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Kevin Murphy

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44 papers
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44

NeurIPS Conference 2025 Conference Paper

Martingale Posterior Neural Networks for Fast Sequential Decision Making

  • Gerardo Duran-Martin
  • Leandro Sánchez-Betancourt
  • Alvaro Cartea
  • Kevin Murphy

We introduce scalable algorithms for online learning of neural network parameters and Bayesian sequential decision making. Unlike classical Bayesian neural networks, which induce predictive uncertainty through a posterior over model parameters, our methods adopt a predictive-first perspective based on martingale posteriors. In particular, we work directly with the one-step-ahead posterior predictive, which we parameterize with a neural network and update sequentially with incoming observations. This decouples Bayesian decision-making from parameter-space inference: we sample from the posterior predictive for decision making, and update the parameters of the posterior predictive via fast, frequentist Kalman-filter-like recursions. Our algorithms operate in a fully online, replay-free setting, providing principled uncertainty quantification without costly posterior sampling. Empirically, they achieve competitive performance–speed trade-offs in non-stationary contextual bandits and Bayesian optimization, offering 10–100 times faster inference than classical Thompson sampling while maintaining comparable or superior decision performance.

NeurIPS Conference 2024 Conference Paper

Bayesian Online Natural Gradient (BONG)

  • Matt Jones
  • Peter Chang
  • Kevin Murphy

We propose a novel approach to sequential Bayesian inference based on variational Bayes (VB). The key insight is that, in the online setting, we do not need to add the KL term to regularize to the prior (which comes from the posterior at the previous timestep); instead we can optimize just the expected log-likelihood, performing a single step of natural gradient descent starting at the prior predictive. We prove this method recovers exact Bayesian inference if the model is conjugate. We also show how to compute an efficient deterministic approximation to the VB objective, as well as our simplified objective, when the variational distribution is Gaussian or a sub-family, including the case of a diagonal plus low-rankprecision matrix. We show empirically that ourmethod outperforms other online VB methods in the non-conjugate setting, such as online learning for neural networks, especially when controlling for computational costs.

YNIMG Journal 2024 Journal Article

Breath-hold BOLD fMRI without CO2 sampling enables estimation of venous cerebral blood volume: potential use in normalization of stimulus-evoked BOLD fMRI data

  • Emma Biondetti
  • Antonio Maria Chiarelli
  • Michael Germuska
  • Ilona Lipp
  • Alessandro Villani
  • Alessandra S. Caporale
  • Eleonora Patitucci
  • Kevin Murphy

BOLD fMRI signal has been used in conjunction with vasodilatory stimulation as a marker of cerebrovascular reactivity (CVR): the relative change in cerebral blood flow (CBF) arising from a unit change in the vasodilatory stimulus. Using numerical simulations, we demonstrate that the variability in the relative BOLD signal change induced by vasodilation is strongly influenced by the variability in deoxyhemoglobin-containing cerebral blood volume (CBV), as this source of variability is likely to be more prominent than that of CVR. It may, therefore, be more appropriate to describe the relative BOLD signal change induced by an isometabolic vasodilation as a proxy of deoxygenated CBV (CBVdHb) rather than CVR. With this in mind, a new method was implemented to map a marker of CBVdHb, termed BOLD-CBV, based on the normalization of voxel-wise BOLD signal variation by an estimate of the intravascular venous BOLD signal from voxels filled with venous blood. The intravascular venous BOLD signal variation, recorded during repeated breath-holding, was extracted from the superior sagittal sinus in a cohort of 27 healthy volunteers and used as a regressor across the whole brain, yielding maps of BOLD-CBV. In the same cohort, we demonstrated the potential use of BOLD-CBV for the normalization of stimulus-evoked BOLD fMRI by comparing group-level BOLD fMRI responses to a visuomotor learning task with and without the inclusion of voxel-wise vascular covariates of BOLD-CBV and the BOLD signal change per mmHg variation in end-tidal carbon dioxide (BOLD-CVR). The empirical measure of BOLD-CBV accounted for more between-subject variability in the motor task-induced BOLD responses than BOLD-CVR estimated from end-tidal carbon dioxide recordings. The new method can potentially increase the power of group fMRI studies by including a measure of vascular characteristics and has the strong practical advantage of not requiring experimental measurement of end-tidal carbon dioxide, unlike traditional methods to estimate BOLD-CVR. It also more closely represents a specific physiological characteristic of brain vasculature than BOLD-CVR, namely blood volume.

NeurIPS Conference 2024 Conference Paper

DMC-VB: A Benchmark for Representation Learning for Control with Visual Distractors

  • Joseph Ortiz
  • Antoine Dedieu
  • Wolfgang Lehrach
  • J. S. Guntupalli
  • Carter Wendelken
  • Ahmad Humayun
  • Guangyao Zhou
  • Sivaramakrishnan Swaminathan

Learning from previously collected data via behavioral cloning or offline reinforcement learning (RL) is a powerful recipe for scaling generalist agents by avoiding the need for expensive online learning. Despite strong generalization in some respects, agents are often remarkably brittle to minor visual variations in control-irrelevant factors such as the background or camera viewpoint. In this paper, we present theDeepMind Control Visual Benchmark (DMC-VB), a dataset collected in the DeepMind Control Suite to evaluate the robustness of offline RL agents for solving continuous control tasks from visual input in the presence of visual distractors. In contrast to prior works, our dataset (a) combines locomotion and navigation tasks of varying difficulties, (b) includes static and dynamic visual variations, (c) considers data generated by policies with different skill levels, (d) systematically returns pairs of state and pixel observation, (e) is an order of magnitude larger, and (f) includes tasks with hidden goals. Accompanying our dataset, we propose three benchmarks to evaluate representation learning methods for pretraining, and carry out experiments on several recently proposed methods. First, we find that pretrained representations do not help policy learning on DMC-VB, and we highlight a large representation gap between policies learned on pixel observations and on states. Second, we demonstrate when expert data is limited, policy learning can benefit from representations pretrained on (a) suboptimal data, and (b) tasks with stochastic hidden goals. Our dataset and benchmark code to train and evaluate agents are available at https: //github. com/google-deepmind/dmc vision benchmark.

NeurIPS Conference 2024 Conference Paper

EM Distillation for One-step Diffusion Models

  • Sirui Xie
  • Zhisheng Xiao
  • Diederik P. Kingma
  • Tingbo Hou
  • Ying N. Wu
  • Kevin Murphy
  • Tim Salimans
  • Ben Poole

While diffusion models can learn complex distributions, sampling requires a computationally expensive iterative process. Existing distillation methods enable efficient sampling, but have notable limitations, such as performance degradation with very few sampling steps, reliance on training data access, or mode-seeking optimization that may fail to capture the full distribution. We propose EM Distillation (EMD), a maximum likelihood-based approach that distills a diffusion model to a one-step generator model with minimal loss of perceptual quality. Our approach is derived through the lens of Expectation-Maximization (EM), where the generator parameters are updated using samples from the joint distribution of the diffusion teacher prior and inferred generator latents. We develop a reparametrized sampling scheme and a noise cancellation technique that together stabilizes the distillation process. We further reveal an interesting connection of our method with existing methods that minimize mode-seeking KL. EMD outperforms existing one-step generative methods in terms of FID scores on ImageNet-64 and ImageNet-128, and compares favorably with prior work on distilling text-to-image diffusion models.

JMLR Journal 2022 Journal Article

Machine Learning on Graphs: A Model and Comprehensive Taxonomy

  • Ines Chami
  • Sami Abu-El-Haija
  • Bryan Perozzi
  • Christopher Ré
  • Kevin Murphy

There has been a surge of recent interest in graph representation learning (GRL). GRL methods have generally fallen into three main categories, based on the availability of labeled data. The first, network embedding, focuses on learning unsupervised representations of relational structure. The second, graph regularized neural networks, leverages graphs to augment neural network losses with a regularization objective for semi-supervised learning. The third, graph neural networks, aims to learn differentiable functions over discrete topologies with arbitrary structure. However, despite the popularity of these areas there has been surprisingly little work on unifying the three paradigms. Here, we aim to bridge the gap between network embedding, graph regularization and graph neural networks. We propose a comprehensive taxonomy of GRL methods, aiming to unify several disparate bodies of work. Specifically, we propose the GraphEDM framework, which generalizes popular algorithms for semi-supervised learning (e.g. GraphSage, GCN, GAT), and unsupervised learning (e.g. DeepWalk, node2vec) of graph representations into a single consistent approach. To illustrate the generality of GraphEDM, we fit over thirty existing methods into this framework. We believe that this unifying view both provides a solid foundation for understanding the intuition behind these methods, and enables future research in the area. [abs] [ pdf ][ bib ] &copy JMLR 2022. ( edit, beta )

YNIMG Journal 2020 Journal Article

Vascular physiology drives functional brain networks

  • Molly G. Bright
  • Joseph R. Whittaker
  • Ian D. Driver
  • Kevin Murphy

We present the first evidence for vascular regulation driving fMRI signals in specific functional brain networks. Using concurrent neuronal and vascular stimuli, we collected 30 BOLD fMRI datasets in 10 healthy individuals: a working memory task, flashing checkerboard stimulus, and CO2 inhalation challenge were delivered in concurrent but orthogonal paradigms. The resulting imaging data were averaged together and decomposed using independent component analysis, and three “neuronal networks” were identified as demonstrating maximum temporal correlation with the neuronal stimulus paradigms: Default Mode Network, Task Positive Network, and Visual Network. For each of these, we observed a second network component with high spatial overlap. Using dual regression in the original 30 datasets, we extracted the time-series associated with these network pairs and calculated the percent of variance explained by the neuronal or vascular stimuli using a normalized R2 parameter. In each pairing, one network was dominated by the appropriate neuronal stimulus, and the other was dominated by the vascular stimulus as represented by the end-tidal CO2 time-series recorded in each scan. We acquired a second dataset in 8 of the original participants, where no CO2 challenge was delivered and CO2 levels fluctuated naturally with breathing variations. Although splitting of functional networks was not robust in these data, performing dual regression with the network maps from the original analysis in this new dataset successfully replicated our observations. Thus, in addition to responding to localized metabolic changes, the brain’s vasculature may be regulated in a coordinated manner that mimics (and potentially supports) specific functional brain networks. Multi-modal imaging and advances in fMRI acquisition and analysis could facilitate further study of the dual nature of functional brain networks. It will be critical to understand network-specific vascular function, and the behavior of a coupled vascular-neural network, in future studies of brain pathology.

YNIMG Journal 2019 Journal Article

Changes in arterial cerebral blood volume during lower body negative pressure measured with MRI

  • Joseph R. Whittaker
  • Molly G. Bright
  • Ian D. Driver
  • Adele Babic
  • Sharmila Khot
  • Kevin Murphy

Cerebral Autoregulation (CA), defined as the ability of the cerebral vasculature to maintain stable levels of blood flow despite changes in systemic blood pressure, is a critical factor in neurophysiological health. Magnetic resonance imaging (MRI) is a powerful technique for investigating cerebrovascular function, offering high spatial resolution and wide fields of view (FOV), yet it is relatively underutilized as a tool for assessment of CA. The aim of this study was to demonstrate the potential of using MRI to measure changes in cerebrovascular resistance in response to lower body negative pressure (LBNP). A Pulsed Arterial Spin Labeling (PASL) approach with short inversion times (TI) was used to estimate cerebral arterial blood volume (CBVa) in eight healthy subjects at baseline and −40mmHg LBNP. We estimated group mean CBVa values of 3. 13 ± 1. 00 and 2. 70 ± 0. 38 for baseline and lbnp respectively, which were the result of a differential change in CBVa during −40mmHg LBNP that was dependent on baseline CBVa. These data suggest that the PASL CBVa estimates are sensitive to the complex cerebrovascular response that occurs during the moderate orthostatic challenge delivered by LBNP, which we speculatively propose may involve differential changes in vascular tone within different segments of the arterial vasculature. These novel data provide invaluable insight into the mechanisms that regulate perfusion of the brain, and establishes the use of MRI as a tool for studying CA in more detail.

NeurIPS Conference 2019 Conference Paper

Language as an Abstraction for Hierarchical Deep Reinforcement Learning

  • Yiding Jiang
  • Shixiang (Shane) Gu
  • Kevin Murphy
  • Chelsea Finn

Solving complex, temporally-extended tasks is a long-standing problem in reinforcement learning (RL). We hypothesize that one critical element of solving such problems is the notion of compositionality. With the ability to learn sub-skills that can be composed to solve longer tasks, i. e. hierarchical RL, we can acquire temporally-extended behaviors. However, acquiring effective yet general abstractions for hierarchical RL is remarkably challenging. In this paper, we propose to use language as the abstraction, as it provides unique compositional structure, enabling fast learning and combinatorial generalization, while retaining tremendous flexibility, making it suitable for a variety of problems. Our approach learns an instruction-following low-level policy and a high-level policy that can reuse abstractions across tasks, in essence, permitting agents to reason using structured language. To study compositional task learning, we introduce an open-source object interaction environment built using the MuJoCo physics engine and the CLEVR engine. We find that, using our approach, agents can learn to solve to diverse, temporally-extended tasks such as object sorting and multi-object rearrangement, including from raw pixel observations. Our analysis find that the compositional nature of language is critical for learning and systematically generalizing sub-skills in comparison to non-compositional abstractions that use the same supervision.

NeurIPS Conference 2019 Conference Paper

Unsupervised learning of object structure and dynamics from videos

  • Matthias Minderer
  • Chen Sun
  • Ruben Villegas
  • Forrester Cole
  • Kevin Murphy
  • Honglak Lee

Extracting and predicting object structure and dynamics from videos without supervision is a major challenge in machine learning. To address this challenge, we adopt a keypoint-based image representation and learn a stochastic dynamics model of the keypoints. Future frames are reconstructed from the keypoints and a reference frame. By modeling dynamics in the keypoint coordinate space, we achieve stable learning and avoid compounding of errors in pixel space. Our method improves upon unstructured representations both for pixel-level video prediction and for downstream tasks requiring object-level understanding of motion dynamics. We evaluate our model on diverse datasets: a multi-agent sports dataset, the Human3. 6M dataset, and datasets based on continuous control tasks from the DeepMind Control Suite. The spatially structured representation outperforms unstructured representations on a range of motion-related tasks such as object tracking, action recognition and reward prediction.

YNIMG Journal 2018 Journal Article

Assessing the repeatability of absolute CMRO2, OEF and haemodynamic measurements from calibrated fMRI

  • Alberto Merola
  • Michael A. Germuska
  • Kevin Murphy
  • Richard G. Wise

As energy metabolism in the brain is largely oxidative, the measurement of cerebral metabolic rate of oxygen consumption (CMRO2) is a desirable biomarker for quantifying brain activity and tissue viability. Currently, PET techniques based on oxygen isotopes are the gold standard for obtaining whole brain CMRO2 maps. Among MRI techniques that have been developed as an alternative are dual calibrated fMRI (dcFMRI) methods, which exploit simultaneous measurements of BOLD and ASL signals during a hypercapnic-hyperoxic experiment to modulate brain blood flow and oxygenation. In this study we quantified the repeatability of a dcFMRI approach developed in our lab, evaluating its limits and informing its application in studies aimed at characterising the metabolic state of human brain tissue over time. Our analysis focussed on the estimates of oxygen extraction fraction (OEF), cerebral blood flow (CBF), CBF-related cerebrovascular reactivity (CVR) and CMRO2 based on a forward model that describes analytically the acquired dual echo GRE signal. Indices of within- and between-session repeatability are calculated from two different datasets both at a bulk grey matter and at a voxel-wise resolution and finally compared with similar indices obtained from previous MRI and PET measurements. Within- and between-session values of intra-subject coefficient of variation (CVintra) calculated from bulk grey matter estimates 6. 7 ± 6. 6% (mean ± std.) and 10. 5 ± 9. 7% for OEF, 6. 9 ± 6% and 5. 5 ± 4. 7% for CBF, 12 ± 9. 7% and 12. 3 ± 10% for CMRO2. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) maps showed the spatial distribution of the repeatability metrics, informing on the feasibility limits of the method. In conclusion, results show an overall consistency of the estimated physiological parameters with literature reports and a satisfactory level of repeatability considering the higher spatial sensitivity compared to other MRI methods, with varied performance depending on the specific parameter under analysis, on the spatial resolution considered and on the study design.

YNIMG Journal 2017 Journal Article

Mapping the pharmacological modulation of brain oxygen metabolism: The effects of caffeine on absolute CMRO2 measured using dual calibrated fMRI

  • Alberto Merola
  • Michael A. Germuska
  • Esther AH Warnert
  • Lewys Richmond
  • Daniel Helme
  • Sharmila Khot
  • Kevin Murphy
  • Peter J. Rogers

This study aims to map the acute effects of caffeine ingestion on grey matter oxygen metabolism and haemodynamics with a novel MRI method. Sixteen healthy caffeine consumers (8 males, age=24. 7±5. 1) were recruited to this randomised, double-blind, placebo-controlled study. Each participant was scanned on two days before and after the delivery of an oral caffeine (250mg) or placebo capsule. Our measurements were obtained with a newly proposed estimation approach applied to data from a dual calibration fMRI experiment that uses hypercapnia and hyperoxia to modulate brain blood flow and oxygenation. Estimates were based on a forward model that describes analytically the contributions of cerebral blood flow (CBF) and of the measured end-tidal partial pressures of CO2 and O2 to the acquired dual-echo GRE signal. The method allows the estimation of grey matter maps of: oxygen extraction fraction (OEF), CBF, CBF-related cerebrovascular reactivity (CVR) and cerebral metabolic rate of oxygen consumption (CMRO2). Other estimates from a multi inversion time ASL acquisition (mTI-ASL), salivary samples of the caffeine concentration and behavioural measurements are also reported. We observed significant differences between caffeine and placebo on average across grey matter, with OEF showing an increase of 15. 6% (SEM±4. 9%, p<0. 05) with caffeine, while CBF and CMRO2 showed differences of −30. 4% (SEM±1. 6%, p<0. 01) and −18. 6% (SEM±2. 9%, p<0. 01) respectively with caffeine administration. The reduction in oxygen metabolism found is somehow unexpected, but consistent with a hypothesis of decreased energetic demand, supported by previous electrophysiological studies reporting reductions in spectral power with EEG. Moreover the maps of the physiological parameters estimated illustrate the spatial distribution of changes across grey matter enabling us to localise the effects of caffeine with voxel-wise resolution. CBF changes were widespread as reported by previous findings, while changes in OEF were found to be more restricted, leading to unprecedented mapping of significant CMRO2 reductions mainly in frontal gyrus, parietal and occipital lobes. In conclusion, we propose the estimation framework based on our novel forward model with a dual calibrated fMRI experiment as a viable MRI method to map the effects of drugs on brain oxygen metabolism and haemodynamics with voxel-wise resolution.

YNIMG Journal 2017 Journal Article

Potential pitfalls when denoising resting state fMRI data using nuisance regression

  • Molly G. Bright
  • Christopher R. Tench
  • Kevin Murphy

In resting state fMRI, it is necessary to remove signal variance associated with noise sources, leaving cleaned fMRI time-series that more accurately reflect the underlying intrinsic brain fluctuations of interest. This is commonly achieved through nuisance regression, in which the fit is calculated of a noise model of head motion and physiological processes to the fMRI data in a General Linear Model, and the “cleaned” residuals of this fit are used in further analysis. We examine the statistical assumptions and requirements of the General Linear Model, and whether these are met during nuisance regression of resting state fMRI data. Using toy examples and real data we show how pre-whitening, temporal filtering and temporal shifting of regressors impact model fit. Based on our own observations, existing literature, and statistical theory, we make the following recommendations when employing nuisance regression: pre-whitening should be applied to achieve valid statistical inference of the noise model fit parameters; temporal filtering should be incorporated into the noise model to best account for changes in degrees of freedom; temporal shifting of regressors, although merited, should be achieved via optimisation and validation of a single temporal shift. We encourage all readers to make simple, practical changes to their fMRI denoising pipeline, and to regularly assess the appropriateness of the noise model used. By negotiating the potential pitfalls described in this paper, and by clearly reporting the details of nuisance regression in future manuscripts, we hope that the field will achieve more accurate and precise noise models for cleaning the resting state fMRI time-series.

YNIMG Journal 2017 Journal Article

Towards a consensus regarding global signal regression for resting state functional connectivity MRI

  • Kevin Murphy
  • Michael D. Fox

The number of resting state functional connectivity MRI studies continues to expand at a rapid rate along with the options for data processing. Of the processing options, few have generated as much controversy as global signal regression and the subsequent observation of negative correlations (anti-correlations). This debate has motivated new processing strategies and advancement in the field, but has also generated significant confusion and contradictory guidelines. In this article, we work towards a consensus regarding global signal regression. We highlight several points of agreement including the fact that there is not a single “right” way to process resting state data that reveals the “true” nature of the brain. Although further work is needed, different processing approaches likely reveal complementary insights about the brain's functional organisation.

YNIMG Journal 2016 Journal Article

Measurement of oxygen extraction fraction (OEF): An optimized BOLD signal model for use with hypercapnic and hyperoxic calibration

  • Alberto Merola
  • Kevin Murphy
  • Alan J. Stone
  • Michael A. Germuska
  • Valerie E.M. Griffeth
  • Nicholas P. Blockley
  • Richard B. Buxton
  • Richard G. Wise

Several techniques have been proposed to estimate relative changes in cerebral metabolic rate of oxygen consumption (CMRO2) by exploiting combined BOLD fMRI and cerebral blood flow data in conjunction with hypercapnic or hyperoxic respiratory challenges. More recently, methods based on respiratory challenges that include both hypercapnia and hyperoxia have been developed to assess absolute CMRO2, an important parameter for understanding brain energetics. In this paper, we empirically optimize a previously presented “original calibration model” relating BOLD and blood flow signals specifically for the estimation of oxygen extraction fraction (OEF) and absolute CMRO2. To do so, we have created a set of synthetic BOLD signals using a detailed BOLD signal model to reproduce experiments incorporating hypercapnic and hyperoxic respiratory challenges at 3T. A wide range of physiological conditions was simulated by varying input parameter values (baseline cerebral blood volume (CBV0), baseline cerebral blood flow (CBF0), baseline oxygen extraction fraction (OEF0) and hematocrit (Hct)). From the optimization of the calibration model for estimation of OEF and practical considerations of hypercapnic and hyperoxic respiratory challenges, a new “simplified calibration model” is established which reduces the complexity of the original calibration model by substituting the standard parameters α and β with a single parameter θ. The optimal value of θ is determined (θ =0. 06) across a range of experimental respiratory challenges. The simplified calibration model gives estimates of OEF0 and absolute CMRO2 closer to the true values used to simulate the experimental data compared to those estimated using the original model incorporating literature values of α and β. Finally, an error propagation analysis demonstrates the susceptibility of the original and simplified calibration models to measurement errors and potential violations in the underlying assumptions of isometabolism. We conclude that using the simplified calibration model results in a reduced bias in OEF0 estimates across a wide range of potential respiratory challenge experimental designs.

YNIMG Journal 2016 Journal Article

The absolute CBF response to activation is preserved during elevated perfusion: Implications for neurovascular coupling measures

  • Joseph R. Whittaker
  • Ian D. Driver
  • Molly G. Bright
  • Kevin Murphy

Functional magnetic resonance imaging (fMRI) techniques in which the blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) response to a neural stimulus are measured, can be used to estimate the fractional increase in the cerebral metabolic rate of oxygen consumption (CMRO2) that accompanies evoked neural activity. A measure of neurovascular coupling is obtained from the ratio of fractional CBF and CMRO2 responses, defined as n, with the implicit assumption that relative rather than absolute changes in CBF and CMRO2 adequately characterise the flow-metabolism response to neural activity. The coupling parameter n is important in terms of its effect on the BOLD response, and as potential insight into the flow-metabolism relationship in both normal and pathological brain function. In 10 healthy human subjects, BOLD and CBF responses were measured to test the effect of baseline perfusion (modulated by a hypercapnia challenge) on the coupling parameter n during graded visual stimulation. A dual-echo pulsed arterial spin labelling (PASL) sequence provided absolute quantification of CBF in baseline and active states as well as relative BOLD signal changes, which were used to estimate CMRO2 responses to the graded visual stimulus. The absolute CBF response to the visual stimuli were constant across different baseline CBF levels, meaning the fractional CBF responses were reduced at the hyperperfused baseline state. For the graded visual stimuli, values of n were significantly reduced during hypercapnia induced hyperperfusion. Assuming the evoked neural responses to the visual stimuli are the same for both baseline CBF states, this result has implications for fMRI studies that aim to measure neurovascular coupling using relative changes in CBF. The coupling parameter n is sensitive to baseline CBF, which would confound its interpretation in fMRI studies where there may be significant differences in baseline perfusion between groups. The absolute change in CBF, as opposed to the change relative to baseline, may more closely match the underlying increase in neural activity in response to a stimulus.

YNIMG Journal 2015 Journal Article

Agreement and repeatability of vascular reactivity estimates based on a breath-hold task and a resting state scan

  • Ilona Lipp
  • Kevin Murphy
  • Xavier Caseras
  • Richard G. Wise

FMRI BOLD responses to changes in neural activity are influenced by the reactivity of the vasculature. By complementing a task-related BOLD acquisition with a vascular reactivity measure obtained through breath-holding or hypercapnia, this unwanted variance can be statistically reduced in the BOLD responses of interest. Recently, it has been suggested that vascular reactivity can also be estimated using a resting state scan. This study aimed to compare three breath-hold based analysis approaches (block design, sine–cosine regressor and CO2 regressor) and a resting state approach (CO2 regressor) to measure vascular reactivity. We tested BOLD variance explained by the model and repeatability of the measures. Fifteen healthy participants underwent a breath-hold task and a resting state scan with end-tidal CO2 being recorded during both. Vascular reactivity was defined as CO2-related BOLD percent signal change/mmHg change in CO2. Maps and regional vascular reactivity estimates showed high repeatability when the breath-hold task was used. Repeatability and variance explained by the CO2 trace regressor were lower for the resting state data based approach, which resulted in highly variable measures of vascular reactivity. We conclude that breath-hold based vascular reactivity estimations are more repeatable than resting-based estimates, and that there are limitations with replacing breath-hold scans by resting state scans for vascular reactivity assessment.

NeurIPS Conference 2015 Conference Paper

Bayesian dark knowledge

  • Anoop Korattikara Balan
  • Vivek Rathod
  • Kevin Murphy
  • Max Welling

We consider the problem of Bayesian parameter estimation for deep neural networks, which is important in problem settings where we may have little data, and/ or where we need accurate posterior predictive densities p(y|x, D), e. g. , for applications involving bandits or active learning. One simple approach to this is to use online Monte Carlo methods, such as SGLD (stochastic gradient Langevin dynamics). Unfortunately, such a method needs to store many copies of the parameters (which wastes memory), and needs to make predictions using many versions of the model (which wastes time). We describe a method for “distilling” a Monte Carlo approximation to the posterior predictive density into a more compact form, namely a single deep neural network. We compare to two very recent approaches to Bayesian neural networks, namely an approach based on expectation propagation [HLA15] and an approach based on variational Bayes [BCKW15]. Our method performs better than both of these, is much simpler to implement, and uses less computation at test time.

YNIMG Journal 2015 Journal Article

Is fMRI “noise” really noise? Resting state nuisance regressors remove variance with network structure

  • Molly G. Bright
  • Kevin Murphy

Noise correction is a critical step towards accurate mapping of resting state BOLD fMRI connectivity. Noise sources related to head motion or physiology are typically modelled by nuisance regressors, and a generalised linear model is applied to regress out the associated signal variance. In this study, we use independent component analysis (ICA) to characterise the data variance typically discarded in this pre-processing stage in a cohort of 12 healthy volunteers. The signal variance removed by 24, 12, 6, or only 3 head motion parameters demonstrated network structure typically associated with functional connectivity, and certain networks were discernable in the variance extracted by as few as 2 physiologic regressors. Simulated nuisance regressors, unrelated to the true data noise, also removed variance with network structure, indicating that any group of regressors that randomly sample variance may remove highly structured “signal” as well as “noise. ” Furthermore, to support this we demonstrate that random sampling of the original data variance continues to exhibit robust network structure, even when as few as 10% of the original volumes are considered. Finally, we examine the diminishing returns of increasing the number of nuisance regressors used in pre-processing, showing that excessive use of motion regressors may do little better than chance in removing variance within a functional network. It remains an open challenge to understand the balance between the benefits and confounds of noise correction using nuisance regressors.

YNIMG Journal 2014 Journal Article

Early anti-correlated BOLD signal changes of physiologic origin

  • Molly G. Bright
  • Marta Bianciardi
  • Jacco A. de Zwart
  • Kevin Murphy
  • Jeff H. Duyn

Negative BOLD signals that are synchronous with resting state fluctuations have been observed in large vessels in the cortical sulci and surrounding the ventricles. In this study, we investigated the origin of these negative BOLD signals by applying a Cued Deep Breathing (CDB) task to create transient hypocapnia and a resultant global fMRI signal decrease. We hypothesized that a global stimulus would amplify the effect in large vessels and that using a global negative (vasoconstrictive) stimulus would test whether these voxels exhibit either inherently negative or simply anti-correlated BOLD responses. Significantly anti-correlated, but positive, BOLD signal changes during respiratory challenges were identified in voxels primarily located near edges of brain spaces containing CSF. These positive BOLD responses occurred earlier than the negative CDB response across most of gray matter voxels. These findings confirm earlier suggestions that in some brain regions, local, fractional changes in CSF volume may overwhelm BOLD-related signal changes, leading to signal anti-correlation. We show that regions with CDB anti-correlated signals coincide with most, but not all, of the regions with negative BOLD signal changes observed during a visual and motor stimulus task. Thus, the addition of a physiological challenge to fMRI experiments can help identify which negative BOLD signals are passive physiological anti-correlations and which may have a putative neuronal origin.

YNIMG Journal 2013 Journal Article

Measurement of OEF and absolute CMRO2: MRI-based methods using interleaved and combined hypercapnia and hyperoxia

  • Richard G. Wise
  • Ashley D. Harris
  • Alan J. Stone
  • Kevin Murphy

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is most commonly used in a semi-quantitative manner to infer changes in brain activity. Despite the basis of the image contrast lying in the cerebral venous blood oxygenation level, quantification of absolute cerebral metabolic rate of oxygen consumption (CMRO2) has only recently been demonstrated. Here we examine two approaches to the calibration of fMRI signal to measure absolute CMRO2 using hypercapnic and hyperoxic respiratory challenges. The first approach is to apply hypercapnia and hyperoxia separately but interleaved in time and the second is a combined approach in which we apply hyperoxic challenges simultaneously with different levels of hypercapnia. Eleven healthy volunteers were studied at 3T using a dual gradient-echo spiral readout pulsed arterial spin labelling (ASL) imaging sequence. Respiratory challenges were conducted using an automated system of dynamic end-tidal forcing. A generalised BOLD signal model was applied, within a Bayesian estimation framework, that aims to explain the effects of modulation of CBF and arterial oxygen content to estimate venous deoxyhaemoglobin concentration ([dHb]0). Using CBF measurements combined with the estimated oxygen extraction fraction (OEF), absolute CMRO2 was calculated. The interleaved approach to hypercapnia and hyperoxia, as well as yielding estimates of CMRO2 and OEF demonstrated a significant increase in regional CBF, venous oxygen saturation (SvO2) (a decrease in OEF) and absolute CMRO2 in visual cortex in response to a continuous (20min) visual task, demonstrating the potential for the method in measuring long term changes in CMRO2. The combined approach to oxygen and carbon dioxide modulation, as well as taking less time to acquire data, yielded whole brain grey matter estimates of CMRO2 and OEF of 184±45μmol/100g/min and 0. 42±0. 12 respectively, along with additional estimates of the vascular parameters α=0. 33±0. 06, the exponent relating relative increases in CBF to CBV, and β=1. 35±0. 13, the exponent relating deoxyhaemoglobin concentration to the relaxation rate R2*. Maps of cerebrovascular and cerebral metabolic parameters were also calculated. We show that combined modulation of oxygen and carbon dioxide can offer an experimentally more efficient approach to estimating OEF and absolute CMRO2 along with the additional vascular parameters that form an important part of the commonly used calibrated fMRI signal model.

YNIMG Journal 2013 Journal Article

Reliable quantification of BOLD fMRI cerebrovascular reactivity despite poor breath-hold performance

  • Molly G. Bright
  • Kevin Murphy

Cerebrovascular reactivity (CVR) can be mapped using BOLD fMRI to provide a clinical insight into vascular health that can be used to diagnose cerebrovascular disease. Breath-holds are a readily accessible method for producing the required arterial CO2 increases but their implementation into clinical studies is limited by concerns that patients will demonstrate highly variable performance of breath-hold challenges. This study assesses the repeatability of CVR measurements despite poor task performance, to determine if and how robust results could be achieved with breath-holds in patients. Twelve healthy volunteers were scanned at 3T. Six functional scans were acquired, each consisting of 6 breath-hold challenges (10, 15, or 20s duration) interleaved with periods of paced breathing. These scans simulated the varying breath-hold consistency and ability levels that may occur in patient data. Uniform ramps, time-scaled ramps, and end-tidal CO2 data were used as regressors in a general linear model in order to measure CVR at the grey matter, regional, and voxelwise level. The intraclass correlation coefficient (ICC) quantified the repeatability of the CVR measurement for each breath-hold regressor type and scale of interest across the variable task performances. The ramp regressors did not fully account for variability in breath-hold performance and did not achieve acceptable repeatability (ICC<0. 4) in several regions analysed. In contrast, the end-tidal CO2 regressors resulted in “excellent” repeatability (ICC=0. 82) in the average grey matter data, and resulted in acceptable repeatability in all smaller regions tested (ICC>0. 4). Further analysis of intra-subject CVR variability across the brain (ICCspatial and voxelwise correlation) supported the use of end-tidal CO2 data to extract robust whole-brain CVR maps, despite variability in breath-hold performance. We conclude that the incorporation of end-tidal CO2 monitoring into scanning enables robust, repeatable measurement of CVR that makes breath-hold challenges suitable for routine clinical practice.

YNIMG Journal 2013 Journal Article

Removing motion and physiological artifacts from intrinsic BOLD fluctuations using short echo data

  • Molly G. Bright
  • Kevin Murphy

Differing noise variance across study populations has been shown to cause artifactual group differences in functional connectivity measures. In this study, we investigate the use of short echo time functional MRI data to correct for these noise sources in blood oxygenation level dependent (BOLD)-weighted time series. A dual‐echo sequence was used to simultaneously acquire data at both a short (TE=3. 3ms) and a BOLD-weighted (TE=35ms) echo time. This approach is effectively “free, ” using dead-time in the pulse sequence to collect an additional echo without affecting overall scan time or temporal resolution. The proposed correction method uses voxelwise regression of the short TE data from the BOLD-weighted data to remove noise variance. In addition to a typical resting state scan, non-compliant behavior associated with patient groups was simulated via increased head motion or physiological fluctuations in 10 subjects. Short TE data showed significant correlations with the traditional motion-related and physiological noise regressors used in current connectivity analyses. Following traditional preprocessing, the extent of significant additional variance explained by the short TE data regressors was significantly correlated with the average head motion across the scan in the resting data (r 2 =0. 93, p <0. 0001). The reduction in data variance following the inclusion of short TE regressors was also correlated with scan head motion (r 2 =0. 48, p =0. 027). Task-related data were used to demonstrate the effects of the short TE correction on BOLD activation time series with known temporal structure; the size and strength of the activation were significantly decreased, but it is not clear whether this reflects BOLD contamination in the short TE data or correlated changes in blood volume. Finally, functional connectivity maps of the default mode network were constructed using a seed correlation approach. The effects of short TE correction and low-pass filtering on the resulting correlations maps were compared. Results suggest that short TE correction more accurately differentiates artifactual correlations from the correlations of interest in conditions of amplified noise.

YNIMG Journal 2013 Journal Article

Resting-state fMRI confounds and cleanup

  • Kevin Murphy
  • Rasmus M. Birn
  • Peter A. Bandettini

The goal of resting-state functional magnetic resonance imaging (fMRI) is to investigate the brain's functional connections by using the temporal similarity between blood oxygenation level dependent (BOLD) signals in different regions of the brain “at rest” as an indicator of synchronous neural activity. Since this measure relies on the temporal correlation of fMRI signal changes between different parts of the brain, any non-neural activity-related process that affects the signals will influence the measure of functional connectivity, yielding spurious results. To understand the sources of these resting-state fMRI confounds, this article describes the origins of the BOLD signal in terms of MR physics and cerebral physiology. Potential confounds arising from motion, cardiac and respiratory cycles, arterial CO2 concentration, blood pressure/cerebral autoregulation, and vasomotion are discussed. Two classes of techniques to remove confounds from resting-state BOLD time series are reviewed: 1) those utilising external recordings of physiology and 2) data-based cleanup methods that only use the resting-state fMRI data itself. Further methods that remove noise from functional connectivity measures at a group level are also discussed. For successful interpretation of resting-state fMRI comparisons and results, noise cleanup is an often over-looked but essential step in the analysis pipeline.

YNIMG Journal 2013 Journal Article

The effects of altered intrathoracic pressure on resting cerebral blood flow and its response to visual stimulation

  • Anja Hayen
  • Mari Herigstad
  • Michael Kelly
  • Thomas W. Okell
  • Kevin Murphy
  • Richard G. Wise
  • Kyle T.S. Pattinson

Investigating how intrathoracic pressure changes affect cerebral blood flow (CBF) is important for a clear interpretation of neuroimaging data in patients with abnormal respiratory physiology, intensive care patients receiving mechanical ventilation and in research paradigms that manipulate intrathoracic pressure. Here, we investigated the effect of experimentally increased and decreased intrathoracic pressures upon CBF and the stimulus-evoked CBF response to visual stimulation. Twenty healthy volunteers received intermittent inspiratory and expiratory loads (plus or minus 9cmH2O for 270s) and viewed an intermittent 2Hz flashing checkerboard, while maintaining stable end-tidal CO2. CBF was recorded with transcranial Doppler sonography (TCD) and whole-brain pseudo-continuous arterial spin labeling magnetic resonance imaging (PCASL MRI). Application of inspiratory loading (negative intrathoracic pressure) showed an increase in TCD-measured CBF of 4% and a PCASL-measured increase in grey matter CBF of 5%, but did not alter mean arterial pressure (MAP). Expiratory loading (positive intrathoracic pressure) did not alter CBF, while MAP increased by 3%. Neither loading condition altered the perfusion response to visual stimulation in the primary visual cortex. In both loading conditions localized CBF increases were observed in the somatosensory and motor cortices, and in the cerebellum. Altered intrathoracic pressures, whether induced experimentally, therapeutically or through a disease process, have possible significant effects on CBF and should be considered as a potential systematic confound in the interpretation of perfusion-based neuroimaging data.

NeurIPS Conference 2012 Conference Paper

Fast Bayesian Inference for Non-Conjugate Gaussian Process Regression

  • Emtiyaz Khan
  • Shakir Mohamed
  • Kevin Murphy

We present a new variational inference algorithm for Gaussian processes with non-conjugate likelihood functions. This includes binary and multi-class classification, as well as ordinal regression. Our method constructs a convex lower bound, which can be optimized by using an efficient fixed point update method. We then show empirically that our new approach is much faster than existing methods without any degradation in performance.

YNIMG Journal 2012 Journal Article

Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses

  • Ana Diukova
  • Jennifer Ware
  • Jessica E. Smith
  • C. John Evans
  • Kevin Murphy
  • Peter J. Rogers
  • Richard G. Wise

The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A1 and A2A adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG–FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19% reduction over grey matter). We were able to identify vascular effects and hence altered neurovascular coupling through the alteration of low-level task FMRI responses in the face of a preserved visual evoked potential. However, our data also suggest a cognitive effect of caffeine through its positive effect on the frontal BOLD signal consistent with the shortening of oddball EEG response latency. The combined use of EEG–FMRI is a promising methodology for investigating alterations in brain function in drug and disease studies where neurovascular coupling may be altered on a regional basis.

YNIMG Journal 2011 Journal Article

Robustly measuring vascular reactivity differences with breath-hold: Normalising stimulus-evoked and resting state BOLD fMRI data

  • Kevin Murphy
  • Ashley D. Harris
  • Richard G. Wise

Inter-subject differences in local cerebral blood flow (CBF) and cerebral blood volume (CBV) contribute to differences in BOLD signal reactivity and, therefore, unmodelled variance in group level fMRI analyses. A simple way of elevating blood CO2 concentrations to characterise subject differences in vascular reactivity is through breath-holds but two aspects of this measure are often neglected: (1) breath-holds are usually modelled as blocks even though CO2 accumulates over time and (2) increases in CO2 differ between subjects. This study demonstrates that the BOLD breath-hold response is best modelled by convolving the end-tidal CO2 trace with a standard haemodynamic response function and including its temporal derivative. Inclusion of the BOLD breath-hold response as a voxel-dependent covariate in a group level analysis increases the spatial extent of activation in stimulus evoked and resting state datasets. By expressing the BOLD breath-hold response as a percentage signal increase with respect to an absolute change in the partial pressure of CO2 (expressed in mmHg), the spatial extent of stimulus-evoked activation is further improved. This demonstrates that individual end-tidal CO2 increases to breath-hold should be accounted for to provide an accurate measure of vascular reactivity resulting in more statistically active voxels in group level analyses.

YNIMG Journal 2010 Journal Article

Sub-cortical and brainstem sites associated with chemo-stimulated increases in ventilation in humans

  • Leanne C. McKay
  • Hugo D. Critchley
  • Kevin Murphy
  • Richard S.J. Frackowiak
  • Douglas R. Corfield

We investigated the neural basis for spontaneous chemo-stimulated increases in ventilation in awake, healthy humans. Blood oxygen level dependent (BOLD) functional MRI was performed in nine healthy subjects using T2⁎ weighted echo planar imaging. Brain volumes (52 transverse slices, cortex to high spinal cord) were acquired every 3. 9 s. The 30 min paradigm consisted of six, 5-min cycles, each cycle comprising 45 s of hypoxic-isocapnia, 45 s of isooxic-hypercapnia and 45 s of hypoxic-hypercapnia, with 55 s of non-stimulatory hyperoxic-isocapnia (control) separating each stimulus period. Ventilation was significantly (p <0. 001) increased during hypoxic-isocapnia, isooxic-hypercapnia and hypoxic-hypercapnia (17. 0, 13. 8, 24. 9 L/min respectively) vs. control (8. 4 L/min) and was associated with significant (p <0. 05, corrected for multiple comparisons) signal increases within a bilateral network that included the basal ganglia, thalamus, red nucleus, cerebellum, parietal cortex, cingulate and superior mid pons. The neuroanatomical structures identified provide evidence for the spontaneous control of breathing to be mediated by higher brain centres, as well as respiratory nuclei in the brainstem.

NeurIPS Conference 2010 Conference Paper

Variational bounds for mixed-data factor analysis

  • Mohammad Emtiyaz Khan
  • Guillaume Bouchard
  • Kevin Murphy
  • Benjamin Marlin

We propose a new variational EM algorithm for fitting factor analysis models with mixed continuous and categorical observations. The algorithm is based on a simple quadratic bound to the log-sum-exp function. In the special case of fully observed binary data, the bound we propose is significantly faster than previous variational methods. We show that EM is significantly more robust in the presence of missing data compared to treating the latent factors as parameters, which is the approach used by exponential family PCA and other related matrix-factorization methods. A further benefit of the variational approach is that it can easily be extended to the case of mixtures of factor analyzers, as we show. We present results on synthetic and real data sets demonstrating several desirable properties of our proposed method.

NeurIPS Conference 2009 Conference Paper

Accelerating Bayesian Structural Inference for Non-Decomposable Gaussian Graphical Models

  • Baback Moghaddam
  • Emtiyaz Khan
  • Kevin Murphy
  • Benjamin Marlin

In this paper we make several contributions towards accelerating approximate Bayesian structural inference for non-decomposable GGMs. Our first contribution is to show how to efficiently compute a BIC or Laplace approximation to the marginal likelihood of non-decomposable graphs using convex methods for precision matrix estimation. This optimization technique can be used as a fast scoring function inside standard Stochastic Local Search (SLS) for generating posterior samples. Our second contribution is a novel framework for efficiently generating large sets of high-quality graph topologies without performing local search. This graph proposal method, which we call Neighborhood Fusion" (NF), samples candidate Markov blankets at each node using sparse regression techniques. Our final contribution is a hybrid method combining the complementary strengths of NF and SLS. Experimental results in structural recovery and prediction tasks demonstrate that NF and hybrid NF/SLS out-perform state-of-the-art local search methods, on both synthetic and real-world datasets, when realistic computational limits are imposed. "

YNIMG Journal 2009 Journal Article

fMRI in the presence of task-correlated breathing variations

  • Rasmus M. Birn
  • Kevin Murphy
  • Daniel A. Handwerker
  • Peter A. Bandettini

Variations in the subject's heart rate and breathing pattern have been shown to result in significant fMRI signal changes, mediated in part by non-neuronal physiological mechanisms such as global changes in levels of arterial CO2. When these physiological changes are correlated with a task, as may happen in response to emotional stimuli or tasks that change levels of arousal, a concern arises that non-neuronal physiologically-induced signal changes may be misinterpreted as reflecting task-related neuronal activation. The purpose of this study is to provide information that can help in determining whether task activation maps are influenced by task-correlated physiological noise, particularly task-correlated breathing changes. We also compare different strategies to reduce the influence of physiological noise. Two paradigms are investigated — 1) a lexical decision task where some subjects showed task-related breathing changes, and 2) a task where subjects were instructed to hold their breath during the presentation of contrast-reversing checkerboard, an extreme case of task-correlated physiological noise. Consistent with previous literature, we find that MRI signal changes correlated with variations in breathing depth and rate have a characteristic spatial and temporal profile that is different from the typical activation-induced BOLD response. The delineation of activation in the presence of task correlated breathing changes was improved either by independent component analysis, or by including specific nuisance regressors in a regression analysis. The difference in the spatial and temporal characteristics of physiological-induced and neuronal-induced fluctuations exploited by these strategies suggests that activation can be studied even in the presence of task-correlated physiological changes.

YNIMG Journal 2009 Journal Article

The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced?

  • Kevin Murphy
  • Rasmus M. Birn
  • Daniel A. Handwerker
  • Tyler B. Jones
  • Peter A. Bandettini

Low-frequency fluctuations in fMRI signal have been used to map several consistent resting state networks in the brain. Using the posterior cingulate cortex as a seed region, functional connectivity analyses have found not only positive correlations in the default mode network but negative correlations in another resting state network related to attentional processes. The interpretation is that the human brain is intrinsically organized into dynamic, anti-correlated functional networks. Global variations of the BOLD signal are often considered nuisance effects and are commonly removed using a general linear model (GLM) technique. This global signal regression method has been shown to introduce negative activation measures in standard fMRI analyses. The topic of this paper is whether such a correction technique could be the cause of anti-correlated resting state networks in functional connectivity analyses. Here we show that, after global signal regression, correlation values to a seed voxel must sum to a negative value. Simulations also show that small phase differences between regions can lead to spurious negative correlation values. A combination breath holding and visual task demonstrates that the relative phase of global and local signals can affect connectivity measures and that, experimentally, global signal regression leads to bell-shaped correlation value distributions, centred on zero. Finally, analyses of negatively correlated networks in resting state data show that global signal regression is most likely the cause of anti-correlations. These results call into question the interpretation of negatively correlated regions in the brain when using global signal regression as an initial processing step.

YNIMG Journal 2007 Journal Article

How long to scan? The relationship between fMRI temporal signal to noise ratio and necessary scan duration

  • Kevin Murphy
  • Jerzy Bodurka
  • Peter A. Bandettini

Recent advances in MRI receiver and coil technologies have significantly improved image signal-to-noise ratios (SNR) and thus temporal SNR (TSNR). These gains in SNR and TSNR have allowed the detection of fMRI signal changes at higher spatial resolution and therefore have increased the potential to localize small brain structures such as cortical layers and columns. The majority of current fMRI processing strategies employ multi-subject averaging and therefore require spatial smoothing and normalization, effectively negating these gains in spatial resolution higher than about 10 mm3. Reliable detection of activation in single subjects at high resolution is becoming a more common desire among fMRI researchers who are interested in comparing individuals rather than populations. Since TSNR decreases with voxel volume, detection of activation at higher resolutions requires longer scan durations. The relationship between TSNR, voxel volume and detectability is highly non-linear. In this study, the relationship between TSNR and the necessary fMRI scan duration required to obtain significant results at varying P values is determined both experimentally and theoretically. The results demonstrate that, with a TSNR of 50, detection of activation of above 2% requires at most 350 scan volumes (when steps are taken to remove the influence of physiological noise from the data). Importantly, these results also demonstrate that, for activation magnitude on the order of 1%, the scan duration required is more sensitive to the TSNR level than at 2%. This study showed that with voxel volumes of ∼10 mm3 at 3 T, and a corresponding TSNR of ∼50, the required number of time points that guarantees detection of signal changes of 1% is about 860, but if TSNR increases by only 20%, the time for detection decreases by more than 30%. More than just being an exercise in numbers, these results imply that imaging of columnar resolution (effect size=1% and assuming a TR of 1 s) at 3 T will require either 10 min for a TSNR of 60 or 40 min for a TSNR of 30. The implication is that at these resolutions, TSNR is likely to be critical for determining success or failure of an experiment.

YNIMG Journal 2005 Journal Article

Deriving the optimal number of events for an event-related fMRI study based on the spatial extent of activation

  • Kevin Murphy
  • Hugh Garavan

Event-related fMRI is a powerful tool for localising psychological functions to specific brain areas. However, the number of events required to produce stable activation maps is a poorly investigated and understood problem. Huettel and McCarthy [Huettel, S. A. , McCarthy, G. , 2001. The effects of single-trial averaging upon the spatial extent of fMRI activation. NeuroReport 12, 2411–2416] have shown that the spatial extent of activation increases monotonically with the number of events in an analysis. In the present paper, this result is replicated and shown to be a consequence of the cross-correlation technique used to determine active voxels and does not hold, for example, for a GLM analysis. Another analysis technique, that does not depend on goodness-of-fit to the data, is also proposed. This technique calculates an impulse response function (IRF) for each voxel, finds the best fitting haemodynamic shape to the IRF and returns an area-under-the-curve (%AUC) activation measure. Using spatial extent as a measure, asymptotic behaviour is evident after as few as 25 events for the %AUC analysis technique in a finger-tapping task with non-overlapping haemodynamic responses and for both the GLM and %AUC techniques in a similar task that allows responses to overlap. The experimental validity of the %AUC technique to identify active brain regions while minimising false positive levels is demonstrated in a group study with 25 participants.

YNIMG Journal 2004 Journal Article

An empirical investigation into the number of subjects required for an event-related fMRI study

  • Kevin Murphy
  • Hugh Garavan

Optimising the number of subjects required for an event-related functional imaging study is critical for ensuring sufficient statistical power. We report an empirical investigation of this issue by employing a resampling approach to the data of 58 subjects drawn from four previous GO/NOGO studies. Using voxelwise measures and setting the activation map from the complete sample to be a “gold standard”, analyses revealed the statistical power to be surprisingly low at typical sample sizes (n = 20). However, voxels that were significantly active from smaller samples tended to be true positives, that is, they were typically active in the gold standard map and correlated well with the gold standard activation measure. The numerous false negatives that resulted from the lower SNR of the smaller samples drove the poor statistical power of those samples. Splitting the sample into two groups provided a test of the reproducibility of activation maps that was assessed using an alternative measure that quantified the distances between centres-of-mass of activated areas. These analyses revealed that although the voxelwise overlap may be poor, the locations of activated areas provide some optimism for studies with typical sample sizes. With n = 20 in each of two groups, it was found that the centres-of-mass for 80% of activated areas fell within 25 mm of each other. The reported analyses, by quantifying the spatial reproducibility for various sample sizes performing a typical event-related cognitive task, thus provide an empirical measure of the disparity to be expected in comparing activation maps.

YNIMG Journal 2004 Journal Article

Beyond common resources: the cortical basis for resolving task interference

  • Robert Hester
  • Kevin Murphy
  • Hugh Garavan

Recent studies have suggested that declining inhibitory control observed during simultaneous increases in working memory (WM) demands may be due to sharing common neural resources, although it is relatively unclear how these processes are successfully combined at a neural level. Event-related functional MRI was used to examine task performance that required inhibition of varying numbers of items held in WM. Common activation regions for WM and inhibition were observed and this functional overlap may constitute the cortical basis for task interference. However, maintaining successful inhibitory control under increasing WM demands tended not to increase activation in these overlapping regions as might be expected if these common areas reflect common resources essential for task performance. Instead, increased activation was observed predominantly in unique, inhibition-specific regions including dorsolateral prefrontal cortex. The finding that successfully maintaining weaker stimulus–response relationships in the face of competition from stronger, prepotent responses requires greater activity in these regions reveals the means by which the brain resolves task interference and supports theories of how top-down attentional control is implemented.

NeurIPS Conference 2004 Conference Paper

Contextual Models for Object Detection Using Boosted Random Fields

  • Antonio Torralba
  • Kevin Murphy
  • William Freeman

We seek to both detect and segment objects in images. To exploit both lo- cal image data as well as contextual information, we introduce Boosted Random Fields (BRFs), which uses Boosting to learn the graph struc- ture and local evidence of a conditional random field (CRF). The graph structure is learned by assembling graph fragments in an additive model. The connections between individual pixels are not very informative, but by using dense graphs, we can pool information from large regions of the image; dense models also support efficient inference. We show how contextual information from other objects can improve detection perfor- mance, both in terms of accuracy and speed, by using a computational cascade. We apply our system to detect stuff and things in office and street scenes. 1 Introduction Our long-term goal is to build a vision system that can examine an image and describe what objects are in it, and where. In many images, such as Fig. 5(a), objects of interest, such as the keyboard or mouse, are so small that they are impossible to detect just by using local features. Seeing a blob next to a keyboard, humans can infer it is likely to be a mouse; we want to give a computer the same abilities. There are several pieces of related work. Murphy et al [9] used global scene context to help object recognition, but did not model relationships between objects. Fink and Perona [4] exploited local dependencies in a boosting framework, but did not allow for multiple rounds of communication between correlated objects. He et al [6] do not model connections between objects directly, but rather they induce such correlations indirectly, via a bank of hidden variables, using a "restricted Boltzmann machine" architecture. In this paper, we exploit contextual correlations between the object classes by introducing Boosted Random Fields (BRFs). Boosted random fields build on both boosting [5, 10] and conditional random fields (CRFs) [8, 7, 6]. Boosting is a simple way of sequentially constructing "strong" classifiers from "weak" components, and has been used for single- class object detection with great success [12]. Dietterich et al [3] combine boosting and 1D CRFs, but they only consider the problem of learning the local evidence potentials; we consider the much harder problem of learning the structure of a 2D CRF. Standard applications of MRFs/ CRFs to images [7] assume a 4-nearest neighbor grid structure. While successful in low-level vision, this structure will fail in capturing im- portant long distance dependencies between whole regions and across classes. We propose a method for learning densely connected random fields with long range connections. The topology of these connections is chosen by a weak learner which has access to a library of graph fragments, derived from patches of labeled training images, which reflect typical spatial arrangments of objects (similar to the segmentation fragments in [2]). At each round of the learning algorithm, we add more connections from other locations in the image and from other classes (detectors). The connections are assumed to be spatially invariant, which means this update can be performed using convolution followed by a sigmoid nonlinearity. The resulting architecture is similar to a convolutional neural network, although we used a stagewise training procedure, which is much faster than back propagation. In addition to recognizing things, such as cars and people, we are also interested in recog- nizing spatially extended "stuff" [1], such as roads and buildings. The traditional sliding window approach to object detection does not work well for detecting "stuff". Instead, we combine object detection and image segmentation (c. f. , [2]) by labeling every pixel in the image. We do not rely on a bottom-up image segmentation algorithm, which can be fragile without top-down guidance. 2 Learning potentials and graph structure A conditional random field (CRF) is a distribution of the form 1 P (S|x) = Z i(Si) i, j (Si, Sj ) i jNi where x is the input (e. g. , image), Ni are the neighbors of node i, and Si are labels. We have assumed pairwise potentials for notational simplicity. Our goal is to learn the local evidence potentials, i, the compatibility potentials, and the set of neighbors Ni. We propose the following simple approximation: use belief propagation (BP) to estimate the marginals, P (Si|x), and then use boosting to maximize the likelihood of each node's training data with respect to i and. In more detail, the algorithm is as follows. At iteration t, the goal is to minimize the negative log-likelihood of the training data. As in [11], we consider the per-label loss (i. e. , we use marginal probabilities), as opposed to requiring that the joint labeling be correct (as in Viterbi decoding). Hence the cost function to be minimized is Jt = Jti = - bti, m(Si, m) = - bti, m(+1)Si, mbti, m(-1)1-Si, m (1) i m i m i where Si, m {-1, +1} is the true label for pixel i in training case m, Si, m = (Si, m + 1)/2 {0, 1} is just a relabeling, and bti, m = [P (Si = -1|xm, t), P (Si = 1|xm, t)] is the belief state at node i given input image xm after t iterations of the algorithm. The belief at node i is given by the following (dropping the dependence on case m) bti(1) ti(1) Mti(1) where Mti is the product of all the messages coming into i from all its neighbors at time t and where the message that k sends to i is given by bt (s M t+1(1) = t+1 (1) t+1 (1) = k k) i (2) ki ki k, i(sk, 1) t (sk) kN ik i sk{-1, +1} where k, i is the compatility between nodes k and i. If we assume that the local potentials have the form t /2 /2 i(si) = [eF t i; e-F ti ], where F ti is some function of the input data, then: bti(+1) = (F ti + Gti), Gti = log Mti(+1) - log Mti(-1) (3) where (u) = 1/(1 + e-u) is the sigmoid function. Hence each term in Eq. 1 simplifies to a cost function similar to that used in boosting: log Jt +Gt ) i, m i = log 1 + e-Si, m(F ti, m. (4) m 1. Input: a set of labeled pairs {xi, m; Si, m}, bound T Output: Local evidence functions f ti(x) and message update functions gti(bN ). i 2. Initialize: bt=0 i, m = 0; F t=0 i, m = 0; Gt=0 i, m = 0 3. For t=1. .T. (a) Fit local potential fi(xi, m) by weighted LS to Y t +Gt ) i, m i, m = Si, m(1 + e-Si, m(F t i ) (b). Fit compatibilities gti(bt-1 ) to Y t N i, m by weighted LS. i, m (c) Compute local potential F t i, m = F t-1 + f t i, m i (xi, m) (d) Compute compatibilities Gti, m = t gn ) n=1 i (bt-1 Ni, m (e) Update the beliefs bti, m = (F ti, m + Gti, m) (f) Update weights wt+1 = bt i, m i, m(-1) bt i, m(+1) Figure 1: BRF training algorithm. We assume that the graph is very densely connected so that the information that one single node sends to another is so small that we can make the approximation t+1 (+1)/ t+1 (-1) 1. (This is a reasonable approximation in the case of images, ki ki where each node represents a single pixel; only when the influence of many pixels is taken into account will the messages become informative. ) Hence bt (s k, m k ) M t+1(+1) s k, i(sk, +1) t (s Gt+1 = log i = log k [-1, +1] i k ) k i (5) M t+1(-1) bt (sk) i k, m k s k, i(sk, -1) k [-1, +1] t (s i k ) k k, i(sk, +1) bt (s k, m k) log sk[-1, +1] (6) k, i(sk, -1) bt (sk) k sk[-1, +1] k, m With this simplification, Gt+1 (bt i is now a non-linear function of the beliefs Gt+1 i m) at iteration t. Therefore, We can write the beliefs at iteration t as a function of the local evidences and the beliefs at time t - 1: bti(+1) = (F ti(xi, m) + Gti(bt-1 m )). The key idea behind BRFs is to use boosting to learn the G functions, which approximately implement message passing in densely connected graphs. We explain this in more detail below. 2. 1 Learning local evidence potentials Defining F ti(xi, m) = F t-1(x i i, m) + f t i (xi, m) as an additive model, where xi, m are the features of training sample m at node i, we can learn this function in a stagewise fashion by optimizing the second order Taylor expansion of Eq. 4 wrt f ti, as in logitBoost [5]: arg min log Jti arg min wti, m(Y ti, m - fti(xi, m))2 (7) f t f t i i m where Y t +Gt ) i, m i, m = Si, m(1+e-Si, m(F t i ). In the case that the weak learner is a "regression stump", fi(x) = ah(x)+b, we can find the optimal a, b by solving a weighted least squares problem, with weights wti, m = bti(-1) bti(+1); we can find the best basis function h(x) by searching over all elements of a dictionary. 2. 2 Learning compatibility potentials and graph structure In this section, we discuss how to learn the compatibility functions ij, and hence the structure of the graph. Instead of learning the compatibility functions ij, we propose to 1. Input: a set of inputs {xi, m} and functions f ti, gti Output: Set of beliefs bi, m and MAP estimates Si, m. 2. Initialize: bt=0 i, m = 0; F t=0 i, m = 0; Gt=0 i, m = 0 3. From t = 1 to T, repeat (a) Update local evidences F t i, m = F t-1 + f t i, m i (xi, m) (b) Update compatibilities Gti, m = t gn ) n=1 i (bt-1 Ni, m (c) Compute current beliefs bti, m = (F ti, m + Gti, m) 4. Output classification is Si, m = bti, m > 0. 5 Figure 2: BRF run-time inference algorithm. learn directly the function Gt+1 i. We propose to use an additive model for Gt+1 i as we did for learning F: Gt+1 = t gn i, m n=1 i (btm), where btm is a vector with the beliefs of all nodes in the graph at iteration t for the training sample m. The weak learners gn i (btm) can be regression stumps with the form gn i (btm) = a(w btm > ) + b, where a, b, are the parameters of the regression stump, and wi is a set of weights selected from a dictionary. In the case of a graph with weak and almost symmetrical connections (which holds if (s1, s2) 1, for all (s1, s2), which implies the messages are not very informative) we can further simplify the function Gt+1 i by approximating it as a linear function of the beliefs: Gt+1 = i, m k, i btk, m(+1) + k, i (8) kNi This step reduces the computational cost. The weak learners gn i (btm) will also be linear functions. Hence the belief update simplifies to bt+1(+1) = ( i, m i btm + i + F t i, m), which is similar to the mean-field update equations. The neighborhood Ni over which we sum incoming messages is determined by the graph structure, which is encoded in the non-zero values of i. Each weak learner gn i will compute a weighted combination of the beliefs of the some subset of the nodes; this subset may change from iteration to iteration, and can be quite large. At iteration t, we choose the weak learner gti so as to minimize t-1 log Jt +gt(bt-1)+ gn(bt-1)) i m i m i (bt-1) = - log 1 + e-Si, m(F ti, m n=1 m which reduces to a weighted least squares problem similar to Eq. 7. See Fig. 1 for the pseudo-code for the complete learning algorithm, and Fig. 2 for the pseudo-code for run- time inference. 3 BRFs for multiclass object detection and segmentation With the BRF training algorithm in hand, we describe our approach for multiclass object detection and region-labeling using densely connected BRFs. 3. 1 Weak learners for detecting stuff and things The square sliding window approach does not provide a natural way of working with irreg- ular objects. Using region labeling as an image representation allows dealing with irregular and extended objects (buildings, bookshelf, road, .. .). Extended stuff [1] may be a very important source of contextual information for other objects. (a) Examples from the dictionary of about 2000 patches and masks, Ux, y, Vx, y. (b) Examples from the dictionary of 30 graphs, Wx, y, c. f t=0 f t=1 f t=2 F S + +. .. = put thu utO Tr (c) Example feedforward segmentation for screens. Figure 3: Examples of patches from the dictionary and an example of the segmentation obtained using boosting trained with patches from (a). The weak learners we use for the local evidence potentials are based on the segmentation fragments proposed in [2]. Specifically, we create a dictionary of about 2000 image patches U, chosen at random (but overlapping each object), plus a corresponding set of binary (in- class/ out-of-class) image masks, V: see Fig. 3(a). At each round t, for each class c, and for each dictionary entry, we construct the following weak learner, whose output is a binary matrix of the same size as the image I: v(I) = ((I U ) > ) V > 0 (9) where represents normalized cross-correlation and represents convolution. The in- tuition behind this is that I U will produce peaks at image locations that contain this patch/template, and then convolving with V will superimpose the segmentation mask on top of the peaks. As a function of the threshold, the feature will behave more as a template detector ( 1) or as a texture descriptor ( car car building car road car Road F b=(F+G) Car car building building building road building Building x G car road building road road road y c) A car out of context a) Incoming messages (outside 3rd floor windows) to a car node. b) Compatibilities (W'). is less of a car. t=1 t=2 t=4 t=20 t=40 Final labeling b(car) S(all) d) Evolution of the beliefs for the car nodes (b) and labeling (S) for road, building, car. Figure 4: Street scene. The BRF is trained to detect cars, buildings and the road. In Fig. 4(a-b), we show the structures of the graph and the weights W defined by GT for a BRF trained to detect cars, buildings and roads in street scenes. 3. 2 Learning and inference For training we used a labeled dataset of office and street scenes with about 100 images in each set. During the training, in the first 5 rounds we only update the local potentials, to allow local evidence to accrue. After the 5th iteration we start updating also the compatibil- ity functions. At each round, we update only the local potential and compatibility function associated with a single object class that reduces the most the multiclass cost. This allows objects that need many features to have more complicated local potentials. The algorithm learns to first detect easy (and large) objects, since these reduce the error of all classes the fastest. The easy-to-detect objects can then pass information to the harder ones. For instance, in office scenes, the system first detects screens, then keyboards, and finally computer mice. Fig. 5 illustrates this behavior on the test set. A similar behavior is obtained for the car detector (Fig. 4(d)). The detection of building and road provides strong constraints for the locations of the car. 3. 3 Cascade of classifiers with BRFs The BRF can be turned into a cascade [12] by thresholding the beliefs. Computations can then be reduced by doing the convolutions (required for computing f and g) only in pixels that are still candidates for the presence of the target. At each round we update a binary rejection mask for each object class, Rtx, y, c, by thresholding the beliefs at round t: Rtx, y, c = Rt-1 x, y, c (btx, y, c > tc). A pixel in the rejection mask is set to zero when we can decide that the object is not present (when btx, y, c is below the threshold tc 0), and it is set to 1 when more processing is required. The threshold tc is chosen so that the percentage of missed detections is below a predefined level (we use 1%). Similarity we can define a detection mask that will indicate pixels in which we decide the object is present. The mask is then used for computing the features v(I) and messages G by applying the convolutions only on the pixels not yet classified. We can denote those operators as R and R. This Input image screen mouse Ground truth Output labeling keyboard t=5 t=10 t=15 t=25 t=50 b (screen) b (screen) b (screen) b (screen) b (screen) F G b (keyboard) b (keyboard) b (keyboard) b (keyboard) b (keyboard) F G b (mouse) b (mouse) b (mouse) b (mouse) b (mouse) F G 1 ROC Screen Boosting BRF Mouse a under Keyboard re Iteration (t) A 0. 5 t=0 t=20 t=50 Figure 5: Top. In this desk scene, it is easy to identify objects like the screen, keyboard and mouse, even though the local information is sometimes insufficient. Middle: the evolution of the beliefs (b and F and G) during detection for a test image. Bottom. The graph bellow shows the average evolution of the area under the ROC for the three objects on 120 test images. results in a more efficient classifier with only a slight decrease of performance. In Fig. 6 we compare the reduction of the search space when implementing a cascade using independent boosting (which reduces to Viola and Jones [12]), and when using BRF's. We see that for objects for which context is the main source of information, like the mouse, the reduction in search space is much more dramatic using BRFs than using boosting alone. 4 Conclusion The proposed BRF algorithm combines boosting and CRF's, providing an algorithm that is easy for both training and inference. We have demonstrated object detection in cluttered scenes by exploiting contextual relationships between objects. The BRF algorithm is com- putationally efficient and provides a natural extension of the cascade of classifiers by inte- grating evidence from other objects in order to quickly reject certain image regions. The BRF's densely connected graphs, which efficiently collect information over large image regions, provide an alternative framework to nearest-neighbor grids for vision problems.

NeurIPS Conference 2003 Conference Paper

Using the Forest to See the Trees: A Graphical Model Relating Features, Objects, and Scenes

  • Kevin Murphy
  • Antonio Torralba
  • William Freeman

Standard approaches to object detection focus on local patches of the image, and try to classify them as background or not. We propose to use the scene context (image as a whole) as an extra source of (global) information, to help resolve local ambiguities. We present a conditional random field for jointly solving the tasks of object detection and scene classification.

NeurIPS Conference 2001 Conference Paper

Linear-time inference in Hierarchical HMMs

  • Kevin Murphy
  • Mark Paskin

The hierarchical hidden Markov model (HHMM) is a generalization of the hidden Markov model (HMM) that models sequences with structure at many length/time scales [FST98]. Unfortunately, the original infer- is ence algorithm is rather complicated, and takes the length of the sequence, making it impractical for many domains. In this paper, we show how HHMMs are a special kind of dynamic Bayesian network (DBN), and thereby derive a much simpler inference algorithm, which only takes time. Furthermore, by drawing the connection between HHMMs and DBNs, we enable the application of many stan- dard approximation techniques to further speed up inference.

NeurIPS Conference 1999 Conference Paper

Bayesian Map Learning in Dynamic Environments

  • Kevin Murphy

We consider the problem of learning a grid-based map using a robot with noisy sensors and actuators. We compare two approaches: online EM, where the map is treated as a fixed parameter, and Bayesian inference, where the map is a (matrix-valued) random variable. We show that even on a very simple example, online EM can get stuck in local minima, which causes the robot to get "lost" and the resulting map to be useless. By contrast, the Bayesian approach, by maintaining multiple hypotheses, is much more ro(cid: 173) bust. We then introduce a method for approximating the Bayesian solution, called Rao-Blackwellised particle filtering. We show that this approximation, when coupled with an active learning strategy, is fast but accurate.