Application of dynamic olfactometry for MRI examinations of sensory irritant effects

Status:

completed 12/2016

Aims:

Irritation and odour annoyance due to chemical agents at work are of central importance for the prevention work of the social accident insurance institutions, since almost half of the occupational exposure limit values are based on the avoidance of sensory irritation effects at the eyes and the upper respiratory tract. As well as other factors of unfavourable working conditions, e.g. noise, climate, lighting, chemical agents with a particularly unpleasant odour are repeatedly suspected to impair health and also job performance. However, the results of experimental studies on the effects of odours and sensory irritants on job performance are not clear. Regardless of odour quality (pleasant vs. unpleasant) or workload (easy vs. difficult tasks) one finds a deterioration of performance, as well as an improvement or no change. According to the theory of distraction, the processing capacity of the brain is limited, if it has to focus on a task and simultaneously process sensory information. An examination of this theory is possible with the help of functional magnetic resonance imaging (fMRI). With this imaging method the activation of the brain regions that are involved in the management of the two tasks are visualized by blood flow changes. Especially regarding olfaction, the neuronal processes underlying the interaction of task difficulty and distraction or impairment of attention are still rarely studied. The aim of this research project was to study the effects of odour and sensory irritation of different chemical agents on the distraction of job performance. Moreover, it was observed whether and under which conditions (exposure level, task difficulty) adverse effects occur. Furthermore, individual sensitivity is taken into account and the interaction of work-related risk factors like stench and stress will be investigated. Thus, the previous knowledge of handling hazardous substances at the workplace can be expanded and used for the prevention work, e.g. for improvement of workplace design or information about chemical agents.

Activities/Methods:

In the context of this research project voluntary study participants performed memory tasks of different difficulty levels, while they were in a magnetic resonance tomograph (MRT). At the same time different concentration of a chemical agent were presented at their nose, beginning with no discernible concentrations below the odour threshold up to concentrations above the irritation threshold, which are assessed as irritating to the eyes and/or nose, "extremely" uncomfortable, and "substantially" annoying. For application of the odours and the sensory irritants a computer-controlled constant flow olfactometer was developed, with the capacity to generate quantitatively precise concentrations, which is not possible with the equipment available to date. Furthermore, the study of the functional connectivity of certain brain regions in the idle state as well as the determination of GABA as a biomarker was used for the identification and characterization of sensitive groups. With the fMRI technique not only particular brain regions but also entire networks, like the odour or the pain network, could be examined. It was assumed that high connectivity, i.e. a good networking between certain brain regions, is associated with increased sensitivity. In addition, we were interested in the question of whether a correlation between odour sensitivity and the individual pain threshold exist. We also examined the local GABA concentration of the insular cortex. GABA is the major inhibitory neurotransmitter in the human brain. Changes in local GABA concentrations have an influence on neuronal excitability and – this is the hypothesis – on odour sensitivity and pain thresholds.

Results:

The development of an olfactometer which, for the first time, allows a precise quantitative exposure within the environment of a functional magnetic resonance imaging scanner provides a new tool for irritant research in humans for the DGUV. It further allows investigating the transition from pure odouriferous to sensory stimulus effects. These measures are important for the rating of adversity and thus for the assessment of the health relevance of hazardous substances in the low dose range. It is also possible to identify susceptible groups of subjects and to examine the interaction of workloads (e.g., stench and stress). 26 healthy non-smokers (50% women) aged between 19 and 34 participated in the study, including 12 sensory airway-hyperreactive individuals. The results of the fMRI study using benzaldehyde (pleasant smell of marzipan) yield evidence that after increasing the concentration of the odouriferous substance up to the individual odour threshold is associated with activation of brain regions which are typically associated with odour processing. After increasing the smell concentration up to the individual irritation threshold, activation in the thalamus is also recognizable, indicating the involvement of pain-processing Areas in the brain. Thus, these results support the idea that, with an increasing concentration of substances, the corresponding olfactory, and trigeminal cerebral areas are activated before a conscious odour or irritation perception takes place. During performance of a working memory task without additional odours, the expected, typical activation pattern is recognizable in the corresponding brain areas. If benzaldehyde is presented at the same time, this activation is reduced. The postulated distracting effect could be demonstrated: while the activation increases in the odour and stimulus related brain areas, the activation decreases in the regions associated with the task processing. However, the distraction effect was not found on the behavioral level: as the concentration of the odouriferous substance increased, no impairment of work performance was observed up to the maximum concentration offered. Susceptible persons, with sensory airway hyperreactivity ("capsaicin sensitive"), demonstrated increased pain sensitivity and a reduced mechanical pain threshold. Changes in the connections between the olfactory cortex and the default-mode network have been shown at the neural level. Similar mechanisms occur in chronic pain patients, e.g. n patients with fibromyalgia or low back pain. Using this approach, a central mechanism of action could be shown, which is also recognizable, but more pronounced, in the chronic pain syndrome. The results so far indicate that a susceptible subgroup with an increased sensitivity to odour and irritants can also be distinguished in healthy persons, which also may have a negative impact on other perceptual modalities.

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