Birgit Kettenmann

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

Abstract 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°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 artefact‐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.

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

Summary: 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.

Attention to olfaction. A psychophysical investigation.

Abstract. 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.

Population Pharmacokinetics of Fast Release Oral Diclofenac in Healthy Volunteers: Relation to Pharmacodynamics in an Experimental Pain Model

AbstractPurpose. Population pharmacokinetics of a fast release diclofenac wereassessed with special focus on pharmacodynamic implications. Methods In a double blind four-way crossover study, 20 healthyvolunteers 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 wereassessed using a nonlinear mixed effects modeling approach(NON-MEM). Analgesic effects were investigated by means of anexperimental pain model based on both pain-ratings and cortical evoked potentialsafter specific stimulation of nasal nociceptors with short pulses ofgaseous CO2. Results. Pharmacokinetics of fast release diclofenac were bestdescribed by a two-compartment population model, with an estimatedterminal half-life of 1.2 hours. Pharmacokinetics of diclofenac tabletswere highly variable and a population pharmacokinetic model couldnot be obtained. As an indication of an early onset of analgesic effects,100 mg fast release diclofenac but not the tablets significantly reducedthe amplitudes of pain-related evoked potentials at 30 min afteradministration. Conclusions. Earlier drug absorption and lower pharmacokineticvariability of the fast-release formulation are likely to be preserved ina population.

Ictal onset localization of epileptic seizures by magnetoencephalography

Objective– 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. Material 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.

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.

Impact of continuous low level heatwrap therapy in acute low back pain patients: subjective and objective measurements.

ObjectivesMuscular pain is usually associated with increased muscle tension resulting in a vicious tension-pain-cycle, leading to increased alertness and stress. However, this has not been broadly evaluated using objective methods, for example, looking at neurophysiologic changes. The focus of this study was, therefore, to combine objective [spontaneous electroencephalogram (EEG) as a surrogate of alertness and stress] with subjective parameters (self-assessed pain affected variables) to investigate the effect of continuous low-level heat therapy in low back pain (LBP)-patients. MethodsThis investigation was a randomized, active controlled, parallel-designed study. Thirty patients were randomly assigned to one of 2 groups: the control group, in which patients were provided with oral analgesics (nonsteroidal anti-inflammatory drug) and instructed to use it if needed, and the treatment group, in which patients in addition to oral analgesics as rescue medication were provided with a heatwrap therapy. The objective parameters were assessed by measuring the power of frequency bands in the spontaneous EEG. The subjective parameters (sleep pattern, well-being, pain intensity, etc.) were assessed by a Pain, Sleep, and Stress Questionnaire. ResultsIn the EEG-recordings, the heatwrap therapy group showed decreased power in Beta-1 and Beta-2 frequency bands compared with the control group, indicating a reduction in arousal. Also, in comparison to the control group, the heatwrap therapy group reported significantly reduced LBP, everyday situations being less stressful, a better nights sleep, and a decreased number of daytime naps. DiscussionIn addition to classic psychophysical assessment of pain-related parameters and sleep quality, performance in daily life, we were able to obtain objective measures (EEG) that suggest an acute therapeutic relaxation on the basis of the central nervous system effects accompanying the reported significant pain relief. We believe that this was due to a reduced nociceptive information load in LBP-patients after the use of the heatwrap therapy.