Longitudinal changes in the fronto-striatal network are associated with executive dysfunction and behavioral dysregulation in Huntington's disease: 30 months IMAGE-HD data

Dominguez, Juan F. D., Poudel, Govinda, Stout, Julie C., Gray, Marcus, Chua, Phyllis, Borowsky, Beth, Egan, Gary F. and Georgiou-Karistianis, Nellie (2017) Longitudinal changes in the fronto-striatal network are associated with executive dysfunction and behavioral dysregulation in Huntington's disease: 30 months IMAGE-HD data. Cortex, 92 139-149. doi:10.1016/j.cortex.2017.04.001

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Author Dominguez, Juan F. D.
Poudel, Govinda
Stout, Julie C.
Gray, Marcus
Chua, Phyllis
Borowsky, Beth
Egan, Gary F.
Georgiou-Karistianis, Nellie
Title Longitudinal changes in the fronto-striatal network are associated with executive dysfunction and behavioral dysregulation in Huntington's disease: 30 months IMAGE-HD data
Journal name Cortex   Check publisher's open access policy
ISSN 1973-8102
0010-9452
Publication date 2017-07-01
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.cortex.2017.04.001
Open Access Status File (Author Post-print)
Volume 92
Start page 139
End page 149
Total pages 11
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 3206 Neuropsychology and Physiological Psychology
3205 Experimental and Cognitive Psychology
2805 Cognitive Neuroscience
Abstract Neuropsychiatric disturbance−particularly executive dysfunction and behavioral dysregulation−is a common feature of Huntington's disease (HD), with implications for functional capacity and quality of life. No study to date has ascertained whether longitudinal change in brain activity is associated with neuropsychiatric deficits in HD. We used a set-response-shifting task together with functional magnetic resonance imaging to investigate 30-month longitudinal blood-oxygen level dependent (BOLD) signal changes in the fronto-striatal attentional control network in premanifest and symptomatic HD (pre-HD and symp-HD, respectively), relative to healthy control participants. We also assessed the extent to which changes in the BOLD signal over time were related to neuropsychiatric measures in the domains of executive dysfunction and behavioral dysregulation. Associations were also evaluated with clinical and disease severity. We found no longitudinal BOLD differences between pre-HD and controls over 30 months. In contrast, reduction in BOLD response over time was greater in symp-HD, relative to controls, in task-related areas (e.g., anterior cingulate cortex and striatum) and in regions from the default mode network (e.g., medial prefrontal cortex and posterior cingulate/precuneus). Moreover, when considered across both premanifest and symptomatic stages, longitudinal BOLD signal decline in the right dorsolateral prefrontal cortex and putamen was associated with executive dysfunction and behavioral dysregulation measures. In addition, longitudinal reduction in BOLD signal, in fronto-striatal and default mode networks, correlated with disease severity. These results suggest that longitudinal change in fronto-striatal and default mode networks may be useful in understanding the biological underpinnings of functional decline in HD. Such findings offer new avenues for targeted treatments in terms of minimizing psychiatric impairment and potentially maximizing cognitive function.
Keyword Huntington's disease
fMRI
Set shifting
Executive function
Longitudinal
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 606650
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Centre for Advanced Imaging Publications
 
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