Function Brain imaging in disease: what are the activation maps really telling us?

Functional brain imaging methods such as functional magnetic resonance imaging (fMRI) have already revolutionized how we can study the processes and functioning of the healthy human brain and are making an increasing impact on our understanding on what goes wrong in disease of the brain. However, it is important to remember that the signals measured in techniques such as fMRI are not actually telling us about the activity of neurons, but are instead reflecting changes in brain blood flow. An increasingly important issue to address is how do we interpret brain imaging signals in the context of brain disease? It turns out that many of the biological mechanisms that are responsible for the coupling of neuronal activity to blood flow and therefore brain imaging signals may also be altered by common diseases of the brain such as depression, Alzheimer’s disease and stroke to name but a few. In this situation it becomes difficult to interpret brain imaging signals in people with brain diseases as they might either be telling us about the neuronal activity or they might be telling us about the actions of the diseases on these coupling processes. Without more research on this topic, it is difficult to distinguish between these two possibilities. This will substantially impair our future ability to apply functional brain imaging to investigate human brain disease and dysfunction and develop new treatments. This PhD project will involve using a range of in vivo techniques to measure neural activity and brain imaging signals investigate the effect of specific disease processes (such as neurodegeneration or altered neurotransmitter function) of how brain imaging signals relate to the activity of neurons in the clinical context.