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      Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction

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          Abstract

          Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD.

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          Most cited references 71

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          A fast diffeomorphic image registration algorithm.

          This paper describes DARTEL, which is an algorithm for diffeomorphic image registration. It is implemented for both 2D and 3D image registration and has been formulated to include an option for estimating inverse consistent deformations. Nonlinear registration is considered as a local optimisation problem, which is solved using a Levenberg-Marquardt strategy. The necessary matrix solutions are obtained in reasonable time using a multigrid method. A constant Eulerian velocity framework is used, which allows a rapid scaling and squaring method to be used in the computations. DARTEL has been applied to intersubject registration of 471 whole brain images, and the resulting deformations were evaluated in terms of how well they encode the shape information necessary to separate male and female subjects and to predict the ages of the subjects.
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            Unified segmentation.

            A probabilistic framework is presented that enables image registration, tissue classification, and bias correction to be combined within the same generative model. A derivation of a log-likelihood objective function for the unified model is provided. The model is based on a mixture of Gaussians and is extended to incorporate a smooth intensity variation and nonlinear registration with tissue probability maps. A strategy for optimising the model parameters is described, along with the requisite partial derivatives of the objective function.
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              Thresholding of statistical maps in functional neuroimaging using the false discovery rate.

              Finding objective and effective thresholds for voxelwise statistics derived from neuroimaging data has been a long-standing problem. With at least one test performed for every voxel in an image, some correction of the thresholds is needed to control the error rates, but standard procedures for multiple hypothesis testing (e.g., Bonferroni) tend to not be sensitive enough to be useful in this context. This paper introduces to the neuroscience literature statistical procedures for controlling the false discovery rate (FDR). Recent theoretical work in statistics suggests that FDR-controlling procedures will be effective for the analysis of neuroimaging data. These procedures operate simultaneously on all voxelwise test statistics to determine which tests should be considered statistically significant. The innovation of the procedures is that they control the expected proportion of the rejected hypotheses that are falsely rejected. We demonstrate this approach using both simulations and functional magnetic resonance imaging data from two simple experiments. (C)2002 Elsevier Science (USA).
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                Author and article information

                Affiliations
                [1 ]Department of Psychiatry, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
                [2 ]School of Psychology, University of New South Wales, Sydney, New South Wales, Australia
                [3 ]Department of Radiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
                Hangzhou Normal University, China
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JK TA YH. Performed the experiments: JK TA FH AY SH HF. Analyzed the data: JK TA. Contributed reagents/materials/analysis tools: TJW TI. Wrote the paper: JK TA YH.

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                24 March 2014
                : 9
                : 3
                PONE-D-13-43360
                10.1371/journal.pone.0092862
                3963974
                24663245

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Counts
                Pages: 8
                Funding
                This study was supported by grants from the Ministry of Health, Labor and Welfare (Kokoro 200400762A, 200500806A, and 200632005A, B) (Dr. Hirayasu), and from the Grant-in-Aid for Young Scientists (B) of the Japan Society for the Promotion of Science (13 25861023) (Dr. Asami) of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Nervous System
                Neuroscience
                Neuroimaging
                Sensory Perception
                Psychology
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Mental Health and Psychiatry
                Anxiety Disorders
                Neurology
                Radiology and Imaging
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Research and Analysis Methods
                Research Design
                Clinical Research Design

                Uncategorized

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