Automated Recognition of Brain Region Mentions in Neuroscience Literature

The ability to computationally extract mentions of neuroanatomical regions from the literature would assist linking to other entities within and outside of an article. Examples include extracting reports of connectivity or region-specific gene expression. To facilitate text mining of neuroscience literature we have created a corpus of manually annotated brain region mentions. The corpus contains 1,377 abstracts with 18,242 brain region annotations. Interannotator agreement was evaluated for a subset of the documents, and was 90.7% and 96.7% for strict and lenient matching respectively. We observed a large vocabulary of over 6,000 unique brain region terms and 17,000 words. For automatic extraction of brain region mentions we evaluated simple dictionary methods and complex natural language processing techniques. The dictionary methods based on neuroanatomical lexicons recalled 36% of the mentions with 57% precision. The best performance was achieved using a conditional random field (CRF) with a rich feature set. Features were based on morphological, lexical, syntactic and contextual information. The CRF recalled 76% of mentions at 81% precision, by counting partial matches recall and precision increase to 86% and 92% respectively. We suspect a large amount of error is due to coordinating conjunctions, previously unseen words and brain regions of less commonly studied organisms. We found context windows, lemmatization and abbreviation expansion to be the most informative techniques. The corpus is freely available at http://www.chibi.ubc.ca/WhiteText/

Hyper-connectivity of functional networks for brain disease diagnosis

Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer’s disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also help discover disease-related biomarkers important for disease diagnosis

Identification of Proper and Common Names in the Anterior Temporal Lobe: An FMRI Study

Temporal lobe epilepsy is a neurological disease that affects millions of individuals worldwide. They are usually treated through surgical resection of portions of the anterior temporal lobe (ATL). Surgical resection is effective for seizure control, but produces language and verbal memory deficits such as anomic aphasia, which adversely affects an individual\u27s quality of life. The purpose of this study was to develop a functional MRI protocol for mapping the function of ATL in healthy subjects, and to better understand the role of the ATL and other regions of the semantic system. Such a protocol may ultimately be used by surgeons to predict and reduce or prevent side effects of cognitive decline that occur after ATL resection in epilepsy patients. The aims were: (1) To study the ATL response to associations with abstract and concrete concepts and (2) To study the ATL response to names of people and places, and the information associated with these names. Our results indicated that ATL and inferior parietal areas are modulated by the amount of information associated with proper names. ATL is activated for abstract and concrete words relative to nonwords but is not modulated by associative measures. Angular and posterior cingulate gyri, on the other hand, are modulated by information associated with both common and proper names, underlining their role in semantic representations. A very high degree of overlap between person- and word-specific networks suggests that a common semantic system underlies both types of knowledge, rather than segregation of social and non-social knowledge. These results also demonstrate robust activation of ATL by proper and common names, and point to their potential use in mapping eloquent and functionally relevant cortex in epilepsy patients

A Knowledge-based Integrative Modeling Approach for <em>In-Silico</em> Identification of Mechanistic Targets in Neurodegeneration with Focus on Alzheimer’s Disease

Dementia is the progressive decline in cognitive function due to damage or disease in the body beyond what might be expected from normal aging. Based on neuropathological and clinical criteria, dementia includes a spectrum of diseases, namely Alzheimer's dementia, Parkinson's dementia, Lewy Body disease, Alzheimer's dementia with Parkinson's, Pick's disease, Semantic dementia, and large and small vessel disease. It is thought that these disorders result from a combination of genetic and environmental risk factors. Despite accumulating knowledge that has been gained about pathophysiological and clinical characteristics of the disease, no coherent and integrative picture of molecular mechanisms underlying neurodegeneration in Alzheimer’s disease is available. Existing drugs only offer symptomatic relief to the patients and lack any efficient disease-modifying effects. The present research proposes a knowledge-based rationale towards integrative modeling of disease mechanism for identifying potential candidate targets and biomarkers in Alzheimer’s disease. Integrative disease modeling is an emerging knowledge-based paradigm in translational research that exploits the power of computational methods to collect, store, integrate, model and interpret accumulated disease information across different biological scales from molecules to phenotypes. It prepares the ground for transitioning from ‘descriptive’ to “mechanistic” representation of disease processes. The proposed approach was used to introduce an integrative framework, which integrates, on one hand, extracted knowledge from the literature using semantically supported text-mining technologies and, on the other hand, primary experimental data such as gene/protein expression or imaging readouts. The aim of such a hybrid integrative modeling approach was not only to provide a consolidated systems view on the disease mechanism as a whole but also to increase specificity and sensitivity of the mechanistic model by providing disease-specific context. This approach was successfully used for correlating clinical manifestations of the disease to their corresponding molecular events and led to the identification and modeling of three important mechanistic components underlying Alzheimer’s dementia, namely the CNS, the immune system and the endocrine components. These models were validated using a novel in-silico validation method, namely biomarker-guided pathway analysis and a pathway-based target identification approach was introduced, which resulted in the identification of the MAPK signaling pathway as a potential candidate target at the crossroad of the triad components underlying disease mechanism in Alzheimer’s dementia

The structural neurobiology of social anxiety disorder : a clinical neuroimaging study

Includes bibliographical referencesWhile a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), comparatively few studies have investigated the structural underpinnings in SAD. 18 psychopharmacologically and psychotherapeutically naïve adult patients with a primary Axis I diagnosis of generalized social anxiety disorder and 18 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. A manual tracing protocol was specifically developed to compute the volume of the most prominent subcortical gray matter structures implicated in SAD by previous functional research. Cortical thickness was estimated using an automated algorithm and whole brain analyses of white matter structure were performed using FSL's tract - based spatial statistics comparing fractional anisotropy (FA), mean diffusivity (MD) in individuals with SAD. Manual tracing demonstrated that compared to controls, SAD patients showed an enlarged right globus pallidus. Cortical thickness analyses demonstrated significant cortical thinning in the left isthmus of the cingulate gyrus, the left temporal pole, and the left superior temporal gyrus. Analyses of white matter tractographic data demonstrated reduced FA in in the genu, splenium and tapetum of the corpus callosum. Additionally reduced FA was noticed in the fornix and the right cingulum. Reduced FA was also noted in bilateral corticospinal tracts and the right corona radiata. The results demonstrate structural alterations in limbic circuitry as well as involvement of the basal glanglia and their cortical projections and input pathways

Agile in-litero experiments:how can semi-automated information extraction from neuroscientific literature help neuroscience model building?

In neuroscience, as in many other scientific domains, the primary form of knowledge dissemination is through published articles in peer-reviewed journals. One challenge for modern neuroinformatics is to design methods to make the knowledge from the tremendous backlog of publications accessible for search, analysis and its integration into computational models. In this thesis, we introduce novel natural language processing (NLP) models and systems to mine the neuroscientific literature. In addition to in vivo, in vitro or in silico experiments, we coin the NLP methods developed in this thesis as in litero experiments, aiming at analyzing and making accessible the extended body of neuroscientific literature. In particular, we focus on two important neuroscientific entities: brain regions and neural cells. An integrated NLP model is designed to automatically extract brain region connectivity statements from very large corpora. This system is applied to a large corpus of 25M PubMed abstracts and 600K full-text articles. Central to this system is the creation of a searchable database of brain region connectivity statements, allowing neuroscientists to gain an overview of all brain regions connected to a given region of interest. More importantly, the database enables researcher to provide feedback on connectivity results and links back to the original article sentence to provide the relevant context. The database is evaluated by neuroanatomists on real connectomics tasks (targets of Nucleus Accumbens) and results in significant effort reduction in comparison to previous manual methods (from 1 week to 2h). Subsequently, we introduce neuroNER to identify, normalize and compare instances of identify neuronsneurons in the scientific literature. Our method relies on identifying and analyzing each of the domain features used to annotate a specific neuron mention, like the morphological term 'basket' or brain region 'hippocampus'. We apply our method to the same corpus of 25M PubMed abstracts and 600K full-text articles and find over 500K unique neuron type mentions. To demonstrate the utility of our approach, we also apply our method towards cross-comparing the NeuroLex and Human Brain Project (HBP) cell type ontologies. By decoupling a neuron mention's identity into its specific compositional features, our method can successfully identify specific neuron types even if they are not explicitly listed within a predefined neuron type lexicon, thus greatly facilitating cross-laboratory studies. In order to build such large databases, several tools and infrastructureslarge-scale NLP were developed: a robust pipeline to preprocess full-text PDF articles, as well as bluima, an NLP processing pipeline specialized on neuroscience to perform text-mining at PubMed scale. During the development of those two NLP systems, we acknowledged the need for novel NLP approaches to rapidly develop custom text mining solutions. This led to the formalization of the agile text miningagile text-mining methodology to improve the communication and collaboration between subject matter experts and text miners. Agile text mining is characterized by short development cycles, frequent tasks redefinition and continuous performance monitoring through integration tests. To support our approach, we developed Sherlok, an NLP framework designed for the development of agile text mining applications