Neurovascular coupling under the microscope

One of the major remaining scientific frontiers is to understand the workings of the human brain. One of the most advanced methods of investigating brain function is to use functional Magnetic Resonance Imaging (fMRI). However, fMRI does not measure neural activity; rather, it measures the changes in blood volume and oxygen consumption associated with neural activity. This relationship between nerves and blood vessels in the brain is called neurovascular coupling. Though the existence of neurovascular coupling was first discovered over a century ago, to this day how it actually occurs is poorly understood. The research we will perform will try and understand exactly what the relationships and mechanisms of neurovascular coupling are using a anaesthetised rat preparation. A greater understanding of the fMRI signal will lead to increased sophistication in ways to exploit the technique, both in the design of complex experiments and more importantly, how they should be interpreted. Increased understanding of neurovascular coupling will also have wider implications. There are many diseases or illnesses involving changes in neurovascular coupling, including Alzheimers, stroke and brain tumours. If we can uncover how the healthy brain regulates its blood supply we will be in a better position to address problems when this relationship breaks down.

The immediate focus of the proposed research will be to investigate the relationship between neural activity and hemodynamic responses at high spatial resolution.

Neuroimaging procedures such as functional magnetic resonance imaging (fMRI) and optical recording of intrinsic signals can track changes in brain activity as tasks are being performed. Such techniques provide an indirect measure of neural activity based on the spatio-temporal coupling between local changes in neuronal firing and local changes in associated hemodynamic variables. Hence, the interpretation of neuroimaging data is critically dependent on a good understanding of the mechanism(s) of neurovascular coupling. However, an important unresolved issue concerns the fine spatial detail of neurally-evoked hemodynamic responses. This is important because it will place an upper limit on the absolute spatial resolution of neuroimaging techniques. With the advent of more sensitive procedures for measuring simultaneous neural and hemodynamic changes, the focus of work will be to direct this technology to investigate the fine details of neurovascular coupling within fundamental processing units of the brain e.g. the single cortical column. The rat whisker/barrel cortex will, therefore, be the model of choice for this investigation. The somatotopic organisation of this brain region is ideal to investigate the fine spatiotemporal resolution of neural and hemodynamic responses since each facial whisker projects directly to a local cell dense region of cerebral cortex called a ?barrel?. We have developed a range of techniques providing precise measurements of neural and hemodynamic variables, including: 2-dimensional optical imaging spectroscopy (2D-OIS), laser Doppler flowmetry, 16-channel multi-unit and local field-potential electrophysiology, and fMRI.

The project will measure the precise relationship between the neural activity and hemodynamic responses evoked by single whisker stimulation. The investigation will proceed to elucidate the mechanisms directly involved in the processes of neurovascular coupling. Measurement of the fine spatial resolution responses from single whisker stimulation will provide data needed to refine current mathematical models of the biophysical nature of fMRI signals, e.g. the blood oxygen level dependent (BOLD) effect. A better understanding of neurovascular coupling will also have wider implications than just those described for fMRI. There are many diseases or illnesses involving changes in neurovascular coupling including Alzheimers disease, stroke and brain tumours. If we can uncover how the healthy brain is able to regulate its blood supply, we will certainly be in a better position to address problems that arise when this relationship is disturbed by pathological processes.