Activation of olfactory and trigeminal cortical areas following stimulation of the nasal mucosa with low concentrations of S(-)-nicotine vapor--an fMRI study on chemosensory perception

Abstract

Applied to the nasal mucosa in low concentrations, nicotine vapor evokes odorous sensations (mediated by the olfactory system) whereas at higher concentrations nicotine vapor additionally produces burning and stinging sensations in the nose (mediated by the trigeminal system). The objective of this study was to determine whether intranasal stimulation with suprathreshold concentrations of S(-)-nicotine vapor causes brain activation in olfactory cortical areas or if trigeminal cortical areas are also activated. Individual olfactory detection thresholds for S(-)-nicotine were determined in 19 healthy occasional smokers using a computer-controlled air-dilution olfactometer. Functional magnetic resonance images were acquired using a 1.5T MR scanner with applications of nicotine in concentrations at or just above the individual's olfactory detection threshold. Subjects reliably perceived the stimuli as being odorous. Accordingly, activation of brain areas known to be involved in processing of olfactory stimuli was identified. Although most of the subjects never or only rarely observed a burning or painful sensation in the nose, brain areas associated with the processing of painful stimuli were activated in all subjects. This indicates that the olfactory and trigeminal systems are activated during perception of nicotine and it is not possible to completely separate olfactory from trigeminal effects by lowering the concentration of the applied nicotine. In conclusion, even at low concentrations that do not consistently lead to painful sensations, intranasally applied nicotine activates both the olfactory and the trigeminal system.

Figure 1

Stimulation paradigm employed during imaging sessions (Nic, intranasal nicotine stimulation; Beep, auditory stimulation; BL, baseline). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

fMRI activation associated with stimulation of the nasal mucosa with S(−)‐nicotine in concentrations just above the individual olfactory detection thresholds. Activation maps showing significant increases in BOLD signal obtained by statistical group analysis for the contrast nicotine using SPM2. The design matrix was specified in an event‐related design with each nicotine and auditory stimulus modeled as a single event. As primary contrasts, the activations (nicotine stimuli vs. “other times”) and deactivations (“other times” vs. nicotine stimuli) in response to nicotinic chemosensory stimulation were investigated. Activations are projected onto a standard template brain (group analysis, n = 19, P < 0.05 FDR‐corrected for whole brain volume, L = left, R = right). Shown are selected sagittal (x = 0 mm), coronal (y = 4 mm) and axial slices (z = ‐14, 0, 10, 20 and 40 mm). Activation is observed in middle cingulate gyrus (1), supramarginal gyri (2), right middle frontal gyrus (3), left posterior cingulate gyrus (4), right subcentral gyrus (secondary somatosensory cortex, S II) (5), bilaterally in the posterior insula (6), right inferior frontal gyrus (triangular part) (7), left inferior frontal gyrus (opercular part) (8), left thalamus (ventrolateral posterior nucleus) (9), right thalamus (lateral pulvinar nucleus) (10), right piriform cortex (11), right posterior orbital gyrus (12), bilaterally in the anterior insula (13).

Figure 3

Shown are the means and standard error of means (SEMs) of the absolute signal intensities in secondary olfactory cortex (R. piriform cortex (VOI 22, 4, −16)) and in secondary somatosensory cortex (R. subcentral gyrus (VOI 58, −12, 10)) at the beginning (first two events per block) versus the end (last two events per block) of a block. Nicotine vapor stimulation occurred over the first 500 ms and the time course was plotted for 14 s after stimulus application. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]