The influence of affective state on sensory and emotional perception: Application of the Sense'n Feel™ method.

Emotions play a key role in our daily life through their control over our thoughts and behaviors. While it is commonly accepted that depressive patients have emotional perception disorders, it is important to know how these disorders affect patients' sensory perception to develop products to provide them with better support. In this study, we first examined the existence of modifications in the emotional perception of subjects with minor depressive symptoms (MDS, n = 80) compared with healthy controls (HC, n = 80) using a nonverbal method based on pictures to measure projected emotions and personality traits: the Sense'n Feel™ method. The investigated stimuli were two unpleasant and two pleasant odors and one pleasant food product: a madeleine. Second, we investigated the hedonic, familiarity and intensity olfactory perceptions of the subjects using the same stimuli. No significant difference was found in any olfactory qualities between the two groups. Concerning the pleasant olfactory stimuli, however, we did note that the MDS subjects had a significantly lower score for the positive emotion of joy/happiness than the controls. Additionally, the MDS group's attribution of some positive personality traits for the three pleasant stimuli was significantly weaker than that in the HC group. These results could be explained by the affective state of the MDS subjects; they were more anxious and more alexithymic compared with the controls. Further research is needed to validate our study in clinically depressed individuals and to determine whether the modifications of the emotional olfactory perception are due to the disease and/or to neuropsychological alterations.

Neuroinflammation and depression: A review.

Some recent clinical and preclinical evidence suggests that neuroinflammation is a key factor that interacts with the three neurobiological correlates of major depressive disorder: depletion of brain serotonin, dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and alteration of the continuous production of adult-generated neurons in the dentate gyrus of the hippocampus. This review discusses the main players in brain immunity as well as how inflammation interacts with the above three mechanisms. It is reported that kynurenine (KYN) pathway alteration in favour of its excitotoxic component and HPA axis dysregulation have the common effect of increasing extracellular glutamate levels and glutamate neurotransmission, which can impact hippocampal neurogenesis. This pathophysiological cascade appears to be triggered or sustained and reinforced by any chronic inflammatory condition involving increased circulating markers of inflammation that are able to cross the blood-brain barrier and activate microglia; it can also be the consequence of primary brain neuroinflammation, such as in neurodegenerative disorders with early manifestations that are frequently depressive symptoms. Further recent data indicate that primary microglial activation may also result from a direct impact of chronic stress on vascular function. The intricated dynamic crosstalk between neuroinflammation and other relevant neurobiological correlates of depression add to evidence that neuroinflammation may be a key therapeutic target for future therapeutic strategies in major depressive disorder.

What are Probable Olfactory Markers of Alcohol Dependence?

As the olfactory system is closely connected with the brain areas responsible for the most crucial alterations in psychiatric populations, especially cognitive and emotional impairments, the study of olfactory processing may be a relevant approach to identify specific markers of alcohol dependence. The aim of this study was to propose the probable olfactory markers for alcohol dependence through a study of the olfactory parameters that involve the central olfactory pathway. We recruited the same 41 alcohol-dependent patients in an early (day 8) and late (day 67) stage of abstinence and 41 controls matched for gender, age, and smoking status. The participants underwent clinical assessments and several olfactory evaluations. The results revealed on one hand, the persistence of decreased intensity of positive emotion (happy), increased intensity of negative emotion (sad), and increased citation of surprise in patients, suggesting the presence of probable trait markers of alcohol dependence. On the other hand, we found decreased hedonic score for pleasant and neutral odorants, and decreased odor familiarity judgment only in the early stage of evaluation as probable state markers for alcohol dependence. These results may be underpinned by several neuropsychological alterations specific to this disease and their evolution after weaning. Further studies are needed to replicate these findings and to confirm the specificity and sensitivity of the olfactory tests in a larger sample of patients. The olfactory perception of all controls must be also retested in order to determine the specific state and/or trait markers of alcohol dependence.

Improvement of hedonic perception of odors as a marker of treatment response to escitalopram: olfactory changes through an open-label antidepressant trial.

OBJECTIVES: To assess olfactory functions (threshold, identification, and hedonic valence) of depressed subjects before and after an 8-week trial of escitalopram and compare the results of responders and nonresponders. METHODS: Fifty-two depressed subjects were recruited. Participants received escitalopram and were evaluated at two visits: baseline (V0) and week 8 (V8). They were categorized as responders (Montgomery-Åsberg Depression Rating Scale [MADRS] score reduction of > 50%) or nonresponders to treatment. Participants were evaluated with the Mini International Neuropsychiatric Interview (MINI) at V0 and, at V0 and V8, completed psychometric and olfactory assessments, including MADRS and the State-Trait Anxiety Inventory (STAI), as well as the Sniffin' Sticks® test (threshold and identification tasks). The hedonic valence of smell was assessed on a 10-cm linear scale after presenting two pleasant and two unpleasant odors. Forty-three participants completed the study (24 responders and 19 nonresponders). The Mann-Whitney, chi-square, and Fisher's exact tests were used to compare olfactory, clinical, and demographic variables between groups and within the same group at V0 and V8. The Spearman coefficient was used to calculate the correlation between clinical characteristics and olfactory variables. RESULTS: The hedonic score of pleasant odors increased significantly between V0 and V8 only for responders (V = 61.5, p = 0.018), with no significant change in nonresponders (V = 90.5, p = 0.879). Comparison of olfactory performances between groups at V0 and V8 separately did not show a significant difference between responders and nonresponders to escitalopram. Olfactory threshold and identification scores were not different between V0 and V8 for responders or nonresponders. CONCLUSION: Depressed subjects have olfactory anhedonia, which appears to regress following a positive antidepressant response. Hedonic valence may be an indicator of cognitive changes associated with depression; improvement of this valence may indicate a clinical response to antidepressants.

Mania associated olfactory dysfunction: A comparison between bipolar subjects in mania and remission.

OBJECTIVES: The aim of this study was to assess the olfactory functions of patients with bipolar disorder in manic phase and to compare them to those of bipolar subjects in remission and healthy controls. METHODS: We recruited 96 participants divided in 3 groups: bipolar mania (MB), euthymic bipolar in remission (EB) and healthy controls (HC). All participants underwent an assessment of their olfactory functions using the Sniffin' sticks threshold and identification tests. Odors' pleasantness, intensity, familiarity and emotion were assessed. All participants were screened for the presence of psychiatric disorder through the MINI questionnaire. Clinical evaluation explored dimensions of mania, depression, anxiety respectively through YMRS, MADRS and STAI scales. Anhedonia was explored through the Chapman physical and social anhedonia questionnaire. RESULTS: Patients in mania had deficits in identifying positive smells compared to bipolar subjects in remission and to healthy controls (MB < EB < HC; p < 0.001). Hedonic (MB < EB = HC; p < 0.001) and emotional (MB < EB = HC; p < 0.001) ratings of positive smells were lower in patients in manic phase compared to remitted subjects or controls. Mania was associated to higher emotion rating of negative smells compared to remitted subjects and controls (MB > EB = HC; p < 0.001). There was no difference between the 3 groups in the ratings of intensity and familiarity of smells, as well as in the olfactory threshold testing. The 3 groups showed no difference in the identification of negative smells. CONCLUSIONS: Patients in manic episodes showed deficits in identifying positive odors. They evaluated these smells as less pleasant and less emotional compared to remitted bipolar subjects and healthy controls. These olfactory dysfunctions may constitute potential indicators of manic state. The persistence of olfactory dysfunction in remission phase (deficit in the olfactory identification of positive odors compared to healthy controls) may constitute a potential trait indicator of bipolarity.

Decrease in ultrasound Brain Tissue Pulsations as a potential surrogate marker of response to antidepressant.

Previous cross-sectional studies found excessive Brain Tissue Pulsations (BTP) in mid-life depression, which could constitute a mechanism of brain damage in depression. However, it remains unclear whether successful antidepressant therapy restores BTP amplitudes. In this prospective study, we investigated longitudinal changes in BTP in patients with a major depressive episode (MDE), among responders and non-responders to escitalopram. Fifty-two individuals with a MDE, free of antidepressants at baseline, were included in an 8-week open-labeled escitalopram trial. Ultrasound Tissue Pulsatility Imaging (TPI) was applied to measure resting BTP and BTP reactivity in an orthostatic challenge, at baseline and at week 8. TPI data were available for 48 participants divided into responders (n = 28, 58.3%) and non-responders (n = 20, 41.7%) according to change in the MADRS score. MaxBTP significantly decreased between baseline and week 8, only in responders. In addition, changes in MaxBTP during the orthostatic challenge were no longer significant at week 8 but only in responders. Because excessive BTP constitutes a potential mechanism for brain damage, our results suggest that a successful pharmacotherapy could benefit patients to lower the risk of brain damage in individuals with depression, a population exposed to stroke, small arteries disease and brain atrophy. TPI could provide a surrogate biomarker to monitor antidepressant response and brain health in depression in clinical routine.

Olfactory anhedonia and negative olfactory alliesthesia in depressed patients.

The present study aimed to investigate olfactory anhedonia and olfactory negative alliesthesia in depressed patients. Two odorants, one with pleasant (vanillin), and one with unpleasant (butyric acid) hedonic valence were evaluated by 30 depressed inpatients and 30 controls (healthy subjects, matched by age and gender). Participants explored the hedonic valence, intensity (discrimination) and perceived quality (identification) of 16 different stimuli (3 concentrations of odorants, their 9 combinations, and 1 control containing distilled water). The hedonic perception showed that patients perceived the unpleasant odorant as significantly more unpleasant than controls (olfactory negative alliesthesia). Concerning the intensity ratings, controls were able to discriminate between all concentrations of odorants, while patients discriminated between the different concentrations only for the unpleasant component and not for the vanillin (olfactory anhedonia). Regarding the identification task in an iso-intense unmixed odorants mixture, patients perceived significantly less the pleasant odorant than the unpleasant one (olfactory anhedonia), whereas controls perceived both odorants equally well. These results support the notion of an olfactory perception impairment in depression. Further studies are needed to replicate these findings and to confirm that such olfactory anhedonia or/and olfactory negative alliesthesia could be a state or a trait of depression.

[Decision making in the elderly: which tools for its evaluation by the clinician?]. / La prise de décision chez le sujet âgé : quels outils d'évaluation pour le clinicien ?

Numerous decision-making situations occur in the activities of daily living. The consequences of the decision-making capacity disturbances may have a great impact on the patient's autonomy, financial management, and his or her reaction to a diagnosis as well as the ability to accept a therapeutic option or give informed consent. Decision-making is a complex and multi-dimensional process and brings into play attention, memory and executive functions, which are processed in the prefrontal cortex, particularly vulnerable in aging. A better comprehension of the mechanisms of decision-making, and of the resulting social consequences of their dysfunction may improve autonomy of the elderly. Unfortunately, we still lack appropriate tools to explore decision-making in routine practice.

Olfactory markers for depression: Differences between bipolar and unipolar patients.

OBJECTIVES: The aim of the study was to compare olfactory functions between unipolar and bipolar patients according to the thymic states (depressed, euthymic) and determine specific olfactory variations between these different states. METHODS: We recruited 176 participants in 5 groups: depressed bipolar (DB), euthymic bipolar (EB), depressed unipolar (DU), euthymic unipolar (EU), and controls (HC). They were assessed using the Sniffin' sticks threshold and identification tests. Odors' pleasantness, intensity, familiarity and emotion were assessed. Clinical evaluation explored dimensions of depression, mania, anxiety, and anhedonia. RESULTS: Smell identification was lower in DU compared to EU patients and controls. Pleasant odors received lower hedonic rating in DU and DB patients compared to EU and EB patients respectively. Negative correlation was found in EB patients between hedonic rating and social anhedonia. In EU patients hedonic rating was negatively correlated with anxiety-state, and anhedonia. CONCLUSIONS: Odor identification of pleasant odors is altered in both depressive states. Only unipolar patients would recover a regular identification level in symptomatic remission, while bipolar subjects would keep their deficits. Hedonic rating is lower in bipolar depressed patients compared to unipolar ones, and these deficits improve after remission. Hedonic rating of pleasant odors may distinguish bipolar depression from unipolar depression during periods of decompensation and phases of remission. Olfactory assessment may be useful to screen unipolar and bipolar depression, leading to possible future sensory markers in mood disorders.

Olfactory Memory in Depression: State and Trait Differences between Bipolar and Unipolar Disorders.

: Background: Changes in olfactory recognition memory may constitute sensory markers in depression. Significant differences may exist between unipolar and bipolar depression. Our study compares olfactory memory between control, unipolar, and bipolar patients in depressed and euthymic states in order to identify potential markers of depression. METHODS: 176 participants were recruited in 5 groups: depressed bipolar (DB), euthymic bipolar (EB), depressed unipolar (DU), euthymic unipolar (EU), and controls (HC). The participants had a standardized clinical and olfactory assessment (olfactory memory, evaluation of pleasantness, intensity, familiarity, and emotional aspect of smells). RESULTS: DU, DB, and EU patients had a deficit in olfactory memory compared to HC. DB patients had lower capacity to recognize new odors. DB and DU patients had more limited detection of unfamiliar odors than HC. DB patients rated odors as less pleasant compared to the other groups. All groups had lower hedonic ratings than HC. DB patients had lower emotional ratings than EU patients. CONCLUSIONS: Olfactory memory is impaired in depressive states, thus constituting a state marker of depression. Impairments in olfactory memory persist after remission of bipolar depression, thus constituting a possible trait marker of bipolarity. Hedonic rating differentiates unipolar from bipolar depression. This is the first study that identifies a sensory marker differentiating between unipolar and bipolar depression.

Olfaction: a potential cognitive marker of psychiatric disorders.

Cognitive deficits are well documented in psychiatric disorders, particularly in schizophrenia and depression. Cognitive activity roots in perceptions. However, research on sensorial alterations in psychiatric conditions has mainly focused on visual or auditory processes and less on olfaction. Here, we examine data on olfactory deficits in psychiatric patients using a systematic review of recent publications. Schizophrenic patients are mainly characterized by no reliable change in odour sensitivity and by a deficit in odour identification, recognition and discrimination. Depressed patients principally exhibit a deficit in the hedonic aspects of this perception, even if, in some case, alterations in sensitivity or identification are also found. Changes in odour perception are also found in dementia and in some neurodegenerative disease, but in this case alterations concern all aspects of the sensorial experience (detection threshold, identification and recognition). Taken together, these data indicate that olfactory abnormalities might be a marker of psychiatric conditions, with a specific pattern for each disease.

Depression, Olfaction, and Quality of Life: A Mutual Relationship.

Olfactory dysfunction has been well studied in depression. Common brain areas are involved in depression and in the olfactory process, suggesting that olfactory impairments may constitute potential markers of this disorder. Olfactory markers of depression can be either state (present only in symptomatic phases) or trait (persistent after symptomatic remission) markers. This study presents the etiology of depression, the anatomical links between olfaction and depression, and a literature review of different olfactory markers of depression. Several studies have also shown that olfactory impairment affects the quality of life and that olfactory disorders can affect daily life and may be lead to depression. Thus, this study discusses the links between olfactory processing, depression, and quality of life. Finally, olfaction is an innovative research field that may constitute a new therapeutic tool for the treatment of depression.

Hedonic Assessment of Odors: A Comparison of Two Sensory Scales for Use with Alzheimer's Disease Patients and Elderly Individuals.

BACKGROUND: Several clinical studies concerning the olfactory function of patients with cognitive impairment have used sensory scales to investigate hedonic perception. However, no study has focused on the choice of the most appropriate sensory hedonic scale for the individuals with neurodegenerative disorders or other psychiatric diseases involving cognitive deficits. OBJECTIVE: The aim of this study was to investigate the ability of patients with Alzheimer's disease (AD) to use two hedonic scales (category scale and linear scale) and compare their discriminatory capacity, repeatability, and ease of use. This should allow us to identify the most appropriate hedonic scale for patients with AD. METHODS: We recruited 18 patients with mild to moderate AD, and 20 healthy volunteers matched for gender, age, smoking status, and educational level. The participants underwent a clinical assessment and hedonic evaluation of three odorants (pleasant, unpleasant, and neutral), using a five-point category scale and a 10-cm linear scale with a marked mid-point. RESULTS: AD patients were able to use hedonic scales as well as paired healthy elderly subjects. The linear scale performed slightly better in terms of ease of use for both patients and healthy controls and discriminatory capacity for AD patients. The results for AD patients and controls with both scales were repeatable. CONCLUSION: The linear scale may be more appropriate for AD patients pending further studies involving a larger population of patients, using several odorants.

Improvement of hedonic perception of odors as a marker of treatment response to escitalopram: olfactory changes through an open-label antidepressant trial

Objectives: To assess olfactory functions (threshold, identification, and hedonic valence) of depressed subjects before and after an 8-week trial of escitalopram and compare the results of responders and nonresponders. Methods: Fifty-two depressed subjects were recruited. Participants received escitalopram and were evaluated at two visits: baseline (V0) and week 8 (V8). They were categorized as responders (Montgomery-Åsberg Depression Rating Scale [MADRS] score reduction of > 50%) or nonresponders to treatment. Participants were evaluated with the Mini International Neuropsychiatric Interview (MINI) at V0 and, at V0 and V8, completed psychometric and olfactory assessments, including MADRS and the State-Trait Anxiety Inventory (STAI), as well as the Sniffin' Sticks® test (threshold and identification tasks). The hedonic valence of smell was assessed on a 10-cm linear scale after presenting two pleasant and two unpleasant odors. Forty-three participants completed the study (24 responders and 19 nonresponders). The Mann-Whitney, chi-square, and Fisher's exact tests were used to compare olfactory, clinical, and demographic variables between groups and within the same group at V0 and V8. The Spearman coefficient was used to calculate the correlation between clinical characteristics and olfactory variables. Results: The hedonic score of pleasant odors increased significantly between V0 and V8 only for responders (V = 61.5, p = 0.018), with no significant change in nonresponders (V = 90.5, p = 0.879). Comparison of olfactory performances between groups at V0 and V8 separately did not show a significant difference between responders and nonresponders to escitalopram. Olfactory threshold and identification scores were not different between V0 and V8 for responders or nonresponders. Conclusion: Depressed subjects have olfactory anhedonia, which appears to regress following a positive antidepressant response. Hedonic valence may be an indicator of cognitive changes associated with depression; improvement of this valence may indicate a clinical response to antidepressants.

Olfactory and gustatory functions in bipolar disorders: A systematic review.

Olfactory and gustatory dysfunctions have been described in different psychiatric disorders. Several studies have found gustatory and olfactory function change in bipolar disorders with various results. The aim of this study is to have a systematic review of studies evaluating gustatory and olfactory function in bipolar disorders. After a systematic search, 15 studies on olfaction and 5 studies on taste were included in this review. The UPSIT (University of Pennsylvania Smell Identification Test) and Sniffin' Sticks were the most widely used tests to evaluate smell. Some studies on olfaction described dysfunctions in smell identification as potential markers for bipolar disorders. Moreover, olfactory acuity was associated with psychosocial and cognitive performances. For taste, only few studies used standardized tests to evaluate gustation. These studies showed that patients with Bipolar disorders had more gustatory dysfunction compared to controls, and to non-bipolar depressed patients.

An odor identification approach based on event-related pupil dilation and gaze focus.

Olfactory disorders constitute a potential marker of many diseases and are considered valuable clues to the diagnosis and evaluation of progression for many disorders. The most commonly used test for the evaluation of impairments of olfactory identification requires the active participation of the subject, who must select the correct name of the perceived odor from a list. An alternative method is required because speech may be impaired or not yet learned in many patients. As odor identification is known to be facilitated by searching for visual clues, we aimed to develop an objective, vision-based approach for the evaluation of odor identification. We used an eye tracking method to quantify pupillary and ocular responses during the simultaneous presentation of olfactory and visual stimuli, in 39 healthy participants aged from 19 to 77years. Odor presentation triggered an increase in pupil dilation and gaze focus on the picture corresponding to the odor presented. These results suggest that odorant stimuli increase recruitment of the sympathetic system (as demonstrated by the reactivity of the pupil) and draw attention to the visual clue. These results validate the objectivity of this method.

Taste identification used as a potential discriminative test among depression and Alzheimer׳s disease in elderly: A pilot study.

Major Depression and Alzheimer׳s disease (AD) are two diseases in the elderly characterized by an overlap of early symptoms including memory and emotional disorders. The identification of specific markers would facilitate their diagnosis. The aim of this study was to identify such markers by investigating gustatory function in depressed and AD patients. We included 20 patients with unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD and 24 healthy individuals. We investigated the cognitive profile (depression, global cognitive efficiency and social/physical anhedonia) and gustatory function (ability to identify four basic tastes and to judge their intensity and hedonic value) in all participants. We found that AD patients performed worse than healthy participants in the taste identification test (for the analysis of all tastants together); however, this was not the case for depressed patients. We found no significant differences among the three groups in their ability to evaluate the intensity and hedonic value of the four tastes. Overall, our findings suggest that a taste identification test may be useful to distinguish AD and healthy controls but further investigation is required to conclude whether such a test can differentiate AD and depressed patients.

Long-term odor recognition memory in unipolar major depression and Alzheimer׳s disease.

Major depression and Alzheimer׳s disease (AD) are often observed in the elderly. The identification of specific markers for these diseases could improve their screening. The aim of this study was to investigate long-term odor recognition memory in depressed and AD patients, with a view to identifying olfactory markers of these diseases. We included 20 patients with unipolar major depressive episodes (MDE), 20 patients with mild to moderate AD and 24 healthy subjects. We investigated the cognitive profile and olfactory memory capacities (ability to recognize familiar and unfamiliar odors) of these subjects. Olfactory memory test results showed that AD and depressed patients were characterized by significantly less correct responses and more wrong responses than healthy controls. Detection index did not differ significantly between patients with major depression and those with AD when the results were analyzed for all odors. However, MDE patients displayed an impairment of olfactory memory for both familiar and unfamiliar odors, whereas AD subjects were impaired only in the recognition of unfamiliar odors, with respect to healthy subjects. If preservation of olfactory memory for familiar stimuli in patients with mild to moderate AD is confirmed, this test could be used in clinical practice as a complementary tool for diagnosis.

Perceptive biases in major depressive episode.

INTRODUCTION: Alterations in emotional processing occur during a major depressive episode (MDE), and olfaction and facial expressions have implications in emotional and social interactions. To gain a better understanding of these processes, we characterized the perceptive sensorial biases, potential links, and potential remission after antidepressant treatment of MDE. METHODS: We recruited 22 patients with acute MDE, both before and after three months of antidepressant treatment, and 41 healthy volunteers matched by age and smoking status. The participants underwent a clinical assessment (Mini International Neuropsychiatry Interview, Montgomery-Åsberg Depression Rating Scale, State-Trait Anxiety Inventory, Physical and Social Anhedonia scales, Pleasure-Displeasure Scale), an olfactory evaluation (hedonic aspect, familiarity and emotional impact of odors), and a computerized Facial Affect Recognition task. RESULTS: MDE was associated with an olfactory bias concerning hedonic and emotional aspects, including negative olfactory alliesthesia (unpleasant odorants perceived as more unpleasant), facial emotion expression recognition (happy facial expressions), and in part olfactory anhedonia (pleasant odorants perceived as less pleasant). In addition, the results revealed that these impairments represent state markers of MDE, suggesting that the patients recovered the same sensory processing as healthy subjects after antidepressant treatment. DISCUSSION: This study demonstrated that MDE is associated with negative biases toward olfactory perception and the recognition of facial emotional expressions. The link between these two sensory parameters suggests common underlying processes.

The perception of odor objects in everyday life: a review on the processing of odor mixtures.

Smelling monomolecular odors hardly ever occurs in everyday life, and the daily functioning of the sense of smell relies primarily on the processing of complex mixtures of volatiles that are present in the environment (e.g., emanating from food or conspecifics). Such processing allows for the instantaneous recognition and categorization of smells and also for the discrimination of odors among others to extract relevant information and to adapt efficiently in different contexts. The neurophysiological mechanisms underpinning this highly efficient analysis of complex mixtures of odorants is beginning to be unraveled and support the idea that olfaction, as vision and audition, relies on odor-objects encoding. This configural processing of odor mixtures, which is empirically subject to important applications in our societies (e.g., the art of perfumers, flavorists, and wine makers), has been scientifically studied only during the last decades. This processing depends on many individual factors, among which are the developmental stage, lifestyle, physiological and mood state, and cognitive skills; this processing also presents striking similarities between species. The present review gathers the recent findings, as observed in animals, healthy subjects, and/or individuals with affective disorders, supporting the perception of complex odor stimuli as odor objects. It also discusses peripheral to central processing, and cognitive and behavioral significance. Finally, this review highlights that the study of odor mixtures is an original window allowing for the investigation of daily olfaction and emphasizes the need for knowledge about the underlying biological processes, which appear to be crucial for our representation and adaptation to the chemical environment.