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Past research programs:

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"Sensory Dysfunction in Early Parkinson's Disease "

Principal Investigator: Richard L. Doty, Ph.D.
Agency: Department of Defense.

Parkinson’s disease has been associated with altered sensory function, including changes in vision, hearing, smell, touch, taste, and balance.  The purpose of this study is to better understand, using a wide range of tests, these sensory changes in early Parkinson’s disease.  We will assess the relationships of the sensory changes to one another, the influence of dopamine therapy, a common treatment in early-stage Parkinson’s disease, on such changes, and the relationship of such changes to the number of dopamine nerve cells in a motor control region of your brain, determined using a procedure called Single Photon Emission Tomography (SPECT).  During the SPECT part of this study, an Investigational New Drug (IND), termed TRODAT, will be employed.  TRODAT is a chemical that is made to give off a form of light that can be seen by a special camera called a SPECT Scanner.  The amount of light coming from any given area of the brain will show how much of the TRODAT material there is and the number of nerve cells that make a chemical called dopamine. Alternatively, if Technetium-99m TRODAT-1 is not available, you may undergo an [18F]FDOPA PET scan. FDOPA is similar to TRODAT in that it is a chemical that is made to give off light that can be seen by a special camera called a PET scanner. The amount of light coming from any given area of the brain will show how much of the FDOPA material there is and the number of nerve cells that make a chemical called dopamine.

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"Postmenopausal Estrogen Influences on Olfaction"

Principal Investigator: Richard L. Doty, Ph.D.
Agency: National Institute on Aging.
Type: RO1 (AG17496)

The primary goal of this work is to assess retrospectively the association between ERT and both olfactory and cognitive changes. Since olfactory loss is among the first, if not the first, sign of Alzheimer’s disease (AD), and estrogen mitigates some symptoms of AD, does estrogen prevent olfactory loss in the menopause? This study will answer this basic question.

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"Olfaction in Epilepsy"

Principal Investigator: Richard L. Doty, Ph.D.
Agency: National Institute on Deafness and Other Communication Disorders.
Type: RO1 DC04278.

The primary olfactory cortex is compromised in temporal lobe epilepsy (TLE) and by surgical treatments for intractable forms of this disease (e.g., temporal lobe resection or TLR). Although a number of studies have examined olfactory function in both TLE and TLR patients, the results are far from conclusive. In the case of threshold measures, for example, some studies report that TLE decreases sensitivity, others report that TLE increases sensitivity, and still others find no influences of TLE on sensitivity at all. The same is true for TLR. Unfortunately, olfactory tests of unknown or questionable reliability have typically been employed, bilateral testing has been the rule rather than the exception (bilateral test scores reflect the better functioning side of the nose), too few subjects have been evaluated, and the amount or location of brain tissue damaged by TLE has not been quantified. Furthermore, with only one exception, pre-/post TLR designs have not been employed. Thus, very basic questions regarding the influence of TLE and TLR on the ability to smell remain unanswered. For example, are some olfactory abilities (e.g., detection sensitivity), but not others (e.g., odor identification), largely insensitive to central temporal lobe lesions? Is olfactory function altered bilaterally or only on the side of the epileptic foci? To what degree is TLE-related olfactory loss, if present, further attenuated by TLR? Are psychophysical olfactory losses mirrored by changes in EEG activity induced by odorous stimuli? The proposed research will provide definitive answers to these and other basic questions.

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"Olfactory Event Related Potentials and Frontal Limbic Pathology in Schizophrenia"

Principal Investigator: Bruce Turetsky, M.D.
Agency: National Institute of Mental Health.
Type: RO1 MH 59852.

The primary goal of this study is to assess electrophysiological and imaging changes in response to odorant's in patients with schizophrenia.

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"Olfactory Function in Schizophrenia: A Lifespan Analysis"

Principal Investigator: Paul Moberg, Ph.D.
Agency: National Institute of Mental Health.
Type: RO1 MH 63381.

The primary goal of this project is to assess olfactory functions over the lifespan in patients suffering from schizophrenia using a comprehensive psychophysical battery. To detail the potential chronic and acute effects of neuroleptic medication on olfactory function, total neuroleptic burden will be assessed across decade bands as well as in neuroleptic-naïve and previously-medicated patients in a pre-post design.

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"Function of Taurine in the Primary Olfactory Pathway"

Principal Investigator: Igor L. Kratskin, M.D., Ph.D.
Agency: National Institute on Deafness and Other Communication Disorders.
Type: RO1 DC 04083-03

This study investigates the function of the neuroactive amino acid taurine in the olfactory epithelium. Data from this study have demonstrated that (a) specific mRNA for the taurine-synthesizing enzyme is highly expressed in the nasal mucosa of rats, and (b) among cells that constitute the nasal mucosa, only olfactory receptor neurons contain taurine. Two peptides, representing fragments of taurine-synthesizing enzyme, were designed during this period and synthesized. Antibodies to these peptides are used to localize the sites of taurine production at the cellular level and to examine expression of the taurine-synthesizing enzyme under some experimental conditions. This treatment is expected to inhibit translation of the enzyme from specific mRNA and produce taurine deficiency in the olfactory epithelium. Various experimental approaches will be employed to evaluate olfactory function in taurine deficient rats, including behavioral olfactory testing using sophisticated operant conditioning procedures.

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