Testing olfactory function and mapping the structural olfactory networks in the brain.

We perceive the world through our senses. The dependence on these sensory stimuli becomes obvious when we see a visually impaired individual with a guide dog or an individual using sign language. However, individuals with olfactory deficits suffer from a more concealed impairment without any opportunity for diagnostics or treatment in the Danish healthcare system. Around a fifth of the population experience olfactory deficits, of which 1-2% are functionally anosmic. The personal consequences for anosmics can be extensive, lacking not only in hedonic yield related to eating and drinking, but also the socialization during dinners can become niggling. Similarly, social attraction and repulsion can be affected, however, effects linger beyond social consequences and quality of life. An olfactory deficit is a common early symptom in several neurologic, neurodegenerative, and psychiatric diseases. These associations may be due to the central location of the primary olfactory cortex, tugged in and between hedonic hotspots of the brain, and its hard-wired structural connections to key hubs of consciousness and memory in the brain. 
A better knowledge of olfactory receptors and odour perception has emerged during the past few decades. This has given rise to a deeper understanding of the etiologies behind olfactory deficits, to the anticipation of utilising the diagnostic potential of olfaction as a prodromal marker of disease, and ultimately to the prospect of improving treatment options for these patients. Much has been accomplished within the field, but much is still beyond our grasp. 
In Denmark, the focus on olfaction and olfactory testing has been scarce, at best. The first step of my PhD was therefore a review in Danish, published in the most widely distributed and read Danish journal, "Ugeskrift for Læger", in order to raise awareness on olfactory testing and on a clinical olfactory focus in Central Denmark Region. Secondly, we validated a tool for assessing olfactory function in Danish. The Danish 12-odourant "Sniffin' Sticks" identification test (SIT-12) was modified, validated and published, which allowed us to focus on other aspects of olfactory perception and olfactory testing.
 One focus has been to investigate the possible role of overlapping volatile chemical molecules in differentiating closely related descriptors. This study was conducted in order to emphasize the need for a meticulous approach when conducting validation stud-ies of olfactory tests, especially the need for revalidation after a modification process.
 Another focus has been on investigating the differences between olfactory identification abilities in adolescents relative to adults. Previous international studies have shown that the identification skills of adolescents are significantly different from their adult compatriots. Earlier validation studies on adolescents have used the adult version of odorant descriptors as the starting point. In our study we examine the role of odour familiarity in the difference between adult and adolescent identification abilities.
 The main focus of this PhD has been to develop a method for evaluating central olfactory patency and processing, where indi-vidual preferences and sensitivity to specific odours could be removed from the equation, as these parameters has proven trou-blesome in functional neuroimaging of the olfactory system. We identified that a reference area for investigating primary olfactory processing in neuroimaging included several non-primary struc-tures and lacked the structural neural connections to key secondary olfactory areas. Consequently, we redefined the template for olfac-tory processing by combining findings from anatomical and func-tional neuroimaging studies. This has led to the creation of a struc-tural olfactory fingerprint, which is already integrated in six on-going studies as a tool to investigate pathologic and benign chang-es in structural olfactory pathways.
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