Orientation in space using the sense of smell

Several studies reported that respiration interacts with olfactory perception. Therefore, in the pilot study of this experiment series human breathing was investigated during an olfactory experiment. Breathing parameters (respiratory minute volume, respiratory amplitude, and breathing rate) were quantified in response to odor stimulation and olfactory imagery. We provide evidence that respiration changed during smelling and during olfactory imagery in comparison to the baseline condition. In conclusion, olfactory perception and olfactory imagery both have an impact on the human respiratory profile, which is hypothesized to be based on a common underlying mechanism named sniffing. Our findings underline that for certain aspects of olfactory research it may be necessary to control and/or monitor respiration during olfactory stimulation. The human ability to localize odors has been investigated in a limited number of studies, but the findings are contradictory. We hypothesized that this was mainly due to differential effects of olfactory and trigeminal stimulation. Only few substances excite selectively the olfactory system. One of them is hydrogen sulphide (H2S). In contrast, most odorants stimulate both olfactory and trigeminal receptors of the nasal mucosa. The main goal of this study was to test the human ability to localize substances, which excite the olfactory system selectively. For this purpose we performed localization experiment using low and high concentrations of the pure odorant H2S, the olfactory-trigeminal substance isoamyl acetate (IAA), and the trigeminal substance carbon dioxide (CO2). In preparation for the localization study a detection experiment was carried out to ensure that subjects perceived the applied stimuli consciously. The aim of the detection study was to quantify the human sensitivity in response to stimulation with H2S, IAA, and CO2. We tested healthy subjects using an event-related experimental design. The olfactory stimulation was performed using an olfactometer. The results showed that humans are able to detect H2S in low concentration (2 ppm) with moderate sensitivity, and possess a high sensitivity in response to stimulation with 8ppm H2S, 50% v/v CO2, and 17.5% v/v IAA. The localization experiment revealed that subjects can localize H2S neither in low nor in high concentrations. In contrast to that, subjects possess an ability to localize both IAA and CO2 stimuli. These results clearly demonstrate that humans are able to localize odorants which excite the trigeminal system, but they are not able to localize odors that stimulate the olfactory system exclusively, in spite of consciously perceiving the stimuli

Perceiving Smellscapes

We perceive smells as perduring complex entities within a distal array that might be conceived of as smellscapes. However, the philosophical orthodoxy of Odor Theories has been to deny that smells are perceived as having a distal location. Recent challenges have been mounted to Odor Theories’ veracity in handling the timescale of olfactory perception, how it individuates odors as a distal entities, and their claim that olfactory perception is not spatial. The paper does not aim to dispute these criticisms. Rather, what will be shown is that Molecular Structure Theory, a refinement of Odor Theory, can be further developed to handle these challenges. The theory is further refined by focusing on distal perception that requires considering the perceptual object as mereologically complex persisting odor against a background scene conceived of as a smellscape. What will be offered is an expansion of Molecular Structure Theory to account for distal smell perception within natural environments

Excitatory postsynaptic potentials in rat neocortical neurons in vitro. III. Effects of a quinoxalinedione non-NMDA receptor antagonist

1. Intracellular microelectrodes were used to obtain recordings from neurons in layer II/III of rat frontal cortex. A bipolar electrode positioned in layer IV of the neocortex was used to evoke postsynaptic potentials. Graded series of stimulation were employed to selectively activate different classes of postsynaptic responses. The sensitivity of postsynaptic potentials and iontophoretically applied neurotransmitters to the non-N-methyl-D-asparate (NMDA) antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) was examined. 2. As reported previously, low-intensity electrical stimulation of cortical layer IV evoked short-latency early excitatory postsynaptic potentials (eEPSPs) in layer II/III neurons. CNQX reversibly antagonized eEPSPs in a dose-dependent manner. Stimulation at intensities just subthreshold for activation of inhibitory postsynaptic potentials (IPSPs) produced long-latency (10 to 40-ms) EPSPs (late EPSPs or 1EPSPs). CNQX was effective in blocking 1EPSPs. 3. With the use of stimulus intensities at or just below threshold for evoking an action potential, complex synaptic potentials consisting of EPSP-IPSP sequences were observed. Both early, Cl(-)-dependent and late, K(+)-dependent IPSPs were reduced by CNQX. This effect was reversible on washing. This disinhibition could lead to enhanced excitability in the presence of CNQX. 4. Iontophoretic application of quisqualate produced a membrane depolarization with superimposed action potentials, whereas NMDA depolarized the membrane potential and evoked bursts of action potentials. At concentrations up to 5 microM, CNQX selectively antagonized quisqualate responses. NMDA responses were reduced by 10 microM CNQX. D-Serine (0.5-2 mM), an agonist at the glycine regulatory site on the NMDA receptor, reversed the CNQX depression of NMDA responses

Localization of Odors Can Be Learned

Chemicals selectively stimulating the olfactory nerve typically cannot be localized in a lateralization task. Purpose of this study was to investigate whether the ability of subjects to localize an olfactory stimulus delivered passively to 1 of the 2 nostrils would improve under training. Fifty-two young, normosmic women divided in 2 groups participated. One group performed olfactory lateralization training, whereas the other group performed cognitive tasks. Results showed that only subjects performing lateralization training significantly improved in their ability to lateralize olfactory stimuli compared with subjects who did not undergo such trainin

Chemosensory Event-Related Potentials in Response to Nasal Propylene Glycol Stimulation

Propylene glycol, also denoted as 1.2 propanediol (C3H8O2), often serves as a solvent for dilution of olfactory stimuli. It is supposed to serve as a neutral substance and has been used in many behavioral and electrophysiological studies to dilute pure olfactory stimuli. However, the effect of propylene glycol on perception and on neuronal responses has hitherto never been studied. In this study we tested by means of a threshold test, whether a nasal propylene glycol stimulation is recognizable by humans. Participants were able to recognize propylene glycol at a threshold of 42% concentration and reported a slight cooling effect. In addition to the threshold test, we recorded electroencephalography (EEG) during nasal propylene glycol stimulation to study the neuronal processing of the stimulus. We used a flow olfactometer and stimulated 15 volunteers with three different concentrations of propylene glycol (40 trials each) and water as a control condition (40 trials). To evaluate the neuronal response, we analyzed the event-related potentials (ERPs) and power modulations. The task of the volunteers was to identify a change (olfactory, thermal, or tactile) in the continuous air flow generated by the flow olfactometer. The analysis of the ERPs showed that propylene glycol generates a clear P2 component, which was also visible in the frequency domain as an evoked power response in the theta-band. The source analysis of the P2 revealed a widespread involvement of brain regions, including the postcentral gyrus, the insula and adjacent operculum, the thalamus, and the cerebellum. Thus, it is possible that trigeminal stimulation can at least partly account for sensations and brain responses elicited by propylene glycol. Based on these results, we conclude that the use of high propylene glycol concentrations to dilute fragrances complicates the interpretation of presumed purely olfactory effects

Novel measure of olfactory bulb function in health and disease

Present neuroimaging techniques are capable of recording the neural activity from all over the brain but the olfactory bulb (OB). The OB is the first olfactory processing stage of the central nervous system and the site of insult in several neurological disorders, particularly Parkinson’s disease (PD). It has been suggested that the OB has a pivotal role in the olfactory system anal-ogous to primary visual cortex (V1) and thalamus in the visual system. However, due to the existing technical limitations, there has not been any non-invasive technique that can reliably measure the OB function in humans, consequently limiting its functional recording to one in-tracranial study dating back to the 60s. Initially in Study I, a non-invasive method of measuring the function of human OB is devel-oped, so-called electrobulbogram (EBG). In line with previous animal literature as well as the only intracranial study in human OB, it was demonstrated that gamma oscillations on the EBG electrodes occurred shortly after the odor onset. Subsequently, applying source recon-struction analysis provided evidence that observed oscillations were localized to the OB. Ad-ditionally, the OB recording with the EBG method showed a test-retest reliability comparable with visual event related potentials. Notably, the detected gamma oscillations were demon-strated to be insensitive to habituation, the OB’s marked characteristic which has previously been demonstrated in rodents. Last, but not least, assessing the EBG response in an individual who did not have the bilateral OB indicated that the lack of OB results in disappearance of gamma oscillations in the EBG electrodes. Given that Study I determined the possibility of reliably measuring the function of the OB using the EBG, in Study II, I assessed the functional role of OB’s oscillations in the pro-cessing of the odor valence. Odor valence has been suggested to be linked to approach–avoidance responses and therefore, processing of odor valence is thought to be one of the core aspects of odor processing in the olfactory system. Consequently, using combined EBG and EEG recording, OB activity was reconstructed on the source level during processing of odors with different valences. Gamma and beta oscillations were found to be related to va-lence perception in the human OB. Moreover, the early beta oscillations were associated with negative but not positive odors, where these beta oscillations can be linked to preparatory neural responses in the motor cortex. Subsequently, in a separate experiment, negative odors were demonstrated to trigger a whole-body motor avoidance response in the time window overlapping with the valence processes in the OB. These negative odor-elicited motor re-sponses were measured by a force plate as a leaning backward motion. Altogether, the results from Study II indicated that the human OB processes odor valence sequentially in the gamma and beta frequency bands, where the early processing of negative odors in the OB might be facilitating rapid approach-avoidance behaviors. To further evaluate the functional role of the OB in odor processing, in Study III, OB’s communication with its immediate recipient, namely piriform cortex (PC), was assessed. These two areas are critical nodes of the olfactory system which communicate with each other through neural oscillations. The activity of the OB and the PC were reconstructed using a combination of EBG, EEG, and source reconstruction techniques. Subsequently, the cross spectrogram of the OB and the PC was assessed as a measure of functional connectivity where temporal evolution from fast to slow oscillations in the OB–PC connectivity was found during the one second odor processing. Furthermore, the spectrally resolved Granger causal-ity analysis suggested that the afferent connection form the OB to the PC occurred in the gamma and beta bands whereas the efferent connection from the PC to the OB was concen-trated in the theta and delta bands. Notably, odor identity could be deciphered from the low gamma oscillatory pattern in the OB–PC connectivity as early as 100ms after the odor onset. Hence, findings from this study elucidate on our understanding of the bidirectional infor-mation flow in the human olfactory system. Olfactory dysfunction, due to neurodegeneration in the OB, commonly appears several years earlier than the occurrence of the PD-related characteristic motor symptoms. Consequently, a functional measure of the OB may serve as a potential early biomarker of PD. In Study IV, OB function was assessed in PD to answer whether the EBG method can be used to dissociate individuals with a PD diagnosis from healthy age-matched controls. The spectrogram of the EBG signals indicated that there were different values in gamma, beta, and theta for PDs compared with healthy controls. Specifically, six components were found in the EBG re-sponse during early and late time points which together dissociate PDs from controls with a 90% sensitivity and a 100% specificity. Furthermore, these components were linked to med-ication, disease duration and severity, as well as clinical odor identification performance. Overall, these findings support the notion that EBG has a diagnostic value and can be further developed to serve as an early biomarker for PD. In the last study, Study V, the prevalence of COVID-19 was determined using odor intensity ratings as an indication of olfactory dysfunction. Using a large sample data (n = 2440) from a Swedish population, odor intensity ratings of common household items over time were found to be closely associated with prevalence prediction of COVID-19 in the Stockholm region over the same time-period (r = -.83). Impairment in odor intensity rating was further correlated with the number of reported COVID-19 symptoms. Relatedly, individuals who progressed from having no symptoms to having at least one symptom had a marked decline in their odor intensity ratings. The results from this study, given the relatively large sample size, provided a concrete basis for the future studies to further assess the potential association between the deficits in the OB function and olfactory dysfunction in COVID-19. In conclusion, our proposed method for non-invasive measurement of the OB function was shown to provide a reliable recording with a potential as a diagnostic tool for PD. Combining EBG and EEG allowed for reconstruction of the OB signal at the source level, where specific oscillations were found to be critical for odor valence processing and rapid avoidance re-sponse. Moreover, oscillations in different frequency bands were found to be critical for the OB reciprocal communications and transfer of odor identity information to higher order ol-factory subsystems. Finally, COVID-19 was found to be associated with a decline in olfactory acuity which might originate from damage to the patient’s OB. In conclusion, the results from the studies within this thesis provide a new perspective on the functional role of oscillations in the human OB

Uncovering the Correlation between COVID-19 and Neurodegenerative Processes: Toward a New Approach Based on EEG Entropic Analysis

COVID-19 is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Although it primarily attacks the respiratory tract, inflammation can also affect the central nervous system (CNS), leading to chemo-sensory deficits such as anosmia and serious cognitive problems. Recent studies have shown a connection between COVID-19 and neurodegenerative diseases, particularly Alzheimer’s disease (AD). In fact, AD appears to exhibit neurological mechanisms of protein interactions similar to those that occur during COVID-19. Starting from these considerations, this perspective paper outlines a new approach based on the analysis of the complexity of brain signals to identify and quantify common features between COVID-19 and neurodegenerative disorders. Considering the relation between olfactory deficits, AD, and COVID-19, we present an experimental design involving olfactory tasks using multiscale fuzzy entropy (MFE) for electroencephalographic (EEG) signal analysis. Additionally, we present the open challenges and future perspectives. More specifically, the challenges are related to the lack of clinical standards regarding EEG signal entropy and public data that can be exploited in the experimental phase. Furthermore, the integration of EEG analysis with machine learning still requires further investigatio

The Chemical Senses

Long-standing neglect of the chemical senses in the philosophy of perception is due, mostly, to their being regarded as ‘lower’ senses. Smell, taste, and chemically irritated touch are thought to produce mere bodily sensations. However, empirically informed theories of perception can show how these senses lead to perception of objective properties, and why they cannot be treated as special cases of perception modelled on vision. The senses of taste, touch, and smell also combine to create unified perceptions of flavour. The nature of these multimodal experiences and the character of our awareness of them puts pressure on the traditional idea that each episode of perception goes one or other of the five senses. Thus, the chemical senses, far from being peripheral to the concerns of the philosophy of perception, may hold important clues to the multisensory nature of perception in general

Localization of odors can be learned

Chemicals selectively stimulating the olfactory nerve typically cannot be localized in a lateralization task. Purpose of this study was to investigate whether the ability of subjects to localize an olfactory stimulus delivered passively to 1 of the 2 nostrils would improve under training. Fifty-two young, normosmic women divided in 2 groups participated. One group performed olfactory lateralization training, whereas the other group performed cognitive tasks. Results showed that only subjects performing lateralization training significantly improved in their ability to lateralize olfactory stimuli compared with subjects who did not undergo such training