The Bayesian Virtual Epileptic Patient: A probabilistic framework designed to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread

Despite the importance and frequent use of Bayesian frameworks in brain network modeling for parameter inference and model prediction, the advanced sampling algorithms implemented in probabilistic programming languages to overcome the inference difficulties have received relatively little attention in this context. In this technical note, we propose a probabilistic framework, namely the Bayesian Virtual Epileptic Patient (BVEP), which relies on the fusion of structural data of individuals to infer the spatial map of epileptogenicity in a personalized large-scale brain model of epilepsy spread. To invert the individualized whole-brain model employed in this study, we use the recently developed algorithms known as No-U-Turn Sampler (NUTS) as well as Automatic Differentiation Variational Inference (ADVI). Our results indicate that NUTS and ADVI accurately estimate the degree of epileptogenicity of brain regions, therefore, the hypothetical brain areas responsible for the seizure initiation and propagation, while the convergence diagnostics and posterior behavior analysis validate the reliability of the estimations. Moreover, we illustrate the efficiency of the transformed non-centered parameters in comparison to centered form of parameterization. The Bayesian framework used in this work proposes an appropriate patient-specific strategy for estimating the epileptogenicity of the brain regions to improve outcome after epilepsy surgery.

[1]  Viktor K. Jirsa,et al.  Predicting the spatiotemporal diversity of seizure propagation and termination in human focal epilepsy , 2017, Nature Communications.

[2]  J. Zimmermann,et al.  Differentiation of Alzheimer's disease based on local and global parameters in personalized Virtual Brain models , 2018, NeuroImage: Clinical.

[3]  Michael I. Jordan,et al.  An Introduction to Variational Methods for Graphical Models , 1999, Machine Learning.

[4]  G. Deco,et al.  Emerging concepts for the dynamical organization of resting-state activity in the brain , 2010, Nature Reviews Neuroscience.

[5]  D. Rubin,et al.  Inference from Iterative Simulation Using Multiple Sequences , 1992 .

[6]  Aki Vehtari,et al.  Practical Bayesian model evaluation using leave-one-out cross-validation and WAIC , 2015, Statistics and Computing.

[7]  Tom Fawcett,et al.  An introduction to ROC analysis , 2006, Pattern Recognit. Lett..

[8]  A. Connelly,et al.  Improved probabilistic streamlines tractography by 2 nd order integration over fibre orientation distributions , 2009 .

[9]  M. Kramer,et al.  Human seizures self-terminate across spatial scales via a critical transition , 2012, Proceedings of the National Academy of Sciences.

[10]  Viktor Jirsa,et al.  The Hidden Repertoire of Brain Dynamics and Dysfunction , 2019, bioRxiv.

[11]  Christophe Bernard,et al.  Permittivity Coupling across Brain Regions Determines Seizure Recruitment in Partial Epilepsy , 2014, The Journal of Neuroscience.

[12]  M. Betancourt Generalizing the No-U-Turn Sampler to Riemannian Manifolds , 2013, 1304.1920.

[13]  Oscar Benjamin,et al.  Seizure generation: The role of nodes and networks , 2012, Epilepsia.

[14]  N. Crone,et al.  Network dynamics of the brain and influence of the epileptic seizure onset zone , 2014, Proceedings of the National Academy of Sciences.

[15]  S. Vos,et al.  The impact of epilepsy surgery on the structural connectome and its relation to outcome , 2017, NeuroImage: Clinical.

[16]  Karl J. Friston,et al.  Behavioral / Systems / Cognitive Connectivity Changes Underlying Spectral EEG Changes during Propofol-Induced Loss of Consciousness , 2012 .

[17]  Adeel Razi,et al.  A DCM for resting state fMRI , 2014, NeuroImage.

[18]  Christophe Bernard,et al.  Seizures, refractory status epilepticus, and depolarization block as endogenous brain activities. , 2015, Physical review. E, Statistical, nonlinear, and soft matter physics.

[19]  Joachim M. Buhmann,et al.  A generative model of whole-brain effective connectivity , 2018, NeuroImage.

[20]  Andrew Gelman,et al.  General methods for monitoring convergence of iterative simulations , 1998 .

[21]  Karl J. Friston,et al.  Variational Bayesian identification and prediction of stochastic nonlinear dynamic causal models , 2009, Physica D. Nonlinear phenomena.

[22]  Viktor K. Jirsa,et al.  Virtual Brain for neurological disease modeling , 2016 .

[23]  J. Stockman The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study , 2013 .

[24]  Michael Betancourt,et al.  Calibrating Model-Based Inferences and Decisions , 2018, 1803.08393.

[25]  M. Kramer,et al.  Epilepsy as a Disorder of Cortical Network Organization , 2012, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[26]  Simona Olmi,et al.  Controlling seizure propagation in large-scale brain networks , 2018, bioRxiv.

[27]  John S Duncan,et al.  The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study , 2011, The Lancet.

[28]  Axel Hutt,et al.  Optimal Model Parameter Estimation from EEG Power Spectrum Features Observed during General Anesthesia , 2018, Neuroinformatics.

[29]  Pedro A. Valdes-Sosa,et al.  The Statistics of EEG Unipolar References: Derivations and Properties , 2019, Brain Topography.

[30]  E. Beghi,et al.  Predictors of epilepsy surgery outcome: a meta-analysis , 2004, Epilepsy Research.

[31]  S. Duane,et al.  Hybrid Monte Carlo , 1987 .

[32]  Sarah Feldt Muldoon,et al.  Personalized brain network models for assessing structure–function relationships , 2018, Current Opinion in Neurobiology.

[33]  John D. Storey,et al.  Scaling probabilistic models of genetic variation to millions of humans , 2014, Nature Genetics.

[34]  Max Welling,et al.  GPS-ABC: Gaussian Process Surrogate Approximate Bayesian Computation , 2014, UAI.

[35]  Viktor K. Jirsa,et al.  The Virtual Brain: a simulator of primate brain network dynamics , 2013, Front. Neuroinform..

[36]  Gaël Varoquaux,et al.  Scikit-learn: Machine Learning in Python , 2011, J. Mach. Learn. Res..

[37]  Donald Geman,et al.  Stochastic Relaxation, Gibbs Distributions, and the Bayesian Restoration of Images , 1984, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[38]  Jordi García-Ojalvo,et al.  Temporally correlated fluctuations drive epileptiform dynamics , 2017, NeuroImage.

[39]  W. K. Hastings,et al.  Monte Carlo Sampling Methods Using Markov Chains and Their Applications , 1970 .

[40]  Thomas A. Henzinger,et al.  Probabilistic programming , 2014, FOSE.

[41]  Kaspar Anton Schindler,et al.  Estimation of brain network ictogenicity predicts outcome from epilepsy surgery , 2016, Scientific Reports.

[42]  Iain Murray,et al.  Fast $\epsilon$-free Inference of Simulation Models with Bayesian Conditional Density Estimation , 2016, 1605.06376.

[43]  C. Stam Modern network science of neurological disorders , 2014, Nature Reviews Neuroscience.

[44]  Radford M. Neal MCMC Using Hamiltonian Dynamics , 2011, 1206.1901.

[45]  James T. Thorson,et al.  Faster estimation of Bayesian models in ecology using Hamiltonian Monte Carlo , 2017 .

[46]  Andrew Gelman,et al.  Automatic Variational Inference in Stan , 2015, NIPS.

[47]  Karl J. Friston,et al.  Stochastic dynamic causal modelling of fMRI data: Should we care about neural noise? , 2012, NeuroImage.

[48]  David M Blei,et al.  Efficient discovery of overlapping communities in massive networks , 2013, Proceedings of the National Academy of Sciences.

[49]  Viktor Jirsa,et al.  Individual structural features constrain the mouse functional connectome , 2019, Proceedings of the National Academy of Sciences.

[50]  Viktor K. Jirsa,et al.  Individual brain structure and modelling predict seizure propagation , 2017, Brain : a journal of neurology.

[51]  P. Chauvel,et al.  Epileptogenicity of brain structures in human temporal lobe epilepsy: a quantified study from intracerebral EEG. , 2008, Brain : a journal of neurology.

[52]  John Salvatier,et al.  Probabilistic programming in Python using PyMC3 , 2016, PeerJ Comput. Sci..

[53]  David M. Blei,et al.  Variational Inference: A Review for Statisticians , 2016, ArXiv.

[54]  Karl J. Friston,et al.  Gradient-free MCMC methods for dynamic causal modelling , 2015, NeuroImage.

[55]  Dustin Tran,et al.  Edward: A library for probabilistic modeling, inference, and criticism , 2016, ArXiv.

[56]  Karl J. Friston,et al.  Dynamic causal modeling for EEG and MEG , 2009, Human brain mapping.

[57]  Hisashi Q. Higuchi On the nature of , 1999 .

[58]  Michael Betancourt,et al.  A Conceptual Introduction to Hamiltonian Monte Carlo , 2017, 1701.02434.

[59]  Barak A. Pearlmutter,et al.  Automatic differentiation in machine learning: a survey , 2015, J. Mach. Learn. Res..

[60]  Dustin Tran,et al.  Automatic Differentiation Variational Inference , 2016, J. Mach. Learn. Res..

[61]  Edward Meeds,et al.  Optimization Monte Carlo: Efficient and Embarrassingly Parallel Likelihood-Free Inference , 2015, Neural Information Processing Systems.

[62]  Karen Steger-May,et al.  Impact of epilepsy surgery on seizure control and quality of life: A 26‐year follow‐up study , 2012, Epilepsia.

[63]  Michael I. Jordan,et al.  Graphical Models, Exponential Families, and Variational Inference , 2008, Found. Trends Mach. Learn..

[64]  Bernardino Castillo-Toledo,et al.  State and parameter estimation of a neural mass model from electrophysiological signals during the status epilepticus , 2015, NeuroImage.

[65]  M. Betancourt,et al.  The Geometric Foundations of Hamiltonian Monte Carlo , 2014, 1410.5110.

[66]  J. Wehr,et al.  Effective drifts in dynamical systems with multiplicative noise: a review of recent progress , 2016, Reports on progress in physics. Physical Society.

[67]  W. Stacey,et al.  On the nature of seizure dynamics. , 2014, Brain : a journal of neurology.

[68]  Viktor K. Jirsa,et al.  Mathematical framework for large-scale brain network modeling in The Virtual Brain , 2015, NeuroImage.

[69]  Radford M. Neal Slice Sampling , 2003, The Annals of Statistics.

[70]  Lionel Rigoux,et al.  VBA: A Probabilistic Treatment of Nonlinear Models for Neurobiological and Behavioural Data , 2014, PLoS Comput. Biol..

[71]  Mark P. Richardson,et al.  A Critical Role for Network Structure in Seizure Onset: A Computational Modeling Approach , 2014, Front. Neurol..

[72]  John R. Terry,et al.  A unifying explanation of primary generalized seizures through nonlinear brain modeling and bifurcation analysis. , 2006, Cerebral cortex.

[73]  Karl J. Friston,et al.  Dynamic causal modelling of electrographic seizure activity using Bayesian belief updating , 2016, NeuroImage.

[74]  Radford M. Neal Pattern Recognition and Machine Learning , 2007, Technometrics.

[75]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[76]  M. Girolami,et al.  Riemann manifold Langevin and Hamiltonian Monte Carlo methods , 2011, Journal of the Royal Statistical Society: Series B (Statistical Methodology).

[77]  David J. C. MacKay,et al.  Information Theory, Inference, and Learning Algorithms , 2004, IEEE Transactions on Information Theory.

[78]  Karl J. Friston,et al.  Tracking slow modulations in synaptic gain using dynamic causal modelling: Validation in epilepsy , 2015, NeuroImage.

[79]  Karl J. Friston,et al.  Gradient-based MCMC samplers for dynamic causal modelling , 2016, NeuroImage.

[80]  Michael Brady,et al.  Improved Optimization for the Robust and Accurate Linear Registration and Motion Correction of Brain Images , 2002, NeuroImage.

[81]  Levin Kuhlmann,et al.  Seizure pathways: A model-based investigation , 2018, PLoS Comput. Biol..

[82]  Fabrice Wendling,et al.  Brain regions and epileptogenicity influence epileptic interictal spike production and propagation during NREM sleep in comparison with wakefulness , 2018, Epilepsia.

[83]  Charles W Groetsch Inverse Problems: Activities for Undergraduates , 1999 .

[84]  Charles C. Margossian,et al.  A review of automatic differentiation and its efficient implementation , 2018, WIREs Data Mining Knowl. Discov..

[85]  O. Sporns,et al.  Key role of coupling, delay, and noise in resting brain fluctuations , 2009, Proceedings of the National Academy of Sciences.

[86]  S. Walker Invited comment on the paper "Slice Sampling" by Radford Neal , 2003 .

[87]  Karl J. Friston,et al.  a K.E. Stephan, a R.B. Reilly, , 2007 .

[88]  Karl J. Friston,et al.  Multiple sparse priors for the M/EEG inverse problem , 2008, NeuroImage.

[89]  A. Connelly,et al.  Determination of the appropriate b value and number of gradient directions for high‐angular‐resolution diffusion‐weighted imaging , 2013, NMR in biomedicine.

[90]  Andrew Gelman,et al.  The No-U-turn sampler: adaptively setting path lengths in Hamiltonian Monte Carlo , 2011, J. Mach. Learn. Res..

[91]  Aki Vehtari,et al.  Yes, but Did It Work?: Evaluating Variational Inference , 2018, ICML.

[92]  N. Metropolis,et al.  Equation of State Calculations by Fast Computing Machines , 1953, Resonance.

[93]  Viktor Jirsa,et al.  Optimization of surgical intervention outside the epileptogenic zone in the Virtual Epileptic Patient (VEP) , 2019, PLoS Comput. Biol..

[94]  Andrew Gelman,et al.  Handbook of Markov Chain Monte Carlo , 2011 .

[95]  Anthony R. McIntosh,et al.  Functional Mechanisms of Recovery after Chronic Stroke: Modeling with the Virtual Brain123 , 2016, eNeuro.

[96]  Michael U. Gutmann,et al.  Bayesian Optimization for Likelihood-Free Inference of Simulator-Based Statistical Models , 2015, J. Mach. Learn. Res..

[97]  C. Stam,et al.  Functional and structural brain networks in epilepsy: What have we learned? , 2013, Epilepsia.

[98]  S. Spencer Neural Networks in Human Epilepsy: Evidence of and Implications for Treatment , 2002, Epilepsia.

[99]  Karl J. Friston,et al.  Dynamic causal modeling of evoked responses in EEG and MEG , 2006, NeuroImage.

[100]  A. Gelman,et al.  Pareto Smoothed Importance Sampling , 2015, 1507.02646.

[101]  Bradley P. Carlin,et al.  Markov Chain Monte Carlo conver-gence diagnostics: a comparative review , 1996 .

[102]  Dezhong Yao,et al.  Unified Bayesian Estimator of EEG Reference at Infinity: rREST (Regularized Reference Electrode Standardization Technique) , 2018, Front. Neurosci..

[103]  Jiqiang Guo,et al.  Stan: A Probabilistic Programming Language. , 2017, Journal of statistical software.

[104]  Bruce Fischl,et al.  FreeSurfer , 2012, NeuroImage.

[105]  M. Betancourt,et al.  Hamiltonian Monte Carlo for Hierarchical Models , 2013, 1312.0906.

[106]  Noah D. Goodman,et al.  Pyro: Deep Universal Probabilistic Programming , 2018, J. Mach. Learn. Res..

[107]  W. Gilks,et al.  Adaptive Rejection Metropolis Sampling Within Gibbs Sampling , 1995 .

[108]  Alan Connelly,et al.  Robust determination of the fibre orientation distribution in diffusion MRI: Non-negativity constrained super-resolved spherical deconvolution , 2007, NeuroImage.

[109]  Karl J. Friston,et al.  Dynamic causal modelling , 2003, NeuroImage.

[110]  Viktor K. Jirsa,et al.  The Virtual Epileptic Patient: Individualized whole-brain models of epilepsy spread , 2017, NeuroImage.

[111]  Karl J. Friston,et al.  Characterising seizures in anti-NMDA-receptor encephalitis with dynamic causal modelling , 2015, NeuroImage.

[112]  David M. W. Powers,et al.  Evaluation: from precision, recall and F-measure to ROC, informedness, markedness and correlation , 2011, ArXiv.

[113]  Sumio Watanabe,et al.  Asymptotic Equivalence of Bayes Cross Validation and Widely Applicable Information Criterion in Singular Learning Theory , 2010, J. Mach. Learn. Res..

[114]  Aki Vehtari,et al.  Understanding predictive information criteria for Bayesian models , 2013, Statistics and Computing.

[115]  J. Wehr,et al.  Stratonovich-to-Itô transition in noisy systems with multiplicative feedback , 2013, Nature Communications.

[116]  Ole Winther,et al.  Bayesian Leave-One-Out Cross-Validation Approximations for Gaussian Latent Variable Models , 2014, J. Mach. Learn. Res..