Stimulated changes in localized cerebral energy consumption under anesthesia

Abstract

Focal changes in the cerebral metabolic rate of glucose utilization (CMR glc ) are small (10-40%) during sensory activation in awake humans, as well as in awake rodents and primates (20-50%). They are significantly larger (50-250%) in sensory activation studies of anesthetized rats and cats. Our data, in agreement with literature values, show that in the resting anesthetized state values of CMR glc are lower than in the resting nonanesthetized state whereas the final state values, reached upon activation, are similar for the anesthetized and nonanesthetized animals. The lower resting anesthetized state values of CMR glc explain why the increments upon activation from anesthesia are larger than when starting from the nonanesthetized conditions. Recent 13 C NMR measurements in our laboratory have established a quantitative relationship between the energetics of glucose oxidation, CMR glc (oxidative), and the f lux of the glutamate͞ ␥-aminobutyric acid͞glutamine neurotransmitter cycle, V cycle . In both the resting awake value of CMR glc (oxidative), and its increment upon stimulation, a large majority (Ϸ80%) of the brain energy consumption is devoted to V cycle . In the differencing methods of functional imaging, it is assumed that the incremental change in the measured signal represents the modular activity that supports the functional response. However, the same amount of activity must be present during the response to stimulation, irrespective of the initial basal state of the cortex. Thus, whereas the incremental signals of ⌬CMR glc can localize neurotransmitter activity, the magnitude of such activity during the response is represented by the total localized CMR glc , not the increment.Modern imaging methods detect regional changes in functional brain activity by assuming coupling between brain glucose metabolism and the underlying neuronal activity. The principle that the rate of glucose metabolism in the brain reflects functional activity was first expressed by Roy and Sherrington in 1890 (1). Since that time, there has been great progress in understanding the neuronal processes that support brain function such as action potentials and neurotransmitter action (2-4), but understanding of the coupling between these cellular processes and glucose metabolism has been limited (5). Only recently has there been evidence for a stoichiometric relationship between glucose oxidation and functional neuronal processes, in particular, to neurotransmitter fluxes (6).For a variety of technical reasons, functional metabolic imaging measures increments in regional brain glucose metabolism in response to peripheral stimulation. § During sensory stimulation these increments generally are small in awake humans (10) and animals (11), with a maximum increase of about 40% for intense stimulations (12, 13). Increments of about 10% are more usual during physiological visual stimuli (14, 15) or cognitive tasks (16). The focus on incremental glucose metabolism has led to the prevailing view in the field that the increment repr...

Brain-state–independent neural representation of peripheral stimulation in rat olfactory bulb

“…3), but can vary with brain states. However, the total activity for a given stimulus is invariable in different brain states, consistent with the speculation that the total activity represents the event itself (61). However, the neurochemical and neurophysiological basis for these observations are barely known.…”

The Influence of Carbon Dioxide on Brain Activity and Metabolism in Conscious Humans

“…Kety and Schmidt (1948) and Novack et al (1953) used human subjects, and the more recent studies all used animal subjects under anesthesia. It is known that anesthetic agent itself may affect neural activity and metabolism (Shulman et al, 1999). A change in CMRO 2 because of hypercapnia also has important implications for calibrated fMRI.…”

“…More recent findings in brain slices and anesthetized animals provided evidence at the cellular level that higher CO 2 partial pressure can have a profound effect on neural tissue including reducing pH, elevating adenosine concentration, and suppressing synaptic potentials (Dulla et al, 2005;Gourine et al, 2005;Zappe et al, 2008b). However, these previous studies were largely performed under laboratory conditions, and it is unclear if the results were influenced by certain factors including the anesthetic agent, which by itself will reduce neural activity (Shulman et al, 1999). We are therefore interested in conducting measurements in conscious human subjects under physiologically relevant conditions.…”

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