The research will use optical imaging spectroscopy (OIS), laser Doppler flowmetry (LDF) and functional magnetic imaging (fMRI) to study the relationship between the hemodynamic responses to changes in neural activity. Neural activity will be measured using multi-channel microelectrodes. The combination of all these different techniques in one project is rare indeed and will provide a powerful approach to investigate the intrinsic signals underlying modern neuroimaging techniques. A central and integrating feature of the research is the OTT model (Oxygen Transport to Tissue), which is a dynamic biophysical model linking neural activity, through a capillary model of oxygen transport to tissue to the biophysics of the oxygenation and volume changes of the BOLD response. Mathematical relationships will be identified between the various intrinsic signals (blood oxygenation, flow and volume) and neural activity in the cortical laminae. The overall objective of the proposed research is to discover the relationships sufficient to invert the model so that from measurements of the intrinsic signals it is possible to make inferences concerning the neural activity in response to stimulation. In this regard the time series data from OIS, LDF and fMRI will be used to develop the 'forward' biophysical model. This can then be used in the development of the analysis methodologies needed to 'invert' measurements of the BOLD response. This will be of particular importance in the development of methods for the analysis of experiments exploiting modulatory interregional interaction as in event related fMRI studies. This research will be conducted in both anaesthetized and awake animals. In the awake animal preparation both the standard response to sensory stimulation and the modulatory effects of reinforcement induced 'cue salience' on the hemodynamic and neural responses will be investigated. In summary, the research will use an animal model (rat) to investigate the time series of both OIS (measurements of blood volume changes and oxygenation) and LDF (measurements of flow changes) and their relationship to measurements neural activity in the different cortical laminae using multi-channel silicon microelectrodes. This research will use both anaesthetized and awake animals.
