hard cluster assignments used by existing SOM). Furthermore, our approach generates a latent space stratified according to brain age by aligning trajectories inferred from longitudinal MRIs to the reference vector associated with the corresponding SOM cluster. When applied to longitudinal MRIs of the Alzheimer's Disease Neuroimaging Initiative (ADNI, N=632), LSOR generates an interpretable latent space and achieves comparable or higher accuracy than the state-of-the-art representations with respect to the downstream tasks of classification (static vs. progressive mild cognitive impairment) and regression (determining ADAS-Cog score of all subjects). The code is available at https://github.com/ouyangjiahong/longitudinal-som-single-modality.

Imputing Brain Measurements Across Data Sets via Graph Neural Networks

Publicly available data sets of structural MRIs might not contain specific measurements of brain Regions of Interests (ROIs) that are important for training machine learning models. For example, the curvature scores computed by Freesurfer are not released by the Adolescent Brain Cognitive Development (ABCD) Study. One can address this issue by simply reapplying Freesurfer to the data set. However, this approach is generally computationally and labor intensive (e.g., requiring quality control). An alternative is to impute the missing measurements via a deep learning approach. However, the state-of-the-art is designed to estimate randomly missing values rather than entire measurements. We therefore propose to re-frame the imputation problem as a prediction task on another (public) data set that contains the missing measurements and shares some ROI measurements with the data sets of interest. A deep learning model is then trained to predict the missing measurements from the shared ones and afterwards is applied to the other data sets. Our proposed algorithm models the dependencies between ROI measurements via a graph neural network (GNN) and accounts for demographic differences in brain measurements (e.g. sex) by feeding the graph encoding into a parallel architecture. The architecture simultaneously optimizes a graph decoder to impute values and a classifier in predicting demographic factors. We test the approach, called Demographic Aware Graph-based Imputation (DAGI), on imputing those missing Freesurfer measurements of ABCD (N=3760) by training the predictor on those publicly released by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA, N=540)...

An Explainable Geometric-Weighted Graph Attention Network for Identifying Functional Networks Associated with Gait Impairment

One of the hallmark symptoms of Parkinson's Disease (PD) is the progressive loss of postural reflexes, which eventually leads to gait difficulties and balance problems. Identifying disruptions in brain function associated with gait impairment could be crucial in better understanding PD motor progression, thus advancing the development of more effective and personalized therapeutics. In this work, we present an explainable, geometric, weighted-graph attention neural network (xGW-GAT) to identify functional networks predictive of the progression of gait difficulties in individuals with PD. xGW-GAT predicts the multi-class gait impairment on the MDS Unified PD Rating Scale (MDS-UPDRS). Our computational- and data-efficient model represents functional connectomes as symmetric positive definite (SPD) matrices on a Riemannian manifold to explicitly encode pairwise interactions of entire connectomes, based on which we learn an attention mask yielding individual- and group-level explainability. Applied to our resting-state functional MRI (rs-fMRI) dataset of individuals with PD, xGW-GAT identifies functional connectivity patterns associated with gait impairment in PD and offers interpretable explanations of functional subnetworks associated with motor impairment. Our model successfully outperforms several existing methods while simultaneously revealing clinically-relevant connectivity patterns. The source code is available at https://github.com/favour-nerrise/xGW-GAT .

Generating Realistic 3D Brain MRIs Using a Conditional Diffusion Probabilistic Model

Training deep learning models on brain MRI is often plagued by small sample size, which can lead to biased training or overfitting. One potential solution is to synthetically generate realistic MRIs via generative models such as Generative Adversarial Network (GAN). However, existing GANs for synthesizing realistic brain MRIs largely rely on image-to-image conditioned transformations requiring extensive, well-curated pairs of MRI samples for training. On the other hand, unconditioned GAN models (i.e., those generating MRI from random noise) are unstable during training and tend to produce blurred images during inference. Here, we propose an efficient strategy that generates high fidelity 3D brain MRI via Diffusion Probabilistic Model (DPM). To this end, we train a conditional DPM with attention to generate an MRI sub-volume (a set of slices at arbitrary locations) conditioned on another subset of slices from the same MRI. By computing attention weights from slice indices and using a mask to encode the target and conditional slices, the model is able to learn the long-range dependency across distant slices with limited computational resources. After training, the model can progressively synthesize a new 3D brain MRI by generating the first subset of slices from random noise and conditionally generating subsequent slices. Based on 1262 t1-weighted MRIs from three neuroimaging studies, our experiments demonstrate that the proposed method can generate high quality 3D MRIs that share the same distribution as real MRIs and are more realistic than the ones produced by GAN-based models.

Joint Graph Convolution for Analyzing Brain Structural and Functional Connectome

The white-matter (micro-)structural architecture of the brain promotes synchrony among neuronal populations, giving rise to richly patterned functional connections. A fundamental problem for systems neuroscience is determining the best way to relate structural and functional networks quantified by diffusion tensor imaging and resting-state functional MRI. As one of the state-of-the-art approaches for network analysis, graph convolutional networks (GCN) have been separately used to analyze functional and structural networks, but have not been applied to explore inter-network relationships. In this work, we propose to couple the two networks of an individual by adding inter-network edges between corresponding brain regions, so that the joint structure-function graph can be directly analyzed by a single GCN. The weights of inter-network edges are learnable, reflecting non-uniform structure-function coupling strength across the brain. We apply our Joint-GCN to predict age and sex of 662 participants from the public dataset of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) based on their functional and micro-structural white-matter networks. Our results support that the proposed Joint-GCN outperforms existing multi-modal graph learning approaches for analyzing structural and functional networks.

Identifying Auxiliary or Adversarial Tasks Using Necessary Condition Analysis for Adversarial Multi-task Video Understanding

There has been an increasing interest in multi-task learning for video understanding in recent years. In this work, we propose a generalized notion of multi-task learning by incorporating both auxiliary tasks that the model should perform well on and adversarial tasks that the model should not perform well on. We employ Necessary Condition Analysis (NCA) as a data-driven approach for deciding what category these tasks should fall in. Our novel proposed framework, Adversarial Multi-Task Neural Networks (AMT), penalizes adversarial tasks, determined by NCA to be scene recognition in the Holistic Video Understanding (HVU) dataset, to improve action recognition. This upends the common assumption that the model should always be encouraged to do well on all tasks in multi-task learning. Simultaneously, AMT still retains all the benefits of multi-task learning as a generalization of existing methods and uses object recognition as an auxiliary task to aid action recognition. We introduce two challenging Scene-Invariant test splits of HVU, where the model is evaluated on action-scene co-occurrences not encountered in training. We show that our approach improves accuracy by ~3% and encourages the model to attend to action features instead of correlation-biasing scene features.

Multiple Instance Neuroimage Transformer

For the first time, we propose using a multiple instance learning based convolution-free transformer model, called Multiple Instance Neuroimage Transformer (MINiT), for the classification of T1weighted (T1w) MRIs. We first present several variants of transformer models adopted for neuroimages. These models extract non-overlapping 3D blocks from the input volume and perform multi-headed self-attention on a sequence of their linear projections. MINiT, on the other hand, treats each of the non-overlapping 3D blocks of the input MRI as its own instance, splitting it further into non-overlapping 3D patches, on which multi-headed self-attention is computed. As a proof-of-concept, we evaluate the efficacy of our model by training it to identify sex from T1w-MRIs of two public datasets: Adolescent Brain Cognitive Development (ABCD) and the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA). The learned attention maps highlight voxels contributing to identifying sex differences in brain morphometry. The code is available at https://github.com/singlaayush/MINIT.

Bridging the Gap between Deep Learning and Hypothesis-Driven Analysis via Permutation Testing

A fundamental approach in neuroscience research is to test hypotheses based on neuropsychological and behavioral measures, i.e., whether certain factors (e.g., related to life events) are associated with an outcome (e.g., depression). In recent years, deep learning has become a potential alternative approach for conducting such analyses by predicting an outcome from a collection of factors and identifying the most "informative" ones driving the prediction. However, this approach has had limited impact as its findings are not linked to statistical significance of factors supporting hypotheses. In this article, we proposed a flexible and scalable approach based on the concept of permutation testing that integrates hypothesis testing into the data-driven deep learning analysis. We apply our approach to the yearly self-reported assessments of 621 adolescent participants of the National Consortium of Alcohol and Neurodevelopment in Adolescence (NCANDA) to predict negative valence, a symptom of major depressive disorder according to the NIMH Research Domain Criteria (RDoC). Our method successfully identifies categories of risk factors that further explain the symptom.