GABAergic orchestration of brain network states and cognitive ability in the young and old

How do we manage to accurately adapt behavior in a complex and dynamic environment? Accurate behavior requires the brain to consistently adapt distinct brain states given specific behavioral goals. This necessitates switching between functional networks.

It is established that the adaptation of functional networks into distinct brain states is altered in aging, and in neuropsychiatric and neurodegenerative diseases, with potentially severe consequences to behavior. There is no good mechanistic understanding of how the brain manages switching between functional networks.

In this project we propose that the brain´s most abundant inhibitory neurotransmitter GABA has a key role in maintaining a given brain state and in the switching between brain states.We will approach this problem using state of the art hybrid PET/fMRI imaging along with robust cognitive testing in a lifespan sample (20-80y).

Older adults will be stratified according to the presence of biomarkers yielding high risk to develop Alzheimer´s disease. [11C]flumazenil will be used to image both the availability of GABAA receptors during rest, and GABA release during the switching between brain states involving distinct functional networks.This research is of critical importance for approaching a mechanistic explanation of the brains ability to adapt in a complex environment, what explains individual differences in cognitive performance, and processes involved in age-related cognitive decline and Alzheimer´s disease.