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Brain functional network connectivity is an important measure for characterizing changes in a variety of neurological disorders, for example Alzheimer’s Disease, Parkinson Disease, and Epilepsy. Epilepsy is a serious neurological disorder affecting more than 50 million persons worldwide with severe impact on the quality of life of patients and their family members due to recurrent seizures. More than 30% of epilepsy patients are refractive to pharmacotherapy and are considered for resection to disrupt epilepsy seizure networks. However, 20-50% of these patients continue to have seizures after surgery. Therefore, there is a critical need to gain new insights into the characteristics of epilepsy seizure networks involving one of more brain regions and accurately delineate epileptogenic zone as a target for surgery. Although there is growing availability of large volume of high resolution stereotactic electroencephalogram (SEEG) data recorded from intracranial electrodes during presurgical evaluation of patients, there are significant informatics challenges associated with processing and analyzing this large signal dataset for characterizing epilepsy seizure networks. In this paper, we describe the development and application of a high-performance indexing structure for efficient retrieval of large-scale SEEG signal data to compute seizure network patterns corresponding to brain functional connectivity networks. This novel Neuro-Integrative Connectivity (NIC) search and retrieval method has been developed by extending the red-black tree index model together with an efficient lookup algorithm. We systematically perform a comparative evaluation of the proposed NIC index using de-identified SEEG data from a patient with temporal lobe epilepsy to retrieve segments of signal data corresponding to multiple seizure events and demonstrate the significant advantages of the NIC index as compared to existing methods. This new NIC Index enables faster computation of brain functional connectivity measures in epilepsy patients for large-scale network analysis and potentially provide new insights into the organization as well as evolution of seizure networks in epilepsy patients. 

The accurate characterization of how different brain structures interact in terms of both structural and functional networks is an area of active research in neuroscience. A better understanding of these interactions can potentially lead to targeted treatments and improved therapies for many neurological disorders, such as epilepsy, which alone affects over 65 million people worldwide. The study of functional connectivity networks in epilepsy, which is characterized by abnormalities in brain electrical activity, will help to provide new insights into the onset and progression of this complex neurological disorder. In this chapter, we discuss statistical signal processing techniques and their use in determining functional connectivity among brain regions exhibiting epileptic activity. We also discuss computational challenges associated with deriving functional connectivity measures from neurological Big Data, and we introduce our highly scalable signal processing pipeline for quantifying functional connectivity with the goal of addressing these challenges and potentially advancing understanding of the underlying mechanisms of epilepsy. This pipeline makes use of a novel signal data format that facilitates storing and retrieving data in a distributed computing environment. We conclude the chapter by describing our current activities and proposed plans for improving our computational pipeline, such as the inclusion of biomedical ontologies for semantic annotation in order to facilitate the integration and retrieval of signal data. 

Provenance metadata describing the source or origin of data is critical to verify and validate results of scientific experiments. Indeed, reproducibility of scientific studies is rapidly gaining significant attention in the research community, for example biomedical and healthcare research. To address this challenge in the biomedical research domain, we have developed the Provenance for Clinical and Healthcare Research (ProvCaRe) using World Wide Web Consortium (W3C) PROV specifications, including the PROV Ontology (PROV-O). In the ProvCaRe project, we are extending PROV-O to create a formal model of provenance information that is necessary for scientific reproducibility and replication in biomedical research. However, there are several challenges associated with the development of the ProvCaRe ontology, including: (1) Ontology engineering: modeling all biomedical provenance-related terms in an ontology has undefined scope and is not feasible before the release of the ontology; (2) Redundancy: there are a large number of existing biomedical ontologies that already model relevant biomedical terms; and (3) Ontology maintenance: adding or deleting terms from a large ontology is error prone and it will be difficult to maintain the ontology over time. Therefore, in contrast to modeling all classes and properties in an ontology before deployment (also called precoordination), we propose the “ProvCaRe Compositional Grammar Syntax” to model ontology classes on-demand (also called postcoordination). The compositional grammar syntax allows us to re-use existing biomedical ontology classes and compose provenance-specific terms that extend PROV-O classes and properties. We demonstrate the application of this approach in the ProvCaRe ontology and the use of the ontology in the development of the ProvCaRe knowledgebase that consists of more than 38 million provenance triples automatically extracted from 384,802 published research articles using a text processing workflow.