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      Towards artificial intelligence in mental health by improving schizophrenia prediction with multiple brain parcellation ensemble-learning

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          Abstract

          In the literature, there are substantial machine learning attempts to classify schizophrenia based on alterations in resting-state (RS) brain patterns using functional magnetic resonance imaging (fMRI). Most earlier studies modelled patients undergoing treatment, entailing confounding with drug effects on brain activity, and making them less applicable to real-world diagnosis at the point of first medical contact. Further, most studies with classification accuracies >80% are based on small sample datasets, which may be insufficient to capture the heterogeneity of schizophrenia, limiting generalization to unseen cases. In this study, we used RS fMRI data collected from a cohort of antipsychotic drug treatment-naive patients meeting DSM IV criteria for schizophrenia ( N = 81) as well as age- and sex-matched healthy controls ( N = 93). We present an ensemble model -- EMPaSchiz (read as ‘Emphasis’; standing for ‘Ensemble algorithm with Multiple Parcellations for Schizophrenia prediction’) that stacks predictions from several ‘single-source’ models, each based on features of regional activity and functional connectivity, over a range of different a priori parcellation schemes. EMPaSchiz yielded a classification accuracy of 87% (vs. chance accuracy of 53%), which out-performs earlier machine learning models built for diagnosing schizophrenia using RS fMRI measures modelled on large samples ( N > 100). To our knowledge, EMPaSchiz is first to be reported that has been trained and validated exclusively on data from drug-naive patients diagnosed with schizophrenia. The method relies on a single modality of MRI acquisition and can be readily scaled-up without needing to rebuild parcellation maps from incoming training images.

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          Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

          In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.
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            Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia.

            The clinical hallmark of schizophrenia is psychosis. The objective of this overview is to link the neurobiology (brain), the phenomenological experience (mind), and pharmacological aspects of psychosis-in-schizophrenia into a unitary framework. Current ideas regarding the neurobiology and phenomenology of psychosis and schizophrenia, the role of dopamine, and the mechanism of action of antipsychotic medication were integrated to develop this framework. A central role of dopamine is to mediate the "salience" of environmental events and internal representations. It is proposed that a dysregulated, hyperdopaminergic state, at a "brain" level of description and analysis, leads to an aberrant assignment of salience to the elements of one's experience, at a "mind" level. Delusions are a cognitive effort by the patient to make sense of these aberrantly salient experiences, whereas hallucinations reflect a direct experience of the aberrant salience of internal representations. Antipsychotics "dampen the salience" of these abnormal experiences and by doing so permit the resolution of symptoms. The antipsychotics do not erase the symptoms but provide the platform for a process of psychological resolution. However, if antipsychotic treatment is stopped, the dysregulated neurochemistry returns, the dormant ideas and experiences become reinvested with aberrant salience, and a relapse occurs. The article provides a heuristic framework for linking the psychological and biological in psychosis. Predictions of this hypothesis, particularly regarding the possibility of synergy between psychological and pharmacological therapies, are presented. The author describes how the hypothesis is complementary to other ideas about psychosis and also discusses its limitations.
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              Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review.

              Standard univariate analysis of neuroimaging data has revealed a host of neuroanatomical and functional differences between healthy individuals and patients suffering a wide range of neurological and psychiatric disorders. Significant only at group level however these findings have had limited clinical translation, and recent attention has turned toward alternative forms of analysis, including Support-Vector-Machine (SVM). A type of machine learning, SVM allows categorisation of an individual's previously unseen data into a predefined group using a classification algorithm, developed on a training data set. In recent years, SVM has been successfully applied in the context of disease diagnosis, transition prediction and treatment prognosis, using both structural and functional neuroimaging data. Here we provide a brief overview of the method and review those studies that applied it to the investigation of Alzheimer's disease, schizophrenia, major depression, bipolar disorder, presymptomatic Huntington's disease, Parkinson's disease and autistic spectrum disorder. We conclude by discussing the main theoretical and practical challenges associated with the implementation of this method into the clinic and possible future directions. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                +1 780 862 2735 , kalmady@ualberta.ca
                +91 (80) 26995256 , gvs@nimhans.ac.in
                Journal
                NPJ Schizophr
                NPJ Schizophr
                NPJ Schizophrenia
                Nature Publishing Group UK (London )
                2334-265X
                18 January 2019
                18 January 2019
                2019
                : 5
                : 2
                Affiliations
                [1 ]GRID grid.17089.37, Alberta Machine Intelligence Institute, , Department of Computing Science, University of Alberta, ; Edmonton, AB Canada
                [2 ]GRID grid.17089.37, Department of Psychiatry, , University of Alberta, ; Edmonton, AB Canada
                [3 ]ISNI 0000 0001 1516 2246, GRID grid.416861.c, The Schizophrenia Clinic, Department of Psychiatry, , National Institute of Mental Health and Neuro Sciences, ; Bangalore, India
                [4 ]ISNI 0000 0001 1516 2246, GRID grid.416861.c, Translational Psychiatry Laboratory, Neurobiology Research Centre, , National Institute of Mental Health and Neuro Sciences, ; Bangalore, India
                Author information
                http://orcid.org/0000-0002-4876-9121
                Article
                70
                10.1038/s41537-018-0070-8
                6386753
                30659193
                c7e1125f-e73e-498b-a03f-b6525ccc1c1e
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 6 March 2018
                : 6 December 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004489, Mitacs;
                Award ID: IT09558
                Award Recipient :
                Funded by: IBM Center for Advanced Studies
                Funded by: Alberta Machine Intelligence Institute Natural Sciences and Engineering Research Council, Canada
                Funded by: FundRef https://doi.org/10.13039/501100001411, Indian Council of Medical Research (ICMR);
                Award ID: DHR/HRD/Young Scientist/Type-VI-(2)/2015
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100001409, Department of Science and Technology, Ministry of Science and Technology (DST);
                Award ID: DST/SJF/LSA-02/2014-15
                Award Recipient :
                Funded by: Wellcome Trust / DBT India Alliance (500236/Z/11/Z)
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                © The Author(s) 2019

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