Cerebellar Volumes Associate with Behavioral Phenotypes in Prader-Willi Syndrome

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Abstract

The objective of this study was to investigate lobule-specific cerebellar structural alterations relevant to clinical behavioral characteristics of Prader-Willi syndrome (PWS). We performed a case-control study of 21 Japanese individuals with PWS (age; median 21.0, range 13–50 years, 14 males, 7 females) and 40 age- and sex-matched healthy controls with typical development. Participants underwent 3-Tesla magnetic resonance imaging. Three-dimensional T ₁-weighted images were assessed for cerebellar lobular volume and adjusted for total intracerebellar volume (TIV) using a spatially unbiased atlas template to give a relative volume ratio. A region of interest analysis included the deep cerebellar nuclei. A correlation analysis was performed between the volumetric data and the clinical behavioral scores derived from the standard questionnaires (hyperphagia, autism, obsession, and maladaptive index) for global intelligence assessment in paired subgroups. In individuals with PWS, TIV was significantly reduced compared with that of controls ( p < 0.05, family-wise error corrected; mean [standard deviation], 1014.1 [93.0] mm ³). Decreased relative lobular volume ratios were observed in posterior inferior lobules with age, sex, and TIV as covariates (Crus I, Crus II, lobules VIIb, VIIIa, VIIIb, and IX). However, increased ratios were found in the dentate nuclei bilaterally in individuals with PWS ( p < 0.01); the mean (standard deviation) × 10 ⁻³ was as follows: left, 1.58 (0.26); right, 1.67 (0.30). The altered lobular volume ratios showed negative correlations with hyperphagic and autistic characteristics and positive correlations with obsessive and intellectual characteristics. This study provides the first objective evidence of topographic patterns of volume differences in cerebellar structures consistent with clinical behavioral characteristics in individuals with PWS and strongly suggests a cerebellar contribution to altered functional brain connectivity in PWS.

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The cerebellar cognitive affective syndrome.

J Schmahmann (1998)

Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.

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A probabilistic MR atlas of the human cerebellum.

Jörn Diedrichsen, Narender Ramnani, David J Flavell … (2009)

The functional organization of the cerebellum is reflected in large part by the unique afferent and efferent connectivity of the individual cerebellar lobules. This functional diversity on a relatively small spatial scale makes accurate localization methods for human functional imaging and anatomical patient-based research indispensable. Here we present a probabilistic atlas of the cerebellar lobules in the anatomical space defined by the MNI152 template. We separately masked the lobules on T1-weighted MRI scans (1 mm isotropic resolution) of 20 healthy young participants (10 male, 10 female, average age 23.7 yrs). These cerebella were then aligned to the standard or non-linear version of the whole-brain MNI152 template using a number of commonly used normalization algorithms, or to a previously published cerebellum-only template (Diedrichsen, J., 2006. A spatially unbiased atlas template of the human cerebellum. NeuroImage 33, 127-138.). The resulting average overlap was higher for the cerebellum-only template than for any of the whole-brain normalization methods. The probabilistic maps allow for the valid assignment of functional activations to specific cerebellar lobules, while providing a quantitative measure of the uncertainty of such assignments. Furthermore, maximum probability maps derived from these atlases can be used to define regions of interest (ROIs) in functional neuroimaging and neuroanatomical research. The atlas, made freely available online, is compatible with a number of widely used analysis packages.

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The cerebellum and cognition

Jeremy D Schmahmann (2018)

What the cerebellum does to sensorimotor and vestibular control, it also does to cognition, emotion, and autonomic function. This hypothesis is based on the theories of dysmetria of thought and the universal cerebellar transform, which hold that the cerebellum maintains behavior around a homeostatic baseline, automatically, without conscious awareness, informed by implicit learning, and performed according to context. Functional topography within the cerebellum facilitates the modulation of distributed networks subserving multiple different functions. The sensorimotor cerebellum is represented in the anterior lobe with a second representation in lobule VIII, and lesions of these areas lead to the cerebellar motor syndrome of ataxia, dysmetria, dysarthria and impaired oculomotor control. The cognitive / limbic cerebellum is in the cerebellar posterior lobe, with current evidence pointing to three separate topographic representations, the nature of which remain to be determined. Posterior lobe lesions result in the cerebellar cognitive affective syndrome (CCAS), the hallmark features of which include deficits in executive function, visual spatial processing, linguistic skills and regulation of affect. The affective dyscontrol manifests in autism spectrum and psychosis spectrum disorders, and disorders of emotional control, attentional control, and social skill set. This report presents an overview of the rapidly growing field of the clinical cognitive neuroscience of the cerebellum. It commences with a brief historical background, then discusses tract tracing experiments in animal models and functional imaging observations in humans that subserve the cerebellar contribution to neurological function. Structure function correlation studies following focal cerebellar lesions in adults and children permit a finer appreciation of the functional topography and nature of the cerebellar motor syndrome, cerebellar vestibular syndrome, and the third cornerstone of clinical ataxiology - the cerebellar cognitive affective syndrome. The ability to detect the CCAS in real time in clinical neurology with a brief and validated scale should make it possible to develop a deeper understanding of the clinical consequences of cerebellar lesions in a wide range of neurological and neuropsychiatric disorders with a link to the cerebellum.

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Author and article information

Contributors

Kenichi Yamada:

ORCID: http://orcid.org/0000-0002-3163-0158

yamadak@bri.niigata-u.ac.jp

Journal

Journal ID (nlm-ta): Cerebellum

Journal ID (iso-abbrev): Cerebellum

Title: Cerebellum (London, England)

Publisher: Springer US (New York )

ISSN (Print): 1473-4222

ISSN (Electronic): 1473-4230

Publication date (Electronic): 13 July 2020

Publication date PMC-release: 13 July 2020

Publication date (Print): 2020

Volume: 19

Issue: 6

Pages: 778-787

Affiliations

GRID grid.260975.f, ISNI 0000 0001 0671 5144, Center for Integrated Human Brain Science, Brain Research Institute, , University of Niigata, ; 1-757, Asahimachi, Chuo-ku, Niigata 9518585 Japan

Author information

Kenichi Yamada http://orcid.org/0000-0002-3163-0158

Article

Publisher ID: 1163

DOI: 10.1007/s12311-020-01163-1

PMC ID: 7588377

PubMed ID: 32661798

SO-VID: aac2b877-7d86-451a-9d12-32b3caedacda

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;

Award ID: 17K10049

Award Recipient : Kenichi Yamada

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ScienceOpen disciplines: Neurology

Keywords: autism,cerebellum,dentate nucleus,hyperphagia,obesity,prader-willi syndrome

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ScienceOpen disciplines: Neurology

Keywords: autism, cerebellum, dentate nucleus, hyperphagia, obesity, prader-willi syndrome

Cerebellar Volumes Associate with Behavioral Phenotypes in Prader-Willi Syndrome

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Karger: Neurology and Neuroscience

Most cited references 21

The cerebellar cognitive affective syndrome.

A probabilistic MR atlas of the human cerebellum.

The cerebellum and cognition

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