Neurovascular coupling during different information processing states

Lay summary

Disorders of the brain represent a great cost to society. To further understanding of disorders such as schizophrenia and depression we need to be able to watch the human brain at work. There are techniques which can image function in the living brain such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). However, these techniques are based on the metabolic changes that accompany brain activity rather than measuring brain activity itself. These metabolic demands are satisfied by increased blood flow to active areas of the brain in much the same way as increased muscular activity involves increased blood flow to the muscles. Changes in the proportions of oxygenated and deoxygenated blood produce changes in the magnetic resonance BOLD (blood oxygen level dependent) signal which is then used to identify active brain regions. The interpretation of experiments conducted with this technique are hindered by a lack of understanding of the relationships between brain activity, blood oxygenation and the magnetic resonance signal. Although progress has been made in understanding these relationships there are many aspects that remain unresolved. How the relationship between brain activity and imaging signals changes during different ?brain states? such as those produced by attention or arousal is poorly understood. This is the purpose of the proposed research. The results of the proposed experiments will be used to inform the design and analysis of fMRI studies in humans.

The focus of the proposed research is to investigate the relationship between neural activity, hemodynamics and magnetic resonance imaging signals during different states of cortical information processing. Non-invasive human brain imaging techniques such as blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) rely on changes in blood flow, volume and oxygenation (collectively referred to as the hemodynamic response) to infer the loci and magnitude of changes in brain activity. As such techniques are based on indirect measures they are difficult to correctly interpret in terms of underlying brain activity. Although much progress has been made in understanding the link between stimulus-evoked neural activity, hemodynamics and the blood oxygen level dependent (BOLD) fMRI signal, the extent to which neurovascular-coupling relationships remain constant during different states of information processing is poorly understood. This proposal addresses this issue in a rat model using combinations of the following in vivo techniques: optical imaging, laser Doppler flowmetry, multi-channel electrophysiology, polargraphic measurements of oxygen tension in brain tissue and fMRI. The relationship between sensory-evoked neural activity, metabolic responses and imaging signals will be investigated at different states of cortical synchronisation and information processing. Responses to whisker stimuli will be recorded in the barrel cortex of anaesthetised rodents and cortical information processing state will be modulated by electrical and chemical stimulation of afferent brain stem structures. Pilot data indicate that changes in cortical state are likely to be accompanied by changes in blood flow. Therefore to dissociate the effects of changes in cortical state and changes in blood flow, data will be collected during hypercapnia. At low levels hypercapnia (elevated blood CO2) increases blood flow without altering neural activity. This proposal will impact on the interpretation of human imaging data.