Area of Interest: The Effects of Cognition and Emotional States on Chemosensory Perception

Humans associate scents with vivid memories. A unique fragrance or unpleasant odor may trigger recollections of people, places, or events. Odors may even induce deja vu, especially when they have been previously associated with a stressful experience. For example, rescue workers and journalists visiting the World Trade Center site following 9/11 reported severe bouts of grief and anxiety each time they were exposed to a pervasive odor of burning plastics and metals at the Chambers Street subway location. Smells can alternately stimulate reverie and joy, fear or repugnance, and even feelings of devastation and loss.

My current research investigates how and why cognition and emotional states influence our olfactory perceptions. Most people believe that smells are invariant - a matter of chemical composition and the innate molecular properties producing the common odors we experience. The reality, however, is altogether different. There is an intimate relationship between olfactory sensitivities and human expectations. Differences in emotional state, gender, amount of exposure to particular chemicals, and even pre-formed biases against certain odors can affect the intensity and character of the odors we perceive.

Approach: Top-Down Influences on Chemosensation

Hedonic processes involve 'top-down' information processing. For example, odors thought to come from hazardous sources are often described as less pleasant than if they are believed to come from non-hazardous sources. When we present an ambiguous odor to experimental subjects who simultaneously view a mountain scene, they are much more likely to rate the odor differently for both intensity and pleasantness than if they smell the odor while viewing a factory belching smoke. One reason for this phenomenon is that most chemical compounds are virtually ubiquitous in our environment and the context is what helps us interpret what we are smelling. The odor of many aldehydes, for example, accounts for the pleasant fragrances in many fruits along with the distinctly "fruity" (if not noxious) odors of diesel fuels. In turn, apple fragrance will be experienced differently if we are told that a bit of peach fragrance has been added to a perfumed mix. In short, our olfactory perception is based not just on neuroendocrine influences, but on higher order cognitive processes, such as odor identification and odor memory.

Cognitive associations therefore play an important role in the public's perception of odors and its response to suspected health threats. One goal of my research is to investigate how and why emotional valence among individuals influences chemosensory perception - not only the quality, intensity, and pleasantness of odors, but our notions and expectations of whether the odors are healthful or hazardous.

In 2005, for example, psychologist Denise Chen (Rice University) and I published a study (1) examining how olfactory perception is affected by three factors: the emotional 'tone' of the stimuli, the individual's personality, and his/her current emotional state. We found that men perceived odorants more intensely when they are in a positive or negative emotional state rather than in a neutral state. No such effect was found in women, although we did identify an interaction effect between female personality and emotionally suggestive odorants (i.e., those inducing strong pleasant or unpleasant associations). Women scoring high in anxiety on personality tests perceived all kinds of odors more intensely than women with low anxiety levels. Further, women reacted faster to emotionally evocative smells than to a neutral smell; in other words, they respond more quickly than men to smells carrying a large amount of olfactory information.

Our findings strongly suggest that emotions play a stronger role in olfaction than had previously been considered, especially in men. By contrast, the role personality plays is a complex effect - in some cases enhancing, in other cases impeding detections of both pleasant and unpleasant odors.

Sensory Effects of Exposure Irritants: Adaptation and Sensitization

Since public health concerns are increasingly rooted in the perception of chemical odors and irritants - many Americans in fact are suing construction, industrial, agricultural, and sanitation companies over 'nuisance' odorants - it is especially important to track all factors contributing to health behaviors. One of the areas I study is the adaptation and sensitization to odor. For example, in 2002 our laboratory demonstrated gender-specific induction of enhanced olfactory sensitivity (2). We saw marked changes in olfactory acuity among women of reproductive age who were repeatedly exposed at very low levels to several specific odorants, among them benzaldehyde, a substance present in cherry-almond flavorings. Whereas researchers previously believed that robust gender differences in olfaction were restricted to odor identification ability, our research showed that women of reproductive age could become up to five orders of magnitude more sensitive to an odorant following repeated attention-directed exposure. Neither men nor post-menopausal women not on hormone replacement therapy showed these heightened sensitivities. Our repeated threshold testing was replicable and odorant-specific, lending support to the idea that induction of olfactory sensitivity among young females may be associated with reproductive behaviors, such as pair bonding, mother-infant bonding, and kinship recognition. In addition, females of reproductive age may also demonstrate greater sensitivity to nutrient sources and potentially hazardous foods. Interestingly, this finding may also have relevance for understanding extreme sensitivity to environmental chemicals, such as multiple chemical sensitivity, (aka idiopathic environmental intolerance), a poorly understood multi-symptom condition in which primarily young females develop hypersensitivity to the odors of many otherwise benign chemical compounds in their environments.

Irrespective of gender, we also observed that the ability to detect an odorant was significantly increased when it was paired with a taste solution that was culturally congruent (i.e. cherry smell + sweet taste), but not when it was incongruent (cherry smell + umami taste) (3). We later demonstrated that this effect was the product of learned associations, which can occur after only a few weeks of daily pairings of unfamiliar combinations of smells and tastes.

Olfactory & Upper Airway Toxicity from Exposure to Volatile Chemicals

Short and long-term exposure to volatile chemicals can produce significant toxicity in the upper airways, although the effects of exposure may differ by population and individual. For example, we conducted a study evaluating trigeminal sensitivity to ammonia among asthmatics and healthy human volunteers (4). Since asthmatics often report the triggering or worsening of respiratory systems following exposure to airborne irritants, we decided to test the effects of repeated exposures to commercially available household ammonia. Our goal was to evaluate the irritation potential among both the asthmatics and healthy volunteers. When we tested 25 healthy and 15 mild to moderate persistent asthmatic volunteers with reported sensitivity to household cleaning products, we found that irritation thresholds did not differ between the asthmatics and healthy controls, nor did the ratings of odor intensity, annoyance, and irritancy following longer exposures lasting 30 seconds. Importantly, no changes in lung function occurred after exposure to ammonia for any individuals in either group. Thus, despite the asthmatics' heightened symptom reports during exposure to environmental irritants, their ocular and nasal trigeminal system did not appear in this case to be more sensitive or reactive than the healthy volunteers. This suggests that in brief exposures, cognitive factors may be contributing to asthmatics' reports of adverse respiratory responses rather than purely trigeminal-mediated reflexes.

One phenomenon that can occur with long-term occupational exposure to certain volatile chemicals is desensitization, a diminished olfactory acuity that may accompany damage to the primary sensory neurons. In one recent study we conducted (5) with researchers from the Bloomberg School of Public Health at Johns Hopkins University (Baltimore) and the Institute and Policlinic of Occupational and Social Medicine in Heidelberg, Germany, we examined olfactory function in two groups of workers in a German reinforced-plastics boat manufacturing facility. One group had a minimum of 2 years of exposure to volatile styrene resins (the average was 15-25 ppm as calculated from urinary metabolite concentrations, with historical exposures up to 85 ppm). We compared this group's olfactory function with a group of age-matched workers from the same facility who were not working directly with the resins. The results were also compared against normative data previously collected from healthy, unexposed individuals. Although the workers with the highest styrene exposures performed less well on odor identification tests, this may have been due to cultural unfamiliarity with the odorants tested. A more robust finding was that although they had become desensitized to the styrene vapor odor as a function of exposure, our study found no evidence of general impairment of olfactory function across any of the study groups. These results taken together with a prior study of workers in the US, suggest that styrene is not a significant olfactory toxicant in humans at current exposure levels. These and other findings underscore the need for individual, controlled study of volatile chemical irritants. Intuitive judgments about the presumed health or hazard of certain chemicals based on smell are certainly not reliable.

Advanced Research Techniques

At Monell, we continue to study the effects of chemical irritants on upper airway morphology and function using a variety of techniques - from acoustic rhinometry and anterior rhinomanometry to laser Doppler velocimetry of nasal blood flow. Psychophysical evaluations employ both static and dynamic olfactometry. Our routine psychophysiological evaluations include assessment of respiration and autonomic nervous system parameters.

We use the analysis of nasal lavage fluid to index the influx of inflammatory cytokines/chemokines & other inflammatory cells such as eosinophils and neutrophils among chemically-exposed populations. This allows us to document the degree to which inflammation induced by airway irritants alters chemosensory perception and total nasal function. Among sensitive subpopulations, we also assess the impact of airborne chemicals on pulmonary function and airway inflammation using spirometry and chemoluminescence detection of exhaled lung and nasal nitric oxide levels.

Other Areas of Interest

Chemosensation in Susceptible Populations

Our laboratory is continuing to assess ocular and nasal irritation challenges among asthmatics and other susceptible populations. We have found in controlled studies of mild and moderate asthmatics that there is little evidence to confirm anecdotal reports of increased ocular and nasal irritation following exposure to fragranced, cosmetic products (6). When we assessed asthmatics for ocular hyperemia and nasal irritation using macro-photography and acoustic rhinometry, we found no health differences among mild, moderate, and control groups. All groups had an initial 5 minute exposure and a 30 minute exposure to either of two fragranced aerosol products and a clean air control. While physiological mechanisms may in fact be responsible for some of the adverse symptom reports, our results suggest that cognition influences symptom perception triggered by other sensory cues.

Peri-Receptor Events in Olfactory Perception

The ability to model the transport of odors through individualized computer models of nasal passages holds promise for relating anatomical deviations to generalized or selective disturbances of smell. In collaboration with bioengineers at the University of Pennsylvania and Dr. Kai Zhao, now an assistant member at Monell, (7) we validated a method of quickly converting (<few days) nasal CT scans from an individual patient into an anatomically correct 3D numerical nasal model that could be used to predict dynamic airflow and odorant transport. Using computational fluid dynamics (CFD, the initial study measured the correlations between odorant uptake in specific anatomical areas and performance on olfactory assessments. The computer simulations of airflow patterns and accompanying anatomical changes in the olfactory regions (specifically, the upper meatus below the cribriform plate) following odorant transport can provide important guidance for treating nasal-sinus disease, including occupational rhinitis. They can also help to predict and confirm the locations of chemical-induced damage to the olfactory and respiratory epithelium and nasal structures in occupationally-exposed populations, a study of which is currently underway.

Occupational Exposure Guidelines

Many, if not most, of the occupational exposure limits (OELs) for workplace chemicals are set based on the endpoint of sensory irritation - the lowest level at which individuals may experience trigeminally-stimulated sensations in the eyes or upper airways. However, the basis for chemical concentrations which elicit this adverse endpoint are not always established using the best possible methodologies. For instance, many limits have been set by asking individuals in chamber exposures to report when they experience 'irritancy', a response which is often confounded by psychological reactions to the unpleasant or unwanted odor of a chemical. For this reason, it is important to establish objective techniques for determining thresholds for irritation and applying those to the setting of OELs. Based on data from our laboratory and others, in numerous publications (8,9), we have enumerated the criteria that should be evaluated when attempting to set OELs for avoidance of sensory irritation in the workplace.

References

1. Chen, D. & Dalton, P. (2005). The effect of emotion and personality on olfactory perception. Chemical Senses, 30, 345-351.

2. Dalton, P, Doolittle, N., & Breslin, P.A.S. (2002). Gender-specific induction of enhanced sensitivity to odors. Nature Neuroscience, 5, 199-200.

3. Dalton, P., Doolittle, N., Nagata, H. & Breslin, P. (2000) Merging of the senses: Sub-threshold integration of taste and smell. Nature Neuroscience, 5, 431-432.

4. Petrova, M, Diamond, J, Schuster, B, Dalton, P. (2008). Evaluation of Trigeminal sensitivity to ammonia in asthmatics and healthy human volunteers. Inhalation Toxicology, 20, 1095-1092.

5. Dalton, P., Lees, P. S. J., Cowart, B. J., Emmett, E. A., Dilks, D. D., Stefaniak, A. et al. (2003). Olfactory function in workers exposed to styrene in the reinforced-plastics industry. American Journal of Industrial Medicine, 44, 1-11.

6. Opiekun, R. E., Smeets, M. J., Sulewski, M., Rogers, R., Prasad, N., Vedula, U. end Dalton, P. (2003). Assessment of ocular and nasal irritation in asthmatics resulting from fragrance exposure. Clin. Exp. Allergy, 33, 1256-1265.

7. Zhao, K., Scherer, P. W., Hajiloo, S. A., & Dalton, P. (2004). Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction. Chem Senses, 29, 365-379.

8. Dalton, P. (2003) Upper airway irritation, odor perception and health risk due to airborne chemicals. Toxicology Letters, 140-141,239-248.

9. Smeets, M.A.M., Kroeze, J. & Dalton, P.H. (2006) Setting occupational exposure limits in humans: contributions from the field of experimental psychology. International Archives of Occupational and Environmental Health, 79, 299-307.