Correlation between olfactory function, age, sex, and cognitive reserve index in the Italian population.

PURPOSE: Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults. METHODS: Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18-86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18-29 years (N = 157), 30-39 years (N = 129), 40-49 years (N = 99), 50-59 years (N = 106), > 60 years (N = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin' Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected. RESULTS: About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores. CONCLUSION: This study provides data on the prevalence of olfactory dysfunction in different Italian regions.

Detection thresholds for quinine, PTC, and PROP measured using taste strips.

PURPOSE: In clinical practice, when ability to perceive bitter taste is studied, quinine is preferred to phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) as taste stimulus, because many subjects are genetically non-tasters for PTC/PROP. However, it is poorly known how sensitive anterior (front) and posterior (back) parts of the tongue are to different bitter tastants that are detected by different bitter taste receptors (TAS2Rs). In the present study, we aimed to characterize sensitivity to bitter taste at front and back parts of tongue. METHODS: We measured thresholds for quinine, PTC, and PROP using the "taste strips", employing seven concentrations of each stimulus both at front and back parts of tongue in 203 healthy participants (56% females, mean age 28 years). RESULTS: Our data confirmed the hypothesis that the inability to perceive quinine was less frequent than the inability to perceive PTC and PROP: People can still perceive the bitter taste of quinine even if they are "non-tasters" for PROP/PTC. As expected, strong correlations between PTC and PROP thresholds were observed. Interestingly, correlations between thresholds for quinine and PTC/PROP also emerged. Overall, the detection thresholds were lower when measured at front part of the tongue. CONCLUSIONS: Our data suggest that determining taster status for quinine using paper "taste strips", applied to front part of the tongue, represents a suitable method for the screening for ageusia for bitter taste.

When preschoolers follow their eyes and older children follow their noses: visuo-olfactory social affective matching in childhood.

Recognition of emotional facial expressions is a crucial skill for adaptive behavior that most often occurs in a multi-sensory context. Affective matching tasks have been used across development to investigate how people integrate facial information with other senses. Given the relative affective strength of olfaction and its relevance in mediating social information since birth, we assessed olfactory-visual matching abilities in a group of 140 children between the ages of 3 and 11 years old. We presented one of three odor primes (rose, fish and no-odor, rated as pleasant or unpleasant by individual children) before a facial choice task (happy vs. disgusted face). Children were instructed to select one of two faces. As expected, children of all ages tended to choose happy faces. Children younger than 5 years of age were biased towards choosing the happy face, irrespective of the odor smelled. After age 5, an affective matching strategy guided children's choices. Smelling a pleasant odor predicted the choice of happy faces, whereas smelling the unpleasant or fish odor predicted the choice of disgusted faces. The present study fills a gap in the developmental literature on olfactory-visual affective strategies that affect decision-making, and represents an important step towards understanding the underlying developmental processes that shape the typical social mind.

A Cross-Cultural Adaptation of the Sniffin' Sticks Olfactory Identification Test for US children.

Disorders associated with smell loss are common in adolescents. However, current odor identification tests focus on children from age 6 and older and no cross-cultural test has to date been validated and fully implemented. Here, we aimed to investigate how 3-to-11-year-old US children performed to an adapted and shortened (11 odors instead of 14) version of a European odor identification test-the Sniffin' Kids (Schriever VA, Mori E, Petters W, Boerner C, Smitka M, Hummel T. 2014. The "Sniffin'Kids" test: a 14-item odor identification test for children. Plos One. 9:e101086.). Results confirmed that cued odor identification performance increases with age and revealed little to no differences between girls and boys. Scores below 3 and below 6 may raise hyposmia concerns in US children aged 3-7 years and 8-10 years, respectively. Even though the completion rate of the task reached the 88%, suggesting that children below age 5 were able to finish the test, their performance was relatively poor. In comparing the overall identification performance of US children with that of German children, for whom the test was specifically developed, significant differences emerged, with higher scores obtained by the German sample. Analysis of errors indicated that a lack of semantic knowledge for the olfactory-presented objects may be at the root of poor identification skills in US children and therefore constitutes a problem in the development of an odor identification test for younger children valid across cultures.

Intentional binding as a marker of agency across the lifespan.

The feeling of control over actions and their external effects is known as Sense of Agency (SoAg). People usually have a distinctive SoAg for events caused by their own actions. However, if the agent is a child or an older person, this feeling of being responsible for the consequences of an action may differ from what an adult would feel. The idea would be that children and elderly may have a reduced SoAg since their frontal lobes are developing or have started to loose their efficiency. The aim of this study was to elucidate whether the SoAg changes across lifespan, using the Intentional Binding (i.e., the temporal attraction between a voluntary action and its sensory consequence) as implicit measure. Data show that children and elderly are characterized by a reduced SoAg as compared to adults. These findings provide a fundamental step in the characterization of SoAg dynamics throughout individuals' lifetime.

Neural underpinnings of the 'agent brain': new evidence from transcranial direct current stimulation.

Intentional binding (IB) refers to the temporal compression between a voluntary action and its sensory effect, and it is considered an implicit measure of sense of agency (SoA), that is, the capacity to control one's own actions. IB has been thoroughly studied from a behavioural point of view but only few studies have investigated its neural underpinnings, always using the same two paradigms. Although providing evidence that the supplementary motor complex is involved, findings are still too scarce to draw definitive conclusions. The aim of the present study was to establish a causal relationship between the pre-supplementary motor area (pre-SMA), known for its key role in action planning and initiation, and IB by means of transcranial direct current stimulation (tDCS). Participants underwent anodal, cathodal and sham control stimulations during three separate sessions (Experiment I). Subsequently, they underwent the same stimulation protocol (Experiment II) using as control a region potentially involved in the processing of the sensory effects of voluntary action (i.e., the right primary auditory cortex for the auditory effects of action). A significant reduction in IB was found only after stimulation of the pre-SMA, which supports the causal contribution of this prefrontal area in the perceived linkage between action and its effects. As SoA could be disrupted in many psychiatric and neurological diseases, these results have direct clinical relevance as tDCS could be successfully used in this domain in virtue of the promising advantages it offers for rehabilitation.

One, two, three, four, or is there something more? Numerical discrimination in day-old domestic chicks.

Human adults master sophisticated, abstract numerical calculations that are mostly based on symbolic language and thus inimitably human. Humans may nonetheless share a subset of non-verbal numerical skills, available soon after birth and considered the evolutionary foundation of more complex numerical reasoning, with other animals. These skills are thought to be based on the two systems: the object file system which processes small values (<3) and the analogue magnitude system which processes large magnitudes (>4). Infants' ability to discriminate 1 vs. 2, 1 vs. 3, 2 vs. 3, but not 1 vs. 4, seems to indicate that the two systems are independent, implying that the conception of a continuous number processing system is based on precursors that appear to be interrupted at or about the number four. The findings from the study being presented here indicating that chicks are able to make a series of discriminations regarding that borderline number (1 vs. 4, 1 vs. 5, 2 vs. 4) support the hypothesis that there is continuity in the number system which processes both small and large numerousness.

Neural processing of odor-associated words: an fMRI study in patients with acquired olfactory loss.

Perception of olfactory information is mediated by both bottom-up (from molecules to perception) and top-down (e.g. cross-modal associative learning) processes. Acquired olfactory loss is a frequent disorder which is typically due to alterations in the bottom-up pathway. However, it is unclear how the top-down modulation of olfactory processing is affected by olfactory impairment. Our study aimed to investigate the top-down olfactory processing in patients with acquired olfactory loss and participants with normal olfaction. Using functional MRI, brain responses from 14 patients and 16 healthy controls were assessed during a task of expectation and reading of words with strong olfactory associations (OW) (e.g. "Rose") and control words with little to no olfactory associations (CW) (e.g. "Door"). The expectation but not reading of the OW was associated with stronger neural activation in the angular gyrus and the inferior frontal gyrus extending to insula in the group of patients. During OW reading, the brain activation in the left OFC and right putamen was negatively correlated with odor identification score in patient and control groups, respectively. In addition, the duration of olfactory loss among patients was positively associated with activation in the left putamen during OW expectation. Taken together, these findings suggest an enhanced top-down olfactory modulation in patients with olfactory loss.

Arousal influences olfactory abilities in adults with different degree of food neophobia.

Food neophobia, i.e., the aversion to novel foods, and olfaction are both factors strongly affecting food choices. Mounting evidence suggests a higher arousal towards food as a key factor underlying the reluctance to eat what is unfamiliar to us. As the role of olfaction behind this phenomenon is poorly understood, we explored the associations between food neophobia and trait anxiety, olfactory functions (odor threshold, discrimination and identification) and retronasal aroma release from a reference food in a healthy cohort of 83 adult volunteers. We grouped participants in Low-Neophobics or neophilics (n = 35), Medium-Neophobics (n = 32) and High-Neophobics (n = 16) according to the widely recognized Food Neophobia Scale. Participants with higher neophobic tendencies were found to have marginally higher trait anxiety levels than neophilics (p = 0.10). A lower global olfactory functioning and odor discrimination abilities characterized High-Neophobics, while Medium-Neophobics showed a higher odor sensitiveness than Low-Neophobics. Lastly, High-Neophobics showed a lower extent of retronasal aroma release, likely due to a shorter duration of oral processing and higher anxiety-related physiological responses (such as breathing rate). In summary, this study supports the assumption that the conflicting relationship that neophobics have with food may be led by higher levels of arousal toward foods, rather than different chemosensory functions.

The scent of the other women: Body odor-induced behavioral and physiological effects on face categorization.

In body odor research, the interaction of female donors and receivers is scarcely investigated. With the aim to investigate effects of female body odor in a competitive context, we tested 51 women divided into two groups (i.e., a competitive and a non-competitive group, based on verbal instructions). Between groups, we explored whether female body odor exposure (vs. masker odor) modulates emotion categorization (via RT variance and distribution) and physiological reactions (via instantaneous heart rate) in a task with dynamic male and female faces as either angry or happy. Women in the competitive group reported to feel more competitive and performed more accurately. They gathered more emotional information to categorize dynamic faces and when additionally exposed to female body odor, they showed a resistance to cardiac deceleration. Lapses of attention (via RT distribution) occurred irrespective of body odor exposure. Our results support the idea that female body odors, presented in a competitive context, contrast cardiac deceleration and, by tendency, modulate emotion categorization. Data are discussed in the context of chemosignaling and social interactions among women.

Specific intranasal and central trigeminal electrophysiological responses in Parkinson's disease.

Olfactory dysfunction is a frequent early non-motor symptom of Parkinson's disease (PD). There is evidence that with regard to trigeminal perception, PD-related olfactory dysfunction is different from other olfactory disorders. More specifically, trigeminal sensitivity, when measured behaviorally, was unimpaired in PD patients as opposed to patients with non-Parkinsonian olfactory dysfunction (NPOD). We sought to investigate the trigeminal pathway by measuring electrophysiological recordings from the nasal epithelium and EEG-derived event-related potentials in response to a specific trigeminal stimulus in 21 PD patients and compare them to 23 patients with NPOD and 25 controls (C). The peripheral trigeminal response, as measured by the negative-mucosa potential, showed no difference between patients with PD and controls whereas PD patients showed faster responses than patients with NPOD, the latter having shown slower and larger responses than controls (18 PD, 14 NPOD, 20 C). The central trigeminal response, as measured by event-related potentials, revealed larger early component response in PD patients compared to patients with NPOD (15 PD, 21 NPOD, 23 C). As expected, psychophysical olfactory testing showed impaired olfactory function in both groups of patients as opposed to controls. Discriminant analysis revealed a model that could predict group membership for 80% of participants based on the negative-mucosa potential latency, olfactory threshold and discrimination tests. These results provide novel insights into the pattern of trigeminal activation in PD which will help to differentiate PD-related olfactory loss from NPOD, a crucial step towards establishing early screening batteries for PD including smell tests.

Sensory-specific impairment among older people. An investigation using both sensory thresholds and subjective measures across the five senses.

Age-related sensory impairment is a slow and gradual progress, which affects multiple modalities. Two contradictory hypotheses exist about the age-related decline of sensory thresholds. The common factor theory assumes one underlying factor-which accounts for the loss of several sensory modalities simultaneously-and the specific factor theory predicts that the sensory decline is uncorrelated between different modalities. In this study, we aimed to explore whether (i) there is a common factor of sensory thresholds in older people, (ii) older people assume that sensory decline in one modality also affects other modalities, (iii) there is a relation between sensory threshold and the subjective assessment of sensory function. This was accomplished by collecting both threshold measures and self-reported ratings for smell, hearing, taste, vision, and touch function in a group of 104 older people (mean age: 67.2 years; SD: 9.85; range: 50-100 years). Results indicated that there was no common factor of sensory thresholds, hence an impairment in one modality did not necessarily imply a shortfall in other modalities. In contrast, our results suggested one or two common factor(s) for the participants' ratings. Participants who reported a diminished function in one sense tended to generalize this rating to the other senses as well. The correspondence between subjective ratings and sensory thresholds was relatively good for vision and audition, although no correlations were observed for the other domains. These findings have implications for clinicians, suggesting that subjective measures should be combined with sensory threshold measurements when evaluating sensory dysfunction. Also, these data convey a positive message for older people and their physicians by showing that loss in one sensory modality does not necessarily generalize to losses across all sensory modalities.

Postinfectious olfactory loss: A retrospective study on 791 patients.

OBJECTIVES/HYPOTHESIS: Postinfectious olfactory loss is among the most common causes of olfactory impairment and has substantial negative impact on patients' quality of life. Recovery rates have been shown to spontaneously improve in most of patients, usually within 2 to 3 years. However, existing studies are limited by small sample sizes and short follow-up. We aimed to assess the prognostic factors for recovery in a large sample of 791 patients with postinfectious olfactory disorders. STUDY DESIGN: Retrospective cohort. METHODS: We performed a retrospective analysis of 791 patients with postinfectious olfactory loss. Olfactory functions were assessed using the Sniffin' Sticks test at the first and final visits (mean follow-up = 1.94 years). RESULTS: Smell test scores improved over time. In particular, patient's age and the odor threshold (T), odor discrimination (D), and odor identification (I) (TDI) score at first visit were significant predictors of the extent of change. The percentage of anosmic and hyposmic patients exhibiting clinically significant improvement was 46% and 35%, respectively. CONCLUSIONS: This study provides new evidence within the postinfectious olfactory loss literature, shedding light on the prognostic factors and showing that recovery of olfactory function is very frequent, even many years after the infection. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:10-15, 2018.

Electro-olfactogram Responses Before and After Aversive Olfactory Conditioning in Humans.

The aim of the present study was to investigate whether repetitive aversive odor conditioning induced changes at the level of the peripheral olfactory system in humans. A total of 51 volunteers participated. A pair of indistinguishable odor enantiomers [(+)-rose oxide and (-)-rose oxide] were used as stimuli. During the pre-conditioning, participants' ability to discriminate between the two odors was assessed using a three-alternative, forced-choice discrimination test. In addition, electro-olfactograms (EOG) from the olfactory epithelium were recorded. Participants underwent three conditioning sessions on consecutive days. The experimental group received an electrical stimulus to the forearm only following (+)-rose oxide presentation, whereas its enantiomer sibling was never paired with the aversive stimulus; the control group did not receive any electrical stimulation. During the post-conditioning session, their ability to discriminate the two enantiomers was assessed again using the discrimination test and EOG recordings were obtained similarly to the pre-conditioning session. Results showed significant differences in the peripheral electrophysiological responses between the conditioned and the unconditioned stimulus, demonstrating contextually induced changes at the level of the first neuron in the olfactory system.

Indistinguishable odour enantiomers: Differences between peripheral and central-nervous electrophysiological responses.

The ability of humans to discriminate enantiomeric odour pairs is substance -specific. Current literature suggests that psychophysical discrimination of odour enantiomers mainly depends on the peripheral processing at the level of the olfactory sensory neurons (OSN). To study the influence of central processing in discrimination, we investigated differences in the electrophysiological responses to psychophysically indistinguishable (+)- and (-)- rose oxide enantiomers at peripheral and central-nervous levels in humans. We recorded the electro-olfactogram (EOG) from the olfactory epithelium and the EEG-derived olfactory event-related potentials (OERP). Results from a psychophysical three alternative forced choice test indicated indistinguishability of the two odour enantiomers. In a total of 19 young participants EOG could be recorded in 74 and OERP in 95% of subjects. Significantly different EOG amplitudes and latencies were recorded in response to the 2 stimuli. However, no such differences in amplitude or latency emerged for the OERP. In conclusion, although the pair of enantiomer could be discriminated at a peripheral level this did not lead to a central-nervous/cognitive differentiation of the two stimuli.

It's a Matter of Mind! Cognitive Functioning Predicts the Athletic Performance in Ultra-Marathon Runners.

The present study was aimed at exploring the influence of cognitive processes on performance in ultra-marathon runners, providing an overview of the cognitive aspects that characterize outstanding runners. Thirty runners were administered a battery of computerized tests right before their participation in an ultra-marathon. Then, they were split according to the race rank into two groups (i.e., faster runners and slower runners) and their cognitive performance was compared. Faster runners outperformed slower runners in trials requiring motor inhibition and were more effective at performing two tasks together, successfully suppressing the activation of the information for one of the tasks when was not relevant. Furthermore, slower runners took longer to remember to execute pre-defined actions associated with emotional stimuli when such stimuli were presented. These findings suggest that cognitive factors play a key role in running an ultra-marathon. Indeed, if compared with slower runners, faster runners seem to have a better inhibitory control, showing superior ability not only to inhibit motor response but also to suppress processing of irrelevant information. Their cognitive performance also appears to be less influenced by emotional stimuli. This research opens new directions towards understanding which kinds of cognitive and emotional factors can discriminate talented runners from less outstanding runners.

Intentional binding effect in children: insights from a new paradigm.

Intentional binding (IB) refers to the temporal attraction between a voluntary action and its sensory consequence. Since its discovery in 2002, it has been considered to be a valid implicit measure of sense of agency (SoA), since it only occurs in the context of voluntary actions. The vast majority of studies considering IB have recruited young adults as participants, while neglecting possible age-related differences. The aim of the present work is to study the development of IB in 10-year-old children. In place of Libet's classical clock method, we decided to implement a new and more suitable paradigm in order to study IB, since children could have some difficulties in dealing with reading clocks. A stream of unpredictable letters was therefore used: participants had to remember which letter was on the screen when they made a voluntary action, heard a sound, or felt their right index finger moved down passively. In Experiment I, a group of young adults was tested in order to replicate the IB effect with this new paradigm. In Experiment II, the same paradigm was then administered to children in order to investigate whether such an effect has already emerged at this age. The data from Experiment I showed the presence of the IB effect in adults. However, Experiment II demonstrated a clear reduction of IB. The comparison of the two groups revealed that the young adult group differed from the children, showing a significantly stronger linkage between actions and their consequences. The results indicate a developmental trend in the IB effect. This finding is discussed in light of the maturation process of the frontal cortical network.

Clinical psychological and neuropsychological issues with left ventricular assist devices (LVADs).

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly being used to treat patients in end-stage heart failure (HF) as bridge-to-transplantation, lifetime support or destination therapy. However, the importance of this newer technique for chronic cardiac support compared to heart transplantation is still open to discussion. To date, there are few studies that extensively explore the psychological and cognitive profiles of patient with ventricular assist devices (VADs). METHODS: We studied the psychological aspects, quality of life (QOL) and cognitive profiles of 19 patients with HF before VAD implantation and then at two, five and 16 months post-implantation. RESULTS: Our results showed that after VAD implantation, patients did not show any psychopathological problems such as anxiety and/or depression. More interestingly, despite the constant risk of neurological events determined by the continuous-blood-flow pump (CBFP), patients' cognitive functioning did not worsen. In fact, significant enhancements were observed over time. CONCLUSIONS: Psychological and cognitive deficits are common in advanced HF and often worsen over time. Appropriately designed and randomized studies are needed to demonstrate whether earlier VAD implantation is warranted to arrest cognitive decline and encourage better post-implantation adaptation.