Functional connectivity of the prefrontal cortex in Huntington’s disease
- D R Thiruvady1,
- N Georgiou-Karistianis2,
- G F Egan3,
- S Ray1,
- A Sritharan2,
- M Farrow2,
- A Churchyard4,
- P Chua5,
- J L Bradshaw2,
- T-L Brawn3,
- R Cunnington3
- 1Clayton School of Information Technology, Monash University, Clayton, Victoria, Australia
- 2Experimental Neuropsychology Research Unit, School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria, Australia
- 3Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia
- 4Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia
- 5Department of Psychological Medicine, School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria, Australia
- Correspondence to: Dr Nellie Georgiou-Karistianis Experimental Neuropsychology Research Unit, School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria 3800, Australia;nellie.georgiou-karistianis{at}med.monash.edu.au
- Received 22 May 2006
- Accepted 27 September 2006
- Revised 22 August 2006
- Published Online First 6 October 2006
Abstract
Background: Huntington’s disease is a progressive neurodegenerative disorder that results in deterioration and atrophy of various brain regions.
Aim: To assess the functional connectivity between prefrontal brain regions in patients with Huntington’s disease, compared with normal controls, using functional magnetic resonance imaging.
Patients and methods: 20 patients with Huntington’s disease and 17 matched controls performed a Simon task that is known to activate lateral prefrontal and anterior cingulate cortical regions. The functional connectivity was hypothesised to be impaired in patients with Huntington’s disease between prefrontal regions of interest, selected from both hemispheres, in the anterior cingulate and dorsal lateral prefrontal cortex.
Results: Controls showed a dynamic increase in interhemispheric functional connectivity during task performance, compared with the baseline state; patients with Huntington’s disease, however, showed no such increase in prefrontal connectivity. Overall, patients with Huntington’s disease showed significantly impaired functional connectivity between anterior cingulate and lateral prefrontal regions in both hemispheres compared with controls. Furthermore, poor task performance was predicted by reduced connectivity in patients with Huntington’s disease between the left anterior cingulate and prefrontal regions.
Conclusions: This finding represents a loss of synchrony in activity between prefrontal regions in patients with Huntington’s disease when engaged in the task, which predicted poor task performance. Results show that functional interactions between critical prefrontal regions, necessary for cognitive performance, are compromised in Huntington’s disease. It is speculated whether significantly greater levels of activation in patients with Huntington’s disease (compared with controls) observed in several brain regions partially compensate for the otherwise compromised interactions between cortical regions.
- BOLD, blood-oxygen level-dependent
- CAG, cytosine–adenine–guanine
- fMRI, functional magnetic resonance imaging
- LAC, left anterior cingulate cortex
- LPF, left prefrontal cortex
- MRI, magnetic resonance image
- RAC, right anterior cingulate cortex
- ROI, region of interest
- RPF, right prefrontal cortex
- UHDRS, Unified Huntington’s Disease Rating Scale
Footnotes
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Published Online First 6 October 2006
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Funding: This work was supported by funding from Neurosciences Victoria and the National Health and Medical Research Council (Australia), Project Grant (284247) and Fellowships to RC (217025) and GFE.
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Competing interests: None.
