Functional magnetic resonance imaging (fMRI) is an indispensable tool for noninvasively mapping human brain functions in the research and clinical settings. However, fMRI indirectly measures neuronal activity via the vascular response to the increased metabolic demand of functioning neurons. Thus, several problems exist including: 1) unknown contributions of inhibitory neuronal activity to the fMRI signal and 2) unknown spatial specificity of the fMRI signal to the sites of neuronal activity. Resolving these issues are criticl for the accurate interpretation of fMRI maps because the site of increased fMRI signal could actually indicate a decrease in neuronal activity or could indicate a mere vascular artifact without accompanying neuronal activity. The objective in this particular application is to determine 1) whether the activation of inhibitory neurons increases the fMRI signal and 2) whether the activation of a specific layer evokes fMRI signal changes only to that layer. To attain this objective, we will apply well-established techniques to the in vivo olfactory bulb model. Since the olfactory bulb consists of distinctive layers containing sharply differentiated cel types, it allows us to activate only inhibitory neurons and to selectively activate individual layes by stimulating remote fibers to (or from) the bulb, which cannot be accomplished in other brain regions. Once the project is fulfilled, it is our expectation that important insights will be brougt into neurovascular coupling. Lack of such knowledge is a serious problem, because, without it, comprehensive understanding of the neural basis of fMRI and the ultimate spatial resolution of fMRI are highly unlikely. Such findings will also lay the groundwork for further studies about how neurovascular coupling is impaired in neurodegenerative diseases expressing olfactory dysfunction, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, etc. For example, massive cortical feedback projections that target olfactory bulb inhibitory neurons may be compromised in such diseases. Thus, understanding how inhibitory neuronal activities link to vascular responses and whether fMRI detects activation at the laminar resolution are of clinical relevance.
The proposed research is relevant to public health because the establishment of neural basis of functional MRI and its ultimate spatial resolution is expected to advance the diagnosis and treatment planning of diseases that are associated with neurological disorders.
