Cherrier et al. BMC Cancer 2010, 10:1 http://www.biomedcentral.com/1471-2407/10/1 in the imaging analysis. All participants were right handed. Each subject was scanned twice (baseline, 9 months) with 24 scans sessions and three tasks for a total of 72 runs included in the analysis. Similar to other functional neuroimaging studies, variance in the BOLD signal for our study, for most brain regions across all paradigms was about 1% of the total signal. Given the design of our paradigms this would allow us to detect a 0.5% increase in signal (task-associated acti- vation) with about 50% power and 0.75% change with > 80%power in individual subjects. Review of clusters of significant task-associated activation within individual subjects revealed, as expected from the simplistic prior power calculation, signal changes ranged 0.25-1.0% of the signal (data not shown) As expected, total testosterone was reduced signifi- cantly in the treatment group at the time of the second scan compared to the control group F(1,9) = 37.6, p < .01 and a significant group by time interaction F (1,9) 53.26, p < .01 was evident. The ADT group total serum testosterone levels declined from an average of 3.52 (0.33) ng/ml at baseline to 0.25 (0.10) at month 9. The control group did not change with a baseline tes- tosterone of 3.8 (0.67) ng/ml and a month 9 average of 4.3 (1.3) ng/ml. In scanner behavioral performance on the environ- mental memory task (EMT) or mental rotation did not change significantly for either group, 36.0 (10) average total correct EMT (64 points possible) at time1 and 35.75 (13.6) at time2 for ADT group and 31.3 (13.5) at time1 and 38.0 (10.9) at time2 for control group. To determine whether ADT affected neurovascular responses during these tasks, BOLD-fMRI was acquired prior to treatment (time1) and after 9-months of ADT (or no treatment in the control group) (time2) in both the ADT and CTR groups. Task-related activation, defined as the difference in the BOLD signal between the active tasks (which differ between paradigms) and viewing crosshairs (fixation), was reduced in a single right parietal region in the ADT group but not the CTR group (Figure 1). This region extended superiorly from the right precuneal area and inferiorly to the lateral occipital lobe. BOLD responses during individual para- digms were differentially affected (Table 2 and Figure 2). Task-related activation in this region was reduced in both the ADT and CTR groups during ENCODE. In contrast, during RECOG and MATCH, task-related acti- vation was reduced within the ADT group but not the CTR group and was significantly different between groups. To ensure these findings were not the result of an activation difference between groups at time1 an intergroup analysis was performed for each paradigm. No activation differences at time1 were found between groups. Page 5 of 8 Figure 1 Reduced left parietal activation in the ADT group at time2. Four sections of a standardized brain with the area of reduced activation in the ADT group are shown (outlined by the green circle). No other areas of reduced activation were noted. See Methods and Table 2 for statistical details, p = 0.01 for cluster depicted. Discussion Our results indicate androgen deprivation therapy (ADT) patients had reduced task-related BOLD-fMRI activation following androgen deprivation in the right parietal-occi- pital region for tasks involving manipulation and recall of spatial information. Although in scanner performance did not decline for either task in this small sample the observed reduced task-related activation may help explain our previous findings of impaired rotational abil- ities in a larger sample of men undergoing ADT [11,20]. Cognitive changes in men undergoing ADT using paper and pencil and computerized tests have found impair- ments in verbal memory [9,10], spatial abilities [11,20] and attention [12]. However, declines may be evident for only a subset of participants [31], and some studies have found no appreciable change in cognition from androgen ablation therapy [32]. These findings suggest that gonadal steroids modulate parietal-occipital function and are con- sistent with a report correlating endogenous testosterone levels and neural activation in the inferior parietal lobule and left supramarginal gyrus regions while performing a mental rotation task [18]. Neuroimaging studies of mental rotation have gener- ally found that rotation of three dimensional figures engages occipital and parietal regions with numerous studies supporting the role of the superior parietal lobule in the performance of mental rotation [33,34]. Gender differences have been reported suggesting that women engage or recruit additional brain regions such as the frontal lobes, however the parietal region appears to be reliably activated by both genders [17,35,36]. Sev- eral studies but not all [17] have suggested that men outperform women on the mental rotation task [37] with some evidence for a positive relationship between performance on the task and circulating T levels [38,39]. Our results are certainly consistent with these previous