Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.
The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements.
Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
Clarisse I
CI
Mark
Department of Radiology, University of Calgary, Calgary, AB, Canada.
Erin L
EL
Mazerolle
Rotman Research Institute, Baycrest, University of Toronto, Toronto, ON, Canada.
J Jean
JJ
Chen
D001783:Blood Flow Velocity / Q000502:physiology*; D001810:Blood Volume / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D001927:Brain Diseases / Q000175:diagnosis / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D059907:Functional Neuroimaging / Q000379:methods*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008955:Models, Cardiovascular; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D012146:Rest
calibrated BOLD; cerebral metabolic rate of oxygen consumption; cerebrovascular reactivity; neuropathology; neurovascular uncoupling; resting-state functional connectivity