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Failure to suppress irrelevant brain activity in Alzheimer disease

September 20, 2005

Some people close their eyes when they listen to music, others wear earplugs when they read in noisy places. Both serve to block out inappropriate sensory stimulation, something that happens automatically when we concentrate. A study by Alexander Drzezga and colleagues (of the Technical University Munich, Germany) to be published in the international open access journal PLoS Medicine now shows that this focusing process is defective in people with Alzheimer disease (AD).

Earlier brain imaging studies have shown how the focusing process works in healthy people: When they undergo tasks that depend exclusively on visual clues, they not only activate the areas of the brain involved in visual processing but also de-activate those areas that have to do with auditory processing. The reverse activation/deactivation pattern is seen when the clues are exclusively auditory. The phenomenon, called "cross-modal auditory/visual deactivation," is thought to help with focusing the information processing capacities of the brain on the relevant areas.

To test whether cross-modal inhibition is affected in AD, Drzezga and colleagues examined the activation and deactivation patterns in the brains of patients with AD and individuals with mild cognitive impairment (MCI). The researchers tested 32 participants: 11 healthy individuals, 11 individuals with mild cognitive impairment, and 10 individuals with moderate AD. The participants were trained to perform a navigation task, based exclusively on visual clues, in a virtual reality environment. All participants understood the task and the clues. They then each completed 12 separate PET scans, 8 during active navigation (finding their way from a start point to a specific destination) and 4 under control conditions (traveling along a never-ending pathway). The tasks were performed in complete silence.

The three groups differed in their performance-measured by the time needed to reach the destination-as would be expected. In the scans, the researchers saw significant differences in brain activation patterns, but most striking were differences in the ability to inhibit irrelevant activity: Healthy individuals showed strong bilateral deactivation in the auditory cortex. Auditory deactivation was much less prominent in individuals with MCI, and totally absent in individuals with AD.

Drzezga and colleagues propose that the patients' orientation disability in the outside world may be partially caused by their inability to selectively focus brain activity in task-relevant areas. They are now in the middle of a follow-up study that concentrates on individuals with MCI-some of whom remain stable for years whereas others progress to AD-to see whether the extent of cross-modal inhibition correlates with progression to disease. Preliminary results suggest that it does.



Public Library of Science