Cherrier et al. BMC Cancer 2010, 10:1 http://www.biomedcentral.com/1471-2407/10/1 All paradigms ADTTime1 > ADTtime2 ENCODE ADTtime1 > ADTtime2 RECOG MATCH CTRtime1 > CTRtime2 ADTtime1 > ADTtime2 ΔADT > ΔCTR ADTtime1 > ADTtime2 ΔADT > ΔCTR precuneus, cuneus and lateral occipital lobe cuneus and lateral occipital lobe precuneus precuneus, cuneus and lateral occipital lobe cuneus and precuneus precuneus cuneus and precuneus precuneus Table 2 ACTIVATION CHANGES IN THE RIGHT PARIETAL AREA BETWEEN BASELINE (TIME 1) & TREATMENT (TIME 2) Paradigm Contrast Brain region of cluster (all are right sided) Cluster p-value 0.011 0.006 0.028 0.002 0.001 0.032 0.002 0.031 Area in cm3 4.72 3.9 2.15 5.63 6.74 2.17 6.26 2.34 Z-max 4.15 4.37 4.71 5.14 4.88 3.27 5.67 3.65 Page 6 of 8 Z-max MNI coordinates 26,-62,40 22,-88,-4 26,-68,44 18,-72,46 26,-64,36 26,-64,36 34,-90,8 34,-82,32 Figure 2 Reduced task-related activation in individual subjects during encoding, recognition and rotation at time2. Task specific ROIs were defined by significant activation (over crosshair viewing) during the individual tasks in a mixed-effects GLM and the average Z-scores within these regions were determined for each subject (and for each task) at time1 and time2. For each subject, the difference in average z-scores was calculated (time2 - time1) and thus negative scores represent a decrease in task-related activation within an individual. Each point represents time2 - time1 from a single subject. See Table 2 for statistical details. studies in demonstrating that parietal regions are acti- vated during the mental rotation task and extend these findings to reveal potential interactions with hormone levels. In addition to changes observed in the object rotation task, we also observed changes in neural activation from ADT during the recognition portion of the environmen- tal memory task. Encoding of the complex environments have been reliably shown to activate fusiform gyrus, anterior and posterior superior parietal cortex, medial frontal cortex, and occipital cortex [21,40] similar to patterns of activation observed for the present study. However, only the ADT group demonstrated a decrease in task-related activity at month 9 of androgen depriva- tion treatment compared to baseline in the right parietal lobe during the recognition portion of the EMT while both groups had decreased task-related activation during encoding. Both the environmental memory task and the mental rotation matching task have been shown to acti- vate the parietal region and there is some suggestion that this region may be related to spatial transformation processes (See [40] for discussion). Studies utilizing positron emission tomography (PET) techniques have also reported changes in neural activa- tion in response to changes in androgen levels. Hypogo- nadal (low testosterone) men demonstrate increases in cerebral glucose metabolism after 12 weeks of testoster- one treatment compared in occipital and frontal regions while performing a mental rotation task as measured by F-18-deoxyglucose (FDG) PET [41]. A longitudinal study of healthy, eugonadal older men found that higher free testosterone (T) levels were related with increased regio- nal cerebral blood flow (rCBF) as measured by serial [15O] PET in the hippocampus bilaterally, anterior cingu- late gyrus and right inferior frontal cortex during resting state [42]. A recent study of testosterone supplementa- tion in eugonadal men reported both increases and decreases in regional cerebral blood flow (rCBF) as mea- sured by [F-18] fluorodeoxy glucose (FDG) while per- forming a verbal memory recognition task [43]. Testosterone treatment resulted in increased glucose uti- lization in left entorhinal cortex, right posterior hippo- campus and right parahippocampal gyrus areas and decreased glucose utilization in right entorhinal cortex/ amygdala. A single summary of findings from these stu- dies is difficult given the wide variation of tasks from spa- tial to verbal and resting state as well as populations ranging from eugonadal and hypogonadal. However, there does appear to be general support for a modulation of neural activity in response to manipulation of andro- gens. A consistent pattern of findings amongst studies likely awaits further replication of hormone manipula- tion, imaging technique and cognitive task.