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Delineation of Subregions in the Early Postnatal Human Cerebellum for Design-Based Stereologic Studies

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      Abstract

      Recent design-based stereologic studies have shown that the early postnatal (<1 year of age) human cerebellum is characterized by very high plasticity and may thus be very sensitive to external and internal influences during the first year of life. A potential weakness of these studies is that they were not separately performed on functionally relevant subregions of the cerebellum, as was the case in a few design-based stereologic studies on the adult human cerebellum. The aim of the present study was to assess whether it is possible to identify unequivocally the primary, superior posterior, horizontal, ansoparamedian, and posterolateral fissures in the early postnatal human cerebellum, based on which functionally relevant subregions could be delineated. This was tested in 20 human post mortem cerebellar halves from subjects aged between 1 day and 11 months by means of a combined macroscopic and microscopic approach. We found that the superior posterior, horizontal, and posterolateral fissures can be reliably identified on all of the specimens. However, reliable and reproducible identification of the primary and ansoparamedian fissures was not possible. Accordingly, it appears feasible to perform subregion-specific investigations in the early postnatal human cerebellum when the identification of subregions is restricted to crus I (bordered by the superior posterior and horizontal fissures) and the flocculus (bordered by the posterolateral fissure). As such, it is recommended to define the entire cerebellar cortex as the region of interest in design-based stereologic studies on the early postnatal human cerebellum to guarantee reproducibility of results.

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      Most cited references 78

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      Unbiased stereological estimation of the total number of neurons in thesubdivisions of the rat hippocampus using the optical fractionator.

      A stereological method for obtaining estimates of the total number of neurons in five major subdivisions of the rat hippocampus is described. The new method, the optical fractionator, combines two recent developments in stereology: a three-dimensional probe for counting neuronal nuclei, the optical disector, and a systematic uniform sampling scheme, the fractionator. The optical disector results in unbiased estimates of neuron number, i.e., estimates that are free of assumptions about neuron size and shape, are unaffected by lost caps and overprojection, and approach the true number of neurons in an unlimited manner as the number of samples is increased. The fractionator involves sampling a known fraction of a structural component. In the case of neuron number, a zero dimensional quantity, it provides estimates that are unaffected by shrinkage before, during, and after processing of the tissue. Because the fractionator involves systematic sampling, it also results in highly efficient estimates. Typically only 100-200 neurons must be counted in an animal to obtain a precision that is compatible with experimental studies. The methodology is compared with those used in earlier works involving estimates of neuron number in the rat hippocampus and a number of new stereological methods that have particular relevance to the quantitative study of the structure of the nervous system are briefly described in an appendix.
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        Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies.

        Clinical, experimental and neuroimaging studies indicate that the cerebellum is involved in neural processes beyond the motor domain. Cerebellar somatotopy has been shown for motor control, but topographic organization of higher-order functions has not yet been established. To determine whether existing literature supports the hypothesis of functional topography in the human cerebellum, we conducted an activation likelihood estimate (ALE) meta-analysis of neuroimaging studies reporting cerebellar activation in selected task categories: motor (n=7 studies), somatosensory (n=2), language (n=11), verbal working memory (n=8), spatial (n=8), executive function (n=8) and emotional processing (n=9). In agreement with previous investigations, sensorimotor tasks activated anterior lobe (lobule V) and adjacent lobule VI, with additional foci in lobule VIII. Motor activation was in VIIIA/B; somatosensory activation was confined to VIIIB. The posterior lobe was involved in higher-level tasks. ALE peaks were identified in lobule VI and Crus I for language and verbal working memory; lobule VI for spatial tasks; lobules VI, Crus I and VIIB for executive functions; and lobules VI, Crus I and medial VII for emotional processing. Language was heavily right-lateralized and spatial peaks left-lateralized, reflecting crossed cerebro-cerebellar projections. Language and executive tasks activated regions of Crus I and lobule VII proposed to be involved in prefrontal-cerebellar loops. Emotional processing involved vermal lobule VII, implicated in cerebellar-limbic circuitry. These data provide support for an anterior sensorimotor vs. posterior cognitive/emotional dichotomy in the human cerebellum. Prospective studies of multiple domains within single individuals are necessary to better elucidate neurobehavioral structure-function correlations in the cerebellar posterior lobe.
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          The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging.

          Twenty-five years ago the first human functional neuroimaging studies of cognition discovered a surprising response in the cerebellum that could not be attributed to motor demands. This controversial observation challenged the well-entrenched view that the cerebellum solely contributes to the planning and execution of movement. Recurring neuroimaging findings combined with key insights from anatomy and case studies of neurological patients motivated a reconsideration of the traditional model of cerebellar organization and function. The majority of the human cerebellum maps to cerebral association networks in an orderly manner that includes a mirroring of the prominent cerebral asymmetries for language and attention. These findings inspire exploration of the cerebellum's contributions to a diverse array of functional domains and neuropsychiatric disorders. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Author and article information

            Affiliations
            1Chair of Neuroanatomy, Faculty of Medicine, Institute of Anatomy, Ludwig-Maximilians-Universität München , Munich, Germany
            2Institute of Forensic Medicine, University of Rostock , Rostock, Germany
            3Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai , New York, NY, United States
            Author notes

            Edited by: Bente Pakkenberg, Research Laboratory for Stereology and Neuroscience, Denmark

            Reviewed by: Michela Ferrucci, University of Pisa, Italy; Salvador Martinez, Universidad Miguel Hernández de Elche, Spain

            *Correspondence: Christoph Schmitz christoph_schmitz@ 123456med.uni-muenchen.de
            Contributors
            Journal
            Front Neuroanat
            Front Neuroanat
            Front. Neuroanat.
            Frontiers in Neuroanatomy
            Frontiers Media S.A.
            1662-5129
            08 January 2018
            2017
            : 11
            5766680
            10.3389/fnana.2017.00134
            Copyright © 2018 Fichtl, Büttner, Hof, Schmitz and Kiessling.

            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.

            Counts
            Figures: 6, Tables: 5, Equations: 0, References: 78, Pages: 14, Words: 11322
            Funding
            Funded by: Simons Foundation 10.13039/100000893
            Award ID: FA #345922
            Categories
            Neuroscience
            Original Research

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