bluuebunny/crossref_metadata_2025 huggingface dataset:
Ipsilateral Dominance of Human Olfactory Activated Centers Estimated from Event‐Related Magnetic Fields Measured By 122‐Channel Whole‐Head Neuromagnetometer Using Odorant Stimuli Synchronized with Respirations
Authors: TONOIKE MITSUO , YAMAGUCHI MASAHIKO , KAETSU ISAO , KIDA HIROYUKI , SEO RITSU , KOIZUKA IZUMI
Published: February 2006

ABSTRACT:The aim of this study was to measure and analyze olfactory event‐related magnetic fields using a whole‐cortex biomagnetometer (122‐channel SQUID gradiometer). Amyl‐acetate gas (approx. 1%) was administered for 300 msec into either the right or left nostril in synchronization with respiration using a mask and an optical fiber sensor. Clear olfactory event‐related magnetic fields were asymmetrically obtained on both sides of the forehead in all six subjects. The generators of olfactory magnetic fields were estimated at two regions located fairly asymmetrivally near the bilateral frontal deep areas. The goodness‐of‐fit was better for the two‐dipole model than the one‐dipole model in all experiments.

In almost all subjects the latency and intensity of ipsilateral olfactory magnetoencephalography (MEG) responses were shorter and larger than those of the contralateral responses, respectively.

These results suggest that the olfactory MEG responses on the ipsilateral side are generally larger and more dominant than those on the contralateral side in the human olfactory system.
Age Effects on Central Nervous System Activity Reflected in the Olfactory Event‐Related Potential: Evidence for Decline in Middle Agea
Authors: MURPHY CLAIRE , WETTER SPENCER , MORGAN CHARLIE D. , ELLISON DENNARD W. , GEISLER MARK W.
Published: February 2006

ABSTRACT:A series of studies in this laboratory using the olfactory event‐related potential (OERP) have examined the underlying central nervous system activity associated with age‐related changes in olfactory functioning. Early (sensory) components of the OERP showed reduced amplitude and longer latency in elderly subjects, with larger effects in males. Amplitudes are already decreased in middle age. The late cognitive component, P3, showed a longer latency as well as a decreased amplitude in the elderly, with effect sizes for age significantly larger for the late component than for the early components. We report here the significantly longer latency, particularly for the P3, in middle‐aged persons, suggesting age‐related slowing of olfactory information processing as early as the 50s. Results suggest that the elderly brain, and indeed, the middle‐aged brain shows smaller responses to odors, is less able to allocate attentional resources and slows in its olfactory cognitive processing. The OERP is a potent reflection of these changes.
Olfactory Function in Acute Rhinitisa
Authors: HUMMEL T. , ROTHBAUER C. , BARZ S. , GROSSER K. , PAULI E. , KOBALD G.
Published: February 2006

ABSTRACT: This study was performed to investigate the effects of the common cold on olfactory function, which was assessed using chemosensory event‐related potentials (CSERP, in response to both olfactory [H2S] and trigeminal [CO2] stimuli) and psychophysical measures (intensity ratings, odor discrimination, butanol threshold); nasal volume was assessed by means of acoustic rhinometry. The investigation was performed in 36 subjects (18 women, 18 men). After onset of the rhinitis (day 0) measurements were performed on days 2, 4, 6 and 35. The cold produced a decrease of the volume of the anterior nasal cavity accompanied by an increase of mucus secretion, an increase of olfactory thresholds, a decrease of intensity ratings and a decrease of N1 CSERP amplitudes to olfactory and trigeminal stimuli. When mucus secretion of the contralateral nasal cavity was controlled with oxymetazoline, N1 amplitudes to olfactory stimuli were still affected by the cold as indicated by the significant increase of amplitudes as subjects recovered; this phenomenenon was not found for responses to trigeminal stimuli. This indicates that the common cold has a small effect on olfactory function which may be independent of nasal congestion.
Steady State Visual Evoked Potential (SSVEP) Changes in Response to Olfactory Stimulation
Authors: PATTERSON JOHN , OWEN CAROLINE M. , SILBERSTEIN RICHARD B. , SIMPSON DAVID G. , PIPINGAS ANDREW , NIELD GEOFFREY
Published: February 2006

ABSTRACT: The location, nature and characteristics of brain activity during detection and identification of odors are of importance if brain function techniques are to be of value to sensory systems. Steady state probe topography (SSPT) has been used in our laboratory to record steady state visual evoked potentials (SSVEP), which have demonstrated cognitive task‐related changes in a variety of testing paradigms. The enhanced spatial (when using 64 channels) and temporal resolution (380 ms) of the system enable the brain electrical activity changes occurring before, during and after delivery of an odor to be examined. We have developed a system which can deliver odors during normal respiration and the accurate timing needed for SSVEP recordings. The system is based on the premise that a subject breathing butanol compared with filtered medical air will demonstrate SSVEP topographic changes associated with detection and identification of butanol. During our experiments the subject has either an air sample or an equal volume of butanol injected into the inspiratory airflow. These are randomized, and every breath has the same stimulus system with no known clues as to the differences apart from detection. The results from a panel of 10 female subjects‐who all identified the butanol correctly‐showed that butanol delivery resulted in sequences of changes in SSVEP topography (amplitude and latencies) which involved parietal, frontal and temporal regions. While consistent with other studies (parietal changes), our results revealed more dynamic temporal changes involving prefrontal and parietal regions at different periods around odor delivery.
Central Nervous Correlates of Chemical Communication in Humansa
Authors: KRAUEL KERSTIN , PAUSE BETTINA M. , MUELLER CLAUDIA , SOJKA BERNFRIED , MUELLER‐RUCHHOLTZ WOLFGANG , FERSTL ROMAN
Published: February 2006

ABSTRACT: The recording of chemosensory event‐related potentials (CSERPs) has been established as an objective method in the assessment of central odor processing in humans. In the present study CSERPs were used to investigate whether human body odor is genetically determined by the major histocompatibility complex (MHC), referred to in humans as the human leukocyte antigen (HLA). The immunological function of the MHC is the discrimination of self/nonself within the immune system. In rodents it has been shown that body odor is significantly influenced by the MHC and that it can be discriminated by members of different species.

To create a sufficiently large subject pool, 144 subjects were screened for their HLA class I loci A and B. During the electroencephalography (EEG) session the subjects (n= 40/20 women) were confronted with the body odor (axillary hair) of three different donors. Two donors (d1 and d2) were HLA‐similar but had a different HLA type than the third donor (d3) and the perceiving subject. The third donor and the perceiver shared a similar HLA type. Half of the perceivers received odors from donors of the same sex, the other half smelt odors from donors of the opposite sex. In the EEG session subjects were presented with 200 trials. The odors were delivered through a constant flow olfactometer nonsynchronously to breathing. The odor of d1 appeared frequently (p= 0.6) whereas the odors of d2 and d3 appeared each at a rate of p= 0.2. During half the trials the subjects were instructed to respond to the odor of d2, during the other half to the odor of d3. The EEG was recorded from Fz, Cz, Pz, F3, P3, F4 and P4 in reference to linked mastoids. First results show that male perceivers show enhanced potentials in response to male donors of a similar HLA type (d3). The CSERP results of the other groups as well as valence and attractiveness ratings will be discussed.
Phonological and Perceptual Components of Short‐Term Memory for Odorsa,b
Authors: WHITE THERESA L. , HORNUNG DAVID E. , KURTZ DANIEL B. , TREISMAN MICHEL , SHEEHE PAUL
Published: February 2006

ABSTRACT: Just as a written word can be encoded and retained in memory either verbally or in a visual form, so it might seem that an odor might be retained as either a verbal description/name or as a perceptual (olfactory) code. However, one view has it that olfactory memory in the short term does not exist as a separate perceptual code. This was examined in an experimental paradigm in which errors in memory could be recognized as deriving from the substitution of similar verbal codes or of similar olfactory codes. The set of odorants presented for recall was divided into three groups: (i) base odorants (odorants that might be replaced in memory either by similar verbal or similar olfactory representations); (ii) verbal foils (stimuli dissimilar to the base stimuli in odor but which is similar in name); and (iii) odor foils (the reverse). The substitution errors made when attempting to recall test odorants were classified as verbal errors or olfactory errors. A substantial proportion of the errors were olfactory, but verbal errors also occurred. These results support the presence of short‐term perceptual olfactory memory, rather than simply verbal encoding of olfactory perceptions.
Spatiotemporal Masking in Pure Olfactiona
Authors: RADIL T. , WYSOCKI C. J.
Published: February 2006

ABSTRACT: In olfaction, it is not possible to determine which nostril is being stimulated, i.e., lateralize, when a pure olfactory substance, e.g., phenylethyl alcohol or vanillin, is administered into one nostril, and, simultaneously, an odorless, solvent blank into the contralateral nostril. We subjected volunteers to extensive training, with feedback on each trial, in an attempt to determine whether it was possible, in these well‐trained subjects, to overcome this apparent impossibility. We failed to obtain any evidence to support the notion that a pure olfactory stimulus could be lateralized when the odorant and blank were presented simultaneously. The task, however, became simple when the odorant and the blank entered each nostril sequentially. We investigated, using a two‐channel olfactometer, temporal parameters that enabled such discrimination. We controlled the duration of odorant and blank air puffs, as well as their mutual timing, to determine the threshold stimulus onset‐disparity, i.e., the interval between stimulus onset and blank onset, that resulted in an inability to lateralize. Latencies shorter than the threshold interval would be perceived as simultaneous stimulation. We determined that the onset interval was between 200 and 400 ms, depending on the duration of the stimuli (a shorter interval was noted for stimuli of 150‐ms duration relative to 300‐and 450‐ms stimuli). This was also true when two odorants were applied, rather than an odorant and a blank, and the subject was instructed to focus on the sequence of odorant delivery and side of stimulation. The temporal onset threshold was the same for lateralization and for order of stimulation. Whether the olfactory system per se mediates this discrimination or whether inputs from olfaction and chemesthesis, via trigeminal free nerve endings stimulated by air‐stream onset, combine to allow this discrimination has yet to be determined.
Focused Attention and the Detectability of Weak Gustatory Stimuli: Empirical Measurement and Computer Simulationsa
Authors: MARKS LAWRENCE E. , WHEELER MARY E.
Published: February 2006

ABSTRACT: Attentional processes can modulate the detectability of weak stimuli; for example, the detectability of visual or auditory signals can depend on whether attention is allocated to the appropriate spatial location (vision) or acoustic frequency (hearing). Earlier attempts in the first author's laboratory to find analogous effects of focused attention on the detectability of taste stimuli were equivocal, in part it seems because human gustatory sensitivity can fluctuate substantially over time, a serious problem when using procedures that track sensitivity (d') to a constant stimulus concentration. To circumvent this problem, we adopted an adaptive psychophysical procedure, the transformed up‐down method, using a 3‐down/1‐up rule to determine how the threshold to detect weak concentrations of sucrose and citric acid depended on whether the stimulus presented in a given two‐alternative, forced‐choice trial was expected or unexpected. The results showed threshold sensitivity to he slightly but consistently poorer when the test stimulus was unexpected (e.g., sucrose presented when citric acid was expected) than it was when the test stimulus was expected (e.g., sucrose presented when sucrose was expected).

In this attentional paradigm, the unexpected stimulus must perforce be presented on only a small fraction of the trials. In selecting a procedure, we chose a 3‐down/1‐up adaptive rule rather than the more popular 2‐down/1‐up rule, a choice that turned out to be in line with results of Monte Carlo computer simulations. These simulations suggest that across a wide range of conditions (starting stimulus concentrations, step sizes), the variability in threshold measurements can he smaller with a 3‐down/1‐up rule than with a 2‐down/1‐up rule, even when the total number of trials is the same and not very great.
Sensory Properties of Selected Terpenes: Thresholds for Odor, Nasal Pungency, Nasal Localization, and Eye Irritationa
Authors: COMETTO‐MUÑIZ J. ENRIQUE , CAIN WILLIAM S , ABRAHAM MICHAEL H. , KUMARSINGH RACHEL
Published: February 2006

ABSTRACT: We tested four normosmics and four anosmics in detection thresholds for six terpenes commonly found indoors: cumene, p‐cymene, delta‐3‐carene, linalool, 1,8‐cineole and geraniol. Normosmics provided odor thresholds and anosmics provided nasal pungency thresholds. All subjects provided nasal localization (i.e., right/left nostril) and eye irritation thresholds. Each type of threshold was measured eight times per subject‐stimulus combination. Stimuli were presented from squeeze bottles in a two‐alternative forced‐choice procedure via an ascending method of limits. Odor thresholds ranged between 0.1 and 1.0 parts per million (ppm, by volume). Nasal pungency thresholds lay about three orders of magnitude above odor thresholds. Nasal localization and eye irritation thresholds did not differ between normosmics and anosmics, and fell close to nasal pungency thresholds. Olfactory thresholds could be obtained for all stimuli in all repetitions using the criterion of five correct choices in a row. Trigeminal thresholds (i.e., pungency, localization and eye irritation) could be obtained on all repetitions only for some terpenes using that same criterion. Carene and cineol produced nasal pungency and eye irritation on all repetitions. None of the terpenes could be localized on all repetitions, but cineol was localized a higher percentage of instances than were the other stimuli. At the other extreme, geraniol failed to evoke any of the three trigeminal responses in most instances. Overall, the results indicate that the three trigeminal thresholds produce a uniform view of the potency of these terpenes, with nasal pungency and eye irritation being slightly more sensitive than nasal localization. Furthermore, application of a previously derived linear solvation energy relationship to the results reinforced the view that physico‐chemical properties can predict the chemesthetic impact of volatile organic compounds.
Are Odors the Best Cues to Memory? A Cross‐Modal Comparison of Associative Memory Stimulia
Authors: HERZ RACHEL S.
Published: February 2006

ABSTRACT: To test the claim that odors are the 'best' cues to memory, several cross‐modal experiments were conducted in which odors were compared with verbal, visual, tactile and musical stimuli as associated memory cues. Each experiment comprised two sessions (encoding and retrieval) separated by 48 hr. At the encoding session, a series of stimuli were incidentally associated to a set of emotionally arousing pictures. At the retrieval session, memory accu racy and emotionality were assessed. Across experiments, results revealed that odors were equivalent to other stimuli in their ability to elicit accurate recall, but that odor‐evoked memories were always more emotional. Notably, emotional responses did not vary as a function of stimulus type at encoding. These data indicate that emotional saliency, rather than accuracy, is responsible for the impression that odors are superior reminders, and that retrieval processes (cf. encoding processes) are responsible for the distinctive emotionality of odor‐evoked memories.
Odor Memory in Normal Aging and Alzheimer's Diseasea
Authors: NORDIN STEVEN , MURPHY CLAIRE
Published: February 2006

ABSTRACT: The ability in normal elderly to verbally recall previously presented odors and to learn this task across trials was studied by applying a design which compared performance on the California Verbal Learning Test (CVLT) with an analogous odor test. Results suggest that both immediate and delayed recall of odors, both free and cued, as well as the ability to learn across trials is impaired in normal aging, perhaps more so for olfaction than for audition, which can be referred to poor use of semantic‐clustering strategies and poor identification. Olfactory decline in memory in normal aging is, however, far from as affected as in Alzheimer's disease (AD). Two studies of persons with questionable AD demonstrated significant deficits in both recognition memory and identification of odors. Although further research is required, the findings from these 'preclinical' cases imply that performance on olfactory‐mediated tasks may contribute to early diagnosis of AD.
Differences and Similarities in the Perception of Everyday Odors: A Japanese‐German Cross‐Cultural Study
Authors: AYABE‐KANAMURA SAHO , SAITO SACHIKO , DISTEL HANS , MARTÍNEZ‐GÓMEZ MARGARITA , HUDSON ROBYN
Published: February 2006

ABSTRACT: To investigate the influence of experience on odor perception the responses of 40 Japanese and 44 age‐matched German women to everyday odorants were compared. Subjects were presented with six 'Japanese,' six 'European' and six 'international' odorants and asked to rate them on intensity, familiarity, pleasantness and edibility, and to describe associations elicited by them, and if possible to name them. Significant differences were found between the two populations on all measures, with a close association of pleasantness ratings and edibility judgments suggesting the particular influence of eating habits on odor perceptions. Positive correlations between familiarity and pleasantness, strength of hedonic judgment and intensity, and familiarity and intensity were also found in both groups and for most individuals. The generality of these findings was supported by the results obtained from testing 40 Mexican women with the same odorants.
The Use of Olfactory Receptor Neurons (ORNs) from Biopsies to Study Changes in Aging and Neurodegenerative Diseasesa
Authors: RAWSON NANCY E. , GOMEZ GEORGE , COWART BEVERLY , RESTREPO DIEGO
Published: February 2006

ABSTRACT: A gradual loss of olfactory capability with age and in a number of neurodegenerative diseases is common, and mechanisms underlying these losses are not understood. We determined the feasibility of using ORNs obtained from olfactory epithelial biopsies to identify possible changes in ORN function that may contribute to olfactory impairment in these individuals. ORNs from nine healthy subjects (66‐84 yr), three patients with Alzheimer's disease and one with multi‐infarct dementia were studied with calcium imaging techniques and two odorant mixtures. Seventy‐five viable ORNs were studied; 53% of these were odorant responsive, and twenty percent of these responded to both odorant mixtures. In contrast, 25% of 173 ORNs from younger subjects were odorant responsive, and none of these responded to both odorant mixtures. The proportion of cells responding to each of the odorant mixtures also differed between older and younger subjects.

These studies demonstrate the feasibility of this approach to examine age or disease‐associated changes in neuronal function. Further, age‐related changes in ORN selectivity may contribute to changes in olfactory perfor mance.
Age‐Related Changes in the Prevalence of Smell/Taste Problems among the United States Adult Population: Results of the 1994 Disability Supplement to the National Health Interview Survey (NHIS)
Authors: HOFFMAN HOWARD J. , ISHII ERICK K. , MACTURK ROBERT H.
Published: February 2006

ABSTRACT: Information about the prevalence of disorders of the chemical senses has been limited. In the late 1970s, the consensus among experts convened by the National Institutes of Health (NIH) was that more than 2 million adults in the United States had a disorder of smell or taste. A large, nonrandom survey conducted by the National Geographic Society in 1987 found that 1% of their 1.2 million respondents could not smell 3 or more of 6 odorants using a 'scratch and sniff' test. Age was an important factor, with a decline beginning in the second decade of life. No comparable data have been available for taste, although it has been suggested that the sense of taste remains more robust with age. The National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, began collaborating with the National Center for Health Statistics (NCHS) in 1993 to acquire information on the prevalence of smell/taste problems using the Disability Supplement to the National Health Interview Survey (NHIS). This survey was administered to approximately 42,000 randomly‐selected households (representing about 80,000 adults over 18 years of age) in 1994. Adjusted national estimates derived from this survey showed a prevalence of 2.7 million (1.4%) U.S. adults with an olfactory problem. Also, 1.1 million (0.6%) adults reported a gustatory problem. When smell or taste problems were combined, 3.2 million (1.65%) adults indicated a chronic chemosensory problem. The prevalence rates increased exponentially with age. Almost 40% with a chemosensory problem (1.5 million) were 65 years of age or greater. In a multivariate analysis, the individual's overall health status, other sensory impairments, functional limitations (including difficulty standing or bending), depression, phobia, and several other health‐related characteristics were associated with an increase in the rate of chemosensory disorders.
Very Early Changes in Olfactory Functioning Due to Alzheimer's Disease and the Role of Apolipoprotein E in Olfactiona
Authors: BACON ANNA W. , BONDI MARK W. , SALMON DAVID P. , MURPHY CLAIRE
Published: February 2006

ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative illness marked by memory loss and at least one other cognitive disturbance. Early diagnosis of the disease has proved difficult and has therefore been the focus of much research. Apolipoprotein E (ApoE), a protein manufactured and distributed throughout the body, has shown specificity of binding to the βA4 peptide, the primary component in the senile plaques of AD. Furthermore, the ApoE, epsilon 4 (ɛ4) allele, is overrepresented in AD. These two lines of evidence suggest that ApoE, specifically the ɛ4 allele, plays an important role in the development of AD. Further support for this hypothesis appears in neuropsychological data showing cognitive decrements in ostensibly nondemented individuals with the ɛ4 allele, compared to those without the allele. It is also well known that olfaction is compromised in AD. Thus, the purpose of this study was twofold: (1) to examine very early changes in olfactory functioning due to AD and (2) to examine the role of ApoE in olfactory functioning in people at risk for AD by virtue of early cognitive decline. Results demonstrated changes in olfactory threshold the year immediately preceding change in diagnosis from normal control to AD. Also, in individuals with mild cognitive impairment, those with the ApoE ɛ4 allele show poorer thresholds than those without the ɛ4 allele.
Effect of Psychotropic Drugs on Taste Responses in Young and Elderly Persons
Authors: SCHIFFMAN SUSAN S. , GRAHAM BREVICK G. , SUGGS MARK S. , SATTELY‐MILLER ELIZABETH A.
Published: February 2006

ABSTRACT: The taste of six psychotropic drugs (amitriptyline HCl, clomipramine HCl, desipramine HCl, imipramine HCl, doxepin HCl, and trifluoperazine HCl) 'can be detected at concentrations of 0.1 mM or less in both young and elderly individuals. At concentrations 4 times higher than the detection thresholds, these drugs have bitter as well as other unpleasant taste properties. Oral exposure to these drugs not only induces a taste from the drug itself but also alters taste perception of other compounds such as NaCl and sucrose. These results indicate that both hypogeusia and dysgeusia may be induced by psychotropic medications.
Apolipoprotein E and ALzheimer's Disease: The Tip of the Susceptibility Iceberg
Authors: ROSES ALLEN D.
Published: February 2006

ABSTRACT: Apolipoprotein E (APOE) is a true susceptibility polymorphism of the common form of Alzheimer's disease (AD). There are three APOE alleles (ɛ2, ɛ3, ɛ4) that are universally distributed in the population with some variation in allele frequency due to racial and ethnic differences, and are associated with different risks and age of onset distributions. In multiple studies, the positive predictive value for symptomatic possible or probable AD patients who carry at least one ɛ4 allele was consistently >95%. Thus, early in the clinical course of dementia, when diagnoses are only 60‐70% accurate, the presence of an ɛ4 allele raises the diagnostic accuracy of AD to >95%. With the anticipation of a second major late‐onset AD susceptibility locus on chromosome 12, a matrix of relative susceptibility risks in the population raises many ethical and social questions associated with preclinical prediction.

The metabolism of apoE (protein) in the brain is a new and exciting area of neurobiology research made relevant by the association with AD. We have constructed transgenic animals using large human genomic fragments containing human APOE on an APOE‐deficit mouse background as well as homologous recombination experiments replacing mouse APOE with human APOE promoter elements. The APOE tissue elements, NOT the human APOE gene coding sequence, is associated with the human pattern of intraneuronal apoE immunoreactivity.
The Effects of Topical Anesthesia on Oral Burning in Burning Mouth Syndromea
Authors: FORMARKER B. K. , MOTT A. E. , FRANK M. E.
Published: February 2006

ABSTRACT: Burning mouth syndrome (BMS) is an oral pain disorder of uncertain origin. Central or peripheral pain mechanisms may play a role in the oral burning of BMS. We tested the effect of a topical anesthetic (dyclonine HCl) on patients' intensity ratings for oral burning, taste dysgeusia and the taste of two chemical stimuli (1.0 M NaCl and 1.0 M sucrose). A total of 33 patients (9 male and 24 female, average age: 60 yr) are included in this analysis. The anesthetic reduced the perceptual intensity of both chemicals in these patients on four out of five postanesthesia trials (p <0.01).

The BMS cohort included 12 patients whose burning increased (p <0.001), 14 patients whose burning did not change, and 7 patients whose burning decreased (p <0.001) after anesthesia. Baseline dysgeusias (n= 13) decreased in intensity (p <0.001) after anesthesia, suggesting BMS dysgeusia is related to the activation of peripheral taste mechanisms. The results also suggest that BMS oral burning may be a disorder of peripheral pain pathways in some patients.
Olfactory Dysfunction in Multiple Sclerosis: Relation to Plaque Load in Inferior Frontal and Temporal Lobesa
Authors: DOTY RICHARD L. , LI CHENG , MANNON LOIS J. , YOUSEM DAVID M.
Published: February 2006

ABSTRACT: 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.
Rapid Clinical Evaluation of Anosmia in Children: The Alcohol Sniff Test
Authors: DAVIDSON TERENCE M. , FREED CANDI , HEALY MATTHEW P. , MURPHY CLAIRE
Published: February 2006

ABSTRACT: Smell impairment affects 1‐2% of Americans and leads to frequent physician visits. Olfactory functional testing is available in chemosensory centers, but is frequently omitted in routine cranial nerve examinations. A new smell test, using the standard 70% isopropyl alcohol pad, was developed at the UCSD Nasal Dysfunction Clinic: The Alcohol Sniff Test (AST).3 The current study examined the reliability of the AST in children, using test‐retest measures. A standard 70% isopropyl alcohol pad was moved upward 1 cm per exhalation until the participant reported detection. Test‐retest reliability of the AST in children was significant, r= 0.80. The AST predictably classified children as anosmic, hyposmic or normosmic, p<0.0001. The AST requires only 5 minutes to administer with materials readily available in any physician's office or hospital. The AST is an effective screening tool, even in children, for the average physician who can then refer patients who show less than normal function for further comprehensive testing.
PROP (6‐n‐Propylthiouracil) Supertasters and the Saltiness of NaCla
Authors: BARTOSHUK LINDA M. , DUFFY VALERIE B. , LUCCHINA LAURIE A. , PRUTKIN JORDAN , FAST KATHARINE
Published: February 2006

ABSTRACT: Taste blindness to phenylthiocarbamide (PTC) and its chemical relative 6‐n‐propylthiouracil (PROP) was discovered in the 1930s. Family studies showed that those who could not taste PTC/PROP (nontasters) carried two recessive alleles. In recent years, we have classified tasters into two groups: medium (PROP is moderately bitter) and supertasters (PROP is intensely bitter). With our classification, ∼25% of Americans are nontasters, 50%, medium tasters, and 25%, supertasters. Studies showed that supertasters form a cohesive group. Anatomical studies showed that supertasters have the most fungiform papillae. Psychophysical studies showed that supertasters perceive the most intense bitterness and sweetness from a variety of compounds, the most intense burn from oral irritants, and the most intense tactile sensations from viscous solutions. Oral burn and touch are presumably perceived to be the most intense to supertasters because taste buds in fungiform papillae are innervated by the trigeminal nerve (pain, touch) as well as the chorda tympani nerve (taste).

The psychophysical scaling method used was magnitude matching with NaCl as the control modality. With this method, subjects rated the intensities of a series of NaCl and PROP solutions. The assumption that the taste of NaCl did not vary with PROP status allowed comparisons of the bitterness of PROP across subjects. Early magnitude matching studies, using sound as the control, had suggested that this assumption was reasonable. However, recent studies challenged that conclusion. Larger samples with more diverse populations, using sound as the control, showed that the taste of NaCl varied with PROP bitterness; supertasters perceived the strongest taste and nontasters, the weakest. Thus our earlier conclusions were conservative because differences between nontasters, medium tasters, and supertasters were concealed by using NaCl as a standard. Using magnitude matching with sound as the standard, or using the Green scale, which employs intensity labels, we found that the differences between PROP groups are larger. Note that the association between PROP status and salt taste is interesting in itself, since variability in salt taste may have important nutritional consequences.
Sensory Responses to 6‐n‐Propylthiouracil (PROP) or Sucrose Solutions and Food Preferences in Young Womena
Authors: DREWNOWSKI ADAM , HENDERSON SUSAN AHLSTROM , SHORE AMY B. , BARRATT‐FORNELL ANNE
Published: February 2006

ABSTRACT: Genetic sensitivity to the bitter taste of 6‐n‐propylthiouracil (PROP) has been linked with a greater number of food aversions and reported rejection of some bitter foods. Healthy young women (n= 121) were divided into nontasters, tasters and supertasters of PROP according to their PROP detection thresholds and the ratio of intensity ratings of PROP versus NaCl solutions. Hedonic response profiles to sucrose solutions distinguished between likers and dislikers of sweet. All subjects completed a 171‐item food preference checklist. Food preference data were reduced by factor analyses, subscales of which were tested for reliability using Cronbach's alpha. Greater PROP sensitivity was associated with lower acceptance of coffee, cruciferous vegetables, tart citrus fruit, dark breads, and selected fats. In contrast, liking for sucrose solutions was linked to liking for sugar in tea and coffee, but not to any special pattern of food acceptance. Strategies aimed at increasing the consumption of grains, vegetables, and fruit should consider the role of inherited taste markers and their potential impact on dietary habits.
Comparison of the Green Scale versus Magnitude Estimation for Taste Perceptiona
Authors: ZHENG CHANG‐JIANG , HOFFMAN HOWARD J. , LUCCHINA LAURIE A. , BARTOSHUK LINDA M. , WEIFFENBACH JAMES M.
Published: February 2006

ABSTRACT: The Green scale is a new psychophysical method that is simple for subjects to use, but its relation with magnitude estimation has yet to be fully characterized. In comparing the consistency between the Green scale and magnitude estimation, we found that the former seems to provide a psychological oral sensation measurement that is different from the latter method. A simple correction formula can be derived.
Effect of Gelatin (a Model for Salivary PRP) on the Sensory Astringency of 5‐O‐caffeoylquinic Acid and Tannic Acid
Authors: NAISH M. , CLIFFORD M. N. , BIRCH G. G.
Published: February 2006

ABSTRACT:The present work investigates differences (triangular tests) between the astringency of 5‐O‐caffeoylquinic acid (5‐CQA) and that of 5‐CQA + gelatin. As an overall reference similar tests are reported using tannic acid (which has been shown to elicit a strong response). Finally, a time‐intensity study on aqueous solutions of tannic acid (TA), TA + gelatin and gelatin, reveals relevant temporal factors.

Although, under the experimental conditions, the majority of comparisons revealed statistically significant differences, in the time‐intensity study no significant differences were found between TA + gelatin and gelatin, either for the intensity or the total duration of the response. Moreover, for the fading of the response there was no difference between TA + gelatin and TA.

The main temporal contribution to the difference is in the onset of the response and can be related to the spectral differences observed in the earlier studies. It will be argued that these results may represent an important step in our understanding of the mechanisms of astringency.
Using Sensory and Instrumental Data to Interpret the Effect of Storage at Elevated Temperatures on Aroma of Chardonnay Wines
Authors: DE LA PRESA OWENS C. , SCHLICH P. , WADA K. , NOBLE A. C.
Published: February 2006

ABSTRACT: The effect of elevated temperatures during storage on the aroma of commercial Chardonnay wines was monitored by sensory and instrumental methods. Aromas of wines stored at 40°C for 0, 15, 30 and 45 days were profiled by descriptive analysis by a trained panel. Heated storage decreased intensity of fruity and floral notes, while increasing attributes such as honey, butter/vanilla, oak, and rubber. Volatiles recovered by solvent extraction from the same wines were separated by gas chromatography (GC) and identified by GC‐mass spectrometry (MS). Principal component analysis of instrumental variables (PCAIV) was used to reduce the initial set of 67 quantified GC peaks. Six compounds, selected by PCAIV to yield the configuration closest to that of the principal component analysis of the sensory data, provided a highly significant fit with the sensory configuration, as shown by a permutation test. This solution was the statistically optimal one, but was not unique, as demonstrated by significant fits between the sensory and instrumental spaces upon use of other GC peaks, which were highly correlated with the original six variables.
Molecular Biology and Pharmacology of Galanin Receptors
Authors: BRANCHEK THERESA , SMITH KELLI E. , WALKER MARY W.
Published: February 2006

Abstract: Galanin was first isolated 15 years ago. Diversity of galanin receptors has been suspected from the study of native tissues and functional responses to galanin and galanin‐like peptides in vitro and in vivo. The recent application of molecular biologic techniques to clone galanin receptors has extended this diversity. So far, three galanin receptor subtypes, GALR1, GALR2, and GALR3, have been cloned from both human and rat. Their molecular structure, pharmacologic profiles, tissue distribution, and signal transduction properties have been partially elucidated.
Galanin Activates an Inwardly Rectifying Potassium Conductance and Inhibits a Voltage‐Dependent Calcium Conductance in Mudpuppy Parasympathetic Neurons a
Authors: PARSONS RODNEY L. , MULVANEY JENNIFER M. , MERRIAM LAURA A.
Published: February 2006

Abstract: Galanin‐induced activation of an inwardly rectifying membrane potassium (K+) current and inhibition of barium current (IBa) were studied using whole cell voltage clamp recording techniques in parasympathetic neurons dissociated from the mudpuppy cardiac ganglion. Both activation of the K+ current and inhibition of IBa were concentration‐dependent with an EC50 (or IC50) of ˜35 nM and ˜0.4 nM, respectively. Both actions of galanin were eliminated by pretreatment with pertussis toxin, which suggested involvement of Gi/Go protein activation. Galantide antagonized the galanin‐induced activation of K+ current with an IC50 equal to 4 nM. By contrast, galantide, by itself, inhibited IBa with an EC50 equal to 16 nM. Another galanin analog, M40, primarily antagonized the galanin‐induced activation of K+ current, but in some cells, M40 also acted as a weak agonist. M40, like galantide, inhibited IBa. The NH2‐terminal fragment galanin‐(1–16) activated the K+ current and inhibited IBa, indicating that the first 16 amino acids of the galanin peptide were sufficient for both actions. In summary, it is postulated that the effects of galanin on mudpuppy parasympathetic neurons might be mediated by activation of two different subtypes of galanin receptor, one that regulates membrane K+ conductance and a second that modulates calcium conductance.
LHRH and Sexual Dimorphism
Authors: MERCHENTHALER ISTVAN
Published: February 2006

Abstract: An increasing amount of evidences suggests that galanin plays an important role in the regulation of reproduction in the rat. Galanin is colocalized with luteinizing hormone‐releasing hormone (LHRH) in a subset of LHRH neurons, and the pattern of coexpression is sexually dimorphic, with a higher incidence of colocalization and level of galanin mRNA and peptide expression in females than in males. Therefore, the role of galanin may be unique to females, as are the LH surge and ovulation. The colocalization of LHRH and galanin is neonatally determined by an epigenetic mechanism involving the testis, whereas the expression of galanin in adult LHRH neurons is upregulated by estrogen and modulated by progesterone. The action of these sex steroids requires intact neurotransmission towards LHRH neurons, indicating that their action is mediated by interneurons.
Gonadal Steroid‐Dependent GAL‐IR Cells within the Medial Preoptic Nucleus (MPN) and the Stimulatory Effects of GAL within the MPN on Sexual Behaviors a
Authors: BLOCH G. J. , BUTLER P. C. , ECKERSELL C. B. , MILLS R. H.
Published: February 2006

Abstract: More GAL‐I cells exist within sexually dimorphic cell groups of the medial preoptic nucleus (MPN) in male rats than females, a large percentage of estrogen‐concentrating cells within MPN cell groups are also GAL‐immunoreactive (GAL‐IR), and significantly more GAL‐IR cells are visible with estrogen or its precursor, testosterone. Gonadal steroids also increase the size (diameter) of MPN GAL‐IR cells and the number of GAL‐IR cell processes within a portion of the MPN called the “GAL‐IR MPOA plexus,” which exists in males only. GAL microinjected into the MPN stimulated male‐typical sexual behaviors, with more testosterone required in females than males. Immunoneutralization with anti‐GAL serum inhibited male‐typical sexual behavior, indicating a role for endogenous GAL within the MPN. Microinjection of GAL into the MPN also stimulated female‐typical sexual behaviors in estrogen‐treated females and males, and GAL within the MPN dramatically overrode an inhibition of lordosis by dihydrotestosterone in rats of both sexes.
Galanin: Analysis of Its Coexpression in Gonadotropin‐Releasing Hormone and Growth Hormone‐Releasing Hormone Neurons
Authors: HOHMANN JOHN G. , CLIFTON DONALD K. , STEINER ROBERT A.
Published: February 2006

Abstract: Galanin is coexpressed in a subset of gonadotropin‐releasing hormone (GnRH) and growth hormone‐releasing hormone (GHRH) neurons in the brain and has an important role in the neuroendocrine regulation of gonadotropin and growth hormone secretion. Our overall goal has been to understand the functional significance of galanin as a cotransmitter with GnRH and GHRH in the regulation of these important physiologic processes. To this end, we studied the regulation of galanin's expression in GnRH and GHRH neurons under a variety of physiologic and experimental conditions. Using double‐label in situ hybridization and computerized image analysis, we observed that in GnRH neurons, galanin's expression is increased over the course of development in both sexes. Galanin achieves a higher basal expression in GnRH neurons in females, and it is sexually differentiated in the adult as a result of the differential exposure to testosterone during the neonatal critical period. Galanin is induced in GnRH neurons coincident with and subsequent to the proestrous luteinizing hormone surge (reflecting the combined action of estradiol and progester‐one) acting indirectly on GnRH neurons through a synaptic relay. Galanin's expression in GnRH neurons is inhibited during lactation, when the neuroendocrine reproductive axis is relatively quiescent. In GHRH neurons, the expression of galanin is also induced over the course of development in both sexes. Galanin's expression in GHRH neurons in the adult is sexually differentiated, but in this case, its expression is higher in males than females, reflecting the stimulatory effect of testosterone on galanin in the male. Galanin's expression in GHRH neurons is induced by growth hormone (GH), whereas the absence of GH leads to a reduction of galanin mRNA in these same cells. On the basis of these observations, we conclude that galanin is an important target for regulation by many hormones, and we postulate that as a cotransmitter, galanin acts presynaptically to modulate the secretion of GnRH and GHRH, possibly by altering their pulsatile release patterns, which in turn influences the release of the gonadotropins and GH from the pituitary.
Neuroendocrine Interactions between Galanin, Opioids, and Neuropeptide Y in the Control of Reproduction and Appetite a
Authors: KALRA SATYA P. , HORVATH TAMAS L.
Published: February 2006

Abstract: Galanin is a pleiotropic neuroendocrine signal produced in discrete subpopulations of neurons distributed in several sites in the hypothalamus. Neuropeptide Y and β‐endorphin also display pleiotropism, but they are produced by subpopulations of neurons located only in the arcuate nucleus of the hypothalamus. Each of these neuropeptides exerts a regulatory influence on reproduction and appetitive behavior. Experimental and morphologic evidence from our laboratory show direct contacts and interplay among these diverse signals. Seemingly, an interconnected network composed of these three neuropeptide‐producing neurons provides precision and site specificity in the relay of information necessary to govern reproduction and appetite. Disruptions in this interplay are likely to manifest in untoward consequences such as infertility and obesity.
Galanin Modulates 5‐Hydroxytryptamine Functions: Focus on Galanin and Galanin Fragment/5‐Hydroxytryptamine1A Receptor Interactions in the Braina
Authors: FUXE K. , JANSSON A. , DIAZ‐CABIALE Z. , ANDERSSON A. , TINNER B. , FINNMAN U.‐B. , MISANE I. , RAZANI H. , WANG F.‐H. , AGNATI L. F. , ÖGREN S. O.
Published: February 2006

Abstract: The reciprocal interactions between galanin and 5‐HT1A receptors in the rat brain are presented. Galanin and its NH2‐terminal fragments antagonize 5‐HT1A receptor‐mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5‐HT1A receptor activation at the soma‐dendritic level, leading to reductions of 5‐HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of antidepressant drug, based on the 5‐HT hypothesis of depression, by enhancing 5‐HT release and postjunctional 5‐HT1A‐mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY‐immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.
Galanin Expression within the Basal Forebrain in Alzheimer's Disease: Comments on Therapeutic Potentiala
Authors: MUFSON ELLIOTT J. , KAHL ULRIKA , BOWSER ROBERT , MASH DEBORAH C. , KORDOWER JEFFREY H. , DEECHER DARLENE C.
Published: February 2006

Abstract: The inhibitory neuropeptide galanin has widespread distribution throughout the central nervous system. Studies indicate that galanin modulates cognition by regulating cholinergic basal forebrain (CBF) neuron function. The chemoanatomic organization of galanin within the mammalian CBF differs across species. In monkeys, all CBF neurons coexpress galanin, whereas in apes and humans galanin is found within a separate population of interneurons that are in close apposition to the CBF perikarya. Pharmacologic investigations revealed a low and high affinity galanin receptor within the basal forebrain in humans. In vitro autoradiographic investigations of the primate brain indicate that galanin receptors are concentrated within the anterior subfields of the CBF as well as the bed nucleus of the stria terminalis, amygdala, and entorhinal cortex. Galaninergic fibers hyperinnervate remaining CBF neurons in Alzheimer's disease. Because galanin inhibits the release of acetylcholine in the hippocampus, it has been suggested that the overexpression of galanin in Alzheimer's disease may downregulate the production of acetylcholine within CBF perikarya, further exacerbating cholinergic cellular dysfunction in this disorder. These observations suggest that the development of a potent galanin antagonist would be a useful step towards the successful pharmacologic treatment of Alzheimer's disease.