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.