IN-VIVO IMAGING OF HUMAN LIMBIC RESPONSES TO NITROUS-OXIDE INHALATION

Human behavioral studies have shown that nitrous oxide, in subanesthet ic concentrations, impairs psychomotor function, cognitive performance , and learning and memory processes. However, the cerebral mechanisms of such effects remain unknown. Positron emission tomography (PET) was used to map the brain areas associated with nitrous oxide effects. Re gional cerebral blood flow (rCBF) was measured in eight volunteers, du ring room air (control) or 20% nitrous oxide (nitrous oxide) inhalatio n using O-15-water, to reflect regional neuronal activity. To control for the possibility that 20% nitrous oxide uncoupled cerebral blood fl ow and metabolism, in four of the subjects, regional cerebral metaboli c rate (rCMR) was also measured using F-18-deoxyglucose during the two experimental conditions. Results of rCBF and rCMR scans were compared between conditions using the statistical parametric mapping method, a nd areas of nitrous oxide-related activation or deactivation were iden tified at a significance level of 0.005. Percent changes in rCBF scan pixels from these activated or deactivated areas were then compared wi th those of stereotactically corresponding rCMR scan pixels with t sta tistics (P < 0.05 was defined as a significant difference). It was fou nd that cerebral blood flow and metabolism were not uncoupled by 20% n itrous oxide, since percent changes in rCBF and rCMR, detected during nitrous oxide inhalation, did not differ significantly from each other (P < 0.05). Nitrous oxide inhalation was associated with significant activation in the anterior cingulate cortex, a limbic area known to me diate psychomotor and cognitive processes. Deactivation was found in t he posterior cingulate, hippocampus, parahippocampal gyrus, and visual association cortices in both hemispheres; the former two regions are known to mediate learning and memory. These areas identified by PET in vivo may provide the neuroanatomical basis for the behavioral respons es associated with subanesthetic nitrous oxide inhalation.