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Functional magnetic resonance imaging of working memory in Huntington's disease: cross-sectional data from the IMAGE-HD study

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posted on 01.05.2014, 00:00 authored by N Georgiou-Karistianis, J C Stout, J F Domínguez D., S P Carron, A Ando, A Churchyard, P Chua, I Bohanna, A R Dymowski, G Poudel, G F Egan
We used functional magnetic resonance imaging (fMRI) to investigate spatial working memory (WM) in an N-BACK task (0, 1, and 2-BACK) in premanifest Huntington's disease (pre-HD, n = 35), early symptomatic Huntington's disease (symp-HD, n = 23), and control (n = 32) individuals. Overall, both WM conditions (1-BACK and 2-BACK) activated a large network of regions throughout the brain, common to all groups. However, voxel-wise and time-course analyses revealed significant functional group differences, despite no significant behavioral performance differences. During 1-BACK, voxel-wise blood-oxygen-level-dependent (BOLD) signal activity was significantly reduced in a number of regions from the WM network (inferior frontal gyrus, anterior insula, caudate, putamen, and cerebellum) in pre-HD and symp-HD groups, compared with controls; however, time-course analysis of the BOLD response in the dorsolateral prefrontal cortex (DLPFC) showed increased activation in symp-HD, compared with pre-HD and controls. The pattern of reduced voxel-wise BOLD activity in pre-HD and symp-HD, relative to controls, became more pervasive during 2-BACK affecting the same structures as in 1-BACK, but also incorporated further WM regions (anterior cingulate gyrus, parietal lobe and thalamus). The DLPFC BOLD time-course for 2-BACK showed a reversed pattern to that observed in 1-BACK, with a significantly diminished signal in symp-HD, relative to pre-HD and controls. Our findings provide support for functional brain reorganisation in cortical and subcortical regions in both pre-HD and symp-HD, which are modulated by task difficulty. Moreover, the lack of a robust striatal BOLD signal in pre-HD may represent a very early signature of change observed up to 15 years prior to clinical diagnosis. © 2013 Wiley Periodicals, Inc.

History

Journal

Human brain mapping

Volume

35

Issue

5

Pagination

1847 - 1864

Publisher

Wiley

Location

Chichester, Eng.

ISSN

1065-9471

eISSN

1097-0193

Language

eng

Publication classification

C1 Refereed article in a scholarly journal