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      Voxelwise distribution of acute ischemic stroke lesions in patients with newly diagnosed atrial fibrillation: Trigger of arrhythmia or only target of embolism?

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          Abstract

          Objective

          Atrial fibrillation (AF) is frequently detected after ischemic stroke for the first time, and brain regions involved in autonomic control have been suspected to trigger AF. We examined whether specific brain regions are associated with newly detected AF after ischemic stroke.

          Methods

          Patients with acute cerebral infarctions on diffusion-weighted magnetic resonance imaging were included in this lesion mapping study. Lesions were mapped and modeled voxelwise using Bayesian Spatial Generalised Linear Mixed Modeling to determine differences in infarct locations between stroke patients with new AF, without AF and with AF already known before the stroke.

          Results

          582 patients were included (median age 68 years; 63.2% male). AF was present in 109/582 patients [(18.7%); new AF: 39/109 (35.8%), known AF: 70/109 (64.2%)]. AF patients had larger infarct volumes than patients without AF (mean: 29.7 ± 45.8 ml vs. 15.2 ± 35.1 ml; p<0.001). Lesions in AF patients accumulated in the right central middle cerebral artery territory. Increasing stroke size predicted progressive cortical but not pontine and thalamic involvement. Patients with new AF had more frequently lesions in the right insula compared to patients without AF when stroke size was not accounted for, but no specific brain region was more frequently involved after adjustment for infarct volume. Controlled for stroke size, left parietal involvement was less likely for patients with new AF than for those without AF or with known AF.

          Conclusions

          In the search for brain areas potentially triggering cardiac arrhythmias infarct size should be accounted for. After controlling for infarct size, there is currently no evidence that ischemic stroke lesions of specific brain areas are associated with new AF compared to patients without AF. This challenges the neurogenic hypothesis of AF according to which a relevant proportion of new AF is triggered by ischemic brain lesions of particular locations.

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          Most cited references20

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          Controlling the familywise error rate in functional neuroimaging: a comparative review.

          Functional neuroimaging data embodies a massive multiple testing problem, where 100,000 correlated test statistics must be assessed. The familywise error rate, the chance of any false positives is the standard measure of Type I errors in multiple testing. In this paper we review and evaluate three approaches to thresholding images of test statistics: Bonferroni, random field and the permutation test. Owing to recent developments, improved Bonferroni procedures, such as Hochberg's methods, are now applicable to dependent data. Continuous random field methods use the smoothness of the image to adapt to the severity of the multiple testing problem. Also, increased computing power has made both permutation and bootstrap methods applicable to functional neuroimaging. We evaluate these approaches on t images using simulations and a collection of real datasets. We find that Bonferroni-related tests offer little improvement over Bonferroni, while the permutation method offers substantial improvement over the random field method for low smoothness and low degrees of freedom. We also show the limitations of trying to find an equivalent number of independent tests for an image of correlated test statistics.
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            The brain-heart connection.

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              Neural control of the heart: recent concepts and clinical correlations.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 May 2017
                2017
                : 12
                : 5
                : e0177474
                Affiliations
                [1 ]Department of Neurology, University of Heidelberg, Heidelberg, Germany
                [2 ]Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany
                [3 ]Oxford Centre for Functional MRI of the Brain, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
                [4 ]Department of Neuroradiology, University of Würzburg, Würzburg, Germany
                [5 ]Department of Biostatistics, University of Michigan, Ann Arbor, United States of America
                [6 ]Department of Statistics & Warwick Manufacturing Group, University of Warwick, Coventry, United Kingdom
                [7 ]Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany
                [8 ]Department of Stroke Medicine, Imperial College London, London, United Kingdom
                Fraunhofer Research Institution of Marine Biotechnology, GERMANY
                Author notes

                Competing Interests: TR has received consulting honoraria, speakers honoraria and travel support outside this work from BMS Pfizer, Boehringer Ingelheim, Bayer HealthCare and Daiichi Sankyo. AJB has been supported by the German Research Council (Deutsche Forschungsgemeinschaft), the Doppelfeld Foundation and has received travel support from Bayer HealthCare and the International Society for Magnetic Resonance In Medicine (ISMRM). TDJ has been supported in part by NIH Grant 5-R01-NS-075066-05. The work presented in this manuscript represents the views of the authors and not necessarily that of the NIH. Felix Dittgen reports no competing interests. TEN has been supported in part by NIH Grant 5-R01-NS-075066-05, the United Kingdom’s Medical Research Council Grant G0900908 and the Wellcome Trust. The work presented in this manuscript represents the views of the authors and not necessarily that of the NIH, UKMRC or the Wellcome Trust. UM reports no competing interests. RV received consulting honoraria, research support, travel grants, and speakers’ honoraria outside this work from Bayer HealthCare, Boehringer Ingelheim, BMS Pfizer, Daiichi Sankyo, Roche Diagnostics, St. Jude Medical, Apoplexmedical technologies, Medtronic, Sanofi Aventis Morphosys, Amgen and owns Bayer shares. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                • Conceptualization: TR AJB RV.

                • Data curation: TR AJB TDJ FD TEN RV.

                • Formal analysis: TR AJB TDJ TEN RV.

                • Investigation: TR AJB TDJ FD TEN RV.

                • Methodology: TR AJB TDJ FD TEN UM RV.

                • Project administration: TR AJB RV.

                • Resources: TR AJB TDJ FD TEN RV.

                • Software: AJB DTJ FD TEN.

                • Supervision: TRT AJB RV.

                • Validation: TR AJB TDJ TEN UM RV.

                • Visualization: TR AJB TDJ TEN RV.

                • Writing – original draft: TR AJB RV.

                • Writing – review & editing: TR AJB TDJ FD TEN UM RV.

                Author information
                http://orcid.org/0000-0002-7250-4668
                Article
                PONE-D-16-51620
                10.1371/journal.pone.0177474
                5443524
                28542605
                76e6aaa1-03dd-47ec-b75f-2fd68bfa4643
                © 2017 Rizos et al

                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.

                History
                : 31 December 2016
                : 27 April 2017
                Page count
                Figures: 6, Tables: 2, Pages: 17
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001661, Universität Heidelberg;
                Award ID: for details c.p. cover letter an revised manuscript
                This work was supported by the University of Heidelberg. The funding source provided support in the form of salaries for authors [TR, AB, RV], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Neurology
                Cerebrovascular Diseases
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Vascular Medicine
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Medicine and Health Sciences
                Neurology
                Cerebrovascular Diseases
                Stroke
                Medicine and Health Sciences
                Vascular Medicine
                Stroke
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Lesions
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Lesions
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Neurology
                Cerebral Ischemia
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Biology and Life Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Arteries
                Cerebral Arteries
                Medicine and Health Sciences
                Anatomy
                Cardiovascular Anatomy
                Blood Vessels
                Arteries
                Cerebral Arteries
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                Data are available from https://osf.io/4qfgj/.

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