Behind the scenes of functional brain imaging: A historical and physiological perspective

Abstract

At the forefront of cognitive neuroscience research in normal humans are the new techniques of functional brain imaging: positron emission tomography and magnetic resonance imaging. The signal used by positron emission tomography is based on the fact that changes in the cellular activity of the brain of normal, awake humans and laboratory animals are accompanied almost invariably by changes in local blood flow. This robust, empirical relationship has fascinated scientists for well over a hundred years. Because the changes in blood flow are accompanied by lesser changes in oxygen consumption, local changes in brain oxygen content occur at the sites of activation and provide the basis for the signal used by magnetic resonance imaging. The biological basis for these signals is now an area of intense research stimulated by the interest in these tools for cognitive neuroscience research.Over the past 10 years the field of cognitive neuroscience has emerged as a very important growth area in neuroscience. Cognitive neuroscience combines the experimental strategies of cognitive psychology with various techniques to actually examine how brain function supports mental activities. Leading this research in normal humans are the new techniques of functional brain imaging: positron emission tomography (PET) and magnetic resonance imaging (MRI) along with event-related potentials obtained from electroencephalography or magnetoencephalography.The signal used by PET is based on the fact that changes in the cellular activity of the brain of normal, awake humans and unanesthetized laboratory animals are invariably accompanied by changes in local blood flow (for a review, see ref. 1). This robust, empirical relationship has fascinated scientists for well over a hundred years, but its cellular basis remains largely unexplained despite considerable research.More recently it has been appreciated that these changes in blood flow are accompanied by much smaller changes in oxygen consumption (2, 3). This leads to changes in the actual amount of oxygen remaining in blood vessels at the site of brain activation (i.e., the supply of oxygen is not matched precisely with the demand). Because MRI signal intensity is sensitive to the amount of oxygen carried by hemoglobin (4), this change in blood oxygen content at the site of brain activation can be detected with MRI (5-8).Studies with PET and MRI and magnetic resonance spectroscopy (MRS) have brought to light the fact that metabolic changes accompanying brain activation do not appear to follow exactly the time-honored notion of a close coupling between blood flow and the oxidative metabolism of glucose (9, 10). Changes in blood flow appear to be accompanied by changes in glucose utilization that exceed the increase in oxygen consumption (11, 12), suggesting that the oxidative metabolism of glucose may not supply all of the energy demands encountered transiently during brain activation. Rather, glycolysis alone may provide the energy needed for the transient changes in brain activity ...

Real-time electrochemical monitoring of brain tissue oxygen: A surrogate for functional magnetic resonance imaging in rodents

“…We have previously shown that LIVE measurements of tissue O 2 are closely related to CBF (Lowry et al, 1997), and it has been assumed, but not proven, that BOLD fMRI signals induced during neuronal activity reflect tissue O 2 levels (Dousset et al, 1999;Thompson et al, 2003Thompson et al, , 2004Thompson et al, , 2005Raichle, 1998). The findings of this study now provide strong evidence to support this assumption and demonstrate that this novel combined technology provides a means of interrogating the relationships between metabolism, haemodynamics and neuronal activity.…”

Common deactivation patterns during working memory and visual attention tasks: An intra‐subject fMRI study at 4 Tesla

“…Nevertheless, studies in rodents using optical imaging of hemoglobin oxygenation, and physiological recordings of spiking activity and local field potentials have shown that the negative hemodynamic activity might not correspond to changes in neuronal activity (Devor, et al 2005). fMRI deactivation may also represent a direct hemodynamic response ("blood stealing") in the vascular system in response to changes in adjacent regional cerebral blood flow (rCBF), since negative BOLD signals are accompanied by decreases in rCBF (Hoge, et al 1999b;Raichle 1998;Shmuel, et al 2002;Stefanovic, et al 2004). In this model, rCBF-increases (Δ + )in activated regions would necessitate synchronous rCBF-decreases (Δ − in other brain regions (Δ + = kΔ − , where the constant k depends on the vascular distribution).…”

Functional Tissue Pulsatility Imaging of the Brain During Visual Stimulation

“…As early as the 1870s it was observed that mental activity influences regional brain physiology (Raichle 1998). Several researchers demonstrated that the surface pulsations and the temperature of the brain increase with mental activity (Raichle 1998).…”

“…Several researchers demonstrated that the surface pulsations and the temperature of the brain increase with mental activity (Raichle 1998). The technology necessary to pursue this research was limited, and it was not until the 1950s that the first instrument for quantifying whole brain blood flow and metabolism in humans was developed (Landau et al 1956).…”