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      Cerebellar Structural Abnormality in Autism Spectrum Disorder: A Magnetic Resonance Imaging Study

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          Abstract

          Objective

          This study uses structural magnetic resonance imaging to explore changes in the cerebellar lobules in patients with autism spectrum disorder (ASD) and further analyze the correlation between cerebellar structural changes and clinical symptoms of ASD.

          Methods

          A total of 75 patients with ASD and 97 typically developing (TD) subjects from Autism Brain Imaging Data Exchange dataset were recruited. We adopted an advanced automatic cerebellar lobule segmentation technique called CEREbellum Segmentation to segment each cerebellar hemisphere into 12 lobules. Normalized cortical thickness of each lobule was recorded, and group differences in the cortical measures were evaluated. Correlation analysis was also performed between the normalized cortical thickness and the score of Autism Diagnostic Interview-Revised.

          Results

          Results from analysis of variance showed that the normalized cortical thickness of the ASD group differed significantly from that of the TD group; specifically, the ASD group had lower normalized cortical thickness than the TD group. Post-hoc analysis revealed that the differences were more predominant in the left lobule VI, left lobule Crus I and left lobule X, and in the right lobule VI and right lobule Crus I. Lowered normalized cortical thickness in the left lobule Crus I in the ASD patients correlated positively with the abnormality of development evident at or before 36 months subscore.

          Conclusion

          These results suggest abnormal development of cerebellar lobule structures in ASD patients, and such abnormality might significantly influence the pathogenesis of ASD. These findings provide new insights into the neural mechanisms of ASD, which may be clinically relevant to ASD diagnosis.

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          Most cited references43

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          The organization of the human cerebellum estimated by intrinsic functional connectivity.

          The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map.
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            Harmonization of cortical thickness measurements across scanners and sites

            With the proliferation of multi-site neuroimaging studies, there is a greater need for handling non-biological variance introduced by differences in MRI scanners and acquisition protocols. Such unwanted sources of variation, which we refer to as “scanner effects”, can hinder the detection of imaging features associated with clinical covariates of interest and cause spurious findings. In this paper, we investigate scanner effects in two large multi-site studies on cortical thickness measurements across a total of 11 scanners. We propose a set of tools for visualizing and identifying scanner effects that are generalizable to other modalities. We then propose to use ComBat, a technique adopted from the genomics literature and recently applied to diffusion tensor imaging data, to combine and harmonize cortical thickness values across scanners. We show that ComBat removes unwanted sources of scan variability while simultaneously increasing the power and reproducibility of subsequent statistical analyses. We also show that ComBat is useful for combining imaging data with the goal of studying life-span trajectories in the brain.
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              A spatially unbiased atlas template of the human cerebellum.

              This article presents a new high-resolution atlas template of the human, cerebellum and brainstem, based on the anatomy of 20 young healthy individuals. The atlas is spatially unbiased, i.e., the location of each structure is equal to the expected location of that structure across individuals in MNI space, a result that is cross-validated with an independent sample of 16 individuals. At the same time, the new template preserves the anatomical detail of cerebellar structures through a nonlinear atlas generation algorithm. In comparison to current whole-brain templates, it allows for an improved voxel-by-voxel normalization for functional MRI and lesion analysis. Alignment to the template requires that the cerebellum and brainstem are isolated from the surrounding tissue, a process for which an automated algorithm has been developed. Compared to normalization to the MNI whole-brain template, the new method strongly improves the alignment of individual fissures, reducing their spatial spread by 60%, and improves the overlap of the deep cerebellar nuclei. Applied to functional MRI data, the new normalization technique leads to a 5-15% increase in peak t values and in the activated volume in the cerebellar cortex for movement vs. rest contrasts. This indicates that the new template significantly improves the overlap of functionally equivalent cerebellar regions across individuals. The template and software are freely available as an SPM-toolbox, which also allows users to relate the new template to the annotated volumetric (Schmahmann, J.D., Doyon, J., Toga, A., Petrides, M., Evans, A. (2000). MRI atlas of the human cerebellum. San Diego: Academic Press) and surface-based (Van Essen, D.C. (2002a) Surface-based atlases of cerebellar cortex in the human, macaque, and mouse. Ann. N. Y. Acad. Sci. 978:468-479.) atlas of one individual, the "colin27"-brain.
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                Author and article information

                Journal
                Psychiatry Investig
                Psychiatry Investig
                PI
                Psychiatry Investigation
                Korean Neuropsychiatric Association
                1738-3684
                1976-3026
                April 2023
                20 April 2023
                : 20
                : 4
                : 334-340
                Affiliations
                [1 ]School of Clinical Medicine, Anhui Medical College, Anhui, China
                [2 ]Center for Biomedical Imaging, University of Science and Technology of China, Anhui, China
                [3 ]Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Anhui, China
                Author notes
                Correspondence: Xiaoxiao Wang, PhD Center for Biomedical Imaging, University of Science and Technology of China, Hefei, Anhui 230026, China Tel: +86 18956068202, E-mail: wang506@ 123456ustc.edu.cn
                Correspondence: Bensheng Qiu, PhD Center for Biomedical Imaging, University of Science and Technology of China, Hefei, Anhui 230026, China Tel: +86 15056903508, E-mail: bqiu@ 123456ustc.edu.cn
                Author information
                http://orcid.org/0000-0001-8655-8299
                http://orcid.org/0000-0001-7209-8973
                http://orcid.org/0000-0003-4615-493X
                http://orcid.org/0000-0002-7899-1524
                http://orcid.org/0000-0002-6487-9179
                http://orcid.org/0000-0003-4146-1877
                http://orcid.org/0000-0002-7820-1887
                http://orcid.org/0000-0003-2987-7378
                http://orcid.org/0000-0002-8498-7388
                Article
                pi-2022-0254
                10.30773/pi.2022.0254
                10151665
                37098660
                adc6ae86-2319-47b8-ab7a-b7fd6b21ba51
                Copyright © 2023 Korean Neuropsychiatric Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 September 2022
                : 5 December 2022
                : 15 January 2023
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                magnetic resonance imaging,cerebellum,autism,ceres
                Clinical Psychology & Psychiatry
                magnetic resonance imaging, cerebellum, autism, ceres

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