Search

Background: Among serotonin receptors, 5-HT(1A) receptors are implicated in the regulation of central serotoninergic tone and could be involved in the abnormal brain 5-HT turnover suspected in migraineurs. The aim of this study was to investigate 5-HT(1A) receptors' availability during migraine attacks., Methods: Ten patients suffering from odor-triggered migraine attacks and 10 control subjects were investigated using positron emission tomography (PET) and [(18)F]MPPF PET tracer, a selective 5-HT(1A) antagonist. All subjects underwent calibrated olfactory stimulations prior to the PET study., Results: Four patients developed a migraine attack during the PET study. In these patients, statistical parametrical mapping and region of interest analyses showed an increased [(18)F]MPPF binding potential (BP(ND)) in the pontine raphe when compared to headache-free migraineurs and control subjects. This ictal change was confirmed at the individual level in each of the four affected patients. In comparison with the headache-free migraineurs, patients with a migraine attack also showed significantly increased [(18)F]MPPF BP(ND) in the left orbitofrontal cortex, precentral gyrus and temporal pole. No significant change in [(18)F]MPPF BP(ND) was observed between headache-free migraineurs and controls., Conclusions: Our results emphasize the role of 5HT(1A) receptors in the pontine raphe nuclei during the early stage of migraine attacks.

Cerebral imaging and olfactory disorders: a review. Olfactory disorders are often misjudged and rarely given due clinical consideration. Nevertheless, they occur in a wide range of neurological disorders, and their evaluation can help in diagnosis. Whereas psychophysical tests have been used to evaluate olfactory dysfunction in numerous diseases, functional brain imaging using olfactory stimuli is an emergent technique and few studies have been published to date. After a reminder of cerebral imaging and analysis techniques and a rapid description of our actual knowledge of olfactory processes in healthy subjects, the current review focuses on cerebral imaging studies performed on patients with neurological disorders and presenting olfactory dysfunction. Neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, migraine, multiple chemical sensitivity and schizophrenia are examined.

Olfactory disorders are often misjudged and rarely rated in the clinical setting. They are nevertheless described in a wide range of neurological disorders, and their evaluation can be useful for diagnosis. Usually irreversible olfactory dysfunction is a well-known complication after head trauma. Severe changes in olfactory tests are observed in Parkinson's disease. Dysfunction is present at disease onset and evidenced with all behavioral tests. Regarding other parkinsonian syndromes, olfactory performances are severely impaired in Lewy body disease, less pronounced in multiple system atrophy and usually preserved in corticobasal degeneration. Olfactory deficits are an early feature in Alzheimer's disease and worsen with disease progression. Rarely reported by patients, they must be searched for with olfactory tests. Though epilepsy is mainly known for its olfactory hallucinatory disorders, alterations of olfactory abilities are also described, especially in mesial temporal epilepsy. Disorders of olfactory perception are finally reported in patients with multiple sclerosis and migraine. After a reminder of anatomical data on the olfactory system, and the different methods of testing used to rate olfactory performances, the current review focuses on the type of olfactory dysfunction and damaged brain areas of the olfactory system encountered in the main neurological diseases.

A design for a semi-automatic olfactometric system is described for PET and fMRI experiments. The olfactometer presents several advantages because it enables the use of an 'infinite' number of odorants and the synchronization of stimuli with breathing. These advantages mean that the subject is recorded while breathing normally during olfactory judgment tasks. In addition, the design includes a system for recording the behavioral (rating scale) and physiological (breathing, electrodermal reaction (ED), plethysmography (PL)) signals given by the subject. Both systems present the advantage of being compatible with fMRI magnetic fields since no ferrous material is used in the Faraday cage and signals are transmitted via an optical transmission interface to an acquisition system.

Using simple successive tasks we assessed the influence of Alzheimer's disease on the processing of different odours. Fifteen patients with Alzheimer's disease, 15 old control subjects and 15 young control subjects were tested. The experiment included two sessions. Initially 12 odorants were presented, one odorant every minute. For each odour the subjects were asked to rate intensity, pleasantness, familiarity and edibility using linear rating scales. The odorants were then presented a second time and the subjects were asked to identify them. The results show that the intensity scores were lower in old control subjects and Alzheimer patients than in the young control subjects and that familiarity and identification scores were lower in Alzheimer patients than in old control and young control subjects. When we compared the five olfactory tasks the impairment of performance in Alzheimer patients was relatively higher for identification than familiarity, itself higher than the intensity judgement. No difference was observed between the three groups of subjects for pleasantness and edibility judgements.

Humans routinely make judgments about olfactory stimuli. However, few studies have examined the functional neuroanatomy underlying the cognitive operations involved in such judgments. In order to delineate this functional anatomy, we asked 12 normal subjects to perform different judgments about olfactory stimuli while regional cerebral blood flow (rCBF) was measured with PET. In separate conditions, subjects made judgments about the presence (odor detection), intensity, hedonicity, familiarity, or edibility of different odorants. An auditory task served as a control condition. All five olfactory tasks induced rCBF increases in the right orbitofrontal cortex (OFC), but right OFC activity was highest during familiarity judgments and lowest during the detection task. Left OFC activity increased significantly during hedonic and familiarity judgments, but not during other odor judgments. Left OFC activity was significantly higher during hedonicity judgments than during familiarity or other olfactory judgments. These data demonstrate that aspects of odor processing in the OFC are lateralized depending on the type of olfactory task. They support a model of parallel processing in the left and right OFC in which the relative level of activation depends on whether the judgment involves odor recognition or emotion. Primary visual areas also demonstrated a differential involvement in olfactory processing depending on the type of olfactory task: significant rCBF increases were observed in hedonic and edibility judgments, whereas no significant rCBF increases were found in the other three judgments. These data indicate that judgments of hedonicity and edibility engage circuits involved in visual processing, but detection, intensity, and familiarity judgments do not., (Copyright 2001 Academic Press.)

Sixty-four subjects participated in an olfactory priming experiment comprising separate study and test phases. Priming was measured within the olfactory modality (intramodal condition) and from the visual modality to the olfactory modality (intermodal condition). In the study phase of the intramodal condition, subjects were exposed twice to a series of odours: once performing a semantic orientation task (deciding which of seven categories odour stimuli belonged to) and once performing a perceptual orientation task (judging the intensity, the hedonicity and the familiarity of odour stimuli). Half of the odour stimuli corresponded to edible products, the other half did not. The study phase of the intermodal condition was similar, with the exception that the names of the odours (instead of the odours themselves) were presented. In the test phase, subjects were presented with primed and non-primed odour targets and had to decide as fast as possible whether the target corresponded to an edible product or not. Response times and types were recorded by a computer. The analysis of response times revealed a priming effect in the intramodal condition only. Results are discussed in terms of separate perceptual and semantic subsystems that store odour representations.

Neural correlates of responses to emotionally valenced olfactory, visual, and auditory stimuli were examined using positron emission tomography. Twelve volunteers were scanned using the water bolus method. For each sensory modality, regional cerebral blood flow (rCBF) during presentation of both pleasant and unpleasant stimuli was compared with that measured during presentation of neutral stimuli. During the emotionally valenced conditions, subjects performed forced-choice pleasant and unpleasant judgments. During the neutral conditions, subjects were asked to select at random one of a two key-press buttons. All stimulations were synchronized with inspiration, using an airflow olfactometer, to present the same number of stimuli for each sensory modality. A no-stimulation control condition was also performed in which no stimulus was presented. For all three sensory modalities, emotionally valenced stimuli led to increased rCBF in the orbitofrontal cortex, the temporal pole, and the superior frontal gyrus, in the left hemisphere. Emotionally valenced olfactory and visual but not auditory stimuli produced additional rCBF increases in the hypothalamus and the subcallosal gyrus. Only emotionally valenced olfactory stimuli induced bilateral rCBF increases in the amygdala. These findings suggest that pleasant and unpleasant emotional judgments recruit the same core network in the left hemisphere, regardless of the sensory modality. This core network is activated in addition to a number of circuits that are specific to individual sensory modalities. Finally, the data suggest a superior potency of emotionally valenced olfactory over visual and auditory stimuli in activating the amygdala.

The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothetized that the three tasks were hierarchically organized from a superficial detection level to a deep semantic level. Odorants were presented with an air-flow olfactometer, which allowed the stimulations to be synchronized with breathing. Subtraction of activation images obtained between familiarity and control judgments revealed that familiarity judgments were mainly associated with the activity of the right orbito-frontal area, the subcallosal gyrus, the left inferior frontal gyrus, the left superior frontal gyrus, and the anterior cingulate (Brodmann's areas 11, 25, 47, 9, and 32, respectively). The comestibility minus familiarity comparison showed that comestibility judgments selectively activated the primary visual areas. In contrast, a decrease in rCBF was observed in these same visual areas for familiarity judgments and in the orbito-frontal area for comestibility judgments. These results suggest that orbito-frontal and visual regions interact in odor processing in a complementary way, depending on the task requirements.

This review deals with notions of shape, sizes, numbers, densities and orientation in space, all basic concepts in stereology. With the initiation by Delesse in 1847, but mainly since the beginning of the XXth century, many stereological methods have been published allowing us to relate two-dimensional measurements easily obtainable on flat histological images with three-dimensional characteristics of the structure analysed. Looking at these methods, the neurobiologist, generally impermeable to concepts of sampling, statistical bias, efficiency, cost of effort and distribution-free, is discountenanced and continues old laboratory usages and customs. Furthermore, for the last ten years, the advent of a plethora of new powerful tools, considered as assumption-free and more efficient than the previous ones, increase the risk proportionately the disarray of the potential user. The purpose of this review is to present synthetically all traditional and actual aspects of stereology in order to guide the reader in the labyrinth of this speciality. The necessarily short exposition is compensated by many references to which the beginner or the initiated can refer.

Rats maintained on an unadulterated synthetic food, available from 8 a.m. to 10 a.m. everyday, were submitted to an aversive conditioning schedule on which a first ingestion of eucalyptol-flavored food (EF) was followed by an apomorphine injection (20 mg/kg, ip). In the first experiment the daily food intake was measured from Day 1 to 17, during the first and second hours of the meal. The EF was offered on Days 8, 9, and 17 during the first or the second hour of the meal (Series B or A). On Day 8, the meal was followed in a group of rats by the apomorphine injection. As compared with the intake of Day 8, the mean EF intake of Day 9 was significantly decreased in Series A and B, and of Day 17 in Series A only. No significant EF-intake modification could be observed in a saline-injected group or in an untreated control group. In the second experiment, rats bearing bulbar electrodes for the chronic recording of multiunit mitral cell responses received a 2-hr EF meal before the apomorphine injection. They were stimulated by puffs of odors of pure eucalyptol, unadulterated food, and EF and recorded in hungry and satiated states. Before the aversive conditioning, a significantly greater occurrence of positive responses to the odors of unadulterated food and EF was observed in hungry rats compared with satiated rats. The eucalyptol odor yielded equivalent patterns of responses in hungry and satiated rats before and after conditioning. Conditioning did not alter the modulated responses to unadulterated food odor (a greater occurrence of positive responses was still observed in hungry rats) but modified the responses to the odor of EF (the same high rate of positive responses was then observed in satiated and hungry rats). Electrophysiological data are discussed in terms of palatability changes and food-odor meaning.

An olfactometric cage was constructed in order to perform experiments on olfactory perception in unrestrained rats. Olfactory stimuli were measured with a flame ionization detector (FID). A cylindrical cage was divided into 2 compartments, an upper expansion chamber (B) and a lower stimulation chamber (A) with a perforated metal plate. Before entering B, the odours were diluted with purified air in a mixing chamber. The odorized air was then delivered to a small chamber on top of the cage and distributed by a thin slit surrounding B. A homogeneous distribution of holes in the metal plate provided a laminar flow characterized by a parabolic front. This flow was suitable for long duration exposures of animals of odours. However, for short stimulations (10 sec), variations of amplitude and delay were observed in the horizontal plane of the olfactometric cage. To flatten this parabolic front a new distribution of holes was calculated. A partially turbulent air flow was obtained in A. creating some fluctuations in the time-course of stimulations. However, the amplitude and the delay of the signals were reasonably constant in all parts of the cage floor. It is possible to use this apparatus for other purposes than those originally intended, e.g. behavioural studies.

The mechanisms subserving neophobia and learned aversion have been investigated by recording multiunit olfactory bulb discharges either in hungry rats following food deprivation or in satiated rats. Under the two conditions, rats were stimulated with the smell of their familiar maintenance diet or that of a novel food or of control food-unrelated odor. Responses to the odor of the novel food were tested, following a pairing of the first or the second intake of that food with a LiCl injection, or following its first intake paired with a NaCl control injection. All rats exhibited enhanced level of discharges when they were stimulated in the hungry state with the smell of the familiar food and not when stimulated with the non-alimentary control odor. The hunger to satiety modulation of olfactory bulb discharges, also exhibited in rats tested with the smell of the novel food, previously paired with NaCl, was absent after a LiCl-induced taste aversion to this odor. The small, although significant, modulation observed when the conditioning of aversion occurred with the less novel food is consistent with the view that learned safety prevails upon learned harmfulness. Results are discussed in terms of relations of olfactory bulb electrical responses to odors with food palatability, neophobia and learned aversion.

We have developed a computer-assisted method for analyzing the 2-deoxyglucose (2-DG) autoradiograms of mice olfactory bulbs. The purpose of the study was to numerize the maps of glomerular activation in order to achieve a statistical comparison of the glomerular patterns evoked by different stimuli. The spatial distribution of glomerular activation was displayed on unfolded representations of the glomerular layer which were built up using glomerular optical densities (OD) measured systematically within 13 sections per bulb. Each bulbar sample was converted into an 'OD profile'. A matrix composed of 18 OD profiles was submitted to a principal component analysis. The first factor which accounted for 28% of the variance separated unambiguously two clusters corresponding to the bulbs issued from animals stimulated with amylacetate and isovaleric acid, respectively. The second and third factors which accounted for 14% and 12% of the variance segregated the control group (animals exposed to pure air) from the odor-stimulated ones. It was demonstrated that the cluster separation was actually due to the specific spatial distribution of the most-labelled glomeruli. A particular attention was paid to the well-delineated glomerular activation evoked by isovaleric acid. The results demonstrate the specificity and reliability of the glomerular 2-DG patterns. The method should be useful for further comparisons of patterns elicited by larger sets of odorant compounds.

The ability of adult Rats to accept new foods does not depend only on varied or monotonous experience of diets offered during weaning. Grown-up Rats can get used to alimentary diversity and abate their neophobic behaviour to new foods.

This study investigated the role of the noradrenergic (NA) and the serotoninergic (5-HT) centrifugal fibers on the olfactory bulb (OB). For this purpose, behavioral responses largely depending on olfactory information were measured in rats after discrete bilateral injections into the OB with either 6-hydroxydopamine (6-OHDA) or 5,6-dihydroxytryptamine (5,6-DHT) solutions. The evaluation of the level of endogenous 5-HT in the OB was measured by high performance liquid chromatography. The NA fibers appeared lesioned after the 6-OHDA treatment only, whereas the 5-HT level was significantly reduced in 5,6-DHT treated bulbs only (34% of the control value). The animals were fed on usual stock-diet (S) and had the choice between S and a novel food (V) on neophobia test, and again on the following day after aversive conditioning (0.9 mEq/kg LiCl i.p.). The behavioral results showed that the drug administrations were followed by a significant effect in one case only: the intake of V was significantly enhanced in 6-OHDA treated animals during neophobia test. Thus, neophobia was reduced by 6-OHDA. The data are interpreted as follows: (1) the lesion of the bulbar NA or 5-HT fibers does not induce total anosmia; and (2) the NA innervation of the OB could play a role in the modulation of behavioral responses to biological odorants.

The contribution of ascending olfactory pathways in neophobia and learned aversion to the same food was investigated in male rats bearing lesions of both olfactory peduncles, or one olfactory peduncle and the opposite lateral olfactory tract or anterior limb of the anterior commissure. The animals were fed on usual stock diet (S) offered as a choice with novel vanilla food (V) on test days: during neophobia (N), then before and after aversive conditioning (Aa, At). Daily food intake was measured, and the preference was expressed as V/(V + S). Experiment 1 included a neophobia test, before aversive conditioning (3 mEq/kg LiCl, i.p.). In Experiment 2, aversion only was studied (0.9 mEq/kg). In the neophobia test, the preference ratio was 7% in unoperated controls, and 43-52% in the 3 lesioned groups. The same controls had preference ratios equal to 64% and 22%, before and after aversive learning. Similar drops were observed for any lesioned group in Expt. 1. The decrease was less obvious, although significant, in rats of Expt. 2 with asymmetric lesions; those with both olfactory peduncles cut through maintained the same preference ratio (48%) before and after LiCl treatment. The data are interpreted assuming that: (1) lateral olfactory tract and anterior commissure both contribute to information processing in neophobia and aversion; (2) olfactory cues subserve neophobia prepotently; and (3) one cannot account for the sensory determinism of neophobia and aversion calling for a single mechanism.