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      Normative model detects abnormal functional connectivity in psychiatric disorders

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          Abstract

          Introduction

          The diagnosis of psychiatric disorders is mostly based on the clinical evaluation of the patient's signs and symptoms. Deep learning binary-based classification models have been developed to improve the diagnosis but have not yet reached clinical practice, in part due to the heterogeneity of such disorders. Here, we propose a normative model based on autoencoders.

          Methods

          We trained our autoencoder on resting-state functional magnetic resonance imaging (rs-fMRI) data from healthy controls. The model was then tested on schizophrenia (SCZ), bipolar disorder (BD), and attention-deficit hyperactivity disorder (ADHD) patients to estimate how each patient deviated from the norm and associate it with abnormal functional brain networks' (FBNs) connectivity. Rs-fMRI data processing was conducted within the FMRIB Software Library (FSL), which included independent component analysis and dual regression. Pearson's correlation coefficients between the extracted blood oxygen level-dependent (BOLD) time series of all FBNs were calculated, and a correlation matrix was generated for each subject.

          Results and discussion

          We found that the functional connectivity related to the basal ganglia network seems to play an important role in the neuropathology of BD and SCZ, whereas in ADHD, its role is less evident. Moreover, the abnormal connectivity between the basal ganglia network and the language network is more specific to BD. The connectivity between the higher visual network and the right executive control and the connectivity between the anterior salience network and the precuneus networks are the most relevant in SCZ and ADHD, respectively. The results demonstrate that the proposed model could identify functional connectivity patterns that characterize different psychiatric disorders, in agreement with the literature. The abnormal connectivity patterns from the two independent SCZ groups of patients were similar, demonstrating that the presented normative model was also generalizable. However, the group-level differences did not withstand individual-level analysis implying that psychiatric disorders are highly heterogeneous. These findings suggest that a precision-based medical approach, focusing on each patient's specific functional network changes may be more beneficial than the traditional group-based diagnostic classification.

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          Most cited references53

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          FSL.

          FSL (the FMRIB Software Library) is a comprehensive library of analysis tools for functional, structural and diffusion MRI brain imaging data, written mainly by members of the Analysis Group, FMRIB, Oxford. For this NeuroImage special issue on "20 years of fMRI" we have been asked to write about the history, developments and current status of FSL. We also include some descriptions of parts of FSL that are not well covered in the existing literature. We hope that some of this content might be of interest to users of FSL, and also maybe to new research groups considering creating, releasing and supporting new software packages for brain image analysis. Copyright © 2011 Elsevier Inc. All rights reserved.
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            The organization of the human cerebral cortex estimated by intrinsic functional connectivity.

            Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.
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              Decoding subject-driven cognitive states with whole-brain connectivity patterns.

              Decoding specific cognitive states from brain activity constitutes a major goal of neuroscience. Previous studies of brain-state classification have focused largely on decoding brief, discrete events and have required the timing of these events to be known. To date, methods for decoding more continuous and purely subject-driven cognitive states have not been available. Here, we demonstrate that free-streaming subject-driven cognitive states can be decoded using a novel whole-brain functional connectivity analysis. Ninety functional regions of interest (ROIs) were defined across 14 large-scale resting-state brain networks to generate a 3960 cell matrix reflecting whole-brain connectivity. We trained a classifier to identify specific patterns of whole-brain connectivity as subjects rested quietly, remembered the events of their day, subtracted numbers, or (silently) sang lyrics. In a leave-one-out cross-validation, the classifier identified these 4 cognitive states with 84% accuracy. More critically, the classifier achieved 85% accuracy when identifying these states in a second, independent cohort of subjects. Classification accuracy remained high with imaging runs as short as 30-60 s. At all temporal intervals assessed, the 90 functionally defined ROIs outperformed a set of 112 commonly used structural ROIs in classifying cognitive states. This approach should enable decoding a myriad of subject-driven cognitive states from brief imaging data samples.

                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                15 February 2023
                2023
                : 14
                : 1068397
                Affiliations
                Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon , Lisbon, Portugal
                Author notes

                Edited by: Francisco Xavier Castellanos, Grossman School of Medicine, New York University, United States

                Reviewed by: Hugo Schnack, Utrecht University, Netherlands; Hsiang-Yuan Lin, University of Toronto, Canada

                *Correspondence: Duarte Oliveira-Saraiva ✉ dfsaraiva@ 123456fc.ul.pt

                This article was submitted to Neuroimaging, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2023.1068397
                9975396
                36873218
                88655088-60c4-42cd-a446-6ce83c99971e
                Copyright © 2023 Oliveira-Saraiva and Ferreira.

                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
                : 12 October 2022
                : 23 January 2023
                Page count
                Figures: 10, Tables: 4, Equations: 4, References: 53, Pages: 16, Words: 11111
                Funding
                This work was financially supported by Fundação para a Ciência e Tecnologia (FCT) under the projects UIDB/00645/2020 and DSAIPA/DS/0065/2018. The funder had no role in the study design, data processing, and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                normative model,functional brain network,deep learning,psychiatric disorders,functional connectivity

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