title: Functional magnetic resonance imaging of working memory in Huntington's disease: cross-sectional data from the IMAGE-HD study.
abstract: 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.
authors.affiliation: School of Psychology and Psychiatry, Monash University, Clayton, Victoria, Australia.
authors.forename: Nellie
authors.initials: N
authors.lastname: Georgiou-Karistianis
authors.forename: Julie C
authors.initials: JC
authors.lastname: Stout
authors.forename: Juan F
authors.initials: JF
authors.lastname: Domínguez D
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Carron
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ando
authors.forename: Andrew
authors.initials: A
authors.lastname: Churchyard
authors.forename: Phyllis
authors.initials: P
authors.lastname: Chua
authors.forename: India
authors.initials: I
authors.lastname: Bohanna
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Dymowski
authors.forename: Govinda
authors.initials: G
authors.lastname: Poudel
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications* / Q000473:pathology*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen; D013223:Statistics as Topic; D013997:Time Factors; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: DLPFC; Huntington's Disease; N BACK; fMRI; working memory
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