In the present study, we used positron emission tomography to investigate changes in regional cerebral blood flow (rCBF) during a general anesthetic infusion set to produce a gradual transition from the awake state to unconsciousness. Five right-handed human volunteers participated in the study. They were given propofol with a computer-controlled infusion pump to achieve three stable levels of plasma concentrations corresponding to mild sedation, deep sedation, and unconsciousness, the latter defined as unresponsiveness to verbal commands. During awake baseline and each of the three levels of sedation, two scans were acquired after injection of an H215O bolus. Global as well as regional CBF were determined and correlated with propofol concentrations. In addition, blood flow changes in the thalamus were correlated with those of the entire scanned volume to determine areas of coordinated changes. In addition to a generalized decrease in global CBF, large regional decreases in CBF occurred bilaterally in the medial thalamus, the cuneus and precuneus, and the posterior cingulate, orbitofrontal, and right angular gyri. Furthermore, a significant covariation between the thalamic and midbrain blood flow changes was observed, suggesting a close functional relationship between the two structures. We suggest that, at the concentrations attained, propofol preferentially decreases rCBF in brain regions previously implicated in the regulation of arousal, performance of associative functions, and autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.

Three studies were performed to assess the effects of a high-fat diet and exercise-induced changes in fat oxidation on energy intake in humans. In the first study the short-term effect of a high-fat diet on spontaneous energy intake was investigated. The second study evaluated the long-term effect of a high-fat diet on adiposity and the third study evaluated the effect of exercise-induced changes in fat oxidation on short-term regulation of energy intake when subjects were consuming a high-fat diet. The results of these studies indicate that a high-fat diet induces a short-term hyperphagia, a high percentage of lipids in the usual diet is associated with a higher adiposity, and exercise may attenuate or amplify the high-fat, diet-induced hyperphagia, depending on the magnitude of the exercise-induced increase in fat oxidation.

These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.

The auditory middle latency response (AMLR) and the 40-Hz auditory steady-state response (40-Hz ASSR) are evoked potentials which possibly arise from the same generators in the primary auditory cortex. Both responses are attenuated by most general anaesthetics. Ketamine, however, has been reported to have no effect on the AMLR. Our aim was to evaluate the effects of ketamine on the 40-Hz ASSR. Spectral analysis of the electroencephalogram (EEG) was also conducted to independently examine the effects of ketamine. Ketamine 1.5 mg kg-1 was given to 12 patients for induction of general anaesthesia. Recordings of the 40-Hz ASSR and EEG were obtained every minute from 3 min before administration of ketamine to 5 min after injection, when the study was terminated. Similar recordings were obtained in three control subjects under identical conditions except that no medication was administered. Consciousness, defined as responsiveness to verbal commands, was assessed before each recording. Ketamine caused an increase in the amplitude of the 40-Hz ASSR (P < 0.01). Using published AMLR data, we conducted a simulation experiment that suggested that the effect of ketamine on the AMLR can explain its effects on the amplitude of the 40-Hz ASSR. There was a pronounced increase in relative theta (3.9-7.9 Hz) EEG power and a decrease in relative alpha (8.0-12.8 Hz) power (P < 0.001). These changes were not observed in the control group. Ketamine produced unconsciousness until the end of the study in five patients and transient unconsciousness in five patients. Two patients did not lose consciousness after administration of ketamine. The 40-Hz ASSR and EEG revealed no consistent differences between conscious and unconscious patients. No relationship could be demonstrated between the increase in amplitude of the 40-Hz ASSR or of relative theta power (the hallmark of ketamine effect) and loss of responsiveness to commands. We conclude that ketamine, unlike other anaesthetics, increases the amplitude of the 40-Hz ASSR.