The success of deep learning models deployed in the real world depends critically on their ability to generalize well across diverse data domains. Here, we address a fundamental challenge with selective classification during automated diagnosis with domain-shifted medical images. In this scenario, models must learn to avoid making predictions when label confidence is low, especially when tested with samples far removed from the training set (covariate shift). Such uncertain cases are typically referred to the clinician for further analysis and evaluation. Yet, we show that even state-of-the-art domain generalization approaches fail severely during referral when tested on medical images acquired from a different demographic or using a different technology. We examine two benchmark diagnostic medical imaging datasets exhibiting strong covariate shifts: i) diabetic retinopathy prediction with retinal fundus images and ii) multilabel disease prediction with chest X-ray images. We show that predictive uncertainty estimates do not generalize well under covariate shifts leading to non-monotonic referral curves, and severe drops in performance (up to 50%) at high referral rates (>70%). We evaluate novel combinations of robust generalization and post hoc referral approaches, that rescue these failures and achieve significant performance improvements, typically >10%, over baseline methods. Our study identifies a critical challenge with referral in domain-shifted medical images and finds key applications in reliable, automated disease diagnosis.

Reliable outlier detection is critical for real-world deployment of deep learning models. Although extensively studied, likelihoods produced by deep generative models have been largely dismissed as being impractical for outlier detection. First, deep generative model likelihoods are readily biased by low-level input statistics. Second, many recent solutions for correcting these biases are computationally expensive, or do not generalize well to complex, natural datasets. Here, we explore outlier detection with a state-of-the-art deep autoregressive model: PixelCNN++. We show that biases in PixelCNN++ likelihoods arise primarily from predictions based on local dependencies. We propose two families of bijective transformations -- ``stirring'' and ``shaking'' -- which ameliorate low-level biases and isolate the contribution of long-range dependencies to PixelCNN++ likelihoods. These transformations are inexpensive and readily computed at evaluation time. We test our approaches extensively with five grayscale and six natural image datasets and show that they achieve or exceed state-of-the-art outlier detection, particularly on datasets with complex, natural images. We also show that our solutions work well with other types of generative models (generative flows and variational autoencoders) and that their efficacy is governed by each model's reliance on local dependencies. In sum, lightweight remedies suffice to achieve robust outlier detection on image data with deep generative models.

Deep networks often make confident, yet, incorrect, predictions when tested with outlier data that is far removed from their training distributions. Likelihoods computed by deep generative models (DGMs) are a candidate metric for outlier detection with unlabeled data. Yet, previous studies have shown that DGM likelihoods are unreliable and can be easily biased by simple transformations to input data. Here, we examine outlier detection with variational autoencoders (VAEs), among the simplest of DGMs. We propose novel analytical and algorithmic approaches to ameliorate key biases with VAE likelihoods. Our bias corrections are sample-specific, computationally inexpensive, and readily computed for various decoder visible distributions. Next, we show that a well-known image pre-processing technique -- contrast stretching -- extends the effectiveness of bias correction to further improve outlier detection. Our approach achieves state-of-the-art accuracies with nine grayscale and natural image datasets, and demonstrates significant advantages -- both with speed and performance -- over four recent, competing approaches. In summary, lightweight remedies suffice to achieve robust outlier detection with VAEs.

Brain processes occur at various timescales, ranging from milliseconds (neurons) to minutes and hours (behavior). Characterizing functional coupling among brain regions at these diverse timescales is key to understanding how the brain produces behavior. Here, we apply instantaneous and lag-based measures of conditional linear dependence, based on Granger-Geweke causality (GC), to infer network connections at distinct timescales from functional magnetic resonance imaging (fMRI) data. Due to the slow sampling rate of fMRI, it is widely held that GC produces spurious and unreliable estimates of functional connectivity when applied to fMRI data. We challenge this claim with simulations and a novel machine learning approach. First, we show, with simulated fMRI data, that instantaneous and lag-based GC identify distinct timescales and complementary patterns of functional connectivity. Next, we analyze fMRI scans from 500 subjects and show that a linear classifier trained on either instantaneous or lag-based GC connectivity reliably distinguishes task versus rest brain states, with ~80-85% cross-validation accuracy. Importantly, instantaneous and lag-based GC exploit markedly different spatial and temporal patterns of connectivity to achieve robust classification. Our approach enables identifying functionally connected networks that operate at distinct timescales in the brain.

We describe a neurobiologically plausible model to implement dynamic routing using the concept of neuronal communication through neuronal coherence. The model has a three-tier architecture: a raw input tier, a routing control tier, and an invariant output tier. The correct mapping between input and output tiers is realized byan appropriate alignment of the phases of their respective background oscillations by the routing control units. We present an example architecture, implemented ona neuromorphic chip, that is able to achieve circular-shift invariance.