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R L Doty

Publications and source records attributed to R L Doty.

At least 19 recordsLinked to original sources
PubMed1999

Gender effects on odor-stimulated functional magnetic resonance imaging.

On standardized tests of odor identification and odor detection, women tend to score better than men at nearly all age groups. We sought to determine if these findings would translate to differences between the sexes in the volume of activated brain when odors are presented to subjects as the stimulants for functional magnetic resonance imaging (FMRI) experiments. The activation maps of eight right-handed women (mean age 25.3 years old, range 20-44, S.D. 8.3 years) were compared with those of 8 right-handed men (mean age 30.5, range 18-37, S.D. 6.5 years) given the same olfactory nerve stimuli in an FMRI experiment at 1.5 T. Olfactory stimuli were delivered to the patients in a passive fashion using a Burghart OM4-B olfactometer with a nose piece inserted into the patients' nostrils. We used agents (eugenol, phenyl ethyl alcohol, or phenyl ethyl alcohol alternating with hydrogen sulfide) that were selective for olfactory nerve stimulation in the nose. The odorants were delivered to both nostrils for 1 s every 4 s during a 30 s 'on-period'. During the 30 s 'off-period', the patient received room air at the same flow rate. The women's group-averaged activation maps showed up to eight times more activated voxels than men for specific regions of the brain (frontal and perisylvian regions). The left and right inferior frontal regions showed a statistically significant increase in activation in women at p<0.01. In general, more women showed activation than men. The results suggest that (1) FMRI activation maps in subject groups can demonstrate correlates to psychophysical tests of olfaction, and (2) one must control for gender when performing odor-stimulated FMRI experiments.

Adolescent↗
PubMed1998

Olfactory bulb and tract and temporal lobe volumes. Normative data across decades.

The sense of smell shows a diminution with age as measured by the University of Pennsylvania Smell Identification Test (UPSIT). To ascertain whether the volumes of the olfactory bulbs and tracts (OBTs) and the temporal lobes (TL) declined in parallel to smell function, we examined 36 individuals from ages 22 to 78 who did not complain of any loss of the sense of smell using magnetic resonance (MR) imaging. The OBT volumes showed an initial increase to the 4th decade of life and then a decrease with increasing age, while the trend in TL volume was not as dramatic. There was no correlation between OBT or TL volumes with unilateral or total UPSIT scores. The normative data by decades can be used to assess the OBTs of cohorts of patients with neurodegenerative disorders that affect olfaction.

Adult↗
PubMed1998

Olfactory dysfunction in multiple sclerosis. Relation to plaque load in inferior frontal and temporal lobes.

The question of whether and to what degree multiple sclerosis (MS) influences the ability to smell is controversial. We administered the University of Pennsylvania Smell Identification Test (UPSIT) to 26 MS patients and concurrently employed high-resolution magnetic resonance imaging (MRI) to quantify the number of demyelinating plaques within central brain structures. 38.5% of the patients demonstrated olfactory loss, with 7.7% exhibiting severe microsmia, 19.2% moderate microsmia, and 11.5% mild microsmia. None was anosmic, and no consistent left:right asymmetry in olfactory function or in hemispheric plaque numbers was observed. A strong negative correlation was found (Spearman r = -0.94) between UPSIT scores and the number of plaques within the inferior frontal and temporal lobes, but not within the rest of the brain. This study unequivocally demonstrates that a sizable proportion of MS patients suffer from olfactory loss commensurate with plaque activity within olfactory-related central brain regions, and is the first to explicate a physical basis for the olfactory dysfunction of any common neurologic disease.

Adult↗
PubMed1998

Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases.

BACKGROUND: Olfactory deficits in Alzheimer's disease (AD) and idiopathic Parkinson's disease (PD) have been well established. OBJECTIVE: To clarify and review the literature by evaluating the evidence for olfactory deficits in 3 olfactory domains, including odor identification, recognition, and detection threshold. DATA SOURCES: A literature search of English-language studies of olfaction in AD, PD, and healthy controls was conducted via online databases (PsycInfo and MEDLINE) and reference lists from review articles. STUDY SELECTION: To meet selection criteria for meta-analysis, each study required a control group and complete and usable data. This review yielded 26 publications of olfactory identification, recognition, and/or detection threshold. Because of the inclusion of more than 1 relevant study of olfaction in several of these publications (eg, both identification and threshold assessed), 43 studies were ultimately appropriate for meta-analysis. DATA EXTRACTION: Effect sizes were calculated for each study by expressing differences between patient and control group means in SD units (Cohen's d). DATA SYNTHESIS: Extremely large effect sizes were shown across all tasks in both AD and PD groups. Both between-group analyses using the Mann-Whitney U test and within-group analyses using Friedman 2-way analysis of variance did not reveal any significant differences (all P > .30). CONCLUSIONS: As expected, severe deficits were found for both patients with AD and PD in each of the 3 olfactory domains relative to controls. However, no discriminating olfactory deficits were seen between patient groups or among the 3 measured olfactory domains, suggesting a similar disturbance in olfactory function between patients with AD and PD.

Adult↗
PubMed1998

SKF 38393 enhances odor detection performance.

The purpose of this study was to determine the influence of the D1-selective partial agonist SKF 38393 on the odor detection performance of rats using high precision olfactometry and a go/no-go operant task. Previous studies have found that the D2 receptor partial agonist quinpirole decreases such performance, but the influences of D1 receptor activation are unknown. In experiment 1, such detection performance to the odorant ethyl acetate was enhanced by SKF 38393, relative to saline, in male rats at 7.5 and 10.0 mg/kg i.p. dose levels, but not at the lower doses of 1.0, 2.5, and 5.0 mg/kg. In experiment 2, this enhancement was replicated at the 7.5 and 10.0 mg/kg doses and was shown to occur at the 12.5 mg/kg dose as well. In experiment 3, similar enhancement was shown for the odorant eugenol in female rats at the 7.5, 10.0 and 12.5 mg/kg doses, suggesting this effect is neither sex-specific nor confined to the odorant ethyl acetate. In experiment 4, a 0.025 mg/kg dose of the D1 receptor antagonist SCH 23390 depressed the enhancement produced to ethyl acetate by 7.5 mg/kg SKF 38393 to control levels. Overall, these data demonstrate that, in contrast to quinpirole, SKF 38393 improves odor detection performance in the rat and that this phenomenon can be attenuated by the D1 receptor blocker SCH 23390.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Bilateral detection thresholds in dextrals and sinistrals reflect the more sensitive side of the nose, which is not lateralized.

Several fundamental questions remain enigmatic concerning human olfactory sensitivity, including (i) whether detection threshold differences exist between the two sides of the nose (and, if so, whether such differences are influenced by handedness) and (ii) whether bilateral (i.e. binasal) stimulation leads to lower thresholds than unilateral stimulation (and, if so, whether the degree of facilitation is inversely related to general olfactory ability). In this study, and well-validated single staircase procedure was used to establish bilateral and unilateral detection thresholds for the cranial nerve I stimulant phenyl ethyl alcohol in 130 right- and 33 left-handed subjects. No differences in sensitivity between the left and right sides of the nose were observed in either group. Bilateral thresholds were lower, on average, than unilateral thresholds when the latter were categorized in terms of left and right nares. However, the bilateral thresholds did not differ significantly from those of the side of the nose with the lower threshold. Overall smell ability, as measured by the University of Pennsylvania Smell Identification Test, did not interact with any of the test measures. These data imply that (i) the left and right sides of the nose do not systematically differ in detection threshold sensitivity for either dextrals or sinistrals and (ii) if central integration of left:right olfactory threshold sensitivity occurs, its effects do not exceed the function of the better side of the nose.

Adult↗
PubMed1998

Reduced Purkinje cell size in the cerebellar vermis of elderly patients with schizophrenia.

OBJECTIVE: The authors' goal was to compare the size and linear density of Purkinje cells in the cerebellar vermis of subjects with and without schizophrenia. METHOD: Blocks of alcohol-fixed cerebellar vermis were dissected at autopsy from the brains of 14 elderly patients with schizophrenia and 13 elderly subjects with no history of neuropsychiatric illness. The blocks of vermis were sectioned and stained with 1% cresyl violet. The linear density and cross-sectional area of Purkinje cells were measured by using computer-assisted image analysis. The subjects with schizophrenia had been assessed with clinical rating scales within 1 year prior to death. RESULTS: The average cross-sectional areas of Purkinje cells of the patients with schizophrenia were significantly smaller (by 8.3%) than those of the subjects without neuropsychiatric illness. No difference in Purkinje cell linear density was observed between the two groups. Significant correlations were seen between Purkinje cell size and scores on the Mini-Mental State, the Brief Psychiatric Rating Scale, and the antipsychotic drug dose. CONCLUSIONS: These data indicate cerebellar involvement in schizophrenia; they are also consistent with reports of reduced neuronal size in other brain regions of patients with schizophrenia. These findings support a model of wide-spread central nervous system abnormality in schizophrenia.

Aged↗
PubMed1998

Scratch density differentiates microsmic from normosmic and anosmic subjects on the University of Pennsylvania Smell Identification Test.

During assessment of smell function using the University of Pennsylvania Smell Identification Test, we observed that some persons with diminished smell perception seemed to perserverate in their attempts to release the odorant from the microencapsulated odorant strips. In this study we quantified the marked area of 1680 such strips from tests administered to 42 anosmics, normosmics, and microsmics. The density of pixels on the microencapsulated labels from the microsmic patients was greater than that from the other two groups, which did not differ significantly from one another. These data suggest (i) that persons with diminished olfactory ability attempt to increase the perceived intensity of the stimulus by marking the test's scent strips more vigorously and (ii) that the density of such marking may prove useful in detecting malingerers attempting to feign microsmia.

Aged↗
PubMed1997

Olfactory dysfunction in patients with head trauma.

BACKGROUND: The ability to smell is commonly altered by head trauma (HT). However, the nature, prevalence, prognosis, and etiology of such alterations are poorly understood. OBJECTIVES: To quantitatively determine the degree of olfactory function in patients with HT-related chemosensory complaints and to examine the influences of age, sex, HT severity, time since HT, and other variables on such function. Also, to use quantitative magnetic resonance imaging (MRI) to establish whether and to what degree damage to the olfactory bulbs and tracts, frontal lobes, and temporal lobes occurs. PATIENTS AND METHODS: Two hundred sixty-eight patients with HT from the University of Pennsylvania Smell and Taste Center, Philadelphia, were administered a quantitative odor identification test, a depression inventory, and a medical history questionnaire; 66 were retested after individual test-retest periods ranging from 1 month to 13 years. The volume of olfactory-related brain structures was determined in 15 patients and 15 controls using MRI. RESULTS: One hundred seventy-nine patients (66.8%) had anosmia, 55 (20.5%) had microsmia, and 34 (12.7%) had normosmia. Frontal impacts produced less dysfunction than back or side impacts. Of the 66 retested patients, 24 (36%) improved slightly, 30 (45%) had no change, and 12 (18%) worsened; only 3 patients, none of whom initially had anosmia, regained normal olfactory function. Trauma severity was related to olfactory test scores in patients with microsmia. Parosmia prevalence decreased from 41.1% to 15.4% over an 8-year posttrauma period. Olfactory bulb and tract volumes of male, but not female, patients with HT were greatly reduced relative to volumes of controls. CONCLUSIONS: Patients complaining of HT-related olfactory dysfunction typically have anosmia and rarely regain normal olfactory ability, parosmia prevalence decreases over time in such patients, and damage to olfaction-related brain structures can be observed in most such patients using an appropriate MRI protocol.

Adult↗
PubMed1997

An easily constructed pipette for pressure microinjections into the brain.

A simple device for making pressure microinjections into the brain, its application for delivery of a tracer substance, biotin dextran amine, and an example of the resulting axonal transport are described. The device is based on the use of a Luer Up Hamilton microliter syringe mated directly to the plastic hub of an injection needle assembly in which the metal needle has been replaced by a glass pipette. In model experiments, the injection sites were measured in brain sections of rats, which were perfused with fixative immediately after administration of the tracer, and the relationship between the injected volume and the area of the injection site was evaluated. The results showed that the device provided accurate and reproducible delivery of the fluid.

Animals↗
PubMed1997

Reproducibility and reliability of volumetric measurements of olfactory eloquent structures.

RATIONALE AND OBJECTIVES: The authors assessed the reliability and reproducibility of volumetric measurements of olfactory bulbs and tracts (OBTs) and temporal lobes (TLs) with magnetic resonance (MR) imaging. METHODS: Repetitive MR imaging of two phantoms and OBTs and TLs of patients was performed. Regions of interest were manually drawn around the relevant structures, and their volumes were measured at workstations. Intra- and interobserver variability for the two readers were measured. Intraclass and Pearson correlation coefficients and mean percentage differences were calculated. RESULTS: The measured phantom volumes were within 1.9%-12% of the true volumes with a variability of < or = 5%. Intraclass and Pearson correlation coefficients were > or = 0.919 for measurements by a single reader and > or = 0.924 for measurements by different readers. The inter- and intraobserver variabilities were < or = 4.2% for TL and 11.3%-14.6% for OBTs. CONCLUSION: Volumetric measurements of the olfactory apparatus can be reliably and accurately reproduced from MR images.

Humans↗
PubMed1997

Influence of stimulus duration on a regional measure of NaCl taste sensitivity.

The present study demonstrates that perithreshold temporal integration occurs in the human taste system across stimulus durations ranging from 200 to 1500 ms in a manner analogous to that seen in other major sensory systems. Thus, the notion that gustation is comparatively insensitive to temporal stimulus parameters at threshold levels is disproved.

Adult↗
PubMed1997

Studies of human olfaction from the University of Pennsylvania Smell and Taste Center.

This paper, presented in part as an invited lecture on the occasion of Professor E.P. Köster's retirement from Utrecht University, summarizes a large body of human studies performed at the University of Pennsylvania Smell and Taste Center during the last 17 years. Details of the development of standardized olfactory tests are provided, including their validation and application in a wide variety of clinical and laboratory settings. Included are studies related to transduction mechanisms in olfactory coding and factors that adversely influence olfactory function (e.g. age, gender, smoking, exposure to environmental chemicals, numerous diseases). A brief discussion of the strengths and weaknesses of the olfactory vector hypothesis for neurodegenerative diseases is also presented.

Humans↗
PubMed1997

Influence of age on the 'nasal cycle'.

The nasal cycle is classicially defined as a side-to-side fluctuation in nasal engorgement and airflow, with period lengths ranging from approximately 1 to 5 hours. This cycle, as well as its variants (e.g., cyclic changes on one side of the nose only), is produced by alterations in autonomic tone of the nasal vasculature and reportedly correlates with a number of ultradian rhythms, including asymmetries in left:right cerebral electroencephalographic (EEG) activity and differential performance on visual/spatial psychological tasks. Since the pacemaker for the nasal cycle is believed to lie within the suprachiasmatic nucleus of the hypothalamus, and this nucleus evidences degeneration in later life, we sought to determine whether the nasal cycle or its variants changes with age. To achieve this end, we used a liquid crystal thermography exhalation monitor to measure relative airflow of the two nasal chambers at 15-minute intervals for 6 hours in 60 people representing four age categories: 18 to 29 years (n=12); 30 to 49 years (n=15); 50 to 69 years (n=13); and 70 to 85 years (n=20). Overall, the proportion of subjects exhibiting the alternating rhythmicity associated with the classic nasal cycle decreased with age. No association was present between nasal cycle parameters and scores on the Mini-Mental State Examination (MMSE). The results suggest that the classic nasal cycle may be a marker for age-related central nervous system changes.

Adolescent↗
PubMed1997

Functional MR imaging during odor stimulation: preliminary data.

PURPOSE: To determine the locations and extent of activation in areas of the brain at functional magnetic resonance (MR) imaging with olfactory stimulation and to determine whether accommodation or amplification of brain activation occurs with sequential olfactory stimulation. MATERIALS AND METHODS: Five adult men with normal senses of smell underwent multisection, gradient-echo, echo-planar imaging according to a blood-oxygen-level-dependent experimental paradigm. Odorants that nearly exclusively stimulate the olfactory system and odorants that stimulate the olfactory and trigeminal nerves were compared by using repetitive imaging procedures. RESULTS: Activation with olfactory nerve-mediated odorants was demonstrated in the orbitofrontal cortex (Brodmann area 11) with a right-sided predominance. Mild cerebellar stimulation was also observed. With repeated testing, overall activation with olfactory nerve-mediated odorants declined. Odorants that also stimulated the trigeminal nerve produced additional cingulate, temporal, cerebellar, and occipital activation. Activation with combined trigeminal and olfactory system odors increased more than sixfold with repeated testing. CONCLUSION: Olfactory nerve-mediated and combined olfactory and trigeminal nerve-mediated odorants activate different regions of the brain. Orbitofrontal stimulation spreads to all parts of the brain when a trigeminal component is added. Habituation (deactivation) occurs with repeated testing of olfactory nerve-mediated odorants, while, paradoxically, activation increases with repeated exposure to odors that also stimulate the trigeminal nerve.

Adult↗
PubMed1997

Olfactory identification deficits in schizophrenia: correlation with duration of illness.

OBJECTIVE: The authors examined the relationship between deficits in olfactory identification and duration of illness in young and elderly patients with schizophrenia. METHOD: Olfactory identification performance of 38 patients with schizophrenia and 40 normal subjects was compared by using the University of Pennsylvania Smell Identification Test. RESULTS: The schizophrenic patients demonstrated olfactory deficits relative to the comparison group, and the elderly schizophrenic patients displayed a greater magnitude of olfactory deficit than the younger patients. Independent of normal aging effects and cognitive deficit, patients with schizophrenia showed a strong relationship between olfactory identification scores and duration of illness, which suggests that olfactory abilities decline progressively over the course of the disorder. CONCLUSIONS: In contrast to other neuropsychological measures that have been reported to be stable over the course of illness, olfactory identification abilities deteriorate steadily in patients with schizophrenia, even for those with relatively recent onset.

Adolescent↗