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Gustatory Testing

Editor: Gentle Wong Updated: 1/16/2023 8:15:48 PM

Introduction

Gustation, better known as taste, is an important special sensation that affects diet and human pleasure. Loss of taste or altered taste can occur in many disorders of the peripheral or central nervous system, and gustatory testing allows us to better diagnose and manage these conditions. There is a complex interplay of gustatory, olfactory, somatosensory, and emotional stimuli in taste perception. This poses a difficult task for the clinician wishing to test gustation, and as such, a multidisciplinary approach must be adopted. A further issue is the lack of suitable objective tests. To date, there are no clinically useful objective tests of gustation.[1] and the majority of tests rely on subjective measures of taste. This is unreliable in certain pathologies such as dementia and other neurodegenerative disease. There is also a lack of standardization for taste testing and no universally accepted method.[2] This is not the case for olfactory function, where the University of Pennsylvania Smell Identification Test (UPSIT) and the Sniffin Sticks are regarded as robust and widely used tools for odor testing.[3][4] Additionally, many patients report on loss of taste while they have an impairment of the sense of smell. Therefore gustatory testing is important clinically.[5] Here we review the various methods of gustatory testing and their relevance in clinical practice.

Gustatory Pathway

The sensation of taste is complex, and although the gustatory pathway has been anatomically defined, the perception of flavor is not simply a product of this pathway alone. Chemicals known as tastants are detected by cells from taste buds, which lie within papillae. Fungiform papillae are the most numerous and are found in high concentration on the tongue's anterior two-thirds.[6] Circumvallate papillae are located within the sulcus terminalis in the posterior third, and foliate papillae are located laterally. There are, however, taste buds throughout the entire oral cavity, the posterior wall of the pharynx, and the epiglottis. These signals are carried via cranial nerves VII, IX, and X to the gustatory area in the midbrain (the nucleus of the solitary tract) and thereafter to the thalamus in the central tegmental tract. The thalamus relays this information to the cortex, specifically the anterior insula frontal operculum. There is some crossing of fibers in the central tegmental tract and subsequent synapse in the ventral posteromedial nucleus of the thalamus.[6] 

A key principle in taste detection is that there are five basic tastes: sweet, salty, sour, bitter, and umami (more recently, it has been suggested that fat may also be a further basic taste).[7][8][7] Each sensory cell is capable of detecting multiple tastes due to the presence of receptors to either glucose (sweet), sodium chloride (salty), Hions (sour), glutamate (umami), or bitter substances such as quinine or caffeine. Taste cells contain a variety of different receptors, allowing for different intensities of stimulation.[9] Signal combinations from the five different basic qualities and varying levels of intensity create a vast palette of flavors.

This process is modulated by sensory input from cranial nerves I and V. Olfaction is an important part of taste, as demonstrated in wine tasting: opening the velum without swallowing allows volatile tastants to reach the olfactory epithelium, thus contributing to the perception of flavor.[10] It is also well-documented that the loss of olfactory function limits taste.[11] Texture also informs how we perceive flavor; trigeminal pathways detect somatosensory information such as viscosity and hardness. Chemesthesis describes the sensations of stinging, heat, cooling, or tingling and is carried by fibers from cranial nerves V, IX, and X.[12] There is some debate over which pathway is most important clinically. However, the majority of gustatory studies examine the anterior two-thirds of the tongue, supplied by the chorda tympani branch of the facial nerve (VII).[13] Studies have also suggested that somatosensory trigeminal fibers anastomose with facial taste fibers peripherally, acting in concordance.[14][15] This further blurs the lines of the gustatory pathway. We must also consider the emotional component of flavor perception. There is wide individual variability, driven by experience, likes, and dislikes, allowing for cortical modulation of how taste is perceived.[16] In one study, subjects described an altered taste of bland water after reading about events of moral transgression.[17] Let us not forget the metaphorical connection between taste and emotion, as evidenced in the everyday vernacular: “Home sweet home,” or being “dealt a bitter blow.”

Gustatory Dysfunction

Gustatory disorders are classified clinically as either quantitative or qualitative.[18] The former comprises ageusia (a complete loss of taste), hypogeusia (diminished taste), or hypergeusia (a heightened sense of taste). Dysgeusia is a qualitative disorder where patients experience a distorted taste. This is further classified according to its relation to eating. If occurring while eating, it is described as parageusia, but if permanently present or experienced in the absence of oral stimulation, we call it phantogeusia. A dysgeusia diagnosis is made following descriptions in the patient’s own words and cannot be reliably tested. However, quantitative gustatory disorders can be measured.

Procedures

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Procedures

Several tests have been developed to evaluate quantitative gustatory disorders. These are either chemical or electrical. Chemical testing uses natural stimuli and chemical tastants (sweet, sour, salty, bitter, and umami) to assess taste, whereas electrical testing adopts electrical currents applied directly to the surface of the tongue. Other investigations are employed in the assessment of gustatory dysfunction, such as certain imaging techniques, though these are not as useful in quantifying taste disorders. However, imaging can help diagnose both peripheral and central lesions that may affect the gustatory pathway. 

Chemical Testing

  • Three-drop method

This method makes use of aqueous solutions comprising the 5 basic tastes. Three samples are presented to the subject, one of which contains the tastant, the other 2 being simply water. It is either delivered as 3 droplets or larger volumes that require the participant to sip, swill, and spit. The subject indicates which of the three samples contained the taste solution. This must be correctly identified three times, or else the next (higher) concentration solution is used. It can be used to test for both the detection threshold (the concentration at which the subject correctly identifies the presence of a taste) and the recognition threshold (where the subject also correctly identifies the taste).[19] This style of test, using aqueous solutions, is a whole-mouth test and therefore cannot localize, which is of importance in iatrogenic impairment where a surgical complication might cause a locally isolated defect. The aqueous solution might also wash away the saliva, the usual medium through which tastants are delivered to taste buds, thus altering taste sensitivity.[20] Because the subject must verbalize their result to the examiner, this is a subjective test.[21]

  • Taste tablets

The transport and utilization of aqueous solutions posed some logistical challenges, overcome by developing tablets or wafers impregnated with the basic tastants. These can be easily stored and used for routine clinical practice. They suffer the same drawbacks as any whole-mouth testing method but are a suitable alternative to the three-drop method. The same technique can be employed with taste tablets as long as increasing concentrations of tastant are available.

  • Filter paper discs

Edible or inedible filter paper may be used in discs or ‘taste strips’ and placed in specific tongue or mouth regions, allowing for regional testing. This is particularly used to detect isolated lesions of the chorda tympani (anterior two-thirds of the tongue) or glossopharyngeal nerve (posterior tongue). Typical testing methods include several strips/discs applied to each side of the tongue while it is protruding from the mouth (thus eliminating the role of the olfactory or trigeminal pathways). The correct answers are added up, and a score below a certain threshold, or a difference in score between sides of the tongue, is considered abnormal and requires further investigation.[22]

  • Taste strips

The Taste Strips are another clinical method to assess taste.[23] They are paper strips that are impregnated with one of the four flavors "sweet", "sour", "salty" or "bitter" in four different concentrations. The Taste Strips are placed on the tongue in a predetermined order. Then, the patients are requested to say which taste they perceive. The number of correct answers is summed up. A low score indicates a poor and a high score an excellent result.

Electrical Testing

  • Electrogustometry

A monopolar or bipolar tool is used in the assessment of taste detection thresholds. A current between 1.5 and 400 µA has been proven to reliably stimulate the gustatory pathway, and this test can therefore provide localizing information about gustatory deficits.[24] It cannot distinguish between the different qualities of flavor since electrical stimulation produces the same ‘taste,’ irrespective of current, described as metallic and sour. Once again, the subject must report when they sense a taste, so this method is also a subjective test. 

  • Gustatory evoked potentials

An attempt to develop an objective test of gustation resulted in the assessment of action potentials with electroencephalogram (EEG).[25] Participants are provided with a taste stimulus and undergo a standard EEG simultaneously. The stimulus may be electrical or chemical, but the measured outcome is the latency and waveforms of the EEG instead of the subject’s response. This method's difficulty is that many studies have failed to control for confounding factors like thermal, tactile, or olfactory stimulation.[1] It is also challenging to interpret cortical activity about gustation. Gustatory evoked potentials appear to be ineffective at detecting certain taste types and only provide consistent results with sour tastes. 

Imaging

  • Functional magnetic resonance imaging

Modern magnetic resonance imaging (MRI) techniques allow us to highlight areas of the brain that may be involved in the gustatory pathway. This relies upon the blood-oxygen-level-dependent contrast that occurs after a cascade of physiological events resulting in dynamic cerebral blood flow changes and oxygen consumption.[26] Functional MRI, fMRI, has been used in many patients, including those with known anatomical or neurological lesions, to characterize the gustatory pathway.[27] The thalamus, insula, and frontal operculum are important centers. It is not clear, however, if fMRI is a clinically useful tool in investigating gustatory dysfunction. It has a role in research, but given the expense and technical difficulties of interpreting data, fMRI is not a routinely used method of testing gustation.

  • Positron emission tomography 

Using fludeoxyglucose F18 (FDG) to measure uptake in PET scanning elicits much the same results as fMRI. It has not yet been used to investigate gustatory dysfunction; however, it has been used to investigate the anosmia being widely reported during the COVID-19 pandemic (suggesting a cortical neuronal loss and not just transient damage to the olfactory nerve.[28]

  • Confocal microscopy

Confocal laser scanning microscopy provides a magnified (up to eight hundred times) view of the surface of the tongue.[29] This technique enables visualization of the tongue epithelium and subsequent correlation with gustatory function. It does not, on its own, allow measurement of gustation, but it does let us examine the taste organ closely and relate anatomical lesions to the clinical presentation or other gustatory tests. It is not yet used in routine clinical practice, perhaps because studies have failed to show convincing evidence that the number or distribution of papillae correlates significantly with gustatory function.[30]

  • Photography

A less magnified approach to examining the tongue involves using advanced cameras and dye application to specific areas of the tongue. This then allows counting of the papillae (using photo software) to create a quantitative assessment of fungiform papillae. Papillae quantification has not been shown to correlate with other measures of gustation, but photography might allow us to appreciate oral pathology better when investigating disorders of taste.[31][32][33]

Indications

Gustatory testing is either used in research or for diagnostic purposes in the clinical setting. The latter is challenging due to the subjectivity of most testing methods, meaning the tests cannot be validated or applied to certain patient groups. In terms of research, increasing emphasis is being placed on the need to develop more objective and validated methods. In the clinical environment, gustatory testing is indicated in any patient who reports distorted taste, and only once olfactory pathology has been ruled out. Testing for detection thresholds (using the 3-drop method, taste tablets, or electrogustometry) may be useful in patients suffering from medication-induced hypogeusias to prove and document the disorder, allowing for a comprehensive assessment of medications so that necessary adjustments can be made. If a peripheral nerve lesion is suspected, which most commonly causes an ipsilateral ageusia following a surgical procedure, regional gustatory testing is indicated using taste strips or filter paper disks. Any whole-mouth test would be unsuitable in such a case. Taste-testing might also be useful in appetite disorders, where our perception of flavor plays an important role in diet and nutritional intake.

Interfering Factors

There are clear problems with gustatory testing. The lack of objectivity among the various testing methods means that we cannot apply the tests to individuals without the capacity or use them to discern true pathology from psychogenic phenomena or malingering. The complex nature of gustation also creates interfering factors, forcing the clinician to consider the integration of olfaction, somatosensory, visual, and emotional factors. Tests must be able to localize pathology, whereas whole-mouth testing methods do not, instead giving a less refined interpretation of gustation. Some methods do not directly measure gustation but rather provide a proxy measurement; for example, imaging cannot diagnose ageusia, but reporting the anatomical location of a lesion can assume a gustatory involvement. Other proxy tests such as salivary testing have not been mentioned here, as again they do not directly measure gustation, but saliva creates the optimal environment for taste, and therefore disorders of salivation may alter gustation. It has been suggested that ‘without moisture, there is no taste,’ although analysis of salivary flow rates has failed to prove a correlation to taste perception.[2][34]

Clinical Significance

Although taste is regarded as less important than its sensory counterparts of vision and hearing, it plays an important role in happiness. Gustatory pathology can impact mental health and compromise some peoples' occupations. Taste evolved to allow us to detect the nutritional quality and hazards of potential foods, and as such, a loss of taste may even be considered life-threatening. Identifying and treating the cause of gustatory disorders is therefore of great importance to the individual patient, however as mentioned before, it is difficult to examine a single pathway. Isolated pathologies of the gustatory pathway are rare [35]. It is much more common that patients present with other symptomology often deemed more serious than the loss of taste (such as swallow impairment after a stroke). Consequently, gustatory dysfunction is underreported, and the medical team must look for it.

A full history identifying previous surgical procedures of the head and neck, upper aerodigestive tract pathologies, and a list of medications is paramount. A thorough history will highlight the most prevalent causes of gustatory dysfunction: iatrogenic, drug-induced, post-infectious, or neuropsychiatric. This indicates the need for an interprofessional healthcare team approach to these disorders, utilizing clinicians, specialists, nurses, and pharmacists, all working collaboratively to achieve optimal patient outcomes. [Level 5]

Combined expertise from otorhinolaryngologists, neurologists, and maxillofacial surgeons is recommended to diagnose and manage gustatory pathology. Clinical examination should include a close inspection of the tongue and oropharynx and otoscopy (the ear canal is a common site for lesions affecting the chorda tympani). Cranial nerve examination is crucial. For example, abnormalities in the trigeminal-facial pathways can be detected by testing the blink and masseter reflexes.[36][37]

The history should reveal a temporal relationship between gustatory dysfunction and, say, a new medication, recent surgical procedure, or infection. Other causes of taste disorders affect either the peripheral or central nervous system. Peripheral lesions comprise syndromes of the glossopharyngeal or facial nerve, the most common being idiopathic Bell palsy. Other lesions of the facial nerve include infectious neuritis or space-occupying masses of the cerebellopontine angle. A frequent cause of glossopharyngeal dysfunction is the dissection of the cervical arteries.[34] Central nervous system disorders can be organized into pathologies of the brainstem, thalamus, or cortex. Brainstem lesions present with ipsilateral hemiageusia/hemihypogeusia and are often a consequence of cerebrovascular insults or demyelination. Thalamic lesions, however, cause a contralateral presentation. Culprits for cortical gustatory dysfunction include epilepsy, Alzheimer’s disease, and stroke.

The management of gustatory disorders should be targeted at an accurate diagnosis of the underlying cause. A thorough patient workup is warranted, followed by smoking cessation advice, good oral hygiene measures, and a trial of zinc therapy. Zinc, corticosteroids, and vitamin A have all been attempted despite a lack of convincing clinical data, and there is currently no specific treatment for idiopathic dysgeusia.[38][39]

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