Bayesian varying-effects vector autoregressive models for inference of brain connectivity networks and covariate effects in pediatric traumatic brain injury.

In this article, we develop an analytical approach for estimating brain connectivity networks that accounts for subject heterogeneity. More specifically, we consider a novel extension of a multi-subject Bayesian vector autoregressive model that estimates group-specific directed brain connectivity networks and accounts for the effects of covariates on the network edges. We adopt a flexible approach, allowing for (possibly) nonlinear effects of the covariates on edge strength via a novel Bayesian nonparametric prior that employs a weighted mixture of Gaussian processes. For posterior inference, we achieve computational scalability by implementing a variational Bayes scheme. Our approach enables simultaneous estimation of group-specific networks and selection of relevant covariate effects. We show improved performance over competing two-stage approaches on simulated data. We apply our method on resting-state functional magnetic resonance imaging data from children with a history of traumatic brain injury (TBI) and healthy controls to estimate the effects of age and sex on the group-level connectivities. Our results highlight differences in the distribution of parent nodes. They also suggest alteration in the relation of age, with peak edge strength in children with TBI, and differences in effective connectivity strength between males and females.

Bayesian Tensor Modeling for Image-based Classification of Alzheimer's Disease.

Tensor-based representations are being increasingly used to represent complex data types such as imaging data, due to their appealing properties such as dimension reduction and the preservation of spatial information. Recently, there is a growing literature on using Bayesian scalar-on-tensor regression techniques that use tensor-based representations for high-dimensional and spatially distributed covariates to predict continuous outcomes. However surprisingly, there is limited development on corresponding Bayesian classification methods relying on tensor-valued covariates. Standard approaches that vectorize the image are not desirable due to the loss of spatial structure, and alternate methods that use extracted features from the image in the predictive model may suffer from information loss. We propose a novel data augmentation-based Bayesian classification approach relying on tensor-valued covariates, with a focus on imaging predictors. We propose two data augmentation schemes, one resulting in a support vector machine (SVM) type of classifier, and another yielding a logistic regression classifier. While both types of classifiers have been proposed independently in literature, our contribution is to extend such existing methodology to accommodate high-dimensional tensor valued predictors that involve low rank decompositions of the coefficient matrix while preserving the spatial information in the image. An efficient Markov chain Monte Carlo (MCMC) algorithm is developed for implementing these methods. Simulation studies show significant improvements in classification accuracy and parameter estimation compared to routinely used classification methods. We further illustrate our method in a neuroimaging application using cortical thickness MRI data from Alzheimer's Disease Neuroimaging Initiative, with results displaying better classification accuracy throughout several classification tasks, including classification on pairs of the three diagnostic groups: normal control, AD patients, and MCI patients; gender classification (males vs females); and cognitive performance based on high and low levels of MMSE scores.

Multiomic foundations of human prefrontal cortex tissue function.

The prefrontal cortex (PFC) is a region of the brain that in humans is involved in the production of higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission in the PFC produces higher-order functions by integrating information from other areas of the brain. At the foundation of neurotransmission, and by extension at the foundation of higher-order brain functions, are an untold number of coordinated molecular processes involving the DNA sequence variants in the genome, RNA transcripts in the transcriptome, and proteins in the proteome. These "multiomic" foundations are poorly understood in humans, perhaps in part because most modern studies that characterize the molecular state of the human PFC use tissue obtained when neurotransmission and higher-order brain functions have ceased (i.e., the postmortem state). Here, analyses are presented on data generated for the Living Brain Project (LBP) to investigate whether PFC tissue from individuals with intact higher-order brain function has characteristic multiomic foundations. Two complementary strategies were employed towards this end. The first strategy was to identify in PFC samples obtained from living study participants a signature of RNA transcript expression associated with neurotransmission measured intracranially at the time of PFC sampling, in some cases while participants performed a task engaging higher-order brain functions. The second strategy was to perform multiomic comparisons between PFC samples obtained from individuals with intact higher-order brain function at the time of sampling (i.e., living study participants) and PFC samples obtained in the postmortem state. RNA transcript expression within multiple PFC cell types was associated with fluctuations of dopaminergic, serotonergic, and/or noradrenergic neurotransmission in the substantia nigra measured while participants played a computer game that engaged higher-order brain functions. A subset of these associations - termed the "transcriptional program associated with neurotransmission" (TPAWN) - were reproduced in analyses of brain RNA transcript expression and intracranial neurotransmission data obtained from a second LBP cohort and from a cohort in an independent study. RNA transcripts involved in TPAWN were found to be (1) enriched for RNA transcripts associated with measures of neurotransmission in rodent and cell models, (2) enriched for RNA transcripts encoded by evolutionarily constrained genes, (3) depleted of RNA transcripts regulated by common DNA sequence variants, and (4) enriched for RNA transcripts implicated in higher-order brain functions by human population genetic studies. In PFC excitatory neurons of living study participants, higher expression of the genes in TPAWN tracked with higher expression of RNA transcripts that in rodent PFC samples are markers of a class of excitatory neurons that connect the PFC to deep brain structures. TPAWN was further reproduced by RNA transcript expression patterns differentiating living PFC samples from postmortem PFC samples, and significant differences between living and postmortem PFC samples were additionally observed with respect to (1) the expression of most primary RNA transcripts, mature RNA transcripts, and proteins, (2) the splicing of most primary RNA transcripts into mature RNA transcripts, (3) the patterns of co-expression between RNA transcripts and proteins, and (4) the effects of some DNA sequence variants on RNA transcript and protein expression. Taken together, this report highlights that studies of brain tissue obtained in a safe and ethical manner from large cohorts of living individuals can help advance understanding of the multiomic foundations of brain function.

A predictor-informed multi-subject bayesian approach for dynamic functional connectivity.

Dynamic functional connectivity investigates how the interactions among brain regions vary over the course of an fMRI experiment. Such transitions between different individual connectivity states can be modulated by changes in underlying physiological mechanisms that drive functional network dynamics, e.g., changes in attention or cognitive effort. In this paper, we develop a multi-subject Bayesian framework where the estimation of dynamic functional networks is informed by time-varying exogenous physiological covariates that are simultaneously recorded in each subject during the fMRI experiment. More specifically, we consider a dynamic Gaussian graphical model approach where a non-homogeneous hidden Markov model is employed to classify the fMRI time series into latent neurological states. We assume the state-transition probabilities to vary over time and across subjects as a function of the underlying covariates, allowing for the estimation of recurrent connectivity patterns and the sharing of networks among the subjects. We further assume sparsity in the network structures via shrinkage priors, and achieve edge selection in the estimated graph structures by introducing a multi-comparison procedure for shrinkage-based inferences with Bayesian false discovery rate control. We evaluate the performances of our method vs alternative approaches on synthetic data. We apply our modeling framework on a resting-state experiment where fMRI data have been collected concurrently with pupillometry measurements, as a proxy of cognitive processing, and assess the heterogeneity of the effects of changes in pupil dilation on the subjects' propensity to change connectivity states. The heterogeneity of state occupancy across subjects provides an understanding of the relationship between increased pupil dilation and transitions toward different cognitive states.

Improved data quality and statistical power of trial-level event-related potentials with Bayesian random-shift Gaussian processes.

Studies of cognitive processes via electroencephalogram (EEG) recordings often analyze group-level event-related potentials (ERPs) averaged over multiple subjects and trials. This averaging procedure can obscure scientifically relevant variability across subjects and trials, but has been necessary due to the difficulties posed by inference of trial-level ERPs. We introduce the Bayesian Random Phase-Amplitude Gaussian Process (RPAGP) model, for inference of trial-level amplitude, latency, and ERP waveforms. We apply RPAGP to data from a study of ERP responses to emotionally arousing images. The model estimates of trial-specific signals are shown to greatly improve statistical power in detecting significant differences in experimental conditions compared to existing methods. Our results suggest that replacing the observed data with the de-noised RPAGP predictions can potentially improve the sensitivity and accuracy of many of the existing ERP analysis pipelines.

Diminished Adaptation, Satisfaction, and Neural Responses to Advantageous Social Signals in Anorexia Nervosa and Bulimia Nervosa.

BACKGROUND: Development and recurrence of 2 eating disorders (EDs), anorexia nervosa and bulimia nervosa, are frequently associated with environmental stressors. Neurobehavioral responses to social learning signals were evaluated in both EDs. METHODS: Women with anorexia nervosa (n = 25), women with bulimia nervosa (n = 30), or healthy comparison women (n = 38) played a neuroeconomic game in which the norm shifted, generating social learning signals (norm prediction errors [NPEs]) during a functional magnetic resonance imaging scan. A Bayesian logistic regression model examined how the probability of offer acceptance depended on cohort, block, and NPEs. Rejection rates, emotion ratings, and neural responses to NPEs were compared across groups. RESULTS: Relative to the comparison group, both ED cohorts showed less adaptation (p = .028, ηp2 = 0.060), and advantageous signals (positive NPEs) led to higher rejection rates (p = .014, ηp2 = 0.077) and less positive emotion ratings (p = .004, ηp2 = 0.111). Advantageous signals increased neural activations in the orbitofrontal cortex for the comparison group but not for women with anorexia nervosa (p = .018, d = 0.655) or bulimia nervosa (p = .043, d = 0.527). More severe ED symptoms were associated with decreased activation of dorsomedial prefrontal cortex for advantageous signals. CONCLUSIONS: Diminished neural processing of advantageous social signals and impaired norm adaptation were observed in both anorexia nervosa and bulimia nervosa, while no differences were found for disadvantageous social signals. Development of neurocognitive interventions to increase responsivity to advantageous social signals could augment current treatments, potentially leading to improved clinical outcomes for EDs.

Noradrenaline tracks emotional modulation of attention in human amygdala.

The noradrenaline (NA) system is one of the brain's major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain.1,2 The LC-NA system is believed to regulate arousal and attention3,4 and is a pharmacological target in multiple clinical conditions.5,6,7 Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. Here, we address this problem by showing that electrochemical estimates of sub-second NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring. We made these recordings in the amygdala, an evolutionarily ancient structure that supports emotional processing8,9 and receives dense LC-NA projections,10 while patients (n = 3) performed a visual affective oddball task. The task was designed to induce different cognitive states, with the oddball stimuli involving emotionally evocative images,11 which varied in terms of arousal (low versus high) and valence (negative versus positive). Consistent with theory, the NA estimates tracked the emotional modulation of attention, with a stronger oddball response in a high-arousal state. Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity,12 supported a hypothesis that pupil-NA coupling changes with cognitive state,13,14 with the pupil and NA estimates being positively correlated for oddball stimuli in a high-arousal but not a low-arousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.

A Bayesian joint model for compositional mediation effect selection in microbiome data.

Analyzing multivariate count data generated by high-throughput sequencing technology in microbiome research studies is challenging due to the high-dimensional and compositional structure of the data and overdispersion. In practice, researchers are often interested in investigating how the microbiome may mediate the relation between an assigned treatment and an observed phenotypic response. Existing approaches designed for compositional mediation analysis are unable to simultaneously determine the presence of direct effects, relative indirect effects, and overall indirect effects, while quantifying their uncertainty. We propose a formulation of a Bayesian joint model for compositional data that allows for the identification, estimation, and uncertainty quantification of various causal estimands in high-dimensional mediation analysis. We conduct simulation studies and compare our method's mediation effects selection performance with existing methods. Finally, we apply our method to a benchmark data set investigating the sub-therapeutic antibiotic treatment effect on body weight in early-life mice.

Bayesian feature selection for radiomics using reliability metrics.

Introduction: Imaging of tumors is a standard step in diagnosing cancer and making subsequent treatment decisions. The field of radiomics aims to develop imaging based biomarkers using methods rooted in artificial intelligence applied to medical imaging. However, a challenging aspect of developing predictive models for clinical use is that many quantitative features derived from image data exhibit instability or lack of reproducibility across different imaging systems or image-processing pipelines. Methods: To address this challenge, we propose a Bayesian sparse modeling approach for image classification based on radiomic features, where the inclusion of more reliable features is favored via a probit prior formulation. Results: We verify through simulation studies that this approach can improve feature selection and prediction given correct prior information. Finally, we illustrate the method with an application to the classification of head and neck cancer patients by human papillomavirus status, using as our prior information a reliability metric quantifying feature stability across different imaging systems.

Bayesian inference for stationary points in Gaussian process regression models for event-related potentials analysis.

Stationary points embedded in the derivatives are often critical for a model to be interpretable and may be considered as key features of interest in many applications. We propose a semiparametric Bayesian model to efficiently infer the locations of stationary points of a nonparametric function, which also produces an estimate of the function. We use Gaussian processes as a flexible prior for the underlying function and impose derivative constraints to control the function's shape via conditioning. We develop an inferential strategy that intentionally restricts estimation to the case of at least one stationary point, bypassing possible mis-specifications in the number of stationary points and avoiding the varying dimension problem that often brings in computational complexity. We illustrate the proposed methods using simulations and then apply the method to the estimation of event-related potentials derived from electroencephalography (EEG) signals. We show how the proposed method automatically identifies characteristic components and their latencies at the individual level, which avoids the excessive averaging across subjects that is routinely done in the field to obtain smooth curves. By applying this approach to EEG data collected from younger and older adults during a speech perception task, we are able to demonstrate how the time course of speech perception processes changes with age.

Bayesian continuous-time hidden Markov models with covariate selection for intensive longitudinal data with measurement error.

Intensive longitudinal data collected with ecological momentary assessment methods capture information on participants' behaviors, feelings, and environment in near real-time. While these methods can reduce recall biases typically present in survey data, they may still suffer from other biases commonly found in self-reported data (e.g., measurement error and social desirability bias). To accommodate potential biases, we develop a Bayesian hidden Markov model to simultaneously identify risk factors for subjects transitioning between discrete latent states as well as risk factors potentially associated with them misreporting their true behaviors. We use simulated data to demonstrate how ignoring potential measurement error can negatively affect variable selection performance and estimation accuracy. We apply our proposed model to smartphone-based ecological momentary assessment data collected within a randomized controlled trial that evaluated the impact of incentivizing abstinence from cigarette smoking among socioeconomically disadvantaged adults. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

BAYESIAN NON-HOMOGENEOUS HIDDEN MARKOV MODEL WITH VARIABLE SELECTION FOR INVESTIGATING DRIVERS OF SEIZURE RISK CYCLING.

A major issue in the clinical management of epilepsy is the unpredictability of seizures. Yet, traditional approaches to seizure forecasting and risk assessment in epilepsy rely heavily on raw seizure frequencies, which are a stochastic measurement of seizure risk. We consider a Bayesian non-homogeneous hidden Markov model for unsupervised clustering of zero-inflated seizure count data. The proposed model allows for a probabilistic estimate of the sequence of seizure risk states at the individual level. It also offers significant improvement over prior approaches by incorporating a variable selection prior for the identification of clinical covariates that drive seizure risk changes and accommodating highly granular data. For inference, we implement an efficient sampler that employs stochastic search and data augmentation techniques. We evaluate model performance on simulated seizure count data. We then demonstrate the clinical utility of the proposed model by analyzing daily seizure count data from 133 patients with Dravet syndrome collected through the Seizure Tracker™ system, a patient-reported electronic seizure diary. We report on the dynamics of seizure risk cycling, including validation of several known pharmacologic relationships. We also uncover novel findings characterizing the presence and volatility of risk states in Dravet syndrome, which may directly inform counseling to reduce the unpredictability of seizures for patients with this devastating cause of epilepsy.

A Bayesian switching linear dynamical system for estimating seizure chronotypes.

Epilepsy is a disorder characterized by paroxysmal transitions between multistable states. Dynamical systems have been useful for modeling the paroxysmal nature of seizures. At the same time, intracranial electroencephalography (EEG) recordings have recently discovered that an electrographic measure of epileptogenicity, interictal epileptiform activity, exhibits cycling patterns ranging from ultradian to multidien rhythmicity, with seizures phase-locked to specific phases of these latent cycles. However, many mechanistic questions about seizure cycles remain unanswered. Here, we provide a principled approach to recast the modeling of seizure chronotypes within a statistical dynamical systems framework by developing a Bayesian switching linear dynamical system (SLDS) with variable selection to estimate latent seizure cycles. We propose a Markov chain Monte Carlo algorithm that employs particle Gibbs with ancestral sampling to estimate latent cycles in epilepsy and apply unsupervised learning on spectral features of latent cycles to uncover clusters in cycling tendency. We analyze the largest database of patient-reported seizures in the world to comprehensively characterize multidien cycling patterns among 1,012 people with epilepsy, spanning from infancy to older adulthood. Our work advances knowledge of cycling in epilepsy by investigating how multidien seizure cycles vary in people with epilepsy, while demonstrating an application of an SLDS to frame seizure cycling within a nonlinear dynamical systems framework. It also lays the groundwork for future studies to pursue data-driven hypothesis generation regarding the mechanistic drivers of seizure cycles.

Seizure count forecasting to aid diagnostic testing in epilepsy.

OBJECTIVE: Epilepsy monitoring unit (EMU) admissions are critical for presurgical evaluation of drug-resistant epilepsy but may be nondiagnostic if an insufficient number of seizures are recorded. Seizure forecasting algorithms have shown promise for estimating the likelihood of seizures as a binary event in individual patients, but methods to predict how many seizures will occur remain elusive. Such methods could increase the diagnostic yield of EMU admissions and help patients mitigate seizure-related morbidity. Here, we evaluated the performance of a state-space method that uses prior seizure count data to predict future counts. METHODS: A Bayesian negative-binomial dynamic linear model (DLM) was developed to forecast daily electrographic seizure counts in 19 patients implanted with a responsive neurostimulation (RNS) device. Holdout validation was used to evaluate performance in predicting the number of electrographic seizures for forecast horizons ranging 1-7 days ahead. RESULTS: One-day-ahead prediction of the number of electrographic seizures using a negative-binomial DLM resulted in improvement over chance in 73.1% of time segments compared to a random chance forecaster and remained >50% for forecast horizons of up to 7 days. Superior performance (mean error = .99) was obtained in predicting the number of electrographic seizures in the next day compared to three traditional methods for count forecasting (integer-valued generalized autoregressive conditional heteroskedasticity model or INGARCH, 1.10; Croston, 1.06; generalized linear autoregressive moving average model or GLARMA, 2.00). Number of electrographic seizures in the preceding day and laterality of electrographic pattern detections had highest predictive value, with greater number of electrographic seizures and RNS magnet swipes in the preceding day associated with a higher number of electrographic seizures the next day. SIGNIFICANCE: This study demonstrates that DLMs can predict the number of electrographic seizures a patient will experience days in advance with above chance accuracy. This study represents an important step toward the translation of seizure forecasting methods into the optimization of EMU admissions.

Bayesian graphical models for modern biological applications.

Graphical models are powerful tools that are regularly used to investigate complex dependence structures in high-throughput biomedical datasets. They allow for holistic, systems-level view of the various biological processes, for intuitive and rigorous understanding and interpretations. In the context of large networks, Bayesian approaches are particularly suitable because it encourages sparsity of the graphs, incorporate prior information, and most importantly account for uncertainty in the graph structure. These features are particularly important in applications with limited sample size, including genomics and imaging studies. In this paper, we review several recently developed techniques for the analysis of large networks under non-standard settings, including but not limited to, multiple graphs for data observed from multiple related subgroups, graphical regression approaches used for the analysis of networks that change with covariates, and other complex sampling and structural settings. We also illustrate the practical utility of some of these methods using examples in cancer genomics and neuroimaging.

Effective connectivity between resting-state networks in depression.

RATIONALE: Although depression has been widely researched, findings characterizing how brain regions influence each other remains scarce, yet this is critical for research on antidepressant treatments and individual responses to particular treatments. OBJECTIVES: To identify pre-treatment resting state effective connectivity (rsEC) patterns in patients with major depressive disorder (MDD) and explore their relationship with treatment response. METHODS: Thirty-four drug-free MDD patients had an MRI scan and were subsequently treated for 6 weeks with an SSRI escitalopram 10 mg daily; the response was defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score. RESULTS: rsEC networks in default mode, central executive, and salience networks were identified for patients with depression. Exploratory analyses indicated higher connectivity strength related to baseline depression severity and response to treatment. CONCLUSIONS: Preliminary analyses revealed widespread dysfunction of rsEC in depression. Functional rsEC may be useful as a predictive tool for antidepressant treatment response. A primary limitation of the current study was the small size; however, the group was carefully chosen, well-characterized, and included only medication-free patients. Further research in large samples of placebo-controlled studies would be required to confirm the results.

Effective connectivity in the default mode network after paediatric traumatic brain injury.

Children who experience a traumatic brain injury (TBI) are at elevated risk for a range of negative cognitive and neuropsychological outcomes. Identifying which children are at greatest risk for negative outcomes can be difficult due to the heterogeneity of TBI. To address this barrier, the current study applied a novel method of characterizing brain connectivity networks, Bayesian multi-subject vector autoregressive modelling (BVAR-connect), which used white matter integrity as priors to evaluate effective connectivity-the time-dependent relationship in functional magnetic resonance imaging (fMRI) activity between two brain regions-within the default mode network (DMN). In a prospective longitudinal study, children ages 8-15 years with mild to severe TBI underwent diffusion tensor imaging and resting state fMRI 7 weeks after injury; post-concussion and anxiety symptoms were assessed 7 months after injury. The goals of this study were to (1) characterize differences in positive effective connectivity of resting-state DMN circuitry between healthy controls and children with TBI, (2) determine if severity of TBI was associated with differences in DMN connectivity and (3) evaluate whether patterns of DMN effective connectivity predicted persistent post-concussion symptoms and anxiety. Healthy controls had unique positive connectivity that mostly emerged from the inferior temporal lobes. In contrast, children with TBI had unique effective connectivity among orbitofrontal and parietal regions. These positive orbitofrontal-parietal DMN effective connectivity patterns also differed by TBI severity and were associated with persisting behavioural outcomes. Effective connectivity may be a sensitive neuroimaging marker of TBI severity as well as a predictor of chronic post-concussion symptoms and anxiety.

Latent Network Estimation and Variable Selection for Compositional Data Via Variational EM.

Network estimation and variable selection have been extensively studied in the statistical literature, but only recently have those two challenges been addressed simultaneously. In this article, we seek to develop a novel method to simultaneously estimate network interactions and associations to relevant covariates for count data, and specifically for compositional data, which have a fixed sum constraint. We use a hierarchical Bayesian model with latent layers and employ spike-and-slab priors for both edge and covariate selection. For posterior inference, we develop a novel variational inference scheme with an expectation-maximization step, to enable efficient estimation. Through simulation studies, we demonstrate that the proposed model outperforms existing methods in its accuracy of network recovery. We show the practical utility of our model via an application to microbiome data. The human microbiome has been shown to contribute too many of the functions of the human body, and also to be linked with a number of diseases. In our application, we seek to better understand the interaction between microbes and relevant covariates, as well as the interaction of microbes with each other. We call our algorithm simultaneous inference for networks and covariates and provide a Python implementation, which is available online.

Evidence of state-dependence in the effectiveness of responsive neurostimulation for seizure modulation.

BACKGROUND: An implanted device for brain-responsive neurostimulation (RNS® System) is approved as an effective treatment to reduce seizures in adults with medically-refractory focal epilepsy. Clinical trials of the RNS System demonstrate population-level reduction in average seizure frequency, but therapeutic response is highly variable. HYPOTHESIS: Recent evidence links seizures to cyclical fluctuations in underlying risk. We tested the hypothesis that effectiveness of responsive neurostimulation varies based on current state within cyclical risk fluctuations. METHODS: We analyzed retrospective data from 25 adults with medically-refractory focal epilepsy implanted with the RNS System. Chronic electrocorticography was used to record electrographic seizures, and hidden Markov models decoded seizures into fluctuations in underlying risk. State-dependent associations of RNS System stimulation parameters with changes in risk were estimated. RESULTS: Higher charge density was associated with improved outcomes, both for remaining in a low seizure risk state and for transitioning from a high to a low seizure risk state. The effect of stimulation frequency depended on initial seizure risk state: when starting in a low risk state, higher stimulation frequencies were associated with remaining in a low risk state, but when starting in a high risk state, lower stimulation frequencies were associated with transition to a low risk state. Findings were consistent across bipolar and monopolar stimulation configurations. CONCLUSION: The impact of RNS on seizure frequency exhibits state-dependence, such that stimulation parameters which are effective in one seizure risk state may not be effective in another. These findings represent conceptual advances in understanding the therapeutic mechanism of RNS, and directly inform current practices of RNS tuning and the development of next-generation neurostimulation systems.

BVAR-Connect: A Variational Bayes Approach to Multi-Subject Vector Autoregressive Models for Inference on Brain Connectivity Networks.

In this paper we propose BVAR-connect, a variational inference approach to a Bayesian multi-subject vector autoregressive (VAR) model for inference on effective brain connectivity based on resting-state functional MRI data. The modeling framework uses a Bayesian variable selection approach that flexibly integrates multi-modal data, in particular structural diffusion tensor imaging (DTI) data, into the prior construction. The variational inference approach we develop allows scalability of the methods and results in the ability to estimate subject- and group-level brain connectivity networks over whole-brain parcellations of the data. We provide a brief description of a user-friendly MATLAB GUI released for public use. We assess performance on simulated data, where we show that the proposed inference method can achieve comparable accuracy to the sampling-based Markov Chain Monte Carlo approach but at a much lower computational cost. We also address the case of subject groups with imbalanced sample sizes. Finally, we illustrate the methods on resting-state functional MRI and structural DTI data on children with a history of traumatic injury.