Johan N. Lundström

Identification of human gustatory cortex by activation likelihood estimation

Over the last two decades, neuroimaging methods have identified a variety of taste‐responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta‐analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region‐of‐interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional “taste map” which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted. Hum Brain Mapp, 2011.

The Scent of Disease Human Body Odor Contains an Early Chemosensory Cue of Sickness

Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals’ level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a “behavioral immune response” that protects healthy individuals from sick ones by altering patterns of interpersonal contact.

Psychological effects of subthreshold exposure to the putative human pheromone 4,16-androstadien-3-one

Research on human putative pheromones has recently focused on the effects of exposure to 4,16-androstadien-3-one (androstadienone). This steroid has been observed in the skin, axillary hair, and blood plasma, primarily in males. In addition to effects of the steroid on measures of physiological arousal and brain blood flow, positive mood effects have also been reported. The current study further investigated mood effects of androstadienone exposure (250 microM) in women in two experiments. Through psychophysical testing of each individual we controlled for whether any observed mood effects could be related to sensory detection of the steroid. In both experiments, we observed positive changes of womens feeling of being focused, which could not be related to sensory detection of the steroid. Overall, the patterns of results were significantly correlated between the two experiments. In conclusion, this study corroborates earlier findings suggesting that androstadienone exposure yields effects on womens mood; the feeling of being focused. The mood effects were not dependent on menstrual cycle phase. Further, these effects are replicable and occur also when androstadienone detection is rigorously controlled for across variation in menstrual cycle.

Subthreshold amounts of social odorant affect mood, but not behavior, in heterosexual women when tested by a male, but not a female, experimenter

Previously, we have demonstrated that exposure to the endogenous steroid androstadienone has the ability to modulate womens mood in that they feel more focused [Lundstrom, J.N., Goncalves, M., Esteves, F., Olsson, M.J., 2003a. Psychological effects of subthreshold exposure to the putative human pheromone 4,16-androstadien-3-one. Hormones and Behaviour 44 (5), 395-401]. Here, we tested the hypothesis that androstadienone exposure would modulate participating womens mood and corresponding behavior as measured by a sustained attention task. Thirty-seven women participated in a double-blind, within-group experiment and were tested by either a female or a male experimenter. Effects on mood, psychophysiological arousal, sustained attention, and ratings of male facial attractiveness were assessed. Sensory detection of the experimental substance was rigorously controlled for by psychophysical testing. The results showed that exposure to a non-detectable amount of androstadienone modulated womens psychophysiological arousal and mood in a positive direction but did not change attention performance or rating of facial attractiveness. Moreover, mood effects were only evident when an experimenter of the opposite sex conducted the testing. This suggests that social context is important for mood effects of androstadienone exposure in women.

Statistical localization of human olfactory cortex

Functional neuroimaging methods have been used extensively during the last decades to explore the neural substrates of olfactory processing. While a general consensus on the functional anatomy of olfactory cortex is beginning to emerge, the mechanisms behind the functions of individual processing nodes still remain debated. Further, it remains unclear to which extent divergent findings result from differences in methodological approaches. Using Activation Likelihood Estimation (ALE), the aim of the present study was to statistically combine all published data on functional neuroimaging of olfaction to provide a probability map reflecting the state of the field to date. Additionally, we grouped studies according to various methodological approaches to investigate whether these systematically affected the reported findings. A total of 45 studies (69 contrasts, 594 foci) met our inclusion criteria. Significant ALE peaks for odor against baseline were observed in areas commonly labeled as primary and secondary olfactory cortex, such as the piriform and orbitofrontal cortex, amygdala, anterior insula, and ventral putamen. In addition, differences were observed in the extent to which different methods were able to induce activation in these different nodes of the olfactory network.

The neuronal correlates of intranasal trigeminal function—an ALE meta-analysis of human functional brain imaging data

Almost every odor we encounter in daily life has the capacity to produce a trigeminal sensation. Surprisingly, few functional imaging studies exploring human neuronal correlates of intranasal trigeminal function exist, and results are to some degree inconsistent. We utilized activation likelihood estimation (ALE), a quantitative voxel-based meta-analysis tool, to analyze functional imaging data (fMRI/PET) following intranasal trigeminal stimulation with carbon dioxide (CO(2)), a stimulus known to exclusively activate the trigeminal system. Meta-analysis tools are able to identify activations common across studies, thereby enabling activation mapping with higher certainty. Activation foci of nine studies utilizing trigeminal stimulation were included in the meta-analysis. We found significant ALE scores, thus indicating consistent activation across studies, in the brainstem, ventrolateral posterior thalamic nucleus, anterior cingulate cortex, insula, precentral gyrus, as well as in primary and secondary somatosensory cortices-a network known for the processing of intranasal nociceptive stimuli. Significant ALE values were also observed in the piriform cortex, insula, and the orbitofrontal cortex, areas known to process chemosensory stimuli, and in association cortices. Additionally, the trigeminal ALE statistics were directly compared with ALE statistics originating from olfactory stimulation, demonstrating considerable overlap in activation. In conclusion, the results of this meta-analysis map the human neuronal correlates of intranasal trigeminal stimulation with high statistical certainty and demonstrate that the cortical areas recruited during the processing of intranasal CO(2) stimuli include those outside traditional trigeminal areas. Moreover, through illustrations of the considerable overlap between brain areas that process trigeminal and olfactory information; these results demonstrate the interconnectivity of flavor processing.

Gustatory and olfactory dysfunction in older adults: a national probability study

BACKGROUND Olfactory and gustatory functions have not been well characterized in older adults in the US. Consequently, their relationships to sociodemographic characteristics, as well as physical and mental health, were studied in a large national probability sample using brief validated tests of chemosensory function. METHODS A five-odour identification test and taste-impregnated strips of filter paper (sweet, sour, bitter, and salty) assessed the ability to identify chemosensory stimuli. RESULTS Severe gustatory dysfunction was more prevalent than severe olfactory dysfunction. Age, education and sex were independently associated with performance on both the olfactory and gustatory identification tasks. Higher scores were associated with female sex, higher level of education, and lower age. Odour identification scores exhibited a positive, albeit weak, correlation with BMI, and food-related odours were better identified than non-food odours. In addition, odour identification performance was also negatively associated with depressive symptoms. CONCLUSIONS These data demonstrate a high prevalence of severe gustatory and, to a somewhat lesser extent, olfactory dysfunction in a population-based sample and demonstrate that even brief tests are capable of detecting correlations between both chemical senses and relevant health measures outside a clinical setting.

The Human Brain Distinguishes between Single Odorants and Binary Mixtures

Single odors are processed differently from odor mixtures in the cortex of rodents. We investigated whether single and binary odor mixtures activate different regions also in the human brain. We analyzed data from positron emission tomography scans using pyridine, citral, and 5 mixtures of pyridine and citral in proportions varying from 10/90 to 90/10, with 50/50 being the most impure. Comparing mixtures with single odorants gave activation in the left cingulate and right parietal and superior frontal cortices and bilateral activation in the anterior and lateral orbitofrontal cortices. We also found that brain activity in the lateral orbitofrontal cortex (OFC) increased with odorant impurity, whereas the anterior OFC was activated for binary odor mixtures and deactivated for single components. We conclude that binary odor mixtures and their individual components are processed differently by the human brain. The lateral portion of the OFC responds to mixture impurity in a graded fashion, whereas the anterior portion acts like an on-off detector of odor mixtures.

Multisensory integration mechanisms during aging.

The rapid demographical shift occurring in our society implies that understanding of healthy aging and age-related diseases is one of our major future challenges. Sensory impairments have an enormous impact on our lives and are closely linked to cognitive functioning. Due to the inherent complexity of sensory perceptions, we are commonly presented with a complex multisensory stimulation and the brain integrates the information from the individual sensory channels into a unique and holistic percept. The cerebral processes involved are essential for our perception of sensory stimuli and becomes especially important during the perception of emotional content. Despite ongoing deterioration of the individual sensory systems during aging, there is evidence for an increase in, or maintenance of, multisensory integration processing in aging individuals. Within this comprehensive literature review on multisensory integration we aim to highlight basic mechanisms and potential compensatory strategies the human brain utilizes to help maintain multisensory integration capabilities during healthy aging to facilitate a broader understanding of age-related pathological conditions. Further our goal was to identify where further research is needed.

Neuroanatomical correlates of olfactory performance

We investigated associations between olfactory function and gray matter thickness in 46 healthy young subjects by means of an automated technique for measuring cortical thickness. We used an extended version of the Sniffin’ Sticks test to assess olfactory function, including odor threshold, concentration discrimination, quality discrimination, and odor identification. We observed a correlation between olfactory performance and cortical thickness of structures involved in earlier and later stages of chemosensory processing such as right medial orbitofrontal cortex, right insula, and adjacent cortex. Furthermore, we found significant bilateral correlations of olfactory performance with cortical thickness of areas around the central sulcus bilaterally, structures responsible for voluntary respiration and sniffing. In addition to expected general sex effects on cortical thickness, we observed areas, such as the entorhinal cortex, occipital cortex, intraparietal sulcus and insula (all in the right hemisphere), where the correlation between higher order olfactory functions and cortical thickness differed between women and men. These data demonstrate, for some neuroanatomical structures, a link between cortical thickness and olfactory function, in that thicker cortex is usually associated with better performance, but not always. This association between anatomy and olfactory performance suggests a possible biological explanation for the high degree of individual differences and sex effects observed in higher order olfactory tasks.