Neuropsychologia 45 (2007) 1791–1800 Increased cortical recruitment in Huntington’s disease using a Simon task Nellie Georgiou-Karistianis a,∗ , Anusha Sritharan a , Maree Farrow b , Ross Cunnington b,c , Julie Stout d , John Bradshaw a , Andrew Churchyard e , Tamara-Leigh Brawn b , Phyllis Chua a , Edmond Chiu f , Dhananjay Thiruvady g , Gary Egan b a School of Psychology, Psychiatry and Psychological Medicine, Monash University, Clayton, Victoria 3800, Australia b Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia c Brain Research Institute, Austin Health, Heidelberg West, Victoria, Australia d Department of Psychology, Indiana University, Bloomington, IN, USA e Department of Neurology, Monash Medical Centre, Clayton, Victoria, Australia f Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia g School of Information Technology, Monash University, Clayton, Victoria, Australia Received 10 July 2006; received in revised form 20 December 2006; accepted 25 December 2006 Available online 18 January 2007 Abstract Cognitive deficits in Huntington’s disease (HD) have been attributed to neuronal degeneration within the striatum; however, postmortem and structural imaging studies have revealed more widespread morphological changes. To examine the impact of HD-related changes in regions outside the striatum, we used functional magnetic resonance imaging (fMRI) in HD to examine brain activation patterns using a Simon task that required a button press response to either congruent or incongruent arrow stimuli. Twenty mild to moderate stage HD patients and 17 healthy controls were scanned using a 3T GE scanner. Data analysis involved the use of statistical parametric mapping software with a random effects analysis model to investigate group differences brain activation patterns compared to baseline. HD patients recruited frontal and parietal cortical regions to perform the task, and also showed significantly greater activation, compared to controls, in the caudal anterior cingulate, insula, inferior parietal lobules, superior temporal gyrus bilaterally, right inferior frontal gyrus, right precuneus/superior parietal lobule, left precentral gyrus, and left dorsal premotor cortex. The significantly increased activation in anterior cingulate–frontal–motor–parietal cortex in HD may represent a primary dysfunction due to direct cell loss or damage in cortical regions, and/or a secondary compensatory mechanism of increased cortical recruitment due to primary striatal deficits. © 2007 Elsevier Ltd. All rights reserved. Keywords: Huntington’s disease; fMRI; Simon task; Hyperactivation; Compensation 1. Introduction Huntington’s disease (HD) is a progressive autosomal dom- inant disorder, and is clinically characterized by the onset of chorea, impaired voluntary movements, cognitive deterioration, and psychiatric symptoms (Joel, 2001). The disease causing mutation is an expanded trinucleotide CAG repeat in the IT15 gene, near the end of the short arm of chromosome 4, and codes for the protein ‘huntingtin’ (Huntington’s Disease Collaborative Research Group, 1993). HD causes progressive neuronal degen- ∗ Corresponding author. Tel.: +61 3 9905 1575; fax: +61 3 9905 3948. E-mail address: nellie.georgiou-karistianis@med.monash.edu.au (N. Georgiou-Karistianis). eration of the striatum (i.e., caudate and putamen) (Aylward, Rosenblatt, & Field, 2003; Aylward et al., 2004; Bamford et al., 1995). Cognitive deficits (i.e., relating to working memory capacity, task-set switching, planning, organizing, sequencing and psychomotor processes) have mostly been attributed to stri- atal atrophy and/or to specific deficits in frontostriatal circuitry (Aron, Watkins, & Sahakian, 2003; Georgiou, Bradshaw, & Phillips, 1995, 1996, 1997; Josiassen, Curry, & Roemer, 1982; Rothlind, Bylsma, & Peyser, 1993). While neuronal degeneration in HD is most pronounced in the striatum, structural imaging and neuropathological studies have provided an accumulation of evidence of brain changes outside the striatum. For example, neuropathological stud- ies have revealed reduced volume across most cortical areas (Halliday, McRitchie, & Macdonald, 1998), and morphological 0028-3932/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2006.12.023