Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

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J Psychiatry Neurosci 2013; 39(2):87-96

Govinda R. Poudel, PhD; Gary F. Egan, PhD; Andrew Churchyard, MD; Phyllis Chua, MD; Julie C. Stout, PhD; Nellie Georgiou-Karistianis, PhD

Poudel, Egan, Chua, Stout, Georgiou-Karistianis — School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, VIC, Australia; Poudel, Egan — Monash Biomedical Imaging, Monash University, Clayton, VIC, Australia; Poudel — Monash e-Research Centre, Monash University, Clayton, VIC, Australia; Churchyard — Department of Neurology, Monash Medical Centre, Clayton, VIC, Australia; Poudel, Egan — VLSCI Life Sciences Computation Centre, Melbourne, VIC, Australia

Abstract

Background: Functional neural impairments have been documented in people with symptomatic Huntington disease (symp-HD) and in premanifest gene carriers (pre-HD). This study aimed to characterize synchrony in resting state cerebral networks in both pre-HD and symp-HD populations and to determine its association with disease burden and neurocognitive functions.

Methods: We acquired functional magnetic resonance imaging (fMRI) data from pre-HD, symp-HD and healthy control participants. The fMRI data were analyzed using multisubject independent component analysis and dual regression. We compared networks of interest among the groups using a nonparametric permutation method and correcting for multiple comparisons.

Results: Our study included 25 people in the pre-HD, 23 in the symp-HD and 18 in the healthy control groups. Compared with the control group, the pre-HD group showed decreased synchrony in the sensorimotor and dorsal attention networks; decreased level of synchrony in the sensorimotor network was associated with poorer motor performance. Compared with the control group, the symp-HD group showed widespread reduction in synchrony in the dorsal attention network, which was associated with poorer cognitive performance. The posterior putamen and superior parietal cortex were functionally disconnected from the frontal executive network in the symp-HD compared with control and pre-HD groups. Furthermore, the left frontoparietal network showed areas of increased synchrony in the symp-HD compared with the pre-HD group.

Limitations: We could not directly correct for influence of autonomic changes (e.g., heart rate) and respiration on resting state synchronization.

Conclusion: Our findings suggest that aberrant synchrony in the sensorimotor and dorsal attention networks may serve as an early signature of neural change in pre-HD individuals. The altered synchrony in dorsal attention, frontoparietal and corticostriatal networks may contribute to the development of clinical symptoms in people with Huntington disease.


Submitted Nov. 7, 2013; Revised Apr. 22, 2013; Accepted June 17, 2013.

Acknowledgments: We acknowledge the contribution of all the participants who took part in this study. We are also grateful to the CHDI Foundation Inc. (grant number A – 3433), New York (USA), and to the National Health and Medical Research Council (NHMRC; grant number 606650) for their support in funding this research. This research was supported by the VLSCI’s Life Sciences Computation Centre, a collaboration between Melbourne, Monash and La Trobe Universities and an initiative of the Victorian Government, Australia. We also thank the Royal Children’s Hospital for the use of their 3T MR scanner. G.F. Egan is a Principal NHMRC Research Fellow.

Competing interests: None declared.

Contributors: All authors designed the study, reviewed the article and approved the final version for publication. A. Churchyard and P. Chua acquired the data, which G. Poudel, G.F. Egan, J. Stout and N. Georgiou-Karistianis analyzed. G. Poudel, G.F. Egan, J. Stout and N. Georgiou-Karistianis wrote the article.

DOI: 10.1503/jpn.120226

Correspondence to: N. Georgiou-Karistianis, Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Monash University, Clayton, Victoria 3800, Australia; nellie.georgiou-karistianis@monash.edu