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Background: Functional magnetic resonance imaging of blood oxygenation level-dependent signal changes offers a very promising approach to investigate activated neural networks during anesthesia, Methods: Sixteen healthy male volunteers, assigned into two groups of eight subjects (isoflurane group, control group), were investigated by functional magnetic resonance imaging during different experimental conditions, The isoflurane group successively breathed air (baseline condition), isoflurane in air (0.42 vol% inspiratory; isoflurane condition) and air again (recovery condition) while performing a visual search task, whereas the control group breathed air during all experimental conditions. Functional magnetic resonance images were acquired during the entire experimental session. In addition, reaction times and error rates were recorded. Results: A significant isoflurane-related decrease (z > 3.1 corresponding to P < 0.001) in task-induced brain activation was found in three distinct cortical regions: the right anterio-superior insula (Talairach coordinates: x = 32, y = 22, z = 8) and the banks of the left and right intraparietal sulcus (Talairach coordinates: x = -34, y = -36, z = 32; x = 22, y = -60, 41, respectively). Subcortical structures (lateral geniculate nucleus) and the primary cortices (motor cortex, visual cortex) were not affected, Ah measured parameters indicated a nearly complete recovery of the affected networks within 5 min, Conclusions: Our findings indicate that subanesthetic isoflurane affected task-induced activation in specific neural networks rather than causing a global decrease in functional activation.