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      Implementation of clinically relevant and robust fMRI-based language lateralization: Choosing the laterality index calculation method

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          Abstract

          The assessment of language lateralization has become widely used when planning neurosurgery close to language areas, due to individual specificities and potential influence of brain pathology. Functional magnetic resonance imaging (fMRI) allows non-invasive and quantitative assessment of language lateralization for presurgical planning using a laterality index (LI). However, the conventional method is limited by the dependence of the LI on the chosen activation threshold. To overcome this limitation, different threshold-independent LI calculations have been reported. The purpose of this study was to propose a simplified approach to threshold-independent LI calculation and compare it with three previously reported methods on the same cohort of subjects. Fifteen healthy subjects, who performed picture naming, verb generation, and word fluency tasks, were scanned. LI values were calculated for all subjects using four methods, and considering either the whole hemisphere or an atlas-defined language area. For each method, the subjects were ranked according to the calculated LI values, and the obtained rankings were compared. All LI calculation methods agreed in differentiating strong from weak lateralization on both hemispheric and regional scales (Spearman’s correlation coefficients 0.59–1.00). In general, a more lateralized activation was found in the language area than in the whole hemisphere. The new method is well suited for application in the clinical practice as it is simple to implement, fast, and robust. The good agreement between LI calculation methods suggests that the choice of method is not key. Nevertheless, it should be consistent to allow a relative comparison of language lateralization between subjects.

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          Assignment of functional activations to probabilistic cytoarchitectonic areas revisited.

          Probabilistic cytoarchitectonic maps in standard reference space provide a powerful tool for the analysis of structure-function relationships in the human brain. While these microstructurally defined maps have already been successfully used in the analysis of somatosensory, motor or language functions, several conceptual issues in the analysis of structure-function relationships still demand further clarification. In this paper, we demonstrate the principle approaches for anatomical localisation of functional activations based on probabilistic cytoarchitectonic maps by exemplary analysis of an anterior parietal activation evoked by visual presentation of hand gestures. After consideration of the conceptual basis and implementation of volume or local maxima labelling, we comment on some potential interpretational difficulties, limitations and caveats that could be encountered. Extending and supplementing these methods, we then propose a supplementary approach for quantification of structure-function correspondences based on distribution analysis. This approach relates the cytoarchitectonic probabilities observed at a particular functionally defined location to the areal specific null distribution of probabilities across the whole brain (i.e., the full probability map). Importantly, this method avoids the need for a unique classification of voxels to a single cortical area and may increase the comparability between results obtained for different areas. Moreover, as distribution-based labelling quantifies the "central tendency" of an activation with respect to anatomical areas, it will, in combination with the established methods, allow an advanced characterisation of the anatomical substrates of functional activations. Finally, the advantages and disadvantages of the various methods are discussed, focussing on the question of which approach is most appropriate for a particular situation.
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            Broca's region revisited: cytoarchitecture and intersubject variability.

            The sizes of Brodmann's areas 44 and 45 (Broca's speech region) and their extent in relation to macroscopic landmarks and surrounding areas differ considerably among the available cytoarchitectonic maps. Such variability may be due to intersubject differences in anatomy, observer-dependent discrepancies in cytoarchitectonic mapping, or both. Because a reliable definition of cytoarchitectonic borders is important for interpreting functional imaging data, we mapped areas 44 and 45 by means of an observer-independent technique. In 10 human brains, the laminar distributions of cell densities were measured vertical to the cortical surface in serial coronal sections stained for perikarya. Thousands of density profiles were obtained. Cytoarchitectonic borders were defined as statistically significant changes in laminar patterns. The analysis of the three-dimensional reconstructed brains and the two areas showed that cytoarchitectonic borders did not consistently coincide with sulcal contours. Therefore, macroscopic features are not reliable landmarks of cytoarchitectonic borders. Intersubject variability in the cytoarchitecture of areas 44 and 45 was significantly greater than cytoarchitectonic differences between these areas in individual brains. Although the volumes of area 44 differed across subjects by up to a factor of 10, area 44 but not area 45 was left-over-right asymmetrical in all brains. All five male but only three of five female brains had significantly higher cell densities on the left than on the right side. Such hemispheric and gender differences were not detected in area 45. These morphologic asymmetries of area 44 provide a putative correlate of the functional lateralization of speech production. Copyright 1999 Wiley-Liss, Inc.
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              Decreased volume of left and total anterior insular lobule in schizophrenia.

              The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: SoftwareRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 March 2020
                2020
                : 15
                : 3
                : e0230129
                Affiliations
                [1 ] Department of Biomedical Engineering, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
                [2 ] Department of Neuroradiology, King’s College Hospital, London, United Kingdom
                [3 ] Department of Medical Physics and Bioengineering, NHS Highland, Inverness, United Kingdom
                Linköping University, SWEDEN
                Author notes

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

                Author information
                http://orcid.org/0000-0002-1936-8687
                Article
                PONE-D-19-25144
                10.1371/journal.pone.0230129
                7067428
                32163517
                d2f403ad-da3f-4f75-9124-bf691cfc25b6
                © 2020 Brumer 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
                : 6 September 2019
                : 23 February 2020
                Page count
                Figures: 6, Tables: 2, Pages: 16
                Funding
                This work was carried out at, and supported by, the Department of Neuroradiology at King’s College Hospital NHS Foundation Trust. EDV is supported by the Wellcome/EPSRC Centre for Medical Engineering [WT 203148/Z/16/Z]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Custom metadata
                The reason why the underlying Data cannot be shared publicly is explained below. Subjects were recruited, and informed written consent was obtained, with ethical approval from the UK National Research Ethics Service (REC 04/Q0706/72). Under the UK Health Research Authority (HRA) system the Research Ethics Committee do not directly regulate access to data, and should not be approached about such issues. Data access lies under the overall governance of the sponsoring organisation - and ultimately depends on what the subjects have consented to. The information sheet given to the healthy volunteers participating to this study states ‘We may share the images we collect with others involved in the research (including researchers at other hospitals or universities, or working for the funding bodies)’. Although we may be able to ask for this in future studies, for the data reported here we do not have the consent from the participants to a) upload the images to a repository b) make the images publicly available c) share the images with researches not involved in this research (and we do not have permission to recontact the participants about this). Therefore, unfortunately, the fMRI raw images and the calculated images (statistical parametric maps) cannot be provided on this occasion. Nonetheless, we do completely appreciate the importance of making all the raw numerical data used in the paper available. We have therefore provided all LI values calculated for each subject using the four presented methods, and also the resulting subject rankings, as supplementary data ( S1 Table). We have also provided the curveLI ‘mean’ and ‘95% confidence interval’ curves for all tasks and ROIs shown in Fig 4 as data points (supplementary data S2 Table). These define and summarize our reference cohort, and can be used for future single subject or cohort comparisons. All these raw data constitute the results from this research.

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