Context-dependent, neural system-specific neurophysiological concomitants of ageing: mapping PET correlates during cognitive activation

We used PET to explore the neurophysiological changes that accompany cognit ive disability in ageing, with a focus on the frontal lobe. Absolute region al cerebral blood flow (rCBF) was measured in 41 healthy volunteers, evenly distributed across an age range of 18-80 years, during two task paradigms: (i) the Wisconsin Card Sorting Test (WCST), which depends heavily on worki ng memory and is particularly sensitive to dysfunction of the dorsolateral prefrontal cortex (DLPFC); and (ii) Raven's Progressive Matrices (RPM), whi ch may also have a working memory component, but depends more on visuo-spat ial processing and is most sensitive to dysfunction of postrolandic regions . We used voxel-wise correlational mapping to determine age-related changes in WCST and RPM activation and developed a method to quantitate and locali ze statistical differences between the correlation maps for the two task pa radigms. Because both WCST and RPM performance declined with age, as expect ed, correlational analyses were performed with and without partialling out the effect of task performance. Task-specific reductions of rCBF activation with age were found in the DLPFC during the WCST and in portions of the in ferolateral temporal cortex involved in visuo-spatial processing during the RPM. We also found reduced ability to suppress rCBF in the right hippocamp al region during the WCST and in mesial and polar portions of the prefronta l cortex during both task conditions. Task-dependent alterations with age i n the relationship between the DLPFC and the hippocampus were also document ed; because the collective pattern of changes in the hippocampal-DLPFC rela tionship with ageing was opposite to that seen in a previous study using de xtroamphetamine, we postulated a dopaminergic mechanism. These results indi cate that, despite some cognitive overlap between the two tasks and the age -related cognitive decline in both, many of the changes in rCBF activation with age were task-specific, reflecting functional alteration of the differ ent neural circuits normally engaged by young subjects during the WCST and RPM. Reduced activation of areas critical for task performance i.e. the DLP FC during the WCST and posterior visual association areas of the inferolate ral temporal cortex during the (RPM), in conjunction with the inability to suppress areas normally not involved in task performance (i.e. the left hip pocampal region during the WCST and mesial polar prefrontal cortex during b oth the WCST and RPM), suggest that, overall, reduced ability to focus neur al activity may be impaired in older subjects. The context dependency of th e age-related changes is most consistent with systems failure and disordere d connectivity.