Neural Responses and Measures with Anosmia

Anosmia, i.e. the complete loss of olfactory sensory perception, is a prevalent neurological disorder which has devastating impacts on nutritional health and safety. Up to 5% of the normal population suffers from a complete loss of the sense of smell, and another 15% exhibits a reduced olfactory function. Currently, there are no commonly accepted therapeutic methods to regain olfactory abilities in persons suffering from anosmia. Recently, work by Hummel and colleagues (2009) found that olfactory perceptual learning recovers olfactory function in anosmics - the neural basis of this is, however, unknown. Indeed, little is known about the neural processing of chemosensory information in anosmics and, most importantly, how experience with odors during the training may shape these processes. This proposal describes an experimental strategy aimed at understanding how olfactory information is encoded in the brains of anosmic subjects with an emphasis on examining the therapeutic basis of olfactory perceptual learning in rescuing olfactory loss. Anosmic subjects do, by definition, not perceive odor. However, olfactory stimulation may still evoke changes in cerebral activity. We aim to test if the act of sniffing induces activity in olfactory brain regions, as well as if and how continuing exposure to odors in an olfactory training paradigm is capable of re-inducing olfactory perception. Furthermore, we want to map morphologically the adaptive plastic changes which are known to occur in the trigeminal system of anosmic subjects. These specific aims can be formulated as followed: AIM 1 of the proposal will be focused on the assessment of the basic neural coding of odors within the olfactory cortex (the neural oscillations entrained to the rhythmic action of sniffing) by utilizing fMRI methods in both anosmic and healthy human subjects. Specifically, we will test the hypothesis that ansomic subjects possess the neural mechanisms necessary to form sniff-driven oscillations in the olfactory cortex. For AIM 2 of this proposal, we will examine the neural basis of olfactory perceptual learning in anosmics by providing subjects with odor experience and later comparing olfactory related cortical fMRI activity both before and after odor experience. Specific analyses will be devoted to elucidating possible alternative olfactory structures which may be activated in anosmics to compensate for olfactory loss. AIM 3 of the proposal will specifically investigate how chemosensory trigeminal stimulation is processed within the olfactory pathway in both anosmics and healthy subjects and if differences elicit due to compensation mechanisms. AIM4 will specifically investigate underlying biochemical principles of intranasal trigeminal perception and its variability due to olfactory loss. The results of these studies will provide novel insights into the way that anosmia effects olfactory processing and how these processing schemes can be modified by experience in a manner potentially useful in therapeutic interventions. Furthermore, a better understanding of the olfactory system will allow us comprehending the changes the olfactory system undergoes in neurodegenerative diseases such as Parkinson`s disease and Alzheimer`s disease.

In this project we investigated the neuronal components of olfactory loss. We showed that the loss of the sense of smell can trigger re-organization of functional networks in the brain. Furthermore, we were able to show that repeated training of the sense of smell may strengthen conflicted neuronal networks in order to re-obtain their initial function of processing chemosensory perceptional input. Besides neural measures of olfactory perception, we investigated a variety of behavioral measures to provide a more profound behavioral basis for the interpretation of functional imaging data, such as interoceptive awareness, the ability to self-evaluate olfactory performance, and olfactory memory. Findings of the project paved the way for a more profound understanding of the sense of smell and smell loss. Results initiated more personalized approaches to help affected patients.