PROJECT SUMMARY/ABSTRACT – OVERALL
We seek to understand the nature of the pial neurovascular circuit, whose dynamics is characterized by
ultralow frequency oscillations near 0.1 Hz that parcellate into separate coherent regions across cortex. We will
use this knowledge to form a mathematical relation between the hemodynamic patterns observed in optical
and functional magnetic resonance imaging experiments and the underlying brain state.
Our proposed studies propose to leverage our experimental expertise in in vivo optical microscopy in
mouse and fMRI in mouse and human. These primary modalities for data acquisition are combined with
behavioral training, electrophysiology, and data analysis. Our experimental effort is parallel by two theoretical
efforts. One mixed analytical/computational effort is on coupled oscillator dynamics to formulate models, at
varying levels of complexity, of the pial neurovascular circuit. A second solely computational effort concerns
the modulation of the transport of oxygen, by regional oscillations of the pial neurovascular circuit.
The pial neurovascular circuit is composed of a two-dimensional network of pial arterioles that undergo
rhythmic oscillations in the ~ 0.1 Hz vasomotor band. Each element in this circuit - a segment of arteriole
whose diameter is modulated by the constriction/dilation of smooth muscle, contains an intrinsic rhythm
generator, much like intrinsic bursting neurons in central pattern generators. The pial arterioles integrate
neuronal activity from neighboring arterioles, underlying neurons, subcortical neurons, and neuromodulatory
centers to produce dynamic patterns of coherent oscillations in arteriolar diameter across the cortical mantle.
These patterns contain regions that oscillate at slightly different frequencies, i.e., they parcellate into separate
regions. The fascinating issue is that the parcellation only partially reflects input from the directly underlying
neuronal input. We seek to understand, model, and exploit this parcellation.
The PIs have collaborated on issues in neuroscience and neurovascular science for many years. This
proposal is a result of their discoveries and converging interest in a structured collaborative effort. Project 1 will
formulate an understanding of fundamental physiology of the pial neurovascular circuit. This includes
determining if brain arterioles truly act as interacting non-linear oscillators, i.e., that they entrain and phase-lock
rather than passively filter. Projects 1, 2, and 4 will explore experimentally and theoretically how four
competitive interactions, viz, input from neighboring arterioles, (ii) input from underlying neurons, (iii) input from
subcortical areas involved in homeostasis; and (iv) input from brain neuromodulatory centers, lead to the
observed patterns of pial neurovascular activity. Projects 2 and 4 will explore and model the regulation of
oxygen in subsurface vessels, while Project 3 will expand the resolution of MR imaging in humans to observe
single vessels CBV changes and thus measure pial neurovascular dynamics with unparalleled resolution. A
particular interest is to transform spatiotemporal patterns of vasomotion into predictions of internal brain state.
