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      Pattern of Reduced Functional Connectivity and Structural Abnormalities in Parkinson’s Disease: An Exploratory Study

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          Abstract

          Background

          MRI brain changes in Parkinson’s disease (PD) are controversial.

          Objectives

          We aimed to describe structural and functional changes in PD.

          Methods

          Sixty-six patients with PD (57.94 ± 10.25 years) diagnosed according to the UK Brain Bank criteria were included. We performed a whole brain analysis using voxel-based morphometry (VBM–SPM 8 software), cortical thickness (CT) using CIVET, and resting-state fMRI using the Neuroimaging Analysis Kit software to compare patients and controls. For VBM and CT we classified subjects into three groups according to disease severity: mild PD [Hoehn and Yahr scale (HY) 1–1.5], moderate PD (HY 2–2.5), and severe PD (HY 3–5).

          Results

          We observed gray matter atrophy in the insula and inferior frontal gyrus in the moderate PD and in the insula, frontal gyrus, putamen, cingulated, and paracingulate gyri in the severe groups. In the CT analysis, in mild PD, cortical thinning was restricted to the superior temporal gyrus, gyrus rectus, and olfactory cortex; in the moderate group, the postcentral gyrus, supplementary motor area, and inferior frontal gyrus were also affected; in the severe PD, areas such as the precentral and postentral gyrus, temporal pole, fusiform, and occipital gyrus had reduced cortical thinning. We observed altered connectivity at the default mode, visual, sensorimotor, and cerebellar networks.

          Conclusion

          Subjects with mild symptoms already have cortical involvement; however, further cerebral involvement seems to follow Braak’s proposed mechanism. Similar regions are affected both structurally and functionally. We believe the combination of different MRI techniques may be useful in evaluating progressive brain involvement and they may eventually be used as surrogate markers of disease progression.

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          Most cited references22

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          Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space.

          In both diagnostic and research applications, the interpretation of MR images of the human brain is facilitated when different data sets can be compared by visual inspection of equivalent anatomical planes. Quantitative analysis with predefined atlas templates often requires the initial alignment of atlas and image planes. Unfortunately, the axial planes acquired during separate scanning sessions are often different in their relative position and orientation, and these slices are not coplanar with those in the atlas. We have developed a completely automatic method to register a given volumetric data set with Talairach stereotaxic coordinate system. The registration method is based on multi-scale, three-dimensional (3D) cross-correlation with an average (n > 300) MR brain image volume aligned with the Talariach stereotaxic space. Once the data set is re-sampled by the transformation recovered by the algorithm, atlas slices can be directly superimposed on the corresponding slices of the re-sampled volume. the use of such a standardized space also allows the direct comparison, voxel to voxel, of two or more data sets brought into stereotaxic space. With use of a two-tailed Student t test for paired samples, there was no significant difference in the transformation parameters recovered by the automatic algorithm when compared with two manual landmark-based methods (p > 0.1 for all parameters except y-scale, where p > 0.05). Using root-mean-square difference between normalized voxel intensities as an unbiased measure of registration, we show that when estimated and averaged over 60 volumetric MR images in standard space, this measure was 30% lower for the automatic technique than the manual method, indicating better registrations. Likewise, the automatic method showed a 57% reduction in standard deviation, implying a more stable technique. The algorithm is able to recover the transformation even when data are missing from the top or bottom of the volume. We present a fully automatic registration method to map volumetric data into stereotaxic space that yields results comparable with those of manually based techniques. The method requires no manual identification of points or contours and therefore does not suffer the drawbacks involved in user intervention such as reproducibility and interobserver variability.
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            Multi-level bootstrap analysis of stable clusters in resting-state fMRI.

            A variety of methods have been developed to identify brain networks with spontaneous, coherent activity in resting-state functional magnetic resonance imaging (fMRI). We propose here a generic statistical framework to quantify the stability of such resting-state networks (RSNs), which was implemented with k-means clustering. The core of the method consists in bootstrapping the available datasets to replicate the clustering process a large number of times and quantify the stable features across all replications. This bootstrap analysis of stable clusters (BASC) has several benefits: (1) it can be implemented in a multi-level fashion to investigate stable RSNs at the level of individual subjects and at the level of a group; (2) it provides a principled measure of RSN stability; and (3) the maximization of the stability measure can be used as a natural criterion to select the number of RSNs. A simulation study validated the good performance of the multi-level BASC on purely synthetic data. Stable networks were also derived from a real resting-state study for 43 subjects. At the group level, seven RSNs were identified which exhibited a good agreement with the previous findings from the literature. The comparison between the individual and group-level stability maps demonstrated the capacity of BASC to establish successful correspondences between these two levels of analysis and at the same time retain some interesting subject-specific characteristics, e.g. the specific involvement of subcortical regions in the visual and fronto-parietal networks for some subjects. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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              Parkinson's Disease Society Brain Bank, London: overview and research.

              The UK Parkinson's Disease Society Brain Bank receives tissue from patients with Parkinson's disease and a variety of different movement disorders. Half of the brain is used for full neuropathological examination prior to allocation for specific research projects. Clinical misdiagnosis occurs in a significant proportion of cases and clinico-pathological correlation provides valuable information for disease recognition. With the expanding number of other specialist brain banks there is a need for agreement on diagnostic criteria. Furthermore, awareness of different methods of tissue handling is essential.
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                Author and article information

                Contributors
                URI : http://frontiersin.org/people/u/201136
                URI : http://frontiersin.org/people/u/201094
                URI : http://frontiersin.org/people/u/45344
                URI : http://frontiersin.org/people/u/201142
                URI : http://frontiersin.org/people/u/201115
                URI : http://frontiersin.org/people/u/117269
                URI : http://frontiersin.org/people/u/391645
                URI : http://frontiersin.org/people/u/201105
                URI : http://frontiersin.org/people/u/8789
                URI : http://frontiersin.org/people/u/72124
                Journal
                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                1664-2295
                13 January 2017
                2016
                : 7
                : 243
                Affiliations
                [1] 1Department of Neurology, University of Campinas , Campinas, Brazil
                [2] 2Laboratory of Neuroimaging, University of Campinas , Campinas, Brazil
                [3] 3Montreal Neurological Institute, Brain Imaging Center, McGill University , Montreal, QC, Canada
                [4] 4Department of Radiology, University of Campinas , Campinas, Brazil
                Author notes

                Edited by: Antonio Pisani, University of Rome Tor Vergata, Italy

                Reviewed by: Benito De Celis Alonso, BUAP, Mexico; Graziella Madeo, University of Rome Tor Vergata, Italy

                *Correspondence: Fernando Cendes, fcendes@ 123456gmail.com

                Specialty section: This article was submitted to Movement Disorders, a section of the journal Frontiers in Neurology

                Article
                10.3389/fneur.2016.00243
                5233672
                28133455
                c4fd470e-3017-48e5-8cac-5dcaf0428004
                Copyright © 2017 Guimarães, Arci Santos, Dagher, Campos, Azevedo, Piovesana, De Campos, Larcher, Zeighami, Scarparo Amato-Filho, Cendes and D’Abreu.

                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) or licensor 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
                : 11 October 2016
                : 21 December 2016
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 47, Pages: 9, Words: 6687
                Funding
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo 10.13039/501100001807
                Award ID: 2012/05286-7, 2011/2011/19958-4 and 2013/03358-3
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 10.13039/501100003593
                Award ID: 74873/2010-2
                Categories
                Neuroscience
                Original Research

                Neurology
                parkinson’s disease,neuroimaging,cortical thickness,functional mri,voxel-based morphometry

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