Raichle, who has for decades taught and studied intrinsic brain activity, was one of the first to describe the default-mode network (Raichle et al., 2001), a web of interconnected brain regions that is most active when a person lets his or her mind wander. He showed that the brain actively suppresses the default network once a person does focus on a specific task, such as remembering a word list, solving a math problem, or navigating a route. The default-mode network became of intense interest to AD researchers when they found that people with subtle memory problems have trouble deactivating it while performing a task (see ARF related news story).

Using a variety of imaging techniques, including functional MRI and PET analysis of amyloid with Pittsburgh Compound B, Buckner and colleagues went on to show that the regions of this network coincide with where amyloid-β (Aβ) is most likely to be deposited and where the brain is most likely to shrink in AD (see ARF related news story). Buckner found that, in particular, the most highly interconnected areas of the cerebral cortex, the cortical hubs, produce the highest amounts of Aβ (see ARF related news story), perhaps as part and parcel of their high metabolic rate. The work indicates that something intrinsic about brain wiring leaves some regions susceptible to Aβ deposition, and suggests that detecting problems in these regions might offer a window into the earliest pathological changes in the AD brain, well before the emergence of symptoms.

Most recently, Raichle and colleagues found a connection between anaerobic glucose metabolism, or glycolysis, and the default-mode network. Though glucose can be fully oxidized to carbon dioxide and water, that does not always happen in the brain, even if enough oxygen is available for that purpose. Instead, some neurons opt to metabolize a certain amount of glucose via glycolysis. Raichle and colleagues discovered that those neurons are predominantly in the default-mode network (see ARF related news story), and that there is a tight correlation between those glycolytic regions and areas of amyloid deposition. That young adults utilize glycolysis in the default-mode network hints that susceptibility to AD might start much earlier than has been realized.

Raichle and Buckner will each receive a $50,000 personal check at a Metlife ceremony held today in New York. The Foundation will also donate $200,000 to each to further their research.—Tom Fagan.