Prediction of thigh skeletal muscle mass using dual energy x-ray absorptiometry compared to magnetic resonance imaging after spinal cord injury.

Objectives: A rapid decline in lean mass (LM), fat-free mass (FFM) and increased intramuscular fat (IMF) predispose persons with spinal cord injury (SCI) to chronic medical conditions including dyslipidemia, insulin resistance, type 2 diabetes mellitus and cardiovascular disease. (1) To determine the relationship between dual energy x ray absorptiometry (DXA) and gold standard magnetic resonance imaging (MRI) LM values; (2) to develop predictive equations based on this relationship for assessing thigh LM in persons with chronic SCI. Study Design: Cross-sectional predicational design. Settings: Clinical research medical center. Participants: Thirty-two men with chronic (>1 y post-injury) motor complete SCI. Methods: Participants completed total body DXA scans to determine thigh LM and were compared to measurements acquired from trans-axial MRI. Outcome measures: MRI was used to measure whole muscle mass (MMMRI-WM), absolute muscle mass (MMMRI-ABS) after excluding IMF, and knee extensor muscle mass (MMMRI-KE). DXA was used to measure thigh LM (LMDXA) and (FFMDXA). To predict MMMRI-KE, LMDXA was multiplied by 0.52 and yielded LMDXA-KE. Results: LMDXA predicted MMMRI-WM [r2 = 0.90, standard error of the estimate (SEE) = 0.23 kg, P < 0.0001] and MMMRI-ABS (r2 = 0.82, SEE = 0.28 kg, P < 0.0001). LMDXA-KE predicted MMMRI-KE (r2 = 0.78, SEE = 0.16 kg, P < 0.0001). Conclusion: DXA measurements revealed an acceptable agreement with the gold standard MRI and may be a viable alternative for assessing thigh skeletal muscle mass after SCI.

Predicting odor perceptual similarity from odor structure.

To understand the brain mechanisms of olfaction we must understand the rules that govern the link between odorant structure and odorant perception. Natural odors are in fact mixtures made of many molecules, and there is currently no method to look at the molecular structure of such odorant-mixtures and predict their smell. In three separate experiments, we asked 139 subjects to rate the pairwise perceptual similarity of 64 odorant-mixtures ranging in size from 4 to 43 mono-molecular components. We then tested alternative models to link odorant-mixture structure to odorant-mixture perceptual similarity. Whereas a model that considered each mono-molecular component of a mixture separately provided a poor prediction of mixture similarity, a model that represented the mixture as a single structural vector provided consistent correlations between predicted and actual perceptual similarity (r≥0.49, p<0.001). An optimized version of this model yielded a correlation of r = 0.85 (p<0.001) between predicted and actual mixture similarity. In other words, we developed an algorithm that can look at the molecular structure of two novel odorant-mixtures, and predict their ensuing perceptual similarity. That this goal was attained using a model that considers the mixtures as a single vector is consistent with a synthetic rather than analytical brain processing mechanism in olfaction.

Perceptual convergence of multi-component mixtures in olfaction implies an olfactory white.

In vision, two mixtures, each containing an independent set of many different wavelengths, may produce a common color percept termed "white." In audition, two mixtures, each containing an independent set of many different frequencies, may produce a common perceptual hum termed "white noise." Visual and auditory whites emerge upon two conditions: when the mixture components span stimulus space, and when they are of equal intensity. We hypothesized that if we apply these same conditions to odorant mixtures, "whiteness" may emerge in olfaction as well. We selected 86 molecules that span olfactory stimulus space and individually diluted them to a point of about equal intensity. We then prepared various odorant mixtures, each containing various numbers of molecular components, and asked human participants to rate the perceptual similarity of such mixture pairs. We found that as we increased the number of nonoverlapping, equal-intensity components in odorant mixtures, the mixtures became more similar to each other, despite not having a single component in common. With ~30 components, most mixtures smelled alike. After participants were acquainted with a novel, arbitrarily named mixture of ~30 equal-intensity components, they later applied this name more readily to other novel mixtures of ~30 equal-intensity components spanning stimulus space, but not to mixtures containing fewer components or to mixtures that did not span stimulus space. We conclude that a common olfactory percept, "olfactory white," is associated with mixtures of ~30 or more equal-intensity components that span stimulus space, implying that olfactory representations are of features of molecules rather than of molecular identity.

Hedonic-specific activity in piriform cortex during odor imagery mimics that during odor perception.

Although it is known that visual imagery is accompanied by activity in visual cortical areas, including primary visual cortex, whether olfactory imagery exists remains controversial. Here we asked whether cue-dependent olfactory imagery was similarly accompanied by activity in olfactory cortex, and in particular whether hedonic-specific patterns of activity evident in olfactory perception would also be present during olfactory imagery. We used functional magnetic resonance imaging to measure activity in subjects who alternated between smelling and imagining pleasant and unpleasant odors. Activity induced by imagining odors mimicked that induced by perceiving real odorants, not only in the particular brain regions activated, but also in its hedonic-specific pattern. For both real and imagined odors, unpleasant stimuli induced greater activity than pleasant stimuli in the left frontal portion of piriform cortex and left insula. These findings combine with findings from other modalities to suggest activation of primary sensory cortical structures during mental imagery of sensory events.

Predicting odor pleasantness from odorant structure: pleasantness as a reflection of the physical world.

Although it is agreed that physicochemical features of molecules determine their perceived odor, the rules governing this relationship remain unknown. A significant obstacle to such understanding is the high dimensionality of features describing both percepts and molecules. We applied a statistical method to reduce dimensionality in both odor percepts and physicochemical descriptors for a large set of molecules. We found that the primary axis of perception was odor pleasantness, and critically, that the primary axis of physicochemical properties reflected the primary axis of olfactory perception. This allowed us to predict the pleasantness of novel molecules by their physicochemical properties alone. Olfactory perception is strongly shaped by experience and learning. However, our findings suggest that olfactory pleasantness is also partially innate, corresponding to a natural axis of maximal discriminability among biologically relevant molecules.

Smelling a single component of male sweat alters levels of cortisol in women.

Rodents use chemosignals to alter endocrine balance in conspecifics. Although responses to human sweat suggest a similar mechanism in humans, no particular component of human sweat capable of altering endocrine balance in conspecifics has yet been isolated and identified. Here, we measured salivary levels of the hormone cortisol in women after smelling pure androstadienone (4,16-androstadien-3-one), a molecule present in the sweat of men that has been suggested as a chemosignal in humans. We found that merely smelling androstadienone maintained significantly higher levels of the hormone cortisol in women. These results suggest that, like rodents, humans can influence the hormonal balance of conspecifics through chemosignals. Critically, this study identified a single component of sweat, androstadienone, as capable of exerting such influence. This result points to a potential role for synthetic human chemosignals in clinical applications.

Mechanisms of scent-tracking in humans.

Whether mammalian scent-tracking is aided by inter-nostril comparisons is unknown. We assessed this in humans and found that (i) humans can scent-track, (ii) they improve with practice, (iii) the human nostrils sample spatially distinct regions separated by approximately 3.5 cm and, critically, (iv) scent-tracking is aided by inter-nostril comparisons. These findings reveal fundamental mechanisms of scent-tracking and suggest that the poor reputation of human olfaction may reflect, in part, behavioral demands rather than ultimate abilities.

A comparison of methods for sniff measurement concurrent with olfactory tasks in humans.

There is a growing appreciation for the role of sniffing in the formation of the olfactory percept. With this in mind, monitoring and measurement of sniffing is an important aspect of olfactory experiments. There are several methods for measuring human sniffs concurrent with odor delivery in olfactory experiments. Here, we set out to compare the temporal sensitivity and power of these different methods by applying them all simultaneously with an olfactory task. We discuss the advantages and disadvantages of each method and conclude in recommending the use of a nasal cannula linked to a pressure sensor whenever possible.

Brain mechanisms for extracting spatial information from smell.

Forty years ago, von Békésy demonstrated that the spatial source of an odorant is determined by comparing input across nostrils, but it is unknown how this comparison is effected in the brain. To address this, we delivered odorants to the left or right of the nose, and contrasted olfactory left versus right localization with olfactory identification during brain imaging. We found nostril-specific responses in primary olfactory cortex that were predictive of the accuracy of left versus right localization, thus providing a neural substrate for the behavior described by von Békésy. Additionally, left versus right localization preferentially engaged a portion of the superior temporal gyrus previously implicated in visual and auditory localization, suggesting that localization information extracted from smell was then processed in a convergent brain system for spatial representation of multisensory inputs.

Neural processing at the speed of smell.

Olfaction is typically described as behaviorally slow, suggesting neural processes on the order of hundreds of milliseconds to seconds as candidate mechanisms in the creation of olfactory percepts. Whereas a recent study challenged this view in suggesting that a single sniff was sufficient for optimal olfactory discrimination, a study by Abraham et al. in this issue of Neuron sets out to negate the challenge by demonstrating increased processing time for discrimination of similar versus dissimilar stimuli. Here we reconcile both studies, which in our view together support the notion of a speed-accuracy tradeoff in olfactory discriminations that are made within about 200 ms. These findings are discussed in light of the challenges related to defining olfactory perceptual similarity in nonhuman animals.

The prevalence of androstenone anosmia.

It has been estimated that approximately 30% of the population is unable to detect the odor of androstenone. These estimates, however, were made using tests and criteria optimized for identifying detection. Such criteria favor Type II over Type I errors--that is, they are excellent at identifying true detectors at the cost of erroneously labeling some detectors as non-detectors. Because these criteria were used to identify non-detectors, it is possible that the rate of non-detection may have been overestimated. To test this we screened 55 subjects for non-detection employing previously used methods. This screen yielded nine putative non-detectors, a 16.3% putative non-detection rate. We then retested these putative non-detectors using a forced choice (yes-no) paradigm to obtain a precise measure of their sensitivity. We found that this group of putative non-detectors was significantly above chance at detecting androstenone (P < 0.001), despite very low self-confidence in their performance. Based on the results of the signal detection analysis in this sample, we estimate the rate of actual androstenone non-detection in young healthy adults is between 1.8 and 5.96%, which is significantly lower than previously estimated. This finding is significant considering the implications of specific anosmias on the understanding of odor discrimination.