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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS044567-03
Application #
6793329
Study Section
Special Emphasis Panel (ZNS1-SRB-R (01))
Program Officer
Babcock, Debra J
Project Start
2002-09-15
Project End
2007-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2004
Total Cost
$135,000
Indirect Cost
Name
University of Sheffield
Department
Type
DUNS #
228147328
City
Sheffield
State
Country
United Kingdom
Zip Code
S10 2-GW
Zheng, Ying; Pan, Yi; Harris, Sam et al. (2010) A dynamic model of neurovascular coupling: implications for blood vessel dilation and constriction. Neuroimage 52:1135-47
Kennerley, Aneurin J; Berwick, Jason; Martindale, John et al. (2009) Refinement of optical imaging spectroscopy algorithms using concurrent BOLD and CBV fMRI. Neuroimage 47:1608-19
Zheng, Ying; Mayhew, John (2009) A time-invariant visco-elastic windkessel model relating blood flow and blood volume. Neuroimage 47:1371-80
Martindale, John; Kennerley, Aneurin J; Johnston, David et al. (2008) Theory and generalization of Monte Carlo models of the BOLD signal source. Magn Reson Med 59:607-18
Martin, Chris; Martindale, John; Berwick, Jason et al. (2006) Investigating neural-hemodynamic coupling and the hemodynamic response function in the awake rat. Neuroimage 32:33-48
Martin, Chris; Jones, Myles; Martindale, John et al. (2006) Haemodynamic and neural responses to hypercapnia in the awake rat. Eur J Neurosci 24:2601-10
Kennerley, Aneurin J; Berwick, Jason; Martindale, John et al. (2005) Concurrent fMRI and optical measures for the investigation of the hemodynamic response function. Magn Reson Med 54:354-65
Martindale, John; Berwick, Jason; Martin, Chris et al. (2005) Long duration stimuli and nonlinearities in the neural-haemodynamic coupling. J Cereb Blood Flow Metab 25:651-61
Kong, Yazhuo; Zheng, Ying; Johnston, David et al. (2004) A model of the dynamic relationship between blood flow and volume changes during brain activation. J Cereb Blood Flow Metab 24:1382-92