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Unveiling the scented spectrum: a mini review of objective olfactory assessment and event-related potentials

Published online by Cambridge University Press:  21 October 2024

Anshika Baranwal Open the ORCID record for Anshika Baranwal [Opens in a new window] ,
Mahesh Arjundhan Gadhvi  and
Abhinav Dixit Open the ORCID record for Abhinav Dixit [Opens in a new window]
Anshika Baranwal
Affiliation:
Department of Physiology, All India Institute of Medical Sciences, Jodhpur, RJ, India
Mahesh Arjundhan Gadhvi
Affiliation:
Department of Physiology, All India Institute of Medical Sciences, Jodhpur, RJ, India
Abhinav Dixit*
Affiliation:
Department of Physiology, All India Institute of Medical Sciences, Jodhpur, RJ, India
*
Corresponding author: Abhinav Dixit; Email: [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Objective

The objective of the study is to examine the current state of research and technology related to objective olfactory assessment, highlighting the merits and demerits of the techniques. It aims to specifically explore olfactory event-related potentials, discussing their potential applications, benefits, drawbacks, and prospects in the field.

Methods

A five-month narrative review examined English-language articles from PubMed, Scopus, and Google Scholar, critically summarising titles, abstracts, and full texts, while excluding non-English and methodologically weak studies.

Results

This study provides a detailed investigation into various objective methods utilised and the applicability of olfactory event-related potentials for assessing olfaction. We reviewed key elements, such as techniques, stimulus delivery methods, optimal electrode placement, and waveform analysis.

Conclusion

Olfactory event-related potentials offers substantial promise in enhancing the diagnostic accuracy of olfactory dysfunction across various clinical contexts. This thorough review highlights the utility and potential of olfactory event-related potentials in improving the precision and efficacy of olfactory assessments.

Keywords

SmellEvoked potentialOlfaction disordersPerceptionSensation
Type
Review Article
Information
The Journal of Laryngology & Otology , First View , pp. 1 - 8
Copyright
© The Author(s), 2024. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED.

Introduction

Olfaction, the sensory modality responsible for detecting and discriminating volatile compounds known as odours or aromas,Reference Ache and Young1 plays a vital role across various species, aiding survival by facilitating the location and pursuit of food, detecting threats, and identifying foes.Reference Sarafoleanu, Mella, Georgescu and Perederco2 While sight is essential for distinguishing objects, the olfactory sense enhances visual perception by adding depth, consistency, and emotion.Reference Zador and Mombaerts3

This inherent ability is evident from infancy, where even amidst synthetic scents, infants can identify and gravitate toward their mothers’ body odours.Reference Schleidt and Genzel4 Moreover, the sense of smell is a crucial indicator of food quality, helps spot damaged food, and alerts individuals to potential environmental threats.Reference Doty5 Certain odours evoke strong emotions and trigger vivid recollections of associated experiences, impacting psychological and physiological states.Reference Kadohisa6

Olfactory dysfunction varies from complete loss (anosmia) to reduced sensitivity (hyposmia), alongside distorted (parosmia) or false (phantosmia) perceptions of odours. Olfactory dysfunction arises from various factors, including age, illness, genetics, lifestyle, diet, medical history, treatments, viral exposure, and occupation.Reference Daramola and Becker7 Mental health conditions like anxiety and depression can also affect smell perception.Reference Croy, Nordin and Hummel8 Olfactory dysfunction has also gained attention due to its association with coronavirus disease 2019 (Covid-19).Reference Dan, Wechter, Gray, Mohanty, Croteau and Bohr9–Reference Purja, Shin, Lee and Kim11

Long-term research on the causes of anosmia and hyposmia has revealed that sinus infections,Reference Raviv and Kern12 upper respiratory virus infections,Reference Mascagni, Consonni, Bregante, Chiappino and Toffoletto13 prolonged exposure to toxins,Reference Gobba14 and skull fracturesReference Haxel, Grant and Mackay-Sim15 are the most common pathological causes of olfactory dysfunction.

In light of these considerations, the availability of dependable techniques for assessing olfactory function is essential. This review seeks to discuss the present state of research and technology concerning objective olfactory assessment and underscore the significance of employing objective assessment techniques in clinical settings. It will specifically delve into event-related potentials, exploring their potential applications, benefits, drawbacks, and prospects within the field.

Methods

A narrative review was conducted over five months by searching for English-language articles in the electronic databases PubMed, Scopus, and Google Scholar. In addition, further relevant articles pertinent to this review were retrieved by inspecting the references of the articles that had been searched. Specific keywords were used individuallyor in combination to aid in retrieving relevant articles. The exclusion criteria were non-English articles, articles with misleading titles, and studies with unclear methodology and weak study designs. The titles, abstracts and full text of all resulting papers, whenever available, were read and kept for reference, and the findings were critically summarised.

Assessment of olfaction

Assessment of olfaction can be categorised into two type of tests: subjective tests and objective tests.

Subjective tests/psychophysical tests

Due to their ease of use and excellent reliability compared to self-evaluation, psychophysical olfactory assessment tests are extensively employed.Reference Nguyen, Rumeau, Gallet and Jankowski16 The four basic principles that underpin psychophysical tests for olfaction assessment are described as follows.

Odor identification test

A preliminary 4-booklet, 40-item version of the University of Pennsylvania Smell Identification Test was used for administration. Each booklet has 10 odorants delivered randomly, except for avoiding similar aromas that follow one another.Reference Doty17, Reference Doty, Shaman and Dann18

Odor threshold test

Finding the lowest concentration of an odorant that the human nose can detect is done using the odour detection threshold methodology. In this technique, an odorant is presented to a panel of trained individuals, and the concentration at which the odour becomes perceptible is determined.Reference Doty17

Odor discrimination test

Olfactory discrimination tests assess one’s ability to differentiate between various odours based on intensity or quality without identifying them. Two stimuli are presented one after the other, and the subject’s task is to tell if they smell the same or different. The number of accurate answers determines the test score. The Sniffin’ Sticks test is a popular technique for evaluating olfactory function, particularly odour recognition, threshold and discrimination skills.Reference Rumeau, Nguyen and Jankowski19, Reference Hummel, Sekinger, Wolf, Pauli and Kobal20

Odor intensity test

Tests of odour intensity are employed to evaluate how people perceive the relative variations in odour intensity when stimulus energy changes. In these tests, rating methods such as category or visual analogue scales are frequently used.Reference Doty17

Odor identification tests tailored to various cultural regions have been developed due to the importance of familiarity with specific scents for accurate identification. Notable examples include the University of Pennsylvania Smell Identification Test, the Connecticut Chemosensory Clinical Research Center Identification Test in the USA, and the Sniffin’ Sticks in Central Europe. The efficacy of each of these tests is region specific. Similarly, the Scandinavian Odor Identification Test was developed for the Scandinavian population.

The Brief Smell Identification Test is a streamlined version of the University of Pennsylvania Smell Identification Test designed to assess olfactory function quickly. It typically includes 12 common odorants encapsulated in scratch-and-sniff format. The test is straightforward to administer, with participants selecting the correct odour from multiple-choice options for each scent. The Brief Smell Identification Test is frequently used in clinical environments to screen for smell impairments.Reference Doty21–Reference Nordin, Brämerson, Lidén and Bende23

The 40-item Monell Extended Sniffin’ Sticks Identification Test is a valuable tool for evaluating odour identification in research. It is particularly useful in functional neuroimaging studies with healthy individuals.Reference Freiherr, Gordon, Alden, Ponting, Hernandez and Boesveldt24

Objective tests

While psychophysical tests have been used frequently over the years due to their affordability, usefulness, effectiveness and relative reliability, given that the subject’s cooperation is required, they are regarded as subjective or semi-objective. These are limited for quantitative assessments,Reference Nguyen, Rumeau, Gallet and Jankowski16, Reference Saltagi, Saltagi, Nag, Wu, Higgins and Knisely25 rendering them unsuitable for children, patients unable to participate effectively, or in medico-legal contexts where sincere participation cannot be assumed.Reference Lötsch and Hummel26 Therefore, researchers have sought objective methods to assess olfactory function, aiming to overcome the limitations mentioned.

Positron emission tomography (PET) scan

Positron emission tomography utilises the H215O bolus to delineate the changes in local cerebral blood flow, which indicates dynamic neural function due to its parallel increase with neural activity. Positron emission tomography imaging offers several advantages, including the simultaneous assessment of neural activity across various brain regions and exceptional visualisation of activity in primary and secondary olfactory cortex. However, PET encounters notable limitations in olfaction assessment. These include restricted temporal resolution, which hampers the precise tracking of rapid neural processes involved in olfactory perception, and exposure to radioactive isotopes, posing potential risks. Furthermore, limited accessibility to PET facilities and spatial resolution challenges, such as discerning closely situated brain foci, impede the accurate depiction of olfactory processing using PET imaging techniques.Reference Zald and Pardo27

Functional magnetic resonance imaging

Functional magnetic resonance imaging (MRI) measures changes in blood flow linked to neural activity using the blood-oxygenation-level-dependant signal, derived from the ratio of oxyhaemoglobin to deoxyhaemoglobin. Functional MRI offers enhanced accessibility and affordability, eliminates radiation exposure concerns, and provides superior spatial and temporal resolution compared to PET. However, susceptibility artifacts in specific brain regions, such as the orbitofrontal cortex, and pulsatile artifacts from respiratory motion can compromise its accuracy and reliability in olfaction assessment. Despite efforts to address these limitations by developing various techniques, conclusive evidence supporting their efficacy in olfactory assessment still needs to be uncovered in the scientific literature.Reference Zald and Pardo27

Electro-olfactography

Electro-olfactography involves measuring electrical signals directly from the olfactory epithelium in the nasal cavity in response to olfactory stimuli. Electro-olfactography recordings detect changes in electrical potential across the olfactory epithelium when odorants bind to olfactory receptor neurons. Electro-olfactography is often used to study the peripheral aspects of olfaction, such as receptor activation and adaptation, and can provide information about the sensitivity and response properties of olfactory receptor neurons.Reference Lapid, Seo, Schuster, Schneidman, Roth and Harel28

Olfactory event-related potentials

Olfactory event-related potentials are based on the electroencephalography (EEG) recording of brain activity responses to the presentation of an olfactory stimulus using electrodes placed on the scalp. Olfactory event-related potential provides distinct advantages in olfactory assessment, correlating directly with neuronal activation and offering high temporal resolution for examining sequential processing. It accommodates subjects with response difficulties (such as children and aphasic patients) and ensures consistency across experimenters, being non-invasive and cost-effective. However, susceptibility to artifacts such as blinking and movements necessitates attention maintenance during recording, and careful analysis is required to extract responses from potentially noisy EEG backgrounds.Reference Lötsch and Hummel26, Reference Kotas, Ciota and Napieralski29

Exploring olfactory event-related potentials: a primer

Olfactory event-related potentials are polyphasic electric potentials generated in the cortex in response to olfactory stimuli.Reference Arpaia, Cataldo, Criscuolo, De Benedetto, Masciullo and Schiavoni30 Olfactory event-related potentials arise from the sequential activation of various anatomical structures involved in olfactory processing. The process begins with olfactory sensory input at the olfactory neuroepithelium in the nasal cavities, then progresses through the olfactory nerve and engages with second-order neurons, including the dendrites of mitral and tufted cells within glomeruli in the olfactory bulbs. Post-synaptic fibres from these neurons extend to primary olfactory areas. The piriform cortex establishes connections with the thalamus, hypothalamus, and orbitofrontal cortex, while the entorhinal cortex interfaces with the hippocampus. The thalamus further disseminates connections to secondary olfactory areas, contributing to the complex neural circuitry underlying olfactory perception.Reference Galletti, Santoro, Mannella, Caminiti, Bonanno and De31

Delivery of stimulus (olfactometer)

Vanillin (a fragrance similar to roses), hydrogen sulphide (H2S), or 2-phenyl ethyl alcohol can all be used to activate olfactory afferents selectively.Reference Kobal and Hummel32 An apparatus capable of delivering chemical stimuli with specific characteristics is required. The apparatus needs to deliver stimuli in a rectangular form, guaranteeing swift onset and precise control over timing, duration, and intensity while preventing simultaneous engagement of other sensory systems apart from olfaction. Currently, the Burghart olfactometer is widely utilised for this purpose. This apparatus enables the delivery of stimuli within a continuously flowing stream of air, seamlessly transitioning from odourless to odourised air without detection by participants. By administering humidified and warmed intranasal airflow, subjects adapt quickly to the continuous airflow, minimising perceived discomfort or awareness of the stimulus delivery process.

With the help of this instrument, control air and odourised diluted air is delivered into the nostril. Two separate inlets for control air and odourised diluted air are directed toward the outlet and delivered directly into the subject’s nostrils. Two other tubes are present, one of which serves as a valve, and the other is connected to a vacuum line. During stimulus, control air plus odourised diluted air has to reach the outlet, so control air is directed to the vacuum line, and during the interstimulus interval, control air plus odourised diluted air is directed to the vacuum line; thus, control air reaches the nostril (Figure 1). There is a fast switch between control air and control air plus odourised diluted air such that the participants are unaware of the control air, and the transition occurs without mechanical or thermal changes.Reference Deeb, Shah, Muhammed, Gunasekera, Gannon and Findley33–Reference Caminiti, De, De, Russo, Bramanti and Marino36

Figure 1. Schematic Illustration of Olfactometer delivering odorised diluted air and control air to the nostril during the stimulus and interstimulus intervals.

Electrode placement

Three scalp electrodes in the positions frontal midline, central midline, and parietal midline were used to record the EEG according to the International 10–20 electrode system. The ground was put on the forehead, and the reference electrode was positioned on the earlobes (positions A1 and A2).Reference Caminiti, De, De, Russo, Bramanti and Marino36–Reference Covington, Geisler, Polich and Murphy40 Positions C3 and C4 were also used in some studies.Reference Lötsch and Hummel26, Reference Guo, Wu, Sun, Yao, Liu and Wei41

An electrode above the right eyebrow recorded eye movements and blinks, a technique known as an electro-oculogram. Blink artifacts were monitored from an additional site, prefrontal 2 (Fp2).Reference Lötsch and Hummel26 Additional muscular artifacts were discarded if observed. Artifact-free EEG epochs were averaged to get the olfactory event-related potentials.Reference Caminiti, De, De, Russo, Bramanti and Marino36

Waveforms of olfactory event-related potential

The olfactory event-related potentials are characterised by a prominent negative component (denoted as N1), succeeded by a substantial positive component (referred to as P2). Components P1 and N2, among other components, are frequently imperceptible.Reference Rombaux, Mouraux, Bertrand, Guerit and Hummel35, Reference Pause, Sojka, Krauel and Ferstl42, Reference Olofsson and Nordin43

Components N1 and N2

Changes in stimulus level and intensity determine the amplitude of the N1 component, an early olfactory event-related potential component regulated by both endogenous and external influences. Although the N1 amplitude in the olfactory modality does not depend on concentration, its latency does decrease as odour concentration rises. The stimulus characteristics and the individuals’ psychological states are reflected in the N1.

The olfactory event-related-potential equivalent of the olfactory mismatch negativity is a negative-deflection N2 that occurs 500–600 milliseconds after the N1 component. The deflection is most significant in the parietal midline electrode, suggesting a particular topographical distribution in response to smells.Reference Pause and Krauel44

Components P1 and P2

The external cortical activity connected to fundamental sensory processing and sensory input detection is reflected in the early olfactory event-related-potential components (N1 and P1). Conversely, the P2 and other subsequent olfactory event-related-potential components show endogenous cortical activity associated with secondary cognitive processes. Component P2 latency has attained a reasonable degree of dependability and is measured between 530 and 800 milliseconds following the start of the stimulus.Reference Caminiti, De, De, Russo, Bramanti and Marino36, Reference Pause, Sojka, Krauel and Ferstl42, Reference Lundström and Hummel45 Maximum amplitudes of the N1 and P2 components are observed over the central midline and parietal midline positions.

Component P3

Component P3 is an ‘attention’-related component,Reference Wang, Walker, Sardi, Fraser and Jacob46 a late positive complex in the olfactory event-related potential that represents psychological processes of processing information from stimuli. These processes are affected by subjective stimulus probability and stimulus meaning, which are linked to emotional and cognitive processes.Reference Pause and Krauel44 The representative waveforms are shown in Figure 2.

Figure 2. A Representative Image of the graph obtained in Olfactory event-related potentials depicting the various positive and negative components of the waveform in which y-axis represents amplitude in µV and x-axis represents time in ms.

The amplitude (not the latency) of the olfactory event-related potential represents the amount of odour. Concentration of the stimulus determines the time constant at which the olfactory event-related potential’s amplitude decays or adapts.Reference Wang, Walker, Sardi, Fraser and Jacob46

Parameters of olfactory event-related potential

The primary parameters governing the olfactory event-related potential components are latency and amplitude. Latency is the duration between onset of the stimulus and the component’s peak, or maximum value. Amplitude is the vertical distance from the most significant peak to the baseline.Reference Arpaia, Cataldo, Criscuolo, De Benedetto, Masciullo and Schiavoni30 Topography is the location on the cranial surface at which the component’s highest amplitude can be recorded, thus enabling determination of the cortical area that is active in response to a given stimulus.

Applications of olfactory event-related potential

Aging

As a method for examining how odour is processed throughout life, the olfactory event-related potential seems to be considerably promising. Interpreting specific psychophysical tasks in older adults and children may be limited by subject bias, researcher effects, and criterion alterations.Reference Murphy, Morgan, Geisler, Wetter, Covington and Madowitz47 The olfactory event-related potential olfactory assessment may be a more accurate indicator of the aging-related impairment in olfactory processing.Reference Covington, Geisler, Polich and Murphy40 It was found that young adults produce larger amplitudes and shorter latencies compared to older individuals.Reference Morgan, Covington, Geisler, Polich and Murphy38, Reference Covington, Geisler, Polich and Murphy40, Reference Murphy, Morgan, Geisler, Wetter, Covington and Madowitz47

Gender differences

Olfactory event-related potential amplitudes and latencies in response to olfactory stimuli are correlated with age, sex, stimulus concentration and interstimulus interval.Reference Morgan, Covington, Geisler, Polich and Murphy38, Reference Stuck, Frey, Freiburg, Hörmann, Zahnert and Hummel48 Olfactory event-related potential can provide important information, such as differences related to gender and age, that cannot be discovered using other olfactory tests.Reference Morgan, Covington, Geisler, Polich and Murphy38 Compared to men, women have shown greater sensitivity and lower thresholds to olfactory event-related potential.Reference Covington, Geisler, Polich and Murphy40

Women exhibited more prominent early components (P1, N1) in the signal-to-noise ratio of individual olfactory event-related potential averages compared to men. Additionally, late positive components (P2/P3) displayed larger amplitudes and shorter latencies in women as opposed to men. These findings imply that gender differences in olfactory processing may stem primarily from heightened levels of brain processing.Reference Olofsson and Nordin43, Reference Scheibe, Opatz and Hummel49 Some researchers have suggested that sex-specific variations exist in the sensory processing of olfactory stimuli. Specifically, women tend to exhibit larger amplitudes and longer latencies in their left-hemisphere responses, whereas men show a comparable pattern in their right hemispheres when exposed to identical stimuli.Reference Lundström and Hummel45

Compared to men, P3 amplitudes in women were higher when they attended but not when they ignored amyl acetate stimuli. Because the P3 component is a sign of higher cognitive processing,Reference Pause and Krauel44, Reference Ohla and Lundström50 this led to the theory that men and women differ in cognitive measures of chemosensory processing.Reference Andersson, Lundberg, Åström and Nordin51

In the current scientific literature, limited olfactory event-related-potential studies are specifically designed to investigate sex differences in olfaction. These studies would contribute valuable insights into the neurophysiological underpinnings of olfaction, facilitating a more nuanced comprehension of sensory perception.

Diagnostics in neurodegenerative diseases

Olfactory dysfunctions have garnered significant attention due to their potential link to the development of idiopathic Parkinson’s disease and Alzheimer’s disease.Reference Mesholam, Moberg, Mahr and Doty52, Reference Schapira, Chaudhuri and Jenner53

Parkinson’s disease

Because olfactory function clinical assessments are affordable and relatively simple, olfaction is a desirable biomarker for Parkinson’s disease, including prognosis, pre-motor diagnostics and differential diagnosis.Reference Pont‐Sunyer, Hotter, Gaig, Seppi, Compta and Katzenschlager54, Reference Bowman55 In general, olfactory testing could be helpful in distinguishing tauopathies (progressive supranuclear palsy and corticobasal degeneration) and non-degenerative forms of parkinsonism (normal pressure hydrocephalus, drug-induced parkinsonism, vascular parkinsonism, and essential tremor) from idiopathic Parkinson’s disease. The olfactory function measured by olfactory event-related potential revealed elevated latency but unaltered amplitude in Parkinson’s disease patients.Reference Deeb, Shah, Muhammed, Gunasekera, Gannon and Findley33, Reference Welge-Lüssen, Wattendorf, Schwerdtfeger, Fuhr, Bilecen and Hummel56

Alzheimer’s disease

The degree and course of Alzheimer’s disease can be clinically identified by olfactory function.Reference Mesholam, Moberg, Mahr and Doty52, Reference Pont‐Sunyer, Hotter, Gaig, Seppi, Compta and Katzenschlager54, Reference Rahayel, Frasnelli and Joubert57–Reference Lafaille-Magnan, Poirier, Etienne, Tremblay-Mercier, Frenette and Rosa-Neto63 Olfactory-function assessment is a low-cost, non-invasive method with low expert interpretation and administration requirements and a sensitive measure for early Alzheimer’s disease detection.Reference Bahar-Fuchs, Chételat, Villemagne, Moss, Pike and Masters64–Reference Devanand, Lee, Manly, Andrews, Schupf and Doty66 Olfactory event-related potentials play a pivotal role in facilitating early diagnosis and prognostication of Alzheimer’s disease. There has been observed augmentation in the latency of distinct components within olfactory event-related potential in apolipoprotein (ApoE) ɛ4-positive individuals, which are implicated in Alzheimer’s disease.Reference Murphy, Solomon, Haase, Wang and Morgan67–Reference Corby, Morgan and Murphy69 The highest genetic risk factor for the late-onset familial and sporadic forms of Alzheimer’s disease is the ApoE ε4 allele.Reference Combarros, Alvarez-Arcaya, Sánchez-Guerra, Infante and Berciano70, Reference Teter, Raber, Nathan and Crutcher71 When used in tandem, ApoE ε4 genetic testing and olfactory event-related potentials may improve risk assessment accuracy and lead to detection far earlier than other cognitive impairment symptoms manifest.Reference Corby, Morgan and Murphy69

Multiple sclerosis

Multiple sclerosis patients exhibit varying degrees of olfactory impairment,Reference Li, Yang, Zhang, Fu, Li and Qi72, Reference Atalar, Erdal, Tekin, Yıldız, Akdoğan and Emre73 and it has been found that direct relationships exist between olfactory dysfunction and the degree of disability and length of disease based on olfactory event-related potential.Reference Caminiti, De, De, Russo, Bramanti and Marino36, Reference Carotenuto, Costabile, Moccia, Falco, Scala and Russo74–Reference Todd, Sivakumar, Lynch, Diebolt, White and Villwock76

We cannot completely rule out the idea that olfactory function assessed at the outset of multiple sclerosis may be predictive of the course of the disease, as seen in the cases of Parkinson’s and Alzheimer’s diseases. Nevertheless, longitudinal research will be necessary to validate the theory and investigate the function of olfaction as a disease sign in multiple sclerosis.Reference Carotenuto, Costabile, Moccia, Falco, Scala and Russo74, Reference Dahlslett, Goektas, Schmidt, Harms, Olze and Fleiner77

Olfactory event-related potentials in intra-operative neuromonitoring

Chemical stimulation is typically used to evaluate olfactory event-related potential, but this method is unreliable during surgery because odorants attached to the olfactory mucosa have a long and unpredictable washout period. Ishimaru et al. introduced a method involving electrical stimulation of the olfactory mucosa to acquire olfactory event-related potentials, utilising surface electrodes positioned bilaterally on the lateral and frontal sectors of the head.Reference Ishimaru, Shimada, Sakumoto, Miwa, Kimura and Furukawa78 Nonetheless, this intra-operative technique is hindered by the limitation that it is not universally applicable in various craniotomy approaches, with the exception of midsagittal incisions, due to potential local interference during surgical procedures. Additionally, reliance on electrical olfactory event-related potentials implies an assumption that olfactory dysfunction is contingent upon damage within a specific pathway, thereby underscoring the superiority of utilising olfactory event-related potential as a more effective tool in outpatient settings.Reference Hariharan, Balzer, Anetakis, Crammond and Thirumala79

A dependable olfactory event-related potential within the surgical setting would prove invaluable for assessing the integrity of the olfactory pathway and mitigating iatrogenic neurologic deficit. In a study by Sato et al.,Reference Sato, Kodama, Sasaki and Ohta80 olfactory event-related potentials were detected in patients undergoing frontotemporal or bifrontal craniotomies in response to electrical stimulation of the mucosa. Despite their failure to disclose any post-operative anosmia or changes to the olfactory event-related potentials during the case, it is unclear what alarm parameters were applied to notify the surgeon in order to stop a potential neurologic deficiency.Reference Thirumala, Habeych, Crammond and Balzer81 Following the American Society of Neurophysiological Monitoring guidelines, the criteria of a 50 per cent amplitude change and a 10 per cent latency change, commonly employed in other modalities,Reference Toleikis82 could also be considered in this context following thorough research. Momjian et al. reported that olfactory event-related potential was acquired intra-operatively during general anaesthesia and was successfully recorded in 5 out of 8 patients undergoing neurosurgery to excise brain lesions.Reference Momjian, Tyrand, Landis and Boëx83

Challenges with the current olfactometer include lengthy stimulus averaging, complex technical setup, large size, and noise levels unsuitable for controlled environments such as operating theatres. Rigid tubing may hinder precise stimulus delivery. The signal-to-noise ratio and habituation effects need improvement for reliable measurements. Real-time statistical analysis integration is required for prompt detection of changes and timely intervention in clinical settings.Reference Momjian, Tyrand, Landis and Boëx83

Contemplating these aspects necessitates further investigation to enhance olfactory event-related potential as an improved intra-operative neuromonitoring tool, with the aim of preventing potential disruptions to olfactory function during surgical interventions.

Conclusion

This research summary provides an overview of various olfaction assessment methods, with particular attention to the emerging objective test olfactory event-related potentials, which shows promise in addressing the limitations of psychophysical tests by offering broader applicability across diverse populations. Olfactory event-related potentials shows promise as an early indicator and prognostic marker for neurodegenerative diseases. Despite notable progress, additional advancements and refinements are required to meet clinical and diagnostic standards.

  • • Olfaction is essential for human perception, and dysfunction can severely affect survival

  • • Subjective psychophysical tests are available, but objective tests are preferred despite certain limitations

  • • Olfactory event-related potentials are non-invasive and safe, providing valuable insights into age and gender differences in olfactory processing, with women showing greater sensitivity and distinct signal components

  • • Olfactory event-related potentials are crucial in diagnosing Parkinson’s and Alzheimer’s diseases by identifying specific olfactory impairments, aiding in early detection and prognosis

  • • Although promising for assessing olfactory pathways during surgery, current olfactory event-related-potential methods face technical challenges, such as lengthy averaging times and complex setups

Data availability statement

No new data were generated or analysed in support of this research.

Author contributions

Conceptualisation: Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit. Data curation: Anshika Baranwal. Formal analysis: Anshika Baranwal and Abhinav Dixit. Investigation: Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit. Methodology: Anshika Baranwal. Project administration: Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit. Resources: Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit. Supervision: Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit. Validation: Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit. Visualisation: Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit. Writing (original draft): Anshika Baranwal. Writing (review and editing): Anshika Baranwal, Mahesh Arjundhan Gadhvi and Abhinav Dixit.

Acknowledgements

Image created in the Mind the Graph platform.

Funding statement

This study was nonfunded.

Conflict of interests

None of the authors have potential conflicts of interest to be disclosed.

Footnotes

Abhinav Dixit takes responsibility for the integrity of the content of the paper

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Figure 0

Figure 1. Schematic Illustration of Olfactometer delivering odorised diluted air and control air to the nostril during the stimulus and interstimulus intervals.

Figure 1

Figure 2. A Representative Image of the graph obtained in Olfactory event-related potentials depicting the various positive and negative components of the waveform in which y-axis represents amplitude in µV and x-axis represents time in ms.