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Title: | Functional and connectivity changes during working memory in Huntington's disease: 18month longitudinal data from the IMAGE-HD study. | Authors: | Egan G.F.;Gray M.A.;Churchyard A.;Chua P.;Borowsky B.;Stout J.C.;Georgiou-Karistianis N. ;Poudel G.R.;Dominguez D J.F.;Langmaid R. | Institution: | (Georgiou-Karistianis, Poudel, Dominguez D, Langmaid, Gray, Chua, Egan, Stout) School of Psychology and Psychiatry, Monash University, Clayton, VIC 3800, Australia (Poudel, Gray, Egan) Monash Biomedical Imaging (MBI), Monash University, Melbourne, VIC 3800, Australia (Poudel) VLSCI Life Sciences Computation Centre, Melbourne, VIC 3010, Australia (Gray) Centre for Advanced Imaging, Gehrmann Laboratory, The University of Queensland, St Lucia, QLD 4072, Australia (Churchyard) Department of Neurology, Monash Medical Centre, Clayton, VIC, Australia (Borowsky) CHDI Management/CHDI Foundation, New York, NY, United States (Egan) Centre for Neuroscience, University of Melbourne, Parkville, VIC, Australia (Egan) Howard Florey Institute, Florey Neuroscience Institutes, Parkville, VIC, Australia | Issue Date: | 9-Sep-2013 | Copyright year: | 2013 | Publisher: | Academic Press Inc. (1250 Sixth Avenue, San Diego, California CA 92101, United States) | Place of publication: | United States | Publication information: | Brain and Cognition. 83 (1) (pp 80-91), 2013. Date of Publication: October 2013. | Abstract: | Background: This study aimed to characterize, for the first time, 18. month longitudinal changes in both functional activation and functional connectivity during working memory in premanifest Huntington's disease (pre-HD) and symptomatic HD (symp-HD). Method(s): Functional magnetic resonance imaging (fMRI) was used to investigate longitudinal changes in neuronal activity during working memory performance via an N-BACK task (0-BACK and 1-BACK) in 27 pre-HD, 17 symp-HD, and 23 control participants. Whole-brain analysis of activation and region-of-interest analysis of functional connectivity was applied to longitudinal fMRI data collected at baseline and 18. months follow-up. Result(s): Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK versus 0-BACK in the lateral and medial prefrontal, anterior cingulate, primary motor, and temporal areas cortically, and caudate and putamen subcortically. Pre-HD far from onset, compared with controls, showed further longitudinal increases in the right and left dorsolateral prefrontal cortex (DLPFC). Longitudinal increased activation in anterior cingulate and medial primary motor areas were associated with disease burden in the pre-HD group. Moreover, in pre-HD increased activation over time in primary motor and putamen regions were associated with average response time during 1-BACK performance. During 1-BACK, functional connectivity between the right DLPFC and posterior parietal, anterior cingulate, and caudate was significantly reduced over 18. months only in the pre-HD group. Conclusion(s): Longitudinal reductions in connectivity over 18. months may represent an early signature of cortico-cortical and cortico-striatal functional disconnectivity in pre-HD, whereas the concomitant increased cortical and subcortical activation may reflect a compensatory response to the demands for cognitive resources required during task performance. Our findings demonstrate that functional imaging modalities have the potential to serve as sensitive methods for the assessment of cortical and subcortical responses to future treatment measures. © 2013 Elsevier Inc. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.bandc.2013.07.004 | PubMed URL: | 23938592 [http://www.ncbi.nlm.nih.gov/pubmed/?term=23938592] | ISSN: | 0278-2626 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/42573 | Type: | Article | Subjects: | follow up functional magnetic resonance imaging gray matter human *Huntington chorea longitudinal study male neuroimaging prefrontal cortex primary motor cortex priority journal putamen response time voxel based morphometry female adult aged anterior cingulate article behavior *brain function brain region clinical article controlled study *working memory response time adult aged anterior cingulate article behavior *brain function brain region clinical article controlled study female follow up functional magnetic resonance imaging gray matter human *Huntington chorea longitudinal study male neuroimaging prefrontal cortex primary motor cortex priority journal putamen voxel based morphometry *working memory |
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