Olfactory detection thresholds and pleasantness of a food-related and a non-food odour in hunger and satiety.

The primary aim of this study was to investigate whether olfactory detection thresholds are dependent on different states of satiety. Using the threshold test of the Sniffin' Sticks test battery (single-staircase, three alternative forced choice procedure), sensitivity to a non-food odour (n-butanol) and a food-related odour (isoamyl acetate) was investigated. Twenty-four healthy, female subjects (mean age 24.2 years, SD 2.7 years) with normal olfactory function performed the tests when hungry and when satiated. Additionally, they rated their emotional condition, arousal, alertness as well as the intensity and pleasantness of both odorants. No significant change in the detection thresholds for the non-food odour n-butanol, but a significant change in detection threshold for the food-related odour isoamyl acetate was found. The detection threshold for isoamyl acetate was significantly lower in the state of satiety compared to the hungry condition. As expected, the perceived pleasantness of isoamyl acetate was significantly lower in satiety. In summary, the results indicate that in our experimental setting the actual state of satiety has effects on detection thresholds of a food-related odour, but not of a non-food odour. Interestingly, the higher sensitivity was found during the state of satiety challenging the current hypothesis that control of food intake is supported by a decrease in sensitivity to food odours. Instead our findings that satiety decreases the pleasantness of a food-related odour support the hypothesis that both odour threshold as well as pleasantness play an important role in the control of food intake.

Comparison of clonidine to sleep deprivation in the potential to induce spike or sharp-wave activity.

OBJECTIVE: This study aimed to investigate previously observed side effects, i.e. increased epileptic activity during clonidine medication. The safety and effectiveness of clonidine as spike inducing agent compared to sleep deprivation were tested. METHODS: Patients suffering from drug-resistant localization related epilepsy took part in 3 magnetoencephalography (MEG) sessions. One session was recorded without any activating measures. The other two sessions were either performed after sleep deprivation or after medication with clonidine. Target parameter was the number of spikes or sharp-waves during a 30 min recording period. RESULTS: About 67% of the patients showed increased spike activity after clonidine, whereas sleep deprivation increased the number of spikes in 33%, and 29% of the patients did not show any activation at all. Clonidine was most effective in temporal lobe epilepsy, when the focus was located in the right hemisphere, and when clonidine serum concentrations were ranging between 0.6 and 1.0 ng/ml. CONCLUSIONS: This study showed for the first time that clonidine can be considered an effective spike or sharp-wave inducing drug that is superior to the potency of sleep deprivation. SIGNIFICANCE: The administration of clonidine increases the probability of recording ictal and interictal epileptic activity during limited acquisition time.

Ictal onset localization of epileptic seizures by magnetoencephalography.

OBJECTIVES: The aim of this study was to localize the ictal onset zone of focal epileptic seizures by magnetoencephalography (MEG) and to compare the results with interictal MEG localizations, ictal and interictal electroencephalography (EEG) results and magnetic resonance imaging (MRI) in epilepsy surgery candidates. MATERIALS AND METHODS: Data of 13 patients with partial seizures during MEG recording were analysed. Measurements were performed with a Magnes II dual unit system. RESULTS: In six of 13 cases, the ictal onset zone could be localized by MEG, with all interictal MEG findings being confirmed by ictal MEG results. In four cases, the ictal MEG localization results were corresponding to the ictal EEG localization results. In two cases, EEG yielded no comparable information. CONCLUSION: Ictal onset localization is feasible with MEG. Both interical and ictal MEG contribute valuable information to the presurgical assessment of epilepsy patients.

Shared attentional resources for processing visual and chemosensory information.

For many years, researchers have argued that we have separate attentional resources for the processing of information impinging on each of our sensory receptor systems. However, a number of recent studies have demonstrated the existence of shared attentional resources for the processing of auditory, visual and tactile stimuli. In the present study, we examined whether there are also common attentional resources for the processing of chemosensory stimuli. Participants made speeded (left vs. right) footpedal discrimination responses to an unpredictable sequence of visual and chemosensory stimuli presented to either nostril. The participants' attention was directed to one or the other modality by means of a symbolic auditory cue (high or low tone) at the start of each trial, which predicted the likely modality for the upcoming target on the majority (80%) of trials. Participants responded more rapidly when the target occurred in the expected modality than when it occurred in the unexpected modality, implying the existence of shared attentional resources for the processing of chemosensory and visual stimuli.

Functional magnetic resonance imaging of human olfaction.

Olfaction is our basic sense phylogenetically and embryologically. Little is known, however, about how the human brain encodes the quality of odors, odor-associated memories, and emotions. Olfactory information is projected from the olfactory bulb to the primary olfactory cortex, which is composed of the anterior olfactory nucleus, the olfactory tubercle, the piriform cortex, the amygdala, the periamygdaloid region, and the entorhinal cortex. From there, the primary olfactory cortex projects to secondary olfactory regions including the hippocampus, ventral striatum and pallidum, hypothalamus, thalamus, orbitofrontal cortex, agranular insular cortex, and cingulate gyrus. Functional MR studies using olfactory stimuli as paradigms show activation of many of these areas and can advance our understanding of odor perception in humans.

Attention to olfaction. A psychophysical investigation.

Olfaction is unique among the senses in that signals from the peripheral sensory receptors bypass the thalamus on their way to the cortex. The fact that olfactory stimuli are not gated by the thalamus has led some researchers to suggest that people may be unable to selectively direct their attention toward the olfactory modality. We examined this issue in an experiment where participants made speeded intensity (strong vs weak)-discrimination responses to an unpredictable sequence of olfactory and visual stimuli. Attention was directed to either olfaction or to vision by means of an informative cue that predicted the likely modality for the upcoming target on the majority of trials. Participants responded more rapidly when the target was presented in the expected rather than the unexpected modality, showing that people can selectively attend to olfaction.

Selective attention to the chemosensory modality.

Previous studies have shown that behavioral responses to auditory, visual, and tactile stimuli are modulated by expectancies regarding the likely modality of an upcoming stimulus (see Spence & Driver, 1997). In the present study, we investigated whether people can also selectively attend to the chemosensory modality (involving responses to olfactory, chemical, and painful stimuli). Participants made speeded spatial discrimination responses (left vs. right) to an unpredictable sequence of odor and tactile targets. Odor stimuli were presented to either the left or the right nostril, embedded in a birhinally applied constant airstream. Tactile stimuli were presented to the left or the right hand. On each trial, a symbolic visual cue predicted the likely modality for the upcoming target (the cue was a valid predictor of the target modality on the majority of trials). Response latencies were faster when targets were presented in the expected modality than when they were presented in the unexpected modality, showing for the first time that behavioral responses to chemosensory stimuli can be modulated by selective attention.

Olfactory functional imaging and physiology.

Over the last few years, several different neuroimaging techniques have been applied to get a better insight into cortical regions activated after olfactory stimulation. Here we report on data obtained by recent magnetic source imaging (MSI) and functional magnetic resonance imaging (fMRI) studies during well-defined olfactory stimulation and compare the results obtained with these two techniques.

Population pharmacokinetics of fast release oral diclofenac in healthy volunteers: relation to pharmacodynamics in an experimental pain model.

PURPOSE: Population pharmacokinetics of a fast release diclofenac were assessed with special focus on pharmacodynamic implications. METHODS: In a double blind four-way crossover study, 20 healthy volunteers received orally 50 and 100 mg diclofenac-Na effervescent ("fast-release NSAID"), 50 mg diclofenac tablets ("control"), or placebo. Population pharmacokinetics of the fast release diclofenac were assessed using a nonlinear mixed effects modeling approach (NON-MEM). Analgesic effects were investigated by means of an experimental pain model based on both pain-ratings and cortical evoked potentials after specific stimulation of nasal nociceptors with short pulses of gaseous CO2. RESULTS: Pharmacokinetics of fast release diclofenac were best described by a two-compartment population model, with an estimated terminal half-life of 1.2 hours. Pharmacokinetics of diclofenac tablets were highly variable and a population pharmacokinetic model could not be obtained. As an indication of an early onset of analgesic effects, 100 mg fast release diclofenac but not the tablets significantly reduced the amplitudes of pain-related evoked potentials at 30 min after administration. CONCLUSIONS: Earlier drug absorption and lower pharmacokinetic variability of the fast-release formulation are likely to be preserved in a population.

Clonidine- and methohexital-induced epileptiform discharges detected by magnetoencephalography (MEG) in patients with localization-related epilepsies.

PURPOSE: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize the epileptogenic focus. To increase the number of epileptiform discharges required for MEG analysis, methohexital a short-acting barbiturate that is known to activate epileptiform activity, was used. Additionally, we investigated the spike-provoking properties of clonidine in comparison to methohexital. METHODS: After oral premedication with clonidine, short-lasting anesthesia was provided by intravenously administered methohexital. The number and location of epileptiform MEG discharges were assessed after clonidine premedication and during methohexital anesthesia. Results were compared with baseline MEG recordings. RESULTS: Methohexital increased the frequency of focal epileptiform discharges in eight of 13 patients (one of the 14 patients did not receive methohexital after premedication with clonidine). Additionally, premedication with clonidine was found to increase focal epileptiform discharges in nine of 14 patients. When compared with baseline MEG recordings, recordings after treatment with both clonidine premedication and methohexital anesthesia showed a significant increase in the total number of epileptiform signals and the number of spikes contributing to MEG source localizations. CONCLUSIONS: This study confirms the selective proconvulsant effects of methohexital on the epileptogenic focus as suggested previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our data establish for the first time that clonidine increases epileptiform activity in patients with seizure disorders. These results indicate that clonidine is suited as an activating agent for the localization of epileptogenic foci by means of MEG. This effect of clonidine on specific epileptic activity also indicates that clonidine should be used with caution as an antihypertensive drug in patients with seizure disorders.

Clonidine and methohexital-induced epileptic magnetoencephalographic discharges in patients with focal epilepsies.

PURPOSE: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings for focus localization. To increase the number of epileptic discharges required for MEG analysis, we administered methohexital (MHT), a short-acting barbiturate known to provoke epileptic activity. We also investigated the spike-provoking properties of clonidine in comparison with MHT. METHODS: Patients were briefly anesthetized with intravenously administered MHT after being premedicated orally with clonidine. Numbers and locations of epileptic MEG discharges were assessed after clonidine premedication as well as during MHT anesthesia. Results were compared with baseline MEG recordings. RESULTS: MHT increased the frequency of focal epileptic discharges in 8 of 13 patients ( of the 14 patients did not receive MHT after premedication with clonidine). Premedication with clonidine also increased focal epileptic discharges in 9 of 14 patients. The numbers of epileptic signals and numbers of spikes contributing to MEG source localizations were significantly increased in MEG recordings under both treatment conditions (clonidine premedication and MHT anesthesia) as compared with baseline MEG recordings. CONCLUSIONS: Our results confirmed the selective proconvulsive effects of MHT on the epileptic focus, as previously suggested by EEG and electrocorticographic (ECoG) investigations. However, our present data establish for the first time that clonidine increases epileptic activity in patients with seizure disorders and indicate that clonidine is suitable as an activating agent for localization of epileptogenic foci by MEG. This effect of clonidine on specific epileptic activity also indicates that specific care must be taken when clonidine is used as an antihypertensive drug in patients with seizure disorders.

Multiple olfactory activity in the human neocortex identified by magnetic source imaging.

To date, cortical regions activated by olfactory stimulation have not been identified precisely in humans. In this study we used magnetic source imaging to localize neuronal activity following olfactory stimulation with two odorants, hydrogen sulphide and vanillin. Peak latencies of the olfactory event-related magnetic fields corresponded to the ascending and descending slopes of the major deflections of the olfactory event-related potentials (OERP). At these latencies we obtained consistent activation of the anterior-central parts of the insula (agranular-periallocortical and dysgranular regions) the parainsular cortex and the superior temporal sulcus. No reproducible equivalent current dipoles were found in other brain areas, including the orbitofrontal cortex. For the first time, brain areas were identified that generate most components of olfactory bioresponses (OERPs) in humans.

Right-hemisphere preponderance of responses to painful CO2 stimulation of the human nasal mucosa.

We recorded whole-scalp cerebral magnetic fields from healthy adults to painful CO2 pulses (duration 200 ms, concentration 65-90%), led to the left or right nostril once every 20 or 30 s. The stimuli were embedded in a continuous airflow (140 ml/s, 36.5 degrees C, relative humidity 80%) to prevent alterations in the mechanical and thermal conditions of the nasal mucosa. The recording passband was 0.03-90 Hz and 16 single responses were averaged per run. Five out of the 9 subjects showed replicable and artifact-free responses 280-400 ms after stimulus onset. The main responses originated close to the second somatosensory cortex (SII), most frequently in the right hemisphere, and also in the rolandic areas, mostly on the left. The signals were considerably stronger over the right than the left frontotemporal region, with a right-to-left ratio of 2.3 for areal mean signal amplitudes calculated across 16 channels, for both left and right nostril stimuli. Air puffs delivered to the nasal mucosa resulted in a trend for right-hemisphere dominant responses, but responses to air puff stimulation of the lip and the forehead were symmetric. The right-hemisphere dominance of the SII responses may be associated with the painful, and thus unpleasant, nature of the CO2 stimulus, thereby suggesting involvement of the right hemisphere in emotional/motivational aspects of trigeminal pain, in agreement with the role of the trigeminal pathways as a general warning system.

Loss of olfactory function leads to a decrease of trigeminal sensitivity.

Healthy controls were compared to patients with decreased olfactory sensitivity (n = 32) to investigate interactions between the olfactory and trigeminal systems. Amplitudes of chemo-somatosensory event-related potentials in response to suprathreshold trigeminal stimuli (CO2) were found to be smaller in patients (P < 0.05) indicating a decrease of trigeminally mediated sensations.

Odorants activate the human superior temporal sulcus.

The human olfactory pathways are well defined up to the level of the prepiriform cortex but the neocortical projections and their functional organization are still largely unknown. We recorded whole-scalp neuromagnetic signals to olfactory stimulation with boluses of phenylethyl alcohol, hydrogen sulphide, and vanillin. The main magnetic response peaked about 700 ms after the stimulus onset. The three odorants activated overlapping cortical areas around the superior temporal sulci of both hemispheres, revealing a neocortical area involved in olfactory processing.

Chemosensory event-related potentials in patients with temporal lobe epilepsy.

We investigated chemosensory functions in patients with temporal lobe epilepsy (TLE) to discover whether olfactory and trigeminal stimuli applied either ipsilaterally or contralaterally to the epileptic focus are processed differently. Twenty-two patients were investigated, 12 of whom had epilepsy with a focus located in left temporal lobe (LTL). The remaining 10 patients had a right temporal lobe (RTL) focus. Input from the trigeminal system was examined by use of CO2; input from the olfactory system was evaluated with vanillin and hydrogen sulfide as stimuli. Chemosensory function was assessed by evaluation of chemosensory event-related potentials (CSERP) and the patients' verbal reports in an odor identification test. In both groups of patients, prolonged CSERP latencies were noted after stimulation of the left nostril with CO2 as compared with stimulation of the right nostril. In contrast, a different pattern emerged for olfactory stimuli. After right-sided olfactory stimulation, latencies were prolonged in patients with right-sided epileptical foci. Similarly, when the left nostril was stimulated in patients with a left-sided focus, CSERP latencies were prolonged. Thus, neocortical processing of olfactory, but not trigeminally mediated information evidently is affected by functional lesions of the temporal lobe. After olfactory stimulation in patients with a right-sided focus, the distribution of amplitudes was different from normal. Moreover, analyses showed nonoverlapping 95% confidence intervals (CI) for latency N1 when vanillin was applied to the right nostril. These results indicate that RTL may play a different role in processing of olfactory information as compared with LTL.

Nociceptive and reflexive responses recorded from the human nasal mucosa.

Slow electrical responses after painful stimulation with carbon dioxide, which is known to specifically activate nociceptors, were recorded from the nasal respiratory epithelium in human volunteers. The negative component of these potentials (negative mucosal potential NMP) has been hypothesized to be a summated receptor potential. The aim of the present study was to characterize the stimulus-response relationship and to demonstrate that the NMP is restricted to the site of stimulation, i.e., to the area of activated nociceptors. Eight healthy volunteers participated in the experiments. The NMP was recorded from the nasal septum and intensity ratings were obtained for each of the applied stimuli. To control for autonomic reflexes, blood flow changes were additionally recorded using a laser Doppler flow meter. Both increasing stimulus duration and increasing concentration produced a significant increase in the subjects' intensity estimates, in the NMP's amplitudes and areas under the curve, but did not change the local blood flow in a dose-related manner. The odorant hydrogen sulphide, which was used as a non-painful control stimulus, did not elicit mucosal potentials or produce blood flow changes. By recording both ipsi- and contralaterally it was also demonstrated that the NMP could only be obtained at the stimulated site, thus supporting the hypothesis that the NMP is a specific peripheral nociceptive correlate.