Nicotine presented to the nasal cavity at low concentrations evokes 'odorous' sensations, and at higher concentrations 'burning' and 'stinging' sensations. A study in smokers and nonsmokers provided evidence of a relationship between the experience with the pharmacological action of S-(À)-nicotine and the perceived pleasantness/unpleasantness following nasal stimulation with S-(À)-nicotine. Mecamylamine, a nicotinic acetylcholine-receptor-(nAch-R) antagonist, was able to block painful responses following chemical stimulation of the human tongue and to block responses from the rat's ethmoidal nerve. The aim of our study in humans was to investigate the effects of mecamylamine on the olfactory and the trigeminal chemoreception of nicotine enantiomers. In order to achieve this aim, we determinedFbefore and after mecamylamineF(1) detection thresholds, trigeminal thresholds, and intensity estimates (stimulus intensity) and (2) recorded the negative mucosal potential (NMP) following nasal stimulation with nicotine in a placebo-controlled double blind study (n ¼ 15). CO 2 was used as a trigeminal and H 2 S as an olfactory control stimulus. Mecamylamine significantly increased trigeminal thresholds of S-(À)-nicotine and reduced intensity estimates and NMPs following stimulation with nicotine enantiomers, whereas mecamylamine did not influence NMPs and trigeminal intensity estimates following stimulation with CO 2 . In contrast, mecamylamine did neither influence detection thresholds nor olfactory intensity estimates following stimulation with olfactory nicotine concentrations. These results demonstrate that the trigeminal nasal chemoreception of nicotine enantiomers, in contrast to CO 2 , is mediated by nAch-Receptors and give evidence that the olfactory chemoreception of nicotine is independent from peripheral nAchReceptors.

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Understanding of delirium pathogenesis remains limited despite improved diagnosis, and elucidation of risk factors and prognosis. Major advances in neuroimaging offer the possibility of probing the mechanisms and networks involved in delirium and hence improving understanding of this often devastating syndrome. This review describes the current literature of imaging studies in delirium and related conditions, introduces some of the newer capabilities of neuroimaging with magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography, and discusses how these techniques may be applied to the study of delirium. Despite considerable challenges in patient recruitment, study design, intersubject variability, and scanner and contrast agent availability, imaging offers great potential for the identification and clarification of pathogenic mechanisms of delirium and its long-term sequelae.T HE rapid advancement of neuroimaging methods over the last few decades has made available a wide array of tools for research and clinical management of brain disorders. Imaging can be used to quantify normal or pathologic physiology and to localize abnormalities to specific regions of the brain. In clinical studies, imaging results can also help to control for intersubject variation due to varying severity of related or comorbid pathologies. These capabilities of imaging could prove highly valuable in the study of delirium, an important and highly prevalent syndrome in elderly people, but one for which understanding of pathophysiology remains limited.In this review article, we discuss the shortcomings of our current understanding of delirium and distill from this a series of target questions about the pathophysiology of delirium that might be addressable by neuroimaging studies and whose answers would provide a major advance in the understanding of delirium. We survey the existing literature on imaging studies in delirium and highlight the gaps that remain. Subsequently, we introduce a number of newer neuroimaging techniques and describe how some of these methods might be used to answer our target questions about delirium. Finally, we consider the obstacles to performing such neuroimaging studies and discuss potential solutions. This article may provide a useful framework to guide future neuroimaging studies investigating the pathophysiology of delirium.

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