87c0306c1241d3e538b3c410880afe96 256656.pdf 22aae945831c04982bb6f45c2c3df5b8a0dac8f2 256656.pdf 833138ceb8594ed4bd4c91c8a62c15b01ad87bc57e1406842d39453aef40579c 256656.pdf Title: Cerebellar Dysfunction in Adults with Prader Willi Syndrome Subject: Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination. Keywords: cerebellum; fMRI; motor system; Prader Willi syndrome Author: Laura Blanco-Hinojo, Laia Casamitjana, Jesus Pujol, Gerard Martínez-Vilavella, Susanna Esteba-Castillo, Olga Giménez-Palop, Valentín Freijo, Joan Deus and Assumpta Caixàs Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jul 29 09:31:56 2021 CEST ModDate: Thu Jul 29 09:37:35 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 19892635 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- FJMGBM+VnURWPalladioL Type 1 Custom yes yes no 10 0 XXDXUT+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 DIEZEP+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 MWCNLP+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 GGHKEL+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes no 84 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 88 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-10-21 02:42:21 CEST RepresentationInformation: 256656.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-05-30 12:44:25 CEST Size: 19892635 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 338 FreeObjects: 9 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Participants Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Behavioral Assessment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Motor Tests during fMRI Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Functional MRI Acquisition Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Functional MRI Preprocessing Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Behavioral Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Functional MRI Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Children: Item: Title: Behavioral Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Functional MRI Data Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Info: Title: Cerebellar Dysfunction in Adults with Prader Willi Syndrome Author: Laura Blanco-Hinojo, Laia Casamitjana, Jesus Pujol, Gerard Martínez-Vilavella, Susanna Esteba-Castillo, Olga Giménez-Palop, Valentín Freijo, Joan Deus and Assumpta Caixàs Subject: Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination. 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