Purpose: Our goal was to use functional MRI (fMRI) to measure brain ac
tivation in response to olfactory stimuli. Method: fMRI brain scans we
re obtained in 17 normal subjects (9 men, 8 women) using multislice FL
ASH MRI in response to three olfactory stimuli (pyridine, menthone, am
yl acetate) in three coronal brain sections selected from anterior to
posterior temporal brain regions. Activation images were derived using
correlation analysis, and ratios of areas of brain activated to total
brain areas were calculated. Results: Activation was present in each
section in all subjects. Subjective estimation of vapor intensity foll
owed relative vapor pressure of stimuli presented (pyridine > amyl ace
tate > menthone) and were similar for both men and women. However, bra
in activation did not follow subjective responsiveness order but rathe
r pyridine > menthone > amyl acetate, a pattern demonstrated by both m
en and women. Brain activation in women was consistently lower than in
men for all vapors in all brain sections, although regions of activat
ion did not differ. Activation occurred in regions previously recogniz
ed as associated with olfactory stimulation, including orbitofrontal a
nd entorhinal cortex; however, extensive regions within frontal cortex
including cingulate gyrus were also activated. Brain regions activate
d to odors considered pleasant or unpleasant did not differ. Conclusio
n: The techniques used in this study demonstrated that brain activatio
n to olfactory stimuli could be measured quantitatively such that diff
erences between groups of subjects (in this case men and women) could
be compared. Although localization of brain activation was not the maj
or thrust of this study, activation to olfactory stimuli was found not
only in brain regions previously associated with processing of olfact
ory information but also in several other areas of frontal cortex, in
cingulate gyrus, and in several components of the limbic system. This
is the first study in which activation in human brain parenchyma of no
rmal humans to olfactory stimuli has been quantitated by fMRI.