Cherrier et al. BMC Cancer 2010, 10:1 http://www.biomedcentral.com/1471-2407/10/1 Table 1 SUMMARY OF STATISTICAL COMPARISONS Inputs STEP 1: ENCODE data ICA data review (Separate for each RECOG data paradigm and subject) MATCH data STEP 2: ENCODE* data Subject paradigm analysis (Separate RECOG* data for each paradigm and subject) STEP 3: Intra-subject analysis (Separate for each subject) STEP 4: Group time1 vs. time2 analysis STEP 5: Group paradigm analysis (Separate for each paradigm) STEP 6: Determining average z-scores (Separate for each paradigm and subject) MATCH* data C13 from each paradigm C21 from each subject C11 or C13 from each subject C13 from each subject n.a. EVs in model n.a. EV1: route (or 3D) EV2: survey (or 2D) Output/contrasts ENCODE* data RECOG* data MATCH* data C11 = EV1-EV2 C12 = EV2-EV1 EV3: fixation C13 = (EV1+EV2)-2*EV3 EV4-9: motion parameters of no C14 = 2*EV3-(EV1+EV2) interest EV1: time1 > time2 C21 = EV1 EV2-4: paired t-test parameters of no C22 = -EV1 interest EV1: ADT C31 = EV1 EV2: CTR C32 = -EV1 C33 = EV2 C34 = -EV2 C35 = EV1-EV2 C36 = EV2-EV1 EV1: ADTtime1 > ADTtime2 C41 = EV1 EV2: CTRtime1 > CTRtime2 C42 = -EV1 EV3-14: paired t-test parameters of no interest C43 = EV2 C44 = -EV2 C45 = EV1-EV2 C46 = EV2-EV1 n.a. Page 4 of 8 Independent components analysis (ICA), explanatory variable (EV), contrast (C) functional data was mapped onto their high-resolution structural images using 7 DOF and into standard space (MNI152 brain) with a 12 DOF affine transformation [28]. Registration was confirmed by visual inspection and manually re-aligned as appropriate. Individually for each subject, task-related activation at time1 was com- pared to time2 using a fixed-effects paired t-test. This allowed us to assess the change in task-related activation averaged across the three tasks for each subject. STEP 4: Between-group comparisons were done using a full mixed-effects GLM using the parameter estimates from STEP 3 as inputs [29,30] and activated clusters were identified based on random field theory correcting for multiple comparisons (FLAME). STEP 5: A post-hoc region of interest (ROI) analysis was performed sepa- rately for each paradigm to determine how time1 vs. time2 changes in the individual paradigm contributed to the findings in STEP 4. For STEP 4 a z-threshold of 2.7 and p < 0.01 was set to minimize type 1 error while for STEP 5 stringency was relaxed by decreasing the z- threshold to 2.0 and p < 0.05 to reduce type 2 error. STEP 6: A unique statistically defined ROI was generated for each paradigm corresponding to the region where ΔADT > ΔCTR (RECOG and MATCH) or ADTtime1 > ADTtime2 ∩ CTRtime1 > CTRtime2 (ENCODE). These three paradigm specific ROIs were used in the calculation of the average z-scores for indivi- dual subjects during the corresponding tasks within the parietal lobe. Results Both ADT patients and controls (CTR) ranged in age from 56 to 78 years with a mean age of 65 years and education ranged from 12 to 21 years with a mean edu- cation level of 17 years. Because the groups were range matched on age and education they were not signifi- cantly different on these demographic variables. One CTR and one ADT participant dropped out prior to baseline scanning due to concerns about ‘feeling closed in’ in the scanner. One CTR participant and two ADT patients did not complete the month 9 imaging session due to scheduling conflicts. Three CTR and ADT patients were not analyzed due to excessive motion. In all, seven controls and five ADT patients were included