Cherrier et al. BMC Cancer 2010, 10:1 http://www.biomedcentral.com/1471-2407/10/1 imaging (fMRI). We hypothesized that men undergoing ADT would show reduced activation in the task-related parietal region during spatial reasoning and spatial memory tasks compared to baseline and to healthy controls. Methods Participants Participants were a subset of participants from a larger study examining cognitive and mood changes in ADT who agreed to the additional neuroimaging procedures (See [20] for details). The sample is a convenience sam- ple comprised of those participants who were willing to undergo neuroimaging procedures in addition to the cognitive assessment procedures in the larger study. Twelve prostate cancer patients with rising PSA (bio- chemical relapse) following primary therapy (radiation, brachytherapy or prostatectomy) in which intermittent androgen suppression (ADT) therapy is indicated were eligible and gave informed consent to participate. Inter- mittent ADT is a treatment strategy that cycles andro- gen withdrawal with an “off treatment” period allowing the testosterone levels to return to eugonadal levels. This approach has allowed for characterization of the biological, psychological, and quality of life effects of ADT and which effects are reversible or attenuated when the testosterone levels increase during the ‘off treatment’ period. Additional eligibility criteria included age greater than 21 years, no disturbance in daily func- tioning and normal pretreatment serum testosterone. Exclusion criteria included moderate pain related to prostate cancer, history of prior psychiatric illness invol- ving hospitalization, dementia, central nervous system metastasis, history of systemic chemotherapy, current renal dysfunction or hepatic dysfunction, prior exposure to welding or any surgery resulting in metal implants in the brain or presence of any unusual findings from mag- netic resonance imaging (MRI). The University of Washington Institutional Review Board approved this study and written informed consent was obtained from all patients prior to study procedures. A placebo or non-treated group in this population was not feasible, therefore a comparable non-treatment group of twelve community dwelling eugonadal men without prostate cancer range matched for age within four years and edu- cation within two years underwent the same neuroima- ging procedures at a matching time interval to the ADT group. Radiology technicians who performed scanning operations were blind to conditions. Imaging data were identified only by coded numbers and group member- ship was coded during image analysis. Study Design Baseline evaluations for ADT patients included a bone scan, CT scan of the abdomen and pelvis, chest x-ray, Page 2 of 8 cognitive function testing, and baseline laboratory values including renal and hepatic function, PSA and total tes- tosterone. Patients were treated with an anti-androgen (flutamide 250 mg TID or bicalutamide 50 mg per day if intolerant of flutamide) lead-in alone for 2 weeks fol- lowed by the addition of leuprolide 7.5 mg administered by monthly intramuscular injection for nine doses. Thereafter, the PSA was followed monthly. The ADT group underwent neuroimaging procedures prior to the start of treatment (time1) and again after nine months of androgen deprivation (time2). The control group underwent two neuroimaging sessions nine months apart. In addition to high resolution structural scans, subjects underwent blood oxygen level dependent (BOLD) -fMRI imaging while performing three cognitive tasks; i) encoding and ii) recognition in a spatial mem- ory task and iii) a mental rotation task. Environmental Memory Task (EMT) An environmental memory task designed by Shelton and colleagues [21,22] was used for a spatial memory task. The task was modified for older individuals by using a single environment (either a park or market) during both encoding and recognition portions and allowing subjects 6 seconds (rather then 3) to identify still images during recognition. This task is composed of separate, sequentially presented encoding and recogni- tion runs lasting 348 and 478 seconds, respectively. During both encoding and recognition the environ- ment is viewed from the ground (route) and the aerial (survey) perspective in an alternating, pseudorandom order. To ensure that subjects were familiar with identi- fying objects from the route and survey perspective and that they understood the requirements of the task they completed a practice session outside the MRI suite with an environment not subsequently used during the scan- ning session. All subjects demonstrated satisfactory understanding and performance of the task after this practice session and the practice session was repeated at the second visit. During the fMRI session verbal instruc- tions were provided though headphones and visual sti- muli through goggles connected via high-resolution fiber optic cables. Stimuli were presented using an Apple computer running PsyScope [23]. Radiology tech- nicians who were responsible for scanning the partici- pants were blind to condition and only subject numbers identified the imaging data. Encoding task (ENCODE) During the encoding task subjects viewed animated movies of an environment (either a park or market) pre- sented from both the route perspective and the survey perspective. The environment was shown six times, 3× from the route and 3× from the survey perspective, in an alternating psuedorandom order. The individual movies were 46 seconds long and were preceded by