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      Classification and Prediction of Brain Disorders Using Functional Connectivity: Promising but Challenging

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          Abstract

          Brain functional imaging data, especially functional magnetic resonance imaging (fMRI) data, have been employed to reflect functional integration of the brain. Alteration in brain functional connectivity (FC) is expected to provide potential biomarkers for classifying or predicting brain disorders. In this paper, we present a comprehensive review in order to provide guidance about the available brain FC measures and typical classification strategies. We survey the state-of-the-art FC analysis methods including widely used static functional connectivity (SFC) and more recently proposed dynamic functional connectivity (DFC). Temporal correlations among regions of interest (ROIs), data-driven spatial network and functional network connectivity (FNC) are often computed to reflect SFC from different angles. SFC can be extended to DFC using a sliding-window framework, and intrinsic connectivity states along the time-varying connectivity patterns are typically extracted using clustering or decomposition approaches. We also briefly summarize window-less DFC approaches. Subsequently, we highlight various strategies for feature selection including the filter, wrapper and embedded methods. In terms of model building, we include traditional classifiers as well as more recently applied deep learning methods. Moreover, we review representative applications with remarkable classification accuracy for psychosis and mood disorders, neurodevelopmental disorder, and neurological disorders using fMRI data. Schizophrenia, bipolar disorder, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease and mild cognitive impairment (MCI) are discussed. Finally, challenges in the field are pointed out with respect to the inaccurate diagnosis labeling, the abundant number of possible features and the difficulty in validation. Some suggestions for future work are also provided.

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            Deep Learning in Neural Networks: An Overview

            (2014)
            In recent years, deep artificial neural networks (including recurrent ones) have won numerous contests in pattern recognition and machine learning. This historical survey compactly summarises relevant work, much of it from the previous millennium. Shallow and deep learners are distinguished by the depth of their credit assignment paths, which are chains of possibly learnable, causal links between actions and effects. I review deep supervised learning (also recapitulating the history of backpropagation), unsupervised learning, reinforcement learning & evolutionary computation, and indirect search for short programs encoding deep and large networks.
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              A comparison of methods for multiclass support vector machines.

              Support vector machines (SVMs) were originally designed for binary classification. How to effectively extend it for multiclass classification is still an ongoing research issue. Several methods have been proposed where typically we construct a multiclass classifier by combining several binary classifiers. Some authors also proposed methods that consider all classes at once. As it is computationally more expensive to solve multiclass problems, comparisons of these methods using large-scale problems have not been seriously conducted. Especially for methods solving multiclass SVM in one step, a much larger optimization problem is required so up to now experiments are limited to small data sets. In this paper we give decomposition implementations for two such "all-together" methods. We then compare their performance with three methods based on binary classifications: "one-against-all," "one-against-one," and directed acyclic graph SVM (DAGSVM). Our experiments indicate that the "one-against-one" and DAG methods are more suitable for practical use than the other methods. Results also show that for large problems methods by considering all data at once in general need fewer support vectors.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                06 August 2018
                2018
                : 12
                : 525
                Affiliations
                [1] 1The Mind Research Network , Albuquerque, NM, United States
                [2] 2School of Computer & Information Technology, Shanxi University , Taiyuan, China
                [3] 3Department of Electrical and Computer Engineering, University of New Mexico , Albuquerque, NM, United States
                Author notes

                Edited by: Russell A. Poldrack, Stanford University, United States

                Reviewed by: Emily Finn, National Institute of Mental Health (NIMH), United States; Dante R. Chialvo, Center for Complex Systems & Brain Sciences (CEMSC3), Argentina

                *Correspondence: Yuhui Du ydu@ 123456mrn.org

                This article was submitted to Brain Imaging Methods, a section of the journal Frontiers in Neuroscience

                †Co-first author.

                Article
                10.3389/fnins.2018.00525
                6088208
                30127711
                bd25385c-eebe-424a-af73-9c49cf336741
                Copyright © 2018 Du, Fu and Calhoun.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 22 March 2018
                : 12 July 2018
                Page count
                Figures: 4, Tables: 6, Equations: 0, References: 296, Pages: 29, Words: 25321
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: 5P20RR021938/P20GM103472
                Award ID: R01EB020407
                Funded by: National Science Foundation 10.13039/100000001
                Award ID: 1539067
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 61703253
                Funded by: Natural Science Foundation of Shanxi Province 10.13039/501100004480
                Award ID: 2016021077
                Categories
                Neuroscience
                Review

                Neurosciences
                fmri,functional connectivity,biomarker,classification,brain disorders
                Neurosciences
                fmri, functional connectivity, biomarker, classification, brain disorders

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