Browsing by Author "Stern, John M."
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Item A Hierarchical Bayesian Model for the Identification of PET Markers Associated to the Prediction of Surgical Outcome after Anterior Temporal Lobe Resection(Frontiers Media S.A., 2017) Chiang, Sharon; Guindani, Michele; Yeh, Hsiang J.; Dewar, Sandra; Haneef, Zulfi; Stern, John M.; Vannucci, MarinaWe develop an integrative Bayesian predictive modeling framework that identifies individual pathological brain states based on the selection of fluoro-deoxyglucose positron emission tomography (PET) imaging biomarkers and evaluates the association of those states with a clinical outcome. We consider data from a study on temporal lobe epilepsy (TLE) patients who subsequently underwent anterior temporal lobe resection. Our modeling framework looks at the observed profiles of regional glucose metabolism in PET as the phenotypic manifestation of a latent individual pathologic state, which is assumed to vary across the population. The modeling strategy we adopt allows the identification of patient subgroups characterized by latent pathologies differentially associated to the clinical outcome of interest. It also identifies imaging biomarkers characterizing the pathological states of the subjects. In the data application, we identify a subgroup of TLE patients at high risk for post-surgical seizure recurrence after anterior temporal lobe resection, together with a set of discriminatory brain regions that can be used to distinguish the latent subgroups. We show that the proposed method achieves high cross-validated accuracy in predicting post-surgical seizure recurrence.Item Epilepsy as a dynamic disease: A Bayesian model for differentiating seizure risk from natural variability(Wiley, 2018) Chiang, Sharon; Vannucci, Marina; Goldenholz, Daniel M.; Moss, Robert; Stern, John M.Objective: A fundamental challenge in treating epilepsy is that changes in observed seizure frequencies do not necessarily reflect changes in underlying seizure risk. Rather, changes in seizure frequency may occur due to probabilistic variation around an underlying seizure risk state caused by normal fluctuations from natural history, leading to seizure unpredictability and potentially suboptimal medication adjustments in epilepsy management. However, no rigorous statistical approach exists to systematically distinguish expected changes in seizure frequency due to natural variability from changes in underlying seizure risk. Methods: Using data from SeizureTracker.com, a patient‐reported seizure diary tool containing over 1.2 million recorded seizures across 8 years, a novel epilepsy seizure risk assessment tool (EpiSAT) employing a Bayesian mixed‐effects hidden Markov model for zero‐inflated count data was developed to estimate changes in underlying seizure risk using patient‐reported seizure diary and clinical measurement data. Accuracy for correctly assessing underlying seizure risk was evaluated through a simulation comparison. Implications for the natural history of tuberous sclerosis complex (TSC) were assessed using data from SeizureTracker.com. Results: EpiSAT led to significant improvement in seizure risk assessment compared to traditional approaches relying solely on observed seizure frequencies. Applied to TSC, four underlying seizure risk states were identified. The expected duration of each state was <12 months, providing a data‐driven estimate of the amount of time a person with TSC would be expected to remain at the same seizure risk level according to the natural course of epilepsy. Significance: We propose a novel Bayesian statistical approach for evaluating seizure risk on an individual patient level using patient‐reported seizure diaries, which allows for the incorporation of external clinical variables to assess impact on seizure risk. This tool may improve the ability to distinguish true changes in seizure risk from natural variations in seizure frequency in clinical practice. Incorporation of systematic statistical approaches into antiepileptic drug (AED) management may help improve understanding of seizure unpredictability as well as timing of treatment interventions for people with epilepsy.Item Temporal and spectral characteristics of dynamic functional connectivity between resting-state networks reveal information beyond static connectivity(Public Library of Science, 2018) Chiang, Sharon; Vankov, Emilian R.; Yeh, Hsiang J.; Guindani, Michele; Vannucci, Marina; Haneef, Zulfi; Stern, John M.Estimation of functional connectivity (FC) has become an increasingly powerful tool for investigating healthy and abnormal brain function. Static connectivity, in particular, has played a large part in guiding conclusions from the majority of resting-state functional MRI studies. However, accumulating evidence points to the presence of temporal fluctuations in FC, leading to increasing interest in estimating FC as a dynamic quantity. One central issue that has arisen in this new view of connectivity is the dramatic increase in complexity caused by dynamic functional connectivity (dFC) estimation. To computationally handle this increased complexity, a limited set of dFC properties, primarily the mean and variance, have generally been considered. Additionally, it remains unclear how to integrate the increased information from dFC into pattern recognition techniques for subject-level prediction. In this study, we propose an approach to address these two issues based on a large number of previously unexplored temporal and spectral features of dynamic functional connectivity. A Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model is used to estimate time-varying patterns of functional connectivity between resting-state networks. Time-frequency analysis is then performed on dFC estimates, and a large number of previously unexplored temporal and spectral features drawn from signal processing literature are extracted for dFC estimates. We apply the investigated features to two neurologic populations of interest, healthy controls and patients with temporal lobe epilepsy, and show that the proposed approach leads to substantial increases in predictive performance compared to both traditional estimates of static connectivity as well as current approaches to dFC. Variable importance is assessed and shows that there are several quantities that can be extracted from dFC signal which are more informative than the traditional mean or variance of dFC. This work illuminates many previously unexplored facets of the dynamic properties of functional connectivity between resting-state networks, and provides a platform for dynamic functional connectivity analysis that facilitates its usage as an investigative measure for healthy as well as abnormal brain function.Item Time-dependence of graph theory metrics in functional connectivity analysis(Elsevier, 2016) Chiang, Sharon; Cassese, Alberto; Guindani, Michele; Vannucci, Marina; Yeh, Hsiang J.; Haneef, Zulfi; Stern, John M.Brain graphs provide a useful way to computationally model the network structure of the connectome, and this has led to increasing interest in the use ofᅠgraph theoryᅠto quantitate and investigate the topological characteristics of the healthy brain and brain disorders on the network level. The majority of graph theory investigations of functional connectivity have relied on the assumption of temporal stationarity. However, recent evidence increasingly suggests that functional connectivity fluctuates over the length of the scan. In this study, we investigate the stationarity of brain network topology using a Bayesianᅠhidden Markov modelᅠ(HMM) approach that estimates the dynamic structure of graph theoretical measures of whole-brain functional connectivity. In addition to extracting the stationary distribution and transition probabilities of commonly employed graph theory measures, we propose two estimators of temporal stationarity: theᅠS-index andᅠN-index. These indexes can be used to quantify different aspects of the temporal stationarity of graph theory measures. We apply the method and proposed estimators to resting-stateᅠfunctional MRIᅠdata from healthy controls and patients withᅠtemporal lobe epilepsy. Our analysis shows that several graph theory measures, including small-world index, global integration measures, and betweenness centrality, may exhibit greater stationarity over time and therefore be more robust. Additionally, we demonstrate that accounting for subject-level differences in the level of temporal stationarity of network topology may increase discriminatory power in discriminating between disease states. Our results confirm and extend findings from other studies regarding the dynamic nature of functional connectivity, and suggest that using statistical models which explicitly account for the dynamic nature of functional connectivity in graph theory analyses may improve the sensitivity of investigations and consistency across investigations.