Can Rose Oxide Smell the Same but Trigger Different Nasal Responses?

Two substances can smell the same. When that happens, does the same response occur inside the nose?

A 2017 study used two hard-to-distinguish forms of rose oxide to examine electrical responses in the nasal mucosa and brain responses measured at the scalp at the same time. Participants could not clearly tell the odors apart, but their nasal mucosal responses differed. The study explored the relationship between the initial reception of molecules and the odors we experience.

Do mirror-image molecules always smell different?

Some molecules form pairs that are mirror images but cannot be superimposed, like a right and a left hand. These are called enantiomers.

The receptors that receive odor molecules are also proteins with three-dimensional shapes. They can therefore respond differently to two mirror-image molecules. Whether people experience those molecules as different odors, however, depends on the particular pair of substances.

The researchers chose (+)- and (−)-rose oxide. Using conditions in which the two were difficult to distinguish, they investigated whether differences in the nose’s initial response necessarily appear in brain measurements or people’s ability to tell the odors apart.

Comparing odor judgments, nasal electrical responses, and brain waves

Of 26 people screened beforehand, 19 took part who met conditions including a normal sense of smell and nasal anatomy that made it relatively easy to position a recording electrode deep inside the nose. There were 14 women and 5 men, with a mean age of 25.

A dedicated device delivered the odors to one nostril for 0.5 seconds at a time. Air temperature, humidity, and flow were kept constant, and noise masked the sounds of the equipment. This made it harder to use switching sounds or changes in airflow as clues.

The concentrations were 0.0275% for the (+) form and 0.02% for the (−) form. Pilot testing with other participants established conditions in which the odors were detectable, similar in intensity, and difficult to distinguish. A preliminary task that asked participants to identify which nostril had been stimulated also checked that the conditions did not produce substantial stimulation of the trigeminal nerve, which conveys sensations such as pungency.

Discrimination was measured with a task in which participants selected the one different stimulus from three. Each person completed nine trials. The researchers recorded the electro-olfactogram, or EOG, an odor-related change in electrical potential, from the nasal mucosa. They also recorded olfactory event-related potentials, or OERPs, by averaging brain-wave responses aligned to each stimulus, using an electrode at the center of the scalp.

Although both measure responses to an odor, the EOG reflects activity close to the nose’s sensory input, whereas OERPs reflect processing in the brain. The study examined how these two measurements corresponded to behavior.

Discrimination was at chance level, but nasal responses differed

Participants averaged 3.2 correct answers out of nine in the discrimination task. Random guessing in a three-choice task would yield about three correct answers, and performance was not significantly above that level. Intensity ratings also did not differ significantly: approximately 41 out of 100 for the (+) form and 40 for the (−) form.

However, the EOG recordings obtained from 14 participants did differ. The (+) form produced a larger electrical response and took longer to reach its peak.

For example, the mean amplitude from baseline to the negative peak was approximately 6.42 µV for the (+) form and 3.77 µV for the (−) form. The respective times to that peak were approximately 589 and 415 milliseconds. The researchers interpreted this as an example of different nasal mucosal responses that do not translate directly into conscious odor discrimination.

The two stimuli were presented at different concentrations to make their perceived intensities similar. That concentration difference may also have contributed to the difference in nasal potentials, so the observed difference cannot be isolated as an effect of molecular configuration alone.

No clear difference in the responses measured at the scalp

OERPs were obtained from 18 participants. Neither the amplitudes of the brain-wave peaks examined nor their latencies differed significantly between the two forms of rose oxide.

Nasal responses differed, while the scalp-recorded measures and participants’ discrimination showed no clear difference. This combination is the study’s central finding.

Odor signals travel from sensory neurons in the nose through the olfactory bulb and are processed in regions including the piriform cortex. The authors discuss the possibility that inputs reflecting molecular structure can lead to similar odor experiences through subsequent processing that also involves experience and learning.

The measurements did not identify where that transformation occurs. Finding no difference in particular waveforms recorded at the top of the head should not be equated with finding that all activity throughout the brain is identical.

Limonene showed differences in discrimination and one brain-wave measure

In a supplementary experiment, the authors also studied limonene, another enantiomeric pair. This experiment involved 12 people whose ability to distinguish the two forms had been confirmed beforehand.

In this group, the mean score on the three-choice task was 6.2 out of nine, above chance level. In the brain-wave recordings, the amplitude of a positive peak called P2 differed between the (+) and (−) forms. The other amplitudes and peak latencies did not differ significantly.

This complements the main experiment: with a distinguishable pair, a difference also appeared in one brain-wave measure. Because the participants had been selected for their ability to discriminate the odors, the figures are best read as showing the relationship between behavior and brain responses under these conditions, not the ability of everyone in the general population to distinguish limonene.

Odor differences are not determined at the sensory entrance alone

The study suggests that a different response in the nose cannot be assumed to correspond one-to-one with a person’s experience of a different odor. Understanding odor discrimination requires attention not only to how molecules fit receptors but also to processing in the brain.

The rose oxide results came from a limited group of 19 participants and selected concentrations and tasks. Their value lies less in establishing a fixed property that people can never distinguish the molecules than in showing how nasal and brain measurements correspond under conditions in which the odors seem alike.

Summary

The two forms of rose oxide were not clearly distinguishable in this experiment, but the electrical responses of the nasal mucosa differed. Meanwhile, scalp-recorded brain-wave measures showed no significant difference. In the supplementary limonene experiment, which selected people able to distinguish the odors, a difference appeared in one brain-wave measure.

Smelling the same is not the same as producing the same response at the entrance to the olfactory system. These findings offer a way to think about odor experience as something that emerges through the process from receiving molecules to interpreting their signals in the brain.

The research received support from the German Research Foundation, a Swedish foundation for humanities and social sciences, and a fellowship at Technische Universität Dresden. The authors declared no competing interests.

References

Poletti SC, Cavazzana A, Guducu C, Larsson M, Hummel T. (2017). Indistinguishable odour enantiomers: Differences between peripheral and central-nervous electrophysiological responses. Scientific Reports, 7, 8978. Original article and supplementary information