The overall purpose of the work proposed is to better understand the physical and physiological factors that affect the BOLD (blood oxygenation level dependent) signals detected in functional magnetic resonance imaging (fMRI). FMRI is a very important addition to the methods available for non-invasive mapping of the human brain, and is being widely used in clinical medicine as well as in basic studies of cognition. Although there is general agreement about how BOLD signals originate, there are still many features of the BOLD effect that are uncertain, and the influence of several factors is unknown, especially for so-called event-related fMRI. These deficits in understanding limit our ability to interpret fMRI data quantitatively. Furthermore, we do not understand well what limits the sensitivity of fMRI in practice, nor what gains may be possible as higher field strength magnets become more widely available. In the next phase of this grant we will quantify the effects of several technical and physical factors that modify the shape and amplitude of transient event-related fMRI responses. In both a rat model of somatosensory activation and human cortex, we will quantify the effects of field strength, pulse sequence, stimulation parameters, and intrinsic blood susceptibility, on the latency, magnitude and duration of event related responses, and verify these may add non-linearly when closely spaced. We will also quantify the effects of several physiological and pharmacological factors that commonly vary in humans subjects on the event-related responses, including the effects of altered basal flow, mild hypoglycemia, reduced hematocrit, levels of blood carbon monoxide, nicotine and caffeine, and estrogen, on the characteristics of the event-related BOLD signal. In order to clarify the validity of current models that are used to relate BOLD signals to underlying metabolic and physiological changes, we will measure the relationship between cerebral blood volume and flow in a rat model with graded hypercapnia and with neural stimulation, Finally, we will quantify and characterize the sources of noise that affect the fMRI signal. We will measure the contributions to signal variance that may arise from cardiac, respiratory, movements and vasomotor effects, and assess how these affect the fMRI signal/noise ratio, for different choices of technical factors including field strength, pulse sequence, echo time, and spatial resolution. These studies will further our efforts to understand and interpret data provided from fMRI better, and provide important insights into how to improve the quality of information obtainable by fMRI in diverse applications at different field strengths.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS033332-05
Application #
6199125
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Heetderks, William J
Project Start
1995-06-01
Project End
2004-04-30
Budget Start
2000-06-15
Budget End
2001-04-30
Support Year
5
Fiscal Year
2000
Total Cost
$415,285
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Tang, Lin; Avison, Malcolm J; Gore, John C (2009) Nonlinear blood oxygen level-dependent responses for transient activations and deactivations in V1 - insights into the hemodynamic response function with the balloon model. Magn Reson Imaging 27:449-59
Tang, Lin; Avison, Malcolm J; Gatenby, James C et al. (2008) Failure to direct detect magnetic field dephasing corresponding to ERP generation. Magn Reson Imaging 26:484-9
Leung, H-C; Gore, J C; Goldman-Rakic, P S (2005) Differential anterior prefrontal activation during the recognition stage of a spatial working memory task. Cereb Cortex 15:1742-9
Zeng, Huairen; Gatenby, J Christopher; Zhao, Yansong et al. (2004) New approach for correcting distortions in echo planar imaging. Magn Reson Med 52:1373-8
Olson, Ingrid R; Gatenby, J Christopher; Leung, Hoi Chung et al. (2004) Neuronal representation of occluded objects in the human brain. Neuropsychologia 42:95-104
Olson, Ingrid R; Gatenby, J Christopher; Gore, John C (2002) A comparison of bound and unbound audio-visual information processing in the human cerebral cortex. Brain Res Cogn Brain Res 14:129-38
Gauthier, Isabel; Hayward, William G; Tarr, Michael J et al. (2002) BOLD activity during mental rotation and viewpoint-dependent object recognition. Neuron 34:161-71
Leung, H-C; Gore, J C; Goldman-Rakic, P S (2002) Sustained mnemonic response in the human middle frontal gyrus during on-line storage of spatial memoranda. J Cogn Neurosci 14:659-71
Jacobsen, Leslie K; Gore, John C; Skudlarski, Pawel et al. (2002) Impact of intravenous nicotine on BOLD signal response to photic stimulation. Magn Reson Imaging 20:141-5
Dutka, Michael V; Scanley, B Ellen; Does, Mark D et al. (2002) Changes in CBF-BOLD coupling detected by MRI during and after repeated transient hypercapnia in rat. Magn Reson Med 48:262-70

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