Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Functional MRI of Intranasal Chemosensory Trigeminal Activation
1 Smell & Taste Clinic, Department of ORL, University of Dresden Medical School, Dresden, Germany, 2 University of Pennsylvania Smell and Taste Center, Philadelphia, PA, USA and 3 Department of Radiology, The Johns Hopkins Hospital, Baltimore, MD, USA
Correspondence to: Thomas Hummel, e-mail: thummel{at}rcs.urz.tu-dresden.de
Key words: anosmia, nose, olfaction, pain, stinging
 |
Introduction |
|---|
 Top Introduction Materials and methodsResultsDiscussionAcknowledgements and disclosures...References |
|---|
Numerous brain imaging studies using positron emission tomography or functional magnetic resonance imaging (fMRI) have provided considerable information regarding the processing of sensory information. While many studies have also been performed on olfactory mediated sensations, cerebral activation following intranasal trigeminal stimulation has not been systematically addressed. The aim of this pilot study was to look at cerebral activation following trigeminally induced activation using CO2, a stimulant which almost exclusively activates the trigeminal system. This activation was compared to effects of stimulation with ‘pure’ olfactory stimuli [i.e. H2S and phenyl ethyl alcohol (PEA)].
Based upon the intimate connections between the trigeminal and olfactory systems
(Doty et al., 1978
;
Hummel and Livermore, 2002), we
hypothesized that there would be overlap between central activation induced by separate
stimulation of the olfactory and trigeminal systems. We expected that olfactory
stimulation would produce activation in, for example, the insular, piriform and
orbitofrontal cortices, as well as in the cerebellum and gyrus rectus (Savic, 2002). We sought to determine which, if
any, of these structures were activated by trigeminal stimulation. In terms of
lateralization, stronger activation of the right hemisphere was expected (Hummel et al., 1995;
Hari et al., 1997).
|
Materials and methods |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionAcknowledgements and disclosures...References |
|---|
Subjects were screened for smell dysfunction prior to entering the study using the University of Pennsylvania Smell Identification Test. The project was approved by the IRB of the University of Pennsylvania; patients completed informed consent forms. Nineteen healthy, right-handed subjects participated (seven women, 12 men; mean age 36 years).
Studies were performed on a 1.5 T GE Horizon echospeed scanner. fMRI studies
consisted of a T1-weighted (T1W) sagittal scan
with repetition time (TR) of 500 ms, time to echo
(TE) 11 ms and 1 average (500/11/1). For anatomic overlays this scan
was followed by an axial 500/11/1 scan with a 192 x 256 matrix and 5 mm thick
interleaved sections through the entire brain. fMRI studies were performed in the axial
plane using multislice gradient echo echoplanar imaging. Scans (64 x 40 matrix, 24
x 15 cm2 FOV, TR 3000 ms, TE 30
ms, 5 mm thickness, 90° flip angle) delivered a voxel resolution of 
4 x 4
x 5 mm3. A total of 120 images were acquired at each of 24 slice
locations per paradigm over the course of a 6 min fMRIscan. Each task paradigm consisted
of six alternating rest–stimulus cycles (30 s each). More details of the paradigm
are described elsewhere (Yousem et al.,
1998).
Stimulants were presented birhinally using a Burghart OM4b olfactometer. Chemical stimuli were embedded in a constant flow of odorless air (2 l/min) that was delivered through tubing inserted into the subjects’ nostrils. Stimulants were applied for 1 s every 4 s during the 30 s ‘on-period’. During the 30 s ‘off-period’, subjects received odorless air. For olfactory stimulation we used PEA and H2S; CO2 was chosen for trigeminal stimulation.
Following correction for image distortion and alternate k-space line errors
statistical parametric maps (SPMs) were generated using SPM96. Functional data sets were
motion corrected and normalized to Talairach space. A 60 s time-shifted box-car waveform
was used as the reference paradigm and the ANCOVA model with global activity as a
confound was employed for statistical analysis. The resulting sets of images represent
SPMs of the t-statistic SPM{t}. For details of the analysis,
see
Yousem et al. (1998).
|
Results |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionAcknowledgements and disclosures...References |
|---|
Group analyses indicated that both olfactory and trigeminal stimulation produced activation in the ventral insula, the middle frontal gyrus and supplemental motor area (Figure 1). In addition, both types of stimulation produced a stronger right-sided activation. Unlike trigeminal stimulation, olfactory stimulation activated the cerebellum (left anterior lobe, right posterior lobe) and the parahippocampal gyrus. Trigeminal stimulation activated structures not activated by olfactory stimulation, namely the midbrain, dorsolateral orbito-frontal cortex, frontal operculum, superior temporal gyrus, medial frontal gyrus and anterior caudate nucleus. Overall, trigeminal activation was more pronounced compared to olfactory activation.
|
|
Discussion |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionAcknowledgements and disclosures...References |
|---|
Trigeminal stimulation specifically activated the midbrain, corresponding to the nucleus tractus solitarii. Trigeminal stimulation also produced activation in areas involved in the processing of olfactory information, including (i) the superior temporal gyrus, reported to be involved in the early cognitive processing of olfactory information (Kettenmann et al., 1996
);
(ii) the dorsolateral orbito-frontal cortex, which is typically activated through odors
and has been mentioned in the context of odor identification (Jones-Gotman and Zatorre, 1988); and (iii) the
caudate nucleus found to be involved in odor quality discrimination (Savic et al., 2000).
In addition, results from the present pilot study indicated overlap between
activations through olfactory or trigeminal stimulation which was seen in the ventral
insula and the middle frontal gyrus. In addition, both types of stimuli produced larger
right-sided activation, indicating that the right hemisphere is important to the
processing of chemosensory information (Hummel
et al., 1995;
Hari et al., 1997).
Trigeminal stimulation produced much weaker cerebellar activation than olfactory
stimulation (Sobel et al.,
1998), despite the strong overall activation from trigeminal stimulation. The
cerebellum has been frequently reported to be activated during sniffing and it has been
speculated that it is directly involved in the processing of odorous information. Based
upon the present data, it may be hypothesized that cerebellar activation may be less
important to trigeminal than to olfactory stimulus processing.
Mixed olfactory–trigeminal (OT) stimuli appear to produce a different pattern
of activation than ‘pure’ trigeminal stimulation.
Yousem et al. (1997)
observed that olfactory stimuli activated the right OFC and the cerebellum
‘mildly’. Mixed stimuli produced additional cingulate, temporal and
cerebellar activation.
Savic et al. (2002) also
reported differences between olfactory and mixed OT stimuli. For the mixed stimulus,
strong activation has been found in the anterior/central insula and claustrum, anterior
cingulate, somatosensory cortex, cerebellum, thalamus, lateral hypothalamus and
brainstem.
It is of interest to note that intranasal trigeminal stimulation failed to produce the pattern seen after cutaneous stimulation of the trigeminal nerves, which typically activates the thalamus and the primary and secondary somatosensory cortices. It may be hypothesized that the intransal sensations mediated through the trigeminal nerve are specifically processed, which may argue for a specific role of the ‘common chemical sense’. Overall, the present results highlight the fact that some common brain structures are activated by olfactory and trigeminal stimulation and that there are also marked differences between the two.
|
Acknowledgements and disclosures |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionAcknowledgements and disclosures...References |
|---|
We would like to thank David Alsop, Rena Geckle, Joseph Maldijan, Faez Siddiqi, Warren Bilker and Johannes Gerber for their help during scanning and analysing the data. Support: grant PO1-DC-00161-15 from NIDCD-NIH. Partly supported by a grant to T.H. by Philip Morris USA Inc. and by Philip Morris International. Disclosure: Dr Doty is a major shareholder in Sensonics Inc., a company that manufacturers the UPSIT.
|
References |
|---|
|
TopIntroductionMaterials and methodsResultsDiscussionAcknowledgements and disclosures...References |
|---|
Doty, R.L., Brugger, W.P.E., Jurs, P.C., Orndorff, M.A., Snyder, P.J. and Lowry, L.D. (1978) Intranasal trigeminal stimulation from odorous volatiles: psychometric responses from anosmic and normal humans. Physiol. Behav., 20, 175–185.[CrossRef][Medline]
Hari, R., Portin, K., Kettenmann, B., Jousmäki, V. and Kobal, G. (1997) Right-hemisphere preponderance of responses to painful CO2 stimulation of the human nasal mucosa. Pain, 72, 145–151.[CrossRef][Web of Science][Medline]
Hummel, T. and Livermore, A. (2002) Intranasal chemosensory function of the trigeminal nerve and aspects of its relation to olfaction. Int. Arch. Occup. Environ. Health, 75, 305–313.[CrossRef][Web of Science][Medline]
Hummel, T., Pauli, E., Schuler, P., Kettenmann, B., Stefan, H. and Kobal, G. (1995) Chemosensory event-related potentials in patients with temporal lobe epilepsy. Epilepsia, 36, 79–85.[CrossRef][Web of Science][Medline]
Jones-Gotman, M. and Zatorre, R.J. (1988) Olfactory identification deficits in patients with focal cerebral excision. Neuropsychologia, 26, 387–400.[CrossRef][Web of Science][Medline]
Kettenmann, B., Jousmaki, V., Portin, K., Salmelin, R., Kobal, G. and Hari, R. (1996) Odorants activate the human superior temporal sulcus. Neurosci. Lett., 203, 143–145.[CrossRef][Web of Science][Medline]
Savic, I. (2002) Imaging of brain activation by odorants in humans. Curr. Opin. Neurobiol., 12, 455–461.[CrossRef][Web of Science][Medline]
Savic, I., Gulyas, B., Larsson, M. and Roland, P. (2000) Olfactory functions are mediated by parallel and hierarchical processing. Neuron, 26, 735–745.[CrossRef][Web of Science][Medline]
Savic, I., Gulyas, B. and Berglund, H. (2002) Odorant differentiated pattern of cerebral activation: comparison of acetone and vanillin. Hum. Brain Mapp., 17, 17–27.[CrossRef][Web of Science][Medline]
Sobel, N., Prabhakaran, V., Hartley, C.A., Desmond, J.E., Zhao, Z., Glover, G.H., Gabrieli, J.D. and Sullivan, E.V. (1998) Odorant-induced and sniff-induced activation in the cerebellum of the human. J. Neurosci., 18, 8990–9001.
Yousem, D.M., Williams, S.C., Howard, R.O., Andrew, C., Simmons, A., Allin, M., Geckle, R.J., Suskind, D., Bullmore, E.T., Brammer, M.J. and Doty, R.L. (1997) Functional MR imaging during odor stimulation: preliminary data. Radiology, 204, 833–838.
Yousem, D.M., Maldjian, J., Siddiqi, F., Hummel, T., Alsop, D., Geckle, R.J., Bilker, W.B. and Doty, R.L. (1998) Gender-effects on odor-stimulated functional magnetic resonance imaging. Brain Res., 818, 480–487.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Frasnelli, B. Schuster, and T. Hummel Interactions between Olfaction and the Trigeminal System: What Can Be Learned from Olfactory Loss Cereb Cortex, October 1, 2007; 17(10): 2268 - 2275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Boyle, M. Heinke, J. Gerber, J. Frasnelli, and T. Hummel Cerebral Activation to Intranasal Chemosensory Trigeminal Stimulation Chem Senses, May 1, 2007; 32(4): 343 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Frasnelli, B Schuster, and T Hummel Subjects with Congenital Anosmia Have Larger Peripheral but Similar Central Trigeminal Responses Cereb Cortex, February 1, 2007; 17(2): 370 - 377. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||