UQ-ARMED: Uncertainty quantification of adversarially-regularized mixed effects deep learning for clustered non-iid data

This work demonstrates the ability to produce readily interpretable statistical metrics for model fit, fixed effects covariance coefficients, and prediction confidence. Importantly, this work compares 4 suitable and commonly applied epistemic UQ approaches, BNN, SWAG, MC dropout, and ensemble approaches in their ability to calculate these statistical metrics for the ARMED MEDL models. In our experiment for AD prognosis, not only do the UQ methods provide these benefits, but several UQ methods maintain the high performance of the original ARMED method, some even provide a modest (but not statistically significant) performance improvement. The ensemble models, especially the ensemble method with a 90% subsampling, performed well across all metrics we tested with (1) high performance that was comparable to the non-UQ ARMED model, (2) properly deweights the confounds probes and assigns them statistically insignificant p-values, (3) attains relatively high calibration of the output prediction confidence. Based on the results, the ensemble approaches, especially with a subsampling of 90%, provided the best all-round performance for prediction and uncertainty estimation, and achieved our goals to provide statistical significance for model fit, statistical significance covariate coefficients, and confidence in prediction, while maintaining the baseline performance of MEDL using ARMED

Architectural configurations, atlas granularity and functional connectivity with diagnostic value in Autism Spectrum Disorder

Currently, the diagnosis of Autism Spectrum Disorder (ASD) is dependent upon a subjective, time-consuming evaluation of behavioral tests by an expert clinician. Non-invasive functional MRI (fMRI) characterizes brain connectivity and may be used to inform diagnoses and democratize medicine. However, successful construction of deep learning models from fMRI requires addressing key choices about the model's architecture, including the number of layers and number of neurons per layer. Meanwhile, deriving functional connectivity (FC) features from fMRI requires choosing an atlas with an appropriate level of granularity. Once a model has been built, it is vital to determine which features are predictive of ASD and if similar features are learned across atlas granularity levels. To identify aptly suited architectural configurations, probability distributions of the configurations of high versus low performing models are compared. To determine the effect of atlas granularity, connectivity features are derived from atlases with 3 levels of granularity and important features are ranked with permutation feature importance. Results show the highest performing models use between 2-4 hidden layers and 16-64 neurons per layer, granularity dependent. Connectivity features identified as important across all 3 atlas granularity levels include FC to the supplementary motor gyrus and language association cortex, regions associated with deficits in social and sensory processing in ASD. Importantly, the cerebellum, often not included in functional analyses, is also identified as a region whose abnormal connectivity is highly predictive of ASD. Results of this study identify important regions to include in future studies of ASD, help assist in the selection of network architectures, and help identify appropriate levels of granularity to facilitate the development of accurate diagnostic models of ASD.

Anatomically-Informed Data Augmentation for functional MRI with Applications to Deep Learning

The application of deep learning to build accurate predictive models from functional neuroimaging data is often hindered by limited dataset sizes. Though data augmentation can help mitigate such training obstacles, most data augmentation methods have been developed for natural images as in computer vision tasks such as CIFAR, not for medical images. This work helps to fills in this gap by proposing a method for generating new functional Magnetic Resonance Images (fMRI) with realistic brain morphology. This method is tested on a challenging task of predicting antidepressant treatment response from pre-treatment task-based fMRI and demonstrates a 26% improvement in performance in predicting response using augmented images. This improvement compares favorably to state-of-the-art augmentation methods for natural images. Through an ablative test, augmentation is also shown to substantively improve performance when applied before hyperparameter optimization. These results suggest the optimal order of operations and support the role of data augmentation method for improving predictive performance in tasks using fMRI.