Characterization of in vivo Human Olfactory System and Orbitofrontal Cortex Anatomy, and Olfactory Perceptual Decline in Aging and Dementia

Echevarria-Cooper, Shiloh Luela

doi:https://doi.org/10.21985/n2-jzc6-1683

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Characterization of in vivo Human Olfactory System and Orbitofrontal Cortex Anatomy, and Olfactory Perceptual Decline in Aging and Dementia

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Human olfactory function is important for a myriad of behaviors, including food seeking, social cognition, memory, emotional regulation, and detecting environmental threats. In animal models, particularly dense olfactory inputs have been shown to target orbitofrontal cortex (OFC), a region involved in multimodal sensory integration, reward coding, and flexibly guiding our motivated goal-directed behaviours. Both the primary olfactory cortex and the OFC have been shown in animal models to have widespread connectivity with medial temporal lobe regions involved in learning and memory. However, the specific anatomical properties and physical brain mechanisms through which the olfactory-OFC system influences behavior and memory are not well understood. In this thesis, we have developed optimized diffusion magnetic resonance imaging (dMRI) techniques to image the olfactory and orbitofrontal brain areas, and we have used a diffusion tractography approach to map out the anatomical connectivity of the human lateral olfactory tracts and OFC. By providing a detailed anatomical characterization of the human olfactory-OFC brain networks, we provide a valuable source of information from which to develop mechanistic hypotheses of human olfactory system and OFC function.Interestingly, olfactory perceptual impairments are gaining notice as one of the earliest symptoms in Alzheimer’s disease (AD), suggesting that olfactory perceptual tests may be sensitive to dysfunction in olfactory and medial temporal lobe regions. However, the specific mechanisms causing olfactory perceptual impairments in the earliest stages of AD are not known, and there is an open question about whether detecting olfactory impairments earlier on may help to target preventative treatments to slow the AD progression. In this thesis, we have shown that performance on the NIH Toolbox Odor Identification test declines with age, and is worse in elderly adults with amnestic mild cognitive impairment (aMCI) and AD compared to those with normal cognition (NC). We also found that scores on this same test are able to detect which participants have aMCI versus NC, indicating that olfactory perceptual measures are sensitive to the earliest stages of the AD disease process.

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