Hazlett et al51 reported that old adults who performed like young adults on a verbal memory study showed activation of occipital cortex to perform the verbal memory task, whereas young adults showed primarily dorsolateral prefrontal cortex activation. Cabeza48 distinguishes between dedifferentiation and compensation, suggesting that dedifferentiation involves a “difficulty in engaging Inhibitors,research,lifescience,medical specialized neural

mechanisms,” whereas compensation involves the recruitment of additional neural tissue from specific sites to “counteract neurocognitive deficits,” such as in instances of bilateral recruitment. We would argue that any additional recruitment of brain areas, even homologous areas, is Inhibitors,research,lifescience,medical a form of dedifferentiation, and that dedifferentiation with age may be neutral (has no effect on performance), compensatory (improves performance), or neuropathologi cal (worsens performance or predicts later neurological disease). One important

task of cognitive aging researchers is to understand these patterns and their implications for cognitive health and function, as well as whether they define a future cognitive trajectory. Dedifferentiation of executive functions and long-term memory Nearly all GABA activation studies of the neuroscience of cognitive aging have provided evidence for one of the dedifferentiation mechanisms described above. Executive Inhibitors,research,lifescience,medical function and long-term memory have been the focus of most neuroimaging studies on aging. A summary of some selected and representative findings from this voluminous literature appear below. More detailed reviews of the literature on aging, imaging, and cognitive processes arc available.48-52,56 Working Inhibitors,research,lifescience,medical memory and dedifferentiation. Perhaps the simplest statement about working memory and aging is that older and younger adults show different

patterns of brain activations on these tasks. Before discussing differences, it would be useful to briefly review our present understanding of the neural organization of working memory. There is general agreement that stimuli that have high processing Inhibitors,research,lifescience,medical demands are processed bilaterally in the dorsolateral prefrontal cortex.57-60 Bay 11-7085 Storage or maintenance functions in the working memory subsystems are lateralizcd for content and reside in the ventral lateral prefrontal cortex. Thus, when one presents tasks that are primarily storage-based, young adults will show left frontal activations for verbal materials and right frontal activations for visiospatial materials. The study by Reuter-Lorenz et al49 mentioned earlier provided evidence for contralateral recruitment of neural tissue for visiospatial and verbal working memory. In a related finding, Rypma and D’Esposito61 used an event-related fMRI design to study working memory and aging. Event-related designs permit the investigator to examine activation across the different phases of stimulus presentation, storage, and response.